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Sample records for patients eventually relapse

  1. The eventual outcome of patients who had lower limb amputations ...

    African Journals Online (AJOL)

    C De Klerk

    Background: Peripheral vascular disease (PVD) presenting with irreversible lower limb pathology has a high morbidity and mortality rate. This study aimed to determine the outcome of patients who underwent lower limb amputations (LLAs) because of PVD at Pelonomi Hospital, Bloemfontein, 2008–2011. Methods: ...

  2. Patient and family physician preferences for care and communication in the eventuality of anthrax terrorism.

    Science.gov (United States)

    Kahan, Ernesto; Fogelman, Yacov; Kitai, Eliezer; Vinker, Shlomo

    2003-08-01

    The threat of bioterrorism consequent to the September 11, 2001 attack in the USA generated suggestions for improved medical response mainly through hospital preparedness. The aim of the present study was to investigate the impact of this period of tension on patients' first choice for care and for receiving relevant information, and on primary care doctors' feelings of responsibility in the eventuality of an anthrax attack. During October 11-31, 2001, 500 patients from 30 clinics throughout Israel were asked to complete a questionnaire on their awareness of the anthrax threat, measures taken to prepare for it, and preferred sources of care and information. Their 30 physicians, and an additional 20, completed a questionnaire on knowledge about anthrax and anthrax-related patient behaviours and clinic visits. The outstanding finding was the low rate (30%) of patients who chose the hospital emergency department as their first choice for care or information if they were worried about an anthrax attack or the media communicated that an attack was in progress. The other two-thirds preferred their family doctor or the health authorities. Most of the physicians (89%) felt it was their responsibility to treat anthrax-infected patients and that they should therefore be supplied with appropriate guidelines. This study suggests that in Israel, a country with a high degree of awareness of civil defence aspects, both patients and primary care doctors believe that family physicians should have a major role in the case of bioterrorist attacks. This must be seriously considered during formulation of relevant health services programmes.

  3. An intervention study to prevent relapse in patients with schizophrenia

    NARCIS (Netherlands)

    van Meijel, B.; Kruitwagen, C.; van der Gaag, M.; Kahn, R.S.; Grypdonck, M.H.E.

    2006-01-01

    Purpose: To determine whether the use of relapse prevention plans (RPPs) in nursing practice is an effective intervention in reducing relapse rates among patients with schizophrenia. Design and Methods: Experimental design. Patients with schizophrenia (or a related psychotic disorder) and nurses

  4. Relapse prevention in anorexia nervosa: Experiences of patients and parents.

    Science.gov (United States)

    Berends, Tamara; van de Lagemaat, Marleen; van Meijel, Berno; Coenen, Jasmijn; Hoek, Hans W; van Elburg, Annemarie A

    2018-03-24

    One of the main aims of treatment after successful recovery from anorexia nervosa (AN) is to prevent a relapse. The Guideline Relapse Prevention (GRP) Anorexia Nervosa offers a structured approach to relapse prevention. This study explores how patients and their parents experience working with the guideline. It also describes the factors that support or hinder successful application of the guideline. A descriptive qualitative research design was chosen involving in-depth interviews with seventeen patients with anorexia nervosa and six sets of parents. Patients and family members were generally satisfied with the support provided by the GRP. It contributed significantly to a better understanding of the personal process of relapse. Patients and families valued being able to keep in touch with their professional during the aftercare programme. The GRP supports the patient's use of self-management strategies for relapse prevention. © 2018 Australian College of Mental Health Nurses Inc.

  5. Predictive factors for relapse in patients on buprenorphine maintenance.

    Science.gov (United States)

    Ferri, Michael; Finlayson, Alistair J Reid; Wang, Li; Martin, Peter R

    2014-01-01

    Despite the dramatic increase in the use of buprenorphine for the treatment of opioid dependence, clinical outcomes of this treatment approach continue to need evaluation. This study examines factors associated with relapse and retention during buprenorphine treatment in a sample of opioid dependent outpatients. In a retrospective chart review of 62 patients with opioid dependence, relapse was determined by self-report, urine toxicology screens, and by checking the state controlled substance monitoring database. Data was analyzed using two-way tests of association and logistic regression. Patients with comorbid anxiety disorders, active benzodiazepine use (contrary to clinic policy), or active alcohol abuse, were significantly more likely to relapse. Patients who relapsed were also more likely to be on a higher buprenorphine maintenance dose. This study identifies relapse risk factors during buprenorphine treatment for opioid dependence. Future research is needed to determine whether modifying these factors may lead to improved treatment outcomes. © American Academy of Addiction Psychiatry.

  6. Relapse prevention in patients with schizophrenia : A nursing intervention study

    NARCIS (Netherlands)

    Meijel, Berno van

    2003-01-01

    This thesis describes a study into the development and testing of a nursing intervention with a view to preventing psychotic relapses in patients suffering from schizophrenia or a related disorder. The purpose of the intervention is to recognise the early signs of an oncoming psychotic relapse. If

  7. Relapse of Legionella longbeachae infection in an immunocompromised patient

    NARCIS (Netherlands)

    van't Hullenaar, N. G.; van Ketel, R. J.; Kuijper, E. J.; Bakker, P. J.; Dankert, J.

    1996-01-01

    We describe the first known case of Legionella longbeachae infection in the Netherlands in a patient with myasthenia gravis. Infection with L. longbeachae relapsed after prolonged therapy with erythromycin. No environmental source of L. longbeachae could be traced

  8. Late Relapses in Stage I Testicular Cancer Patients on Surveillance

    DEFF Research Database (Denmark)

    Mortensen, Mette Saksø; Lauritsen, Jakob; Kier, Maria Gry Gundgaard

    2016-01-01

    Cancer (DaTeCa) database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We estimated survival and relapse probabilities and compared the results using log-rank tests and Cox regression analyses. We compared differences in patient characteristics by using χ(2), Fisher exact, and Mann-Whitney tests...... no significant differences in patient characteristics at orchiectomy or relapse. Limitations include retrospective design and exclusion of patients who had been offered adjuvant therapy. CONCLUSIONS: The risk of VLR is minimal, and the patients carry a good prognosis. Patient characteristics of CS-1 surveillance...

  9. Burden of a multiple sclerosis relapse: the patient's perspective.

    Science.gov (United States)

    Oleen-Burkey, Merrikay; Castelli-Haley, Jane; Lage, Maureen J; Johnson, Kenneth P

    2012-01-01

    Relapses are a common feature of relapsing-remitting multiple sclerosis (RRMS) and increasing severity has been shown to be associated with higher healthcare costs, and to result in transient increases in disability. Increasing disability likely impacts work and leisure productivity, and lowers quality of life. The objective of this study was to characterize from the patient's perspective the impact of a multiple sclerosis (MS) relapse in terms of the economic cost, work and leisure productivity, functional ability, and health-related quality of life (HR-QOL), for a sample of patients with RRMS in the US treated with immunomodulatory agents. A cross-sectional, web-based, self-report survey was conducted among members of MSWatch.com, a patient support website now known as Copaxone.com. Qualified respondents in the US had been diagnosed with RRMS and were using an immunomodulatory agent. The survey captured costs of RRMS with questions about healthcare resource utilization, use of community services, and purchased alterations and assistive items related to MS. The Work and Leisure Impairment instrument and the EQ-5D were used to measure productivity losses and HR-QOL (health utility), respectively. The Goodin MS neurological impairment questionnaire was used to measure functional disability; questions were added about relapses in the past year. Of 711 qualified respondents, 67% reported having at least one relapse during the last year, with a mean of 2.2 ± 2.3 relapses/year. Respondents who experienced at least one relapse had significantly higher mean annual direct and indirect costs compared with those who did not experience a relapse ($US38 458 vs $US28 669; p = 0.0004) [year 2009 values]. Direct health-related costs accounted for the majority of the increased cost ($US5201; 53%) and were mainly due to increases in hospitalizations, medications, and ambulatory care. Indirect costs, including informal care and productivity loss, accounted for the

  10. Irinotecan for relapsed Wilms tumor in pediatric patients

    DEFF Research Database (Denmark)

    Hol, Janna A; van den Heuvel-Eibrink, Marry M; Graf, Norbert

    2018-01-01

    While irinotecan has been studied in various pediatric solid tumors, its potential role in Wilms tumor (WT) is less clear. We evaluated response and outcome of irinotecan-containing regimens in relapsed WT and compared our results to the available literature. Among 14 evaluable patients, one...

  11. Post-relapse survival in patients with Ewing sarcoma.

    Science.gov (United States)

    Ferrari, Stefano; Luksch, Roberto; Hall, Kirsten Sundby; Fagioli, Franca; Prete, Arcangelo; Tamburini, Angela; Tienghi, Amelia; DiGirolamo, Stefania; Paioli, Anna; Abate, Massimo Eraldo; Podda, Marta; Cammelli, Silvia; Eriksson, Mikael; Brach del Prever, Adalberto

    2015-06-01

    Post-relapse survival (PRS) was evaluated in patients with Ewing sarcoma (EWS) enrolled in chemotherapy protocols based on the use of high-dose chemotherapy with busulfan and melfalan (HDT) as a first-line consolidation treatment in high-risk patients. EWS patients enrolled in ISG/SSG III and IV trials who relapsed after complete remission were included in the analysis. At recurrence, chemotherapy based on high-dose ifosfamide was foreseen, and patients who responded but had not received HDT underwent consolidation therapy with HDT. Data from 107 EWS patients were included in the analysis. Median time to recurrence (RFI) was 18 months, and 45 (42%) patients had multiple sites of recurrence. Patients who had previously been treated with HDT had a significantly (P = 0.02) shorter RFI and were less likely to achieve a second complete remission (CR2). CR2 status was achieved by 42 (39%) patients. Fifty patients received high-dose IFO (20 went to consolidation HDT). The 5-year PRS was 19% (95% CI 11 to 27%). With CR2, the 5-year PRS was 48% (95% CI 31 to 64%). Without CR2, median time to death was six months (range 1-45 months). According to the multivariate analysis, patients younger than 15 years, recurrence to the lung only, and RFI longer than 24 months significantly influenced the probability of PRS. Age, pattern of recurrence, RFI, and response to second-line chemotherapy influence post-relapse survival in patients with recurrent Ewing sarcoma. No survival advantage was observed from chemotherapy consolidation with HDT. © 2015 Wiley Periodicals, Inc.

  12. Predictors of Long-Term Remission and Relapse of Type 2 Diabetes Mellitus Following Gastric Bypass in Severely Obese Patients.

    Science.gov (United States)

    de Oliveira, Vanessa Lopes Preto; Martins, Gianluca P; Mottin, Cláudio C; Rizzolli, Jacqueline; Friedman, Rogério

    2018-01-01

    Diabetes remission is not observed in all obese patients with type 2 diabetes submitted to bariatric surgery. Relapses occur in patients in whom remission is achieved. We investigated the factors associated with long-term (≥3 years) remission and relapse of type 2 diabetes after Roux-en-Y gastric bypass (RYGB) in these patients. By a retrospective review, we analyzed data from 254 patients with type 2 diabetes who had undergone RYGB from May 2000 to November 2011 and had at least 3 years of follow-up. The criteria for remission and relapse of type 2 diabetes followed the current American Diabetes Association recommendations. Remission was achieved in almost 82% of participants (69.7% complete, and 12.2% partial remission). Of these, 12% relapsed within a mean follow-up of 5.1 ± 2.0 years after surgery. Predictors of complete remission were younger age, better preoperative glycemic control, and shorter diabetes duration. Preoperative insulin use was associated with a ninefold increase in the relapse hazard (HR = 9.1 (95% CI: 3.3-25.4)). Use of two or more oral anti-diabetic agents increased the relapse hazard sixfold (HR = 6.1 (95% CI: 1.8-20.6)). Eighteen point one percent of patients did not achieve any remission during follow-up. However, they exhibited significant improvements in glycemic control. These data indicate that RYGB should not be delayed when remission of type 2 diabetes is a therapeutic goal, and also suggest that the best possible metabolic control should be sought in obese patients who may eventually be candidates for RYGB.

  13. I-131 metaiodobenzylguanidine: diagnostic use in neuroblastoma patients in relapse

    International Nuclear Information System (INIS)

    Heyman, S.; Evans, A.E.; D'Angio, G.J.

    1988-01-01

    Metaiodobenzylguanidine (MIBG) has been used for the detection and treatment of neuroectodermal tumors, including neuroblastoma. We report our experience with 131 I-MIBG used diagnostically in neuroblastoma patients with relapse. Thirty-eight studies were performed in 26 patients. There were 24 children (range 3 months-14 years) and two adults. While the study was found to be both sensitive and specific for the presence of disease, there are instances of discordance. False-negative studies were found with a markedly anaplastic tumor and with two mature ganglioneuromas. A bone lesion was negative with 131 I-MIBG, but positive on bone scan. A biopsy confirmed the presence of neuroblastoma. Caution should be exercised when scanning pretreated patients, and perhaps with newly diagnosed patients as well

  14. Extramedullary Relapse Following Total Marrow and Lymphoid Irradiation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Hyun [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Stein, Anthony [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Tsai, Nicole [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Schultheiss, Timothy E. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Palmer, Joycelynne [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Liu, An [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Rosenthal, Joseph [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Department of Pediatrics, City of Hope National Medical Center, Duarte, California (United States); Forman, Stephen J. [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Wong, Jeffrey Y.C., E-mail: jwong@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States)

    2014-05-01

    Purpose: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. Methods and Materials: Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph node chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. Results: A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. Conclusions: EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk.

  15. Extramedullary Relapse Following Total Marrow and Lymphoid Irradiation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

    International Nuclear Information System (INIS)

    Kim, Ji Hyun; Stein, Anthony; Tsai, Nicole; Schultheiss, Timothy E.; Palmer, Joycelynne; Liu, An; Rosenthal, Joseph; Forman, Stephen J.; Wong, Jeffrey Y.C.

    2014-01-01

    Purpose: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. Methods and Materials: Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph node chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. Results: A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. Conclusions: EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk

  16. [Clinical and biological prognostic factors in relapsed acute myeloid leukemia patients].

    Science.gov (United States)

    Yébenes-Ramírez, Manuel; Serrano, Josefina; Martínez-Losada, Carmen; Sánchez-García, Joaquín

    2016-09-02

    Acute myeloid leukemia (AML) is the most frequent type of acute leukemia in adults. Despite recent advances in the characterization of pathogenesis of AML, the cure rates are under 40%, being leukemia relapse the most common cause of treatment failure. Leukaemia relapse occurs due to clonal evolution or clonal escape. In this study, we aimed to analyze the clinical and biological factors influencing outcomes in patients with AML relapse. We included a total of 75 AML patients who experienced leukaemia relapse after achieving complete remission. We performed complete immunophenotyping and conventional karyotyping in bone marrow aspirates obtained at diagnosis and at leukemia relapse. Overall survival (OS) of the series was 3.7%±2.3, leukaemia progression being the most common cause of death. Patients relapsing before 12 months and those with adverse cytogenetic-molecular risk had statistically significant worse outcomes. A percentage of 52.5 of patients showed phenotypic changes and 50% cytogenetic changes at relapse. We did not find significant clinical factors predicting clonal evolution. The presence of clonal evolution at relapse did not have a significant impact on outcome. Patients with relapsed AML have a dismal prognosis, especially those with early relapse and adverse cytogenetic-molecular risk. Clonal evolution with phenotypic and cytogenetic changes occurred in half of the patients without predictive clinical factors or impact on outcome. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  17. Patterns of Relapse in High-Risk Neuroblastoma Patients Treated With and Without Total Body Irradiation

    International Nuclear Information System (INIS)

    Li, Richard; Polishchuk, Alexei; DuBois, Steven; Hawkins, Randall; Lee, Stephanie W.; Bagatell, Rochelle; Shusterman, Suzanne; Hill-Kayser, Christine; Al-Sayegh, Hasan; Diller, Lisa; Haas-Kogan, Daphne A.; Matthay, Katherine K.; London, Wendy B.

    2017-01-01

    Purpose: External beam radiation therapy to initial sites of disease may influence relapse patterns in high-risk neuroblastoma. However, the effect of systemic irradiation by use of total body irradiation (TBI) on anatomic patterns of relapse has not previously been investigated. Methods and Materials: We retrospectively analyzed patients receiving definitive treatment of high-risk neuroblastoma with subsequent relapse in bony metastatic sites, with a date of relapse between January 1, 1997, and December 31, 2012. Anatomic sites of disease, defined by metaiodobenzylguanidine (MIBG) avidity, were compared at diagnosis and at first relapse. The Fisher exact test was performed to compare relapse in initially involved sites between patients treated with and without TBI. Results: Seventy-four patients with a median age at diagnosis of 3.5 years (range, 0.3-15.3 years) had relapse in 227 sites of MIBG-avid metastatic disease, with a median time to relapse of 1.8 years. Of the 227 sites of first relapse, 154 sites (68%) were involved at diagnosis. When we compared relapse patterns in patients treated with and without TBI, 12 of 23 patients (52%) treated with TBI had relapse in ≥1 previously MIBG-avid site of disease whereas 40 of 51 patients (78%) treated without TBI had relapse in ≥1 previously MIBG-avid site of disease (P=.03). Conclusions: Patients treated with systemic irradiation in the form of TBI were significantly less likely to have relapse in prior sites of disease. These findings support further investigation into the role of radiopharmaceutical therapies in curative multimodality therapy.

  18. Patterns of Relapse in High-Risk Neuroblastoma Patients Treated With and Without Total Body Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Richard [Harvard Medical School, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Polishchuk, Alexei [School of Medicine, University of California San Francisco, San Francisco, California (United States); DuBois, Steven [Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); Hawkins, Randall [School of Medicine, University of California San Francisco, San Francisco, California (United States); Lee, Stephanie W. [Brigham and Women' s Hospital, Boston, Massachusetts (United States); Bagatell, Rochelle [Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States); Shusterman, Suzanne [Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); Hill-Kayser, Christine [Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Al-Sayegh, Hasan [Brigham and Women' s Hospital, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); Diller, Lisa [Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); Haas-Kogan, Daphne A. [Harvard Medical School, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); Matthay, Katherine K. [School of Medicine, University of California San Francisco, San Francisco, California (United States); London, Wendy B. [Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); and others

    2017-02-01

    Purpose: External beam radiation therapy to initial sites of disease may influence relapse patterns in high-risk neuroblastoma. However, the effect of systemic irradiation by use of total body irradiation (TBI) on anatomic patterns of relapse has not previously been investigated. Methods and Materials: We retrospectively analyzed patients receiving definitive treatment of high-risk neuroblastoma with subsequent relapse in bony metastatic sites, with a date of relapse between January 1, 1997, and December 31, 2012. Anatomic sites of disease, defined by metaiodobenzylguanidine (MIBG) avidity, were compared at diagnosis and at first relapse. The Fisher exact test was performed to compare relapse in initially involved sites between patients treated with and without TBI. Results: Seventy-four patients with a median age at diagnosis of 3.5 years (range, 0.3-15.3 years) had relapse in 227 sites of MIBG-avid metastatic disease, with a median time to relapse of 1.8 years. Of the 227 sites of first relapse, 154 sites (68%) were involved at diagnosis. When we compared relapse patterns in patients treated with and without TBI, 12 of 23 patients (52%) treated with TBI had relapse in ≥1 previously MIBG-avid site of disease whereas 40 of 51 patients (78%) treated without TBI had relapse in ≥1 previously MIBG-avid site of disease (P=.03). Conclusions: Patients treated with systemic irradiation in the form of TBI were significantly less likely to have relapse in prior sites of disease. These findings support further investigation into the role of radiopharmaceutical therapies in curative multimodality therapy.

  19. The cost of relapse for patients with a manic/mixed episode of bipolar disorder in the EMBLEM study.

    Science.gov (United States)

    Hong, Jihyung; Reed, Catherine; Novick, Diego; Haro, Josep Maria; Windmeijer, Frank; Knapp, Martin

    2010-01-01

    patients completed all visits during the maintenance phase and were eligible for inclusion in the present analysis. Of these, over half (54.3%) experienced relapse during this period. A total of 792 patients without any missing data were eventually included in the final cost model. Costs incurred by patients who relapsed during the 21-month maintenance phase were approximately double those incurred by patients who never relapsed (pounds sterling 9140 vs pounds sterling 4457; p cost difference, 80.3% was accounted for by inpatient stay. Estimates on the economic impact were higher (pounds sterling 11,781 vs pounds sterling 4789; p cost comparison. The average 6-month costs for patients who relapsed were found to be about three times higher than for those who did not relapse (pounds sterling 4083 vs pounds sterling 1298; p costs only. Such costs were dominated by inpatient stay. Nevertheless, the use of UK unit costs requires caution when interpreting this costing in the context of a specific country, as resource use and the associated costs will differ by country.

  20. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy

    DEFF Research Database (Denmark)

    Coles, Alasdair J; Twyman, Cary L; Arnold, Douglas L

    2012-01-01

    The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment....

  1. Relapse Analysis of Irradiated Patients Within the HD15 Trial of the German Hodgkin Study Group

    Energy Technology Data Exchange (ETDEWEB)

    Kriz, Jan; Reinartz, Gabriele [Department of Radiation Oncology, University of Münster, Münster (Germany); Dietlein, Markus; Kobe, Carsten; Kuhnert, Georg [Department of Nuclear Medicine, University of Cologne, Cologne (Germany); Haverkamp, Heinz [First Department of Internal Medicine, University of Cologne, Cologne (Germany); Haverkamp, Uwe [Department of Radiation Oncology, University of Münster, Münster (Germany); Engenhart-Cabillic, Rita [Department of Radiation Oncology, University of Marburg, Marburg (Germany); Herfarth, Klaus [Department of Radiation Oncology, University Heidelberg, Heidelberg (Germany); Lukas, Peter [Department of Radiation Oncology, University of Innsbruck, Innsbruck (Austria); Schmidberger, Heinz [Department of Radiation Oncology, University of Mainz, Mainz (Germany); Staar, Susanne [Department of Radiation Oncology, Klinikum Bremen-Mitte, Bremen (Germany); Hegerfeld, Kira [Department of Radiation Oncology, University of Münster, Münster (Germany); Baues, Christian [Department of Radiation Oncology, University of Cologne, Cologne (Germany); Engert, Andreas [First Department of Internal Medicine, University of Cologne, Cologne (Germany); Eich, Hans Theodor, E-mail: hans.eich@ukmuenster.de [Department of Radiation Oncology, University of Münster, Münster (Germany)

    2015-05-01

    Purpose: To determine, in the setting of advanced-stage of Hodgkin lymphoma (HL), whether relapses occur in the irradiated planning target volume and whether the definition of local radiation therapy (RT) used by the German Hodgkin Study Group (GHSG) is adequate, because there is no harmonization of field and volume definitions among the large cooperative groups in the treatment of advanced-stage HL. Methods and Materials: All patients with residual disease of ≥2.5 cm after multiagent chemotherapy (CTX) were evaluated using additional positron emission tomography (PET), and those with a PET-positive result were irradiated with 30 Gy to the site of residual disease. We re-evaluated all sites of disease before and after CTX, as well as the PET-positive residual tumor that was treated in all relapsed patients. Documentation of radiation therapy (RT), treatment planning procedures, and portal images were carefully analyzed and compared with the centrally recommended RT prescription. The irradiated sites were compared with sites of relapse using follow-up computed tomography scans. Results: A total of 2126 patients were enrolled, and 225 patients (11%) received RT. Radiation therapy documents of 152 irradiated patients (68%) were analyzed, with 28 irradiated patients (11%) relapsing subsequently. Eleven patients (39%) had an in-field relapse, 7 patients (25%) relapsed outside the irradiated volume, and an additional 10 patients (36%) showed mixed in- and out-field relapses. Of 123 patients, 20 (16%) with adequately performed RT relapsed, compared with 7 of 29 patients (24%) with inadequate RT. Conclusions: The frequency and pattern of relapses suggest that local RT to PET-positive residual disease is sufficient for patients in advanced-stage HL. Insufficient safety margins of local RT may contribute to in-field relapses.

  2. High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients.

    Science.gov (United States)

    Pan, J; Yang, J F; Deng, B P; Zhao, X J; Zhang, X; Lin, Y H; Wu, Y N; Deng, Z L; Zhang, Y L; Liu, S H; Wu, T; Lu, P H; Lu, D P; Chang, A H; Tong, C R

    2017-12-01

    Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD + ) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 × 10 5 /kg and were eventually settled at 1 × 10 5 /kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD + patients achieved MRD - . All of the most recent 20 patients achieved CR/CRi. Most cases only experienced mild to moderate CRS. 8/51 cases had seizures that were relieved by early intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HCT) remained in MRD - with a median follow-up time of 206 (45-427) days, whereas 9 of 18 CR/CRi patients without allo-HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 × 10 5 /kg, is effective and safe for treating refractory or relapsed B-ALL, and subsequent allo-HCT could further reduce the relapse rate.

  3. Regional homogeneity changes between heroin relapse and non-relapse patients under methadone maintenance treatment: a resting-state fMRI study.

    Science.gov (United States)

    Chang, Haifeng; Li, Wei; Li, Qiang; Chen, Jiajie; Zhu, Jia; Ye, Jianjun; Liu, Jierong; Li, Zhe; Li, Yongbin; Shi, Ming; Wang, Yarong; Wang, Wei

    2016-08-18

    Methadone maintenance treatment (MMT) is recognized as one of the most effective treatments for heroin addiction but its effect is dimmed by the high incidence of heroin relapse. However, underlying neurobiology mechanism of heroin relapse under MMT is still largely unknown. Here, we took advantage of a resting-state fMRI technique by analysis of regional homogeneity (ReHo), and tried to explore the difference of brain function between heroin relapsers and non-relapsers in MMT. Forty MMT patients were included and received a 12-month follow-up. All patients were given baseline resting-state fMRI scans by using a 3.0 T GE Signa Excite HD whole-body MRI system. Monthly self-report and urine test were used to assess heroin relapse or non-relapse. Subjective craving was measured with visual analog scale. The correlation between ReHo and the degree of heroin relapse was analyzed. Compared with the non-relapsers, ReHo values were increased in the bilateral medial orbitofrontal cortex, right caudate, and right cerebellum of the heroin relapsers while those in the left parahippocampal gyrus, left middle temporal gyrus, right lingual gyrus, and precuneus were decreased in heroin relapsers. Importantly, altered ReHo in the right caudate were positively correlated with heroin relapse rates or subjective craving response. Using the resting-state fMRI technique by analysis of ReHo, we provided the first resting-state fMRI evidence that right caudate may serve as a potential biomarker for heroin relapse prediction and also as a promising target for reducing relapse risk.

  4. Molecular relapse in chronic myelogenous leukemia patients after bone marrow transplantation detected by polymerase chain reaction

    International Nuclear Information System (INIS)

    Sawyers, C.L.; Timson, L.; Clark, S.S.; Witte, O.N.; Champlin, R.; Kawasaki, E.S.

    1990-01-01

    Relapse of chronic myelogenous leukemia after bone marrow transplantation can be detected by using clinical, cytogenetic, or molecular tools. A modification of the polymerase chain reaction can be used in patients to detect low levels of the BCR-ABL-encoded mRNA transcript, a specific marker for chronic myelogenous leukemia. Early detection of relapse after bone marrow transplantation could potentially alter treatment decisions. The authors prospectively evaluated 19 patients for evidence of molecular relapse, cytogenetic relapse, and clinical relapse after bone marrow transplantation. They used the polymerase chain reaction to detect residual BCR-ABL mRNA in patients followed up to 45 months after treatment and found 4 patients with BCR-ABL mRNA expression following bone marrow transplantation. Fifteen patients did not express detectable BCR-ABL mRNA. All 19 patients remain in clinical remission. In this prospective study of chronic myelogenous leukemia patients treated with bone marrow transplantation, molecular relapse preceded cytogenetic relapse in those patients who persistently express BCR-ABL mRNA. They recommend using standard clinical and cytogenetic testing to make patient care decisions until further follow-up determines the clinical outcome of those patients with residual BCR-ABL mRNA transcripts detected by polymerase chain reaction

  5. Immunotoxin – a new treatment option in patients with relapsed and refractory Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    Novakovic Barbara Jezersek

    2015-12-01

    Full Text Available Background. Even though Hodgkin lymphoma is a highly curable disease, some of the patients have either a refractory disease or experience a relapse following a successful primary therapy. Durable responses and remissions in patients with relapsed or refractory disease may be achieved in approximately one-half with salvage chemotherapy followed by high dose chemotherapy (HDT and autologous hematopoietic cell rescue (SCT. On the other hand, patients who relapse after HDT and autologous SCT or those who have failed at least two prior multi-agent chemotherapy regimens and are not candidates for HDT have limited treatment options.

  6. Patterns and Timing of Initial Relapse in Patients Subsequently Undergoing Transplantation for Hodgkin's Lymphoma

    International Nuclear Information System (INIS)

    Dhakal, Sughosh; Biswas, Tithi; Liesveld, Jane L.; Friedberg, Jonathan W.; Phillips, Gordon L.; Constine, Louis S.

    2009-01-01

    Purpose: To evaluate the patterns and timing of initial recurrence in patients with Hodgkin's lymphoma (HL) who subsequently underwent high-dose chemotherapy with autologous stem cell transplantation to enhance our understanding of the natural history of this disease and its modern treatment strategies and to direct approaches to disease surveillance. Methods and Materials: The records of 69 patients with HL who had undergone high-dose chemotherapy with autologous stem cell transplantation in our center between May 1992 and June 2006 were analyzed. The initial diagnosis had been made between April 1982 and January 2005 at a median patient age of 33 years (range, 19-65). The patients were segregated according to the initial stage (Stage I-II vs. III-IV). Results: Early-stage HL patients developed a relapse at a median of 2.1 years (range, 0.5-10.3), with 91% of relapses at the initial disease site, 71% of which (65% overall) were only in previously involved sites. Advanced-stage HL patients developed a relapse at a median of 1.5 years (range, 0.6-10.5), with 97% at the initial site, 71% of which (69% overall) were only in previously involved sites. Single-site relapses occurred in 47% of early- vs. 26% of advanced-stage patients, and extranodal relapses occurred in 12% of early- vs. 31% of advanced-stage patients. Conclusions: Almost all patients with HL who develop relapse and subsequently undergo high-dose chemotherapy with autologous stem cell transplantation initially developed recurrence in previously involved disease sites. Early-stage HL relapses often occurred in single sites, and advanced-stage disease relapses were more likely in multiple and extranodal sites. The interval to recurrence was brief, suggesting that the frequency of screening should be the greatest in the early post-therapy years.

  7. Clinical significance of determination of serum TRAb levels in patients with relapsing graves' disease

    International Nuclear Information System (INIS)

    Guo Chunlei; Zhou Jiaqiang; Li Wenpeng

    2004-01-01

    Objective: To explore the clinical significance of changes of serum TRAb levels in patients with relapsing Graves' disease. Methods: Serum TRAb (with RRA) and several other thyroid-related hormones (TT 4 , TT 3 , TSH, FT 3 , with CLIA) were determined in the following subjects: 1. 25 cases of relapsing Graves' disease after previous successful treatment; 2. 18 cases of recently diagnosed Graves' disease; 3. 31 cases of successfully treated Graves' disease; 4. 15 cases of simple goiter; 5. 10 cases of nodular goiter; 6. 18 cases of hypothyroidism due to Hashimoto disease. Results: Positive rate of TRAb was 76.00% in patients with relapsing Graves' disease and 77.78% in recently diagnosed Graves' disease cases, both being significantly higher than that in all the other sets of patients studied (P<0.01). Conclusion: Determination of serum TRAb levels was helpful for the diagnosis of relapse in Graves' disease

  8. Impulsive suicide attempts predict post-treatment relapse in alcohol-dependent patients.

    Science.gov (United States)

    Wojnar, Marcin; Ilgen, Mark A; Jakubczyk, Andrzej; Wnorowska, Anna; Klimkiewicz, Anna; Brower, Kirk J

    2008-10-01

    The present study was designed to examine the influence of suicidality on relapse in alcohol-dependent patients. Specifically, a lifetime suicide attempt at baseline was used to predict relapse in the year after treatment. Also, the unique contribution of impulsive suicide attempts was examined. A total of 154 patients with alcohol dependence, consecutively admitted to four addiction treatment facilities in Warsaw, Poland participated in the study. Of the 154 eligible patients, 118 (76.6%) completed a standardized follow-up assessment at 12 months. Previous suicide attempts were common in adults treated for alcohol dependence with 43% patients in the present sample reporting an attempt at some point during their lifetime. Additionally, more than 62% of those with a lifetime suicide attempt reported making an impulsive attempt. Lifetime suicide attempts were not associated with post-treatment relapse (chi-square=2.37, d.f.=1, p=0.124). However, impulsive suicide attempts strongly predicted relapse (OR=2.81, 95% CI=1.13-6.95, p=0.026) and time to relapse (OR=2.10, 95% CI=1.18-3.74, p=0.012) even after adjusting for other measures of baseline psychopathology, depression, impulsivity, hopelessness and alcohol use severity. This study is the first to document the relationship between pre-treatment impulsive suicide attempts and higher likelihood of post-treatment relapse in alcohol-dependent patents. Clinicians should routinely conduct an assessment for previous suicide attempts in patients with alcohol use disorders, and when impulsive suicidality is reported, they should recognize the increased risk for relapse and formulate their patients' treatment plans accordingly with the goals of reducing both alcoholic relapse and suicide rates.

  9. Relapse Risk Assessment for Schizophrenia Patients (RASP): A New Self-Report Screening Tool.

    Science.gov (United States)

    Velligan, Dawn; Carpenter, William; Waters, Heidi C; Gerlanc, Nicole M; Legacy, Susan N; Ruetsch, Charles

    2018-01-01

    The Relapse Assessment for Schizophrenia Patients (RASP) was developed as a six-question self-report screener that measures indicators of Increased Anxiety and Social Isolation to assess patient stability and predict imminent relapse. This paper describes the development and psychometric characteristics of the RASP. The RASP and Positive and Negative Syndrome Scale (PANSS) were administered to patients with schizophrenia (n=166) three separate times. Chart data were collected on a subsample of patients (n=81). Psychometric analyses of RASP included tests of reliability, construct validity, and concurrent validity of items. Factors from RASP were correlated with subscales from PANSS (sensitivity to change and criterion validity [agreement between RASP and evidence of relapse]). Test-retest reliability returned modest to strong agreement at the item level and strong agreement at the questionnaire level. RASP showed good item response curves and internal consistency for the total instrument and within each of the two subscales (Increased Anxiety and Social Isolation). RASP Total Score and subscales showed good concurrent validity when correlated with PANSS Total Score, Positive, Excitement, and Anxiety subscales. RASP correctly predicted relapse in 67% of cases, with good specificity and negative predictive power and acceptable positive predictive power and sensitivity. The reliability and validity data presented support the use of RASP in settings where addition of a brief self-report assessment of relapse risk among patients with schizophrenia may be of benefit. Ease of use and scoring, and the ability to administer without clinical supervision allows for routine administration and assessment of relapse risk.

  10. The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL.

    LENUS (Irish Health Repository)

    Hutchinson, Michael

    2012-02-01

    The AFFIRM and SENTINEL studies showed that natalizumab was effective both as monotherapy and in combination with interferon beta (IFNbeta)-1a in patients with relapsing multiple sclerosis (MS). Further analyses of AFFIRM and SENTINEL data were conducted to determine the efficacy of natalizumab in prespecified patient subgroups according to baseline characteristics: relapse history 1 year before randomization (1, 2, > or = 3), Expanded Disability Status Scale score (< or = 3.5, > 3.5), number of T2 lesions (< 9, > or = 9), presence of gadolinium-enhancing (Gd+) lesions (0, > or = 1), age (< 40, > or = 40) and gender (male, female). A post hoc analysis was conducted to determine the efficacy of natalizumab in patients with highly active disease (i. e., > or = 2 relapses in the year before study entry and > or = 1 Gd+ lesion at study entry). In both AFFIRM and SENTINEL studies natalizumab reduced the annualized relapse rates across all subgroups (except the small subgroups with < 9 baseline T2 lesions) over 2 years. In AFFIRM, natalizumab significantly reduced the risk of sustained disability progression in most subgroups. In SENTINEL, natalizumab significantly reduced the risk of sustained disability progression in the following subgroups: > or = 9 T2 lesions at baseline, > or = 1 Gd+ lesions at baseline, female patients and patients < 40 years of age. Natalizumab reduced the risk of disability progression by 64 % and relapse rate by 81 % in treatment- naive patients with highly active disease and by 58 % and 76 %, respectively, in patients with highly active disease despite IFNbeta-1a treatment. These results indicate that natalizumab is effective in reducing disability progression and relapses in patients with relapsing MS, particularly in patients with highly active disease.

  11. Immunologic prediction of relapse in patients with pemphigus vulgaris (PV) in clinical remission.

    Science.gov (United States)

    Daneshpazhooh, Maryam; Zafarmand Sedigh, Vahid; Balighi, Kamran; Hosseini, S Hamed; Ramezani, Ali; Kalantari, Mohammad-Sadegh; Ghandi, Narges; Ghiasi, Maryam; Nikoo, Azita; Chams-Davatchi, Cheyda

    2016-06-01

    Pemphigus vulgaris (PV) is characterized by multiple relapses, occurring especially in patients on minimal therapy or off therapy. To identify immunologic predictors (anti-desmoglein [Dsg] 1 and 3 antibodies; direct immunofluorescence [DIF]) for relapse in PV patients. Eighty-nine patients in complete clinical remission for at least 6 months and receiving less than or equal to 10 mg prednisolone daily and no immunosuppressive drugs were evaluated using DIF (n=89) and Dsg ELISA (n=46). They were followed until relapse or for at least 18 months. DIF was positive in 44 of 89 patients (49.5%); anti-Dsg 3 antibodies were detected in 18 of 46 patients (39.1%) and anti-Dsg 1 antibodies were detected in 4 of 46 patients (8.7%). Relapse occurred in 38 patients (42.7%). Mean relapse-free time was significantly shorter in anti-Dsg 3-positive patients compared to anti-Dsg 3- negative patients (P = .015) and in DIF-positive patients compared to DIF-negative patients (P = .047), but not in anti-Dsg 1- positive patients compared to anti-Dsg 1-negative patients (P = .501). Sensitivity and predictive values of neither of these tests were high. Small number of anti-Dsg 1-positive patients and use of conventional ELISA. Positive anti-Dsg 3 ELISA and, to a lesser degree, positive DIF are predictors of relapse in PV patients in clinical remission. Decision on discontinuing treatment should be based on the results of these tests as well as on clinical findings. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  12. Relationship between Personality Disorders and Relapses among Sample of Substance Abuse Patients

    OpenAIRE

    Osama Hasan Gaber

    2016-01-01

    This study aimed to examine the relationship between Personality Disorders and Relapses among Sample of 75 Substance Abuse Patients (personality disorder scale (prepared by the researchers) were used Pearson Correlation Coefficient showed that there are statistically significant relationship between Antisocial personality disorder(ASPD), Borderline personality disorder (BPD, Avoidant personality disorder (AVPD) and Dependent personality disorder (DPD) and substance abuse relapses (P≤=0.00)...

  13. Vitamin D supplementation reduces relapse rate in relapsing-remitting multiple sclerosis patients treated with natalizumab

    DEFF Research Database (Denmark)

    Laursen, Julie Hejgaard; Søndergaard, Helle Bach; Sørensen, Per Soelberg

    2016-01-01

    Background Vitamin D insufficiency is common among multiple sclerosis patients, and hypovitaminosis D has been associated with multiple sclerosis (MS) risk and disease activity.  Objective To investigate how recommendations on vitamin D3 supplements affect 25-hydroxyvitamin D (25(OH)D) levels in ...

  14. Relapse risk assessment of transplantation for patients with chronic myeloid leukaemia

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective To analyse the risk factors of relapse before bone marrow transplantation (BMT) and to present the prognostic information as good as possible.Methods A total of 3142 patients, who underwent the allogeneic blood or bone marrow tran splantation between 1989 and 1997 and were documented in the European Group for Blood and Marrow transplantation (EBMT), were included. Six possible risk factors including type of donor, stage of disease, age, gender, donor@#-recipient sex co mbination and the waiting time from diagnosis to transplation of relapse were co nsidered. The time to relapse was analysed by Kaplan-Meier curves and Coxregre ssion with stratification on prognostic factors that did not satisfy the Proport ional Hazard Assumption.Results An amount of 447 patients relapsed out of all 3142 patients. The relapse rate was 14.2%. Type of donor and stage of disease showed a clear prognostic effect, but failed the proportional hazard assumption. Therefore, the data were stratified on the combination of type of donor and stage of disease. Within these strata a n additional significant effect of age could be observed. Relative risk of age ≥40 vs age <40 was 1.32 (95% confidence interval 1.09-1.59). The prognostic model is summarized graphically.Conclusions The combination of type of donor, stage of disease and age of recipient at transplantation are important prognostic factors for relapse after BMT.

  15. Comparing Effectiveness of Mindfulness-Based Relapse Prevention with Treatment as Usual on Impulsivity and Relapse for Methadone-Treated Patients: A Randomized Clinical Trial.

    Science.gov (United States)

    Yaghubi, Mehdi; Zargar, Fatemeh; Akbari, Hossein

    2017-07-01

    Impulsivity is one of the causes of relapse that can affect treatment outcomes. Studies have shown that addiction treatments can reduce impulsivity in drug-dependent individuals. Studies also have suggested that mindfulness is associated with impulsivity. However, no study has investigated the effectiveness of the mindfulness-based intervention on impulsivity in opioid-dependent individuals. This study aimed to compare the effectiveness of mindfulness-based relapse prevention (MBRP) with treatment as usual (TAU) in terms of impulsivity and relapse for methadone-treated patients. The present randomized controlled clinical trial was performed in Kashan, Iran, in 2015. The study population was opioid-dependent patients referred to Maintenance Treatment Centers. Seventy patients were selected by random sampling and were assigned in two groups (MBRP and TAU) randomly. The participants of two groups filled out Barratt impulsivity scale (BIS-11) as a pre-test and 8 weeks later as post-test and 2 months later as a follow-up. Both groups received methadone-therapy. The MBRP group received 8 sessions of group therapy, while the control group did not receive any group psychotherapy session. Finally, data from 60 patients were analyzed statistically. The MBRP group had decreased impulsivity significantly (P relapse frequency (P relapse probability. These findings suggest that MBRP is useful for opioid-dependent individuals with high-level impulsivity, and relapse prevention.

  16. Relapsing peritonitis with Bacillus cereus in a patient on continuous ambulatory peritoneal dialysis

    DEFF Research Database (Denmark)

    Magnussen, Eyð Tausen; Vang, Amanda Gratton; á Steig, Torkil

    2016-01-01

    We present a case where Bacillus cereus was determined to be the causative agent of relapsing peritonitis in a patient on continuous ambulatory peritoneal dialysis (CAPD). The patient, a 70-year-old man from the Faroe Islands, was admitted with relapsing peritonitis four times over a 3-month period....... Peritoneal cultures were positive for growth of B. cereus, a rare bacterial cause of peritonitis. The cultures demonstrated susceptibility to vancomycin, and therefore the patient was treated with intraperitoneal vancomycin, intraperitoneal gentamycin and oral ciprofloxacin. As a result of the relapsing B....... cereus peritonitis diagnosis and a CT scan showing contraction of the peritoneum after longstanding inflammation, the peritoneal catheter was removed and the patient converted to haemodialysis. To date, the patient has not been readmitted due to peritonitis. A lack of proper hygiene when changing...

  17. Treatment and outcome of patients with relapsed clear cell sarcoma of the kidney: a combined SIOP and AIEOP study.

    Science.gov (United States)

    Gooskens, S L; Furtwängler, R; Spreafico, F; van Tinteren, H; de Kraker, J; Vujanic, G M; Leuschner, I; Coulomb-L'Herminé, A; Godzinski, J; Schleiermacher, G; Stoneham, S; Bergeron, C; Pritchard-Jones, K; Graf, N; van den Heuvel-Eibrink, M M

    2014-07-15

    Clear cell sarcoma of the kidney (CCSK) is an uncommon paediatric renal tumour. Relapses occur in about 15% of the patients. Since detailed clinical information on relapsed CCSK is scarce, the current study aims to describe outcome of patients with relapsed CCSK treated according to recent European protocols. We analysed prospectively collected data of all CCSK patients who developed a relapse after complete remission at the end of primary treatment, entered onto SIOP and AIEOP trials between 1992 and 2012. Thirty-seven of 237 CCSK patients (16%) treated according to SIOP and AIEOP protocols developed a relapse. Median time from initial diagnosis to relapse was 17 months (range, 5.5 months - 6.6 years). Thirt-five out of thirty-seven relapses (95%) were metastatic; the most common sites of relapse were the brain (n=13), lungs (n=7) and bone (n=5). Relapse treatment consisted of chemotherapy (n=30), surgery (n=19) and/or radiotherapy (n=18), followed by high-dose chemotherapy and autologous bone marrow transplantation (ABMT) in 14 patients. Twenty-two out of thirty-seven patients (59%) achieved a second complete remission (CR); 15 of whom (68%) developed a second relapse. Five-year event-free survival (EFS) after relapse was 18% (95% CI: 4%-32%), and 5-year overall survival (OS) was 26% (95% CI: 10%-42%). In this largest series of relapsed CCSK patients ever described, overall outcome is poor. Most relapses are metastatic and brain relapses are more common than previously recognised. Intensive treatment aiming for local control, followed by high dose chemotherapy and ABMT, seems to be of benefit to enhance survival. Novel development of targeted therapy is urgently required.

  18. Characteristics of specific immunological indicators in patients with postoperative relapse of Graves’ disease

    Directory of Open Access Journals (Sweden)

    Yu.V. Buldigina

    2018-02-01

    Full Text Available Background. Activity of autoimmune processes had a leading role in the development of relapse of hyperthyroidism. Level of thyroid-stimulating hormone (TSH receptor antibodies is a basic factor that predetermines the relapse and can be used as a criterion to evaluate its development. A research aim was to study the structural and functional state of the thyroid gland, levels of thyroid peroxidase antibodies and TSH receptor antibodies in patients with postoperative relapse of Graves’ disease during antithyroid therapy. Mate­rials and methods. The group of patients consisted of 25 wo­men aged 23 to 73 years (an average of 53.56 ± 2.31 years. The period from the first surgical treatment to the development of relapse of thyrotoxicosis ranged from 1 to 29 years and avera­ged 13.33 ± 1.66 years. Results. It was found that the le­vels of TSH receptor antibodies, which are the main factors in the pathogenesis of Graves’ disease, are not decreased on the background of drug treatment that indicates a lack of perspective of conservative therapy for the post-operative relapse of this disease. Conclusions. When the state of medication compensation for thyrotoxicosis is achieved, it is recommended to conduct the therapy with I131 or surgical treatment of the relapse of Graves’ disease.

  19. Socio-economic correlates of relapsed patients admitted in a Nigerian mental health institution.

    Science.gov (United States)

    Gbiri, Caleb A; Badru, Fatai A; Ladapo, Harry T O; Gbiri, Adefolakemi A

    2011-03-01

    Relapse in psychiatric disorders is highly distressing, costly and engenders burn-out syndrome among mental-health workers. To study the socio-economic factors associated with relapse in individual admitted with psychiatric disorders and the pattern of socio-economic impact of relapse in those groups. A cross-sectional survey of all relapsed patients without cognitive deficit admitted into the federal Neuro-Psychiatric Hospital, Lagos, Nigeria between June and October 2007 was conducted using a self-validated Structured Interview Schedule (Relapse Socio-economic Impact Interview Schedule) and Key Informant Interview Guide. Secondary data were elicited from the patient folders, case notes, ward admission registers and nominal rolls. Data were summarised using mean, standard deviation, frequency and percentiles. Pearson's moment correlation coefficient was used to test the association among variables. The Mann-Whitney U-test was used to compare the pre-morbid and the post-morbid states. This study involved 102 respondents. Their mean age was 36.5 ± 9.8 years, mainly of male gender (72.5%) suffering from schizophrenic disorder (37.8%). Relapse and re-admission ranged between 2 and 12. Unemployment rate, marital separation and divorce increased more than 5-fold from pre-morbid to morbid states. Few (4.9%) could still settle their hospital/drug bills on their own, while most (95.1%) depended on family, philanthropist and government/waivers to pay for their bills. Their social relationships were negatively influenced with most of them expressing social isolation and low quality of life. There were significant relationships (Peconomic status, employment status and marital status of the respondents between the pre-morbid and post-morbid periods. The illness significantly affected the emotional status of the participants. Relapse and readmission in psychiatric patients have a negative impact on socio-economic well-being of patients, family and the society. Efforts should

  20. Dysfunctional Default Mode Network in Methadone Treated Patients Who Have a Higher Heroin Relapse Risk.

    Science.gov (United States)

    Li, Wei; Li, Qiang; Wang, Defeng; Xiao, Wei; Liu, Kai; Shi, Lin; Zhu, Jia; Li, Yongbin; Yan, Xuejiao; Chen, Jiajie; Ye, Jianjun; Li, Zhe; Wang, Yarong; Wang, Wei

    2015-10-15

    The purpose of this study was to identify whether heroin relapse is associated with changes in the functional connectivity of the default mode network (DMN) during methadone maintenance treatment (MMT). Resting-state functional magnetic resonance imaging (fMRI) data of chronic heroin relapsers (HR) (12 males, 1 female, age: 36.1 ± 6.9 years) and abstainers (HA) (11males, 2 female; age: 42.1 ± 8.1 years) were investigated with an independent component analysis to address the functional connectivity of their DMN. Group comparison was then performed between the relapsers and abstainers. Our study found that the left inferior temporal gyrus and the right superior occipital gyrus associated with DMN showed decreased functional connectivity in HR when compared with HA, while the left precuneus and the right middle cingulum had increased functional connectivity. Mean intensity signal, extracted from left inferior temporal gyrus of HR patients, showed a significant negative correlation corresponding to the degree of heroin relapse. These findings suggest that altered functional connectivity of DMN may contribute to the potential neurobiological mechanism(s) of heroin relapse and have a predictive value concerning heroin relapse under MMT.

  1. Second and third responses to the same induction regimen in relapsing patients with multiple myeloma.

    Science.gov (United States)

    Paccagnella, A; Chiarion-Sileni, V; Soesan, M; Baggio, G; Bolzonella, S; De Besi, P; Casara, D; Frizzarin, M; Salvagno, L; Favaretto, A

    1991-09-01

    From September 1975 to December 1986, 115 consecutive previously untreated patients with multiple myeloma (MM) were treated with combination chemotherapy consisting of BCNU, cyclophosphamide, melphalan, vincristine, and prednisone (M-2). No patients were excluded or lost during follow-up. Forty-three percent of the patients were Stage I plus II, and 57% were Stage III. Thirty-eight patients (33%) had blood urea nitrogen greater than or equal to 40 mg/dl (substage B). Reaching an objective response treatment was stopped, generally after 1 year, and restarted at relapse. After induction therapy, 94 patients (82%) responded and had a median duration of response (MDR) of 22 months. After first relapse, 26 of 38 patients (69%) responded again to the same regimen and had an MDR of 11 months. This response rate and MDR are significantly lower than the ones achieved in induction chemotherapy. After second relapse, 7 of 16 patients (44%) again responded with an MDR of 3.5 months. The median survival time (MST) was 50.5 months for all patients. The most relevant side effect was leukopenia. No case of secondary leukemia was noticed. The authors conclude that patients with MM can be treated safely without maintenance therapy after reaching remission because a high response rate can be obtained in first and even second relapse. The planned treatment pause at remission does not adversely affect the survival time. Secondary leukemia is infrequent after this policy. Quality of life improves during the treatment pause.

  2. Use of fingolimod in patients with relapsing remitting multiple sclerosis in Kuwait.

    Science.gov (United States)

    Alroughani, R; Ahmed, S F; Behbehani, R; Al-Hashel, J

    2014-04-01

    Post-marketing studies are important to confirm what was established in clinical trials, and to assess the intermediate and long-term efficacy and safety. To assess efficacy and safety of fingolimod in multiple sclerosis (MS) in Kuwait. We retrospectively evaluated MS patients using the MS registries in 3 MS clinics. Relapsing remitting MS patients according to revised 2010 McDonald criteria who had been treated with fingolimod for at least 12 months were included. Primary endpoint was proportion of relapse-free patients at last follow-up. Secondary endpoints were mean change in EDSS and proportion of patients with MRI activity (gadolinium-enhancing or new/enlarging T2 lesions). 76 patients met the inclusion criteria. Mean age and mean disease duration were 34.43 and 7.82 years respectively. Mean duration of exposure to fingolimod was 18.50 months. Proportion of relapse-free patients was 77.6% at last follow-up. Mean EDSS score significantly improved (2.93 versus 1.95; p<0.0001) while 17.1% of patients continued to have MRI activity versus 77.6% at baseline (p<0.0001). Four patients stopped fingolimod due to disease breakthrough (n=3) and lymphadenitis (n=1). Fingolimod is safe and effective in reducing clinical and radiological disease activity in relapsing remitting MS patients. Our results are comparable to reported results of phase III studies. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Role of Radiation Therapy in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    Ng, Andrea K; Yahalom, Joachim; Goda, Jayant S

    2018-01-01

    Approximately 30% to 40% of patients with diffuse large B-cell lymphoma (DLBCL) will have either primary refractory disease or relapse after chemotherapy. In transplant-eligible patients, those with disease sensitive to salvage chemotherapy will significantly benefit from high-dose therapy with a...

  4. Survival after relapse in patients with endometrial cancer : results from a randomized trial

    NARCIS (Netherlands)

    Creutzberg, CL; van Putten, WLJ; Koper, PC; Lybeert, MLM; Jobsen, JJ; Warlam-Rodenhuis, CC; De Winter, KAJ; Lutgens, LCHW; van den Bergh, ACM; van der Steen-Banasik, E; Beerman, H; van Lent, M

    Objective. The aim of this study was to determine the rates of local control and survival after relapse in patients with stage I endometrial cancer treated in the multicenter randomized PORTEC trial. Methods, The PORTEC trial included 715 patients with stage I endometrial cancer, either grade I or 2

  5. Cognitive Impairment and Whole Brain Diffusion in Patients with Neuromyelitis Optica after Acute Relapse

    Science.gov (United States)

    He, Diane; Wu, Qizhu; Chen, Xiuying; Zhao, Daidi; Gong, Qiyong; Zhou, Hongyu

    2011-01-01

    The objective of this study investigated cognitive impairments and their correlations with fractional anisotropy (FA) and mean diffusivity (MD) in patients with neuromyelitis optica (NMO) without visible lesions on conventional brain MRI during acute relapse. Twenty one patients with NMO and 21 normal control subjects received several cognitive…

  6. SOX9 Expression Predicts Relapse of Stage II Colon Cancer Patients

    DEFF Research Database (Denmark)

    Espersen, Maiken Lise Marcker; Linnemann, Dorte; Christensen, Ib Jarle

    2016-01-01

    The aim of this study was to investigate if the protein expression of Sex-determining region y-box 9 (SOX9) in primary tumors could predict relapse of stage II colon cancer patients.144 patients with stage II primary colon cancer were retrospectively enrolledin the study. SOX9 expression...

  7. Response to pazopanib in two pediatric patients with pretreated relapsing synovial sarcoma.

    Science.gov (United States)

    Casanova, Michela; Basso, Eleonora; Magni, Chiara; Bergamaschi, Luca; Chiaravalli, Stefano; Carta, Roberto; Tirtei, Elisa; Massimino, Maura; Fagioli, Franca; Ferrari, Andrea

    2017-01-21

    Pazopanib is an oral multikinase inhibitor that has proved effective in adults treated for relapsing soft tissue sarcoma and synovial sarcoma in particular. Two cases are reported here of pediatric patients with pretreated relapsing synovial sarcoma whose tumors showed a prolonged response to pazopanib given on compassionate grounds. These results suggest that new agents found effective in adult patients might achieve similar results in adolescents with the same disease. Facilitating the availability of new drugs for children and adolescents is a major challenge for pediatric oncologists.

  8. Durable responses to ibrutinib in patients with relapsed CLL after allogeneic stem cell transplantation.

    Science.gov (United States)

    Link, C S; Teipel, R; Heidenreich, F; Rücker-Braun, E; Schmiedgen, M; Reinhardt, J; Oelschlägel, U; von Bonin, M; Middeke, J M; Muetherig, A; Trautmann-Grill, K; Platzbecker, U; Bornhäuser, M; Schetelig, J

    2016-06-01

    Ibrutinib, a recently approved inhibitor of Bruton's tyrosine kinase (BTK), has shown great efficacy in patients with high-risk CLL. Nevertheless, there are few data regarding its use in patients who relapsed after allogeneic stem cell transplantation (alloSCT). We report clinical data from five CLL patients treated with ibrutinib for relapse after first or even second allogeneic transplantation. Additionally, we performed analyses on cytokine levels and direct measuring of CD4 Th1 and CD4 Th2 cells to evaluate possible clinically relevant immunomodulatory effects of ibrutinib. All patients achieved partial responses including one minimal residual disease (MRD)-negative remission. Within 1 year of follow-up, no relapse was observed. One patient died of severe pneumonia while on ibrutinib treatment. Beside this, no unexpected adverse events were observed. Flow cytometry and analyses of T cell-mediated cytokine levels (IL10 and TNFα) did not reveal substantial changes in T-cell distribution in favor of a CD4 Th1 T-cell shift in our patients. No acute exacerbation of GvHD was reported. In conclusion, these results support further evaluation of ibrutinib in CLL patients relapsing after alloSCT.

  9. Oxidative Stress is Increased in Serum from Mexican Patients with Relapsing-Remitting Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Genaro Gabriel Ortiz

    2009-01-01

    Full Text Available Objective: To determine the oxidative stress markers in serum from patients with relapsing-remitting multiple sclerosis. Methods: Blood samples from healthy controls and 22 patients 15 women (7 aged from 20 to 30 and 8 were > 40 years old and 7 men (5 aged from 20 to 30 and 2 were > 40 years old fulfilling the McDonald Criteria and classified as having Relapsing-Remitting Multiple Sclerosis accordingly with Lublin were collected for oxidative stress markers quantification. Results: Nitric oxide metabolites (nitrates/nitrites, lipid peroxidation products (malondialdehyde plus 4-hidroxialkenals, and glutathione peroxidase activity were significantly increased in serum of subjects with relapsing-remitting multiple sclerosis in comparison with that of healthy controls. These data support the hypothesis that multiple sclerosis is a component closely linked to oxidative stress.

  10. Cost effectiveness and budget impact of natalizumab in patients with relapsing multiple sclerosis.

    Science.gov (United States)

    Chiao, Evelyn; Meyer, Kellie

    2009-06-01

    Disease-modifying therapy (DMT) is the largest single-cost item that contributes to the total per-patient cost of multiple sclerosis (MS), a disabling disorder of the central nervous system. Natalizumab is the most recent DMT to be approved for the treatment of relapsing MS and may be an attractive alternative to interferon beta and glatiramer acetate (GA). To determine from the perspective of a United States payer (1) the incremental cost effectiveness of natalizumab compared with other DMTs and (2) the budgetary impact of utilization of natalizumab for the treatment of relapsing MS. A combined cost effectiveness and budget impact model was developed. Model inputs were drug acquisition costs (wholesale acquisition cost), costs of drug administration and monitoring, costs of treating relapses, anticipated reduction in relapse rates after 2 years of therapy, and estimated market utilization of natalizumab. Outcomes included total 2-year costs of therapy per patient, costs per relapse avoided for each treatment, and overall 2-year costs to the health plan and per member per month (PMPM) costs. Drug acquisition costs are in 2008 US dollars, and all other costs were inflated to 2008 US dollars when necessary. Univariate sensitivity analyses were performed to determine the model inputs with the greatest influence on the cost per relapse avoided for natalizumab. The overall 2-year cost of therapy per patient was $72,120 for natalizumab, $56,790 for intramuscular (IM) interferon beta-1a (IFNbeta-1a), $56,773 for IFNbeta-1b, $57,180 for GA, and $58,538 for subcutaneous (SC) IFNbeta-1a. The cost per relapse avoided was lowest for natalizumab at $56,594, followed by $87,791 for IFNbeta-1b, $93,306 for IM IFNbeta-1a, $96,178 for SC IFNbeta-1a, and $103,665 for GA. The incremental cost-effectiveness ratios of natalizumab relative to IM IFNbeta-1a, IFNbeta-1b, GA, and SC IFNbeta-1a were $23,029, $24,452, $20,671, and $20,403 per additional relapse avoided, respectively. An

  11. Analysis of audiometric relapse-free survival in patients with immune-mediated hearing loss exclusively treated with corticosteroids.

    Science.gov (United States)

    Mata-Castro, Nieves; García-Chilleron, Raimon; Gavilanes-Plasencia, Javier; Ramírez-Camacho, Rafael; García-Fernández, Alfredo; García-Berrocal, José Ramón

    2017-10-12

    To describe the results in terms of audiometric relapse-free survival and relapse rate in immunomediated hearing loss patients treated exclusively with corticosteroids. Retrospective study of patients with audiometric relapses, monitored from 1995 to 2014, in two centres of the Community of Madrid. We evaluated 31 patients with a mean age of 48.52 years (14.67 SD), of which 61.3% were women. Most hearing loss was fluctuating (48.4%). Only 16.1% of patients had systemic autoimmune disease. There is a moderate positive correlation between the sex variable and the systemic involvement variable (Spearman's correlation coefficient=0.356): specifically, between being female and systemic disease. The relative incidence rate of relapse in the first year was 2.01 relapses/year with a 95% CI (1.32 to 2.92). The mean survival time of the event (audiometric relapse) was 5.25 months (SD 0.756). With multivariate analysis, the only variable that achieved statistical significance was age, with a hazard ratio of 1.032 (95% CI; 1.001-1.063, P=.043). Immune-mediated disease of the inner ear is a chronic disease with relapses. Half of the patients with immunomediated hearing loss treated exclusively with corticosteroids relapse before 6 months of follow-up. In addition, if a patient has not relapsed, they are more likely to relapse as each year passes. Analysis of the of audiometric relapse- free survival will enable the effect of future treatments to be compared and their capacity to reduce the rhythm of relapses. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  12. The mortality and response rate after FLANG regimen in patients with refractory/relapsed acute leukemia

    Directory of Open Access Journals (Sweden)

    Vali A Mehrzad

    2012-01-01

    Full Text Available Background: Oncologists today are greatly concerned about the treatment of relapsed/refractory acute leukemia. FLANG regimen, combination of novantron, cytarabine, fludarabine, and granulocyte-colony stimulating factor, has been used in treatment of refractory/relapsed acute leukemia since 1990s. The present study has evaluated mortality and response rate of this regimen. Materials and Methods: In this study, 25 patients with refractory/relapsed acute leukemia aged 15-55 years underwent FLANG regimen at Seyed-Al-Shohada Hospital, Isfahan, Iran during 2008-2009. One month later, bone marrow samples were taken to evaluate the responsiveness to treatment. Participants were followed for a year. The data was analyzed by student-t and chi-square tests, logistic, and Cox regression analysis, and Kaplan-Meier curves in SPSS 19. Results: Out of the 25 patients, 8 patients (32% had acute lymphoblastic leukemia (5 refractory and 3 relapsed cases and 17 subjects had acute myeloid leukemia (7 refractory and 10 relapsed cases. According to the bone marrow biopsies taken one month after FLANG regimen, 10 patients (40% had responded to treatment. Five patients of the 10 responders underwent successful bone marrow transplantation (BMT. On the other hand, 13 patients (52%, who had not entered the CR period, died during the follow-up. Logistic regression analysis did not reveal any significant associations between disease type and responsiveness to treatment. Conclusion: This study indicated higher rates of unresponsiveness to treatment while its mortality rate was comparable with other studies. Overall, according to limitations for BMT (as the only chance for cure in Iran, it seems that FLANG therapy is an acceptable choice for these patients.

  13. Reirradiation and lomustine in patients with relapsed high-grade gliomas

    International Nuclear Information System (INIS)

    Arcicasa, Mauro; Roncadin, Mario; Bidoli, Ettore; Dedkov, Anatolyi; Gigante, Marco; Trovo, Mauro G.

    1999-01-01

    Purpose: The aim of this study was to evaluate the toxicity, response, and survival of patients with relapsed high-grade gliomas after radiation therapy (RT) combined with lomustine (CCNU). Methods and Materials: Thirty-one patients with relapsed gliomas at least 6 months after completion of RT were reirradiated. Twenty-four patients had a pathological diagnosis of high-grade gliomas, whereas 7 had a radiological diagnosis of relapsed malignant gliomas. The study focused on patients with high-grade relapsed gliomas. A total dose of 34.5 Gy was delivered in 23 fractions over 4.5 weeks. Oral administration of CCNU (130 mg/m 2 ) was begun at the same time as RT, and was repeated every 6 weeks until disease progression, or up to 12 courses. Results: Twelve of 24 patients had surgery before RT plus CCNU treatment. Median interval between RT courses was 14 months (range 6-73). All patients received a complete course of RT, and 22 of 24 patients received at least one course of CCNU. Objective responses were seen in 14 evaluable patients: 3 with partial response, 5 with stable disease, and 6 with progressive disease. Duration of partial response was 20, 9, and 8 months. Median time to progression and overall survival from the onset of retreatment were 8.4 months (range 1-22) and 13.7 months (range 1-63+), respectively. One case of G4 thrombocytopenia was observed. Five patients had G1 or G2 leucopenia and 3 patients had G3 leucopenia. Moderate nausea and vomiting were reported in 4 patients. One patient, after one course of CCNU, refused further chemotherapy. No significant difference in survival from relapse was found between patients who underwent surgery before RT plus CCNU and those who received only RT plus CCNU (p = 0.74). Conclusion: Overall, the acute toxicity was moderate, and patient compliance was good. Reirradiation of high-grade glioma was associated with modest subjective and objective response rates. It is remarkable that median overall survival from relapse

  14. Resilience Associated with Self-Disclosure and Relapse Risks in Patients with Alcohol Use Disorders.

    Science.gov (United States)

    Yamashita, Ayako; Yoshioka, Shin-Ichi

    2016-12-01

    The aim of this study was to clarify the self-disclosure and risks of relapse associated with promoting resilience of patients with alcohol use disorders (AUD) and participating in self-help groups. An anonymous, self-administered questionnaire survey was administered to 48 patients with AUD and participating in self-help groups; this questionnaire consisted of basic attributes, a bidimensional resilience scale to assess both innate and acquired resilience factors, a scale to assess depth of self-disclosure, and a scale assessing relapse risks. We conducted an evaluation by dividing the respondents into a high group and low group based on their median values for both innate and acquired resilience. Innate/acquired resilience had a mutually reinforcing relationship, and, compared with the low resilience group, the high resilience group had significantly reduced risks for relapses and resulted in deeper self-disclosure. Patients with high resilience had lower risk of alcohol relapse and deeper self-disclosure. The results suggest that one way of supporting patients with AUD in recovery is assisting them in building personal relationships with others and in deepening self-disclosure in a setting where they can relax, thus promoting their natural ability to recover.

  15. Patient attributes and expressed emotion as risk factors for psychotic relapse

    NARCIS (Netherlands)

    Linszen, D. H.; Dingemans, P. M.; Nugter, M. A.; van der Does, A. J.; Scholte, W. F.; Lenior, M. A.

    1997-01-01

    In the context of a prospective, controlled treatment study, contrasting family interventions with individual treatment, the role of expressed emotion (EE) as a predictor of relapse was examined in patients with recent-onset schizophrenia and related disorders (n = 97). EE was compared with 13

  16. Ab initio vel ex eventu

    Science.gov (United States)

    Thiessen, P. A.; Treder, H.-J.

    Der gegenwärtige Stand der physikalischen Erkenntnis, in Sonderheit die Atomistik und die Quantentheorie, ermöglicht (in wohldefinierten Energie-Bereichen) eine ab initio-Berechnung aller physikalischen und chemischen Prozesse und Strukturen. Die Schrödinger-Gleichung erlaubt zusammen mit den Prinzipien der Quantenstatistik (Pauli-Prinzip) aus dem Planckschen Wirkungsquantum h und den atomischen Konstanten die Berechnung aller Energieumsätze, Zeitabläufe etc., die insbesondere die chemische Physik bestimmen. Die Rechenresultate gelten auch quantitativ bis auf die unvermeidliche Stochastik.Die ab initio-Berechnungen korrespondieren einerseits und sind andererseits komplementär zu den auf den Methoden der theoretischen Chemie und der klassischen Thermodynamik beruhenden Ergebnissen ex eventu. Die theoretische Behandlung ab initio führt zu mathematischen Experimenten, die die Laboratoriums-Experimente ergänzen oder auch substituieren.Translated AbstractAb initio vel ex eventuThe present state of physical knowledge, in peculiar atomistic and quantum theory, makes an ab initio calculation of all physical and chemical processes and structures possible (in well defined reaches of energy). The Schrödinger equation together with the principles of quantum statistics (Pauli principle) permits from the Planck and atomistic constants to calculate all exchanges of energy, courses of time, etc. which govern chemical physics. The calculated results are valid even quantitatively apart from the unavoidable stochastics.These ab initio calculations on the one hand correspond and are on the other complimentary to results ex eventu based on the methods of theoretical chemistry and classical thermodynamics. Theoretical treatment ab initio leads to mathematical experiments which add to or even substitute experiments in the laboratory.

  17. Experience of Glatiramer Acetate in the Treatment of Relapsing-Remitting Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Özlem Taşkapılıoğlu

    2012-03-01

    Full Text Available OBJECTIVE: Glatiramer acetate (GA has been shown to reduce the number of relapses and improve outcomes in relapsing-remitting multiple sclerosis (RRMS patients. The aim of this study is to investigate the efficacy and side effects of GA in RRMS patients treated with it. METHODS: We retrospectively reviewed all the records of RRMS patients treated with GA in our hospital from January 1990 to December 2010. We evaluated 114 records but 71 patients (48 women, 23 men were included in the study due to incompleteness in the other records. Demographic characteristics, time from first symptom to diagnosis, time from diagnosis to treatment, number of relapses and Expanded Disability Status Scale (EDSS scores before and after the treatment, treatment duration, side effects, the other agents used in MS treatment during the disease duration and the presence of oligoclonal bands were recorded. RESULTS: The mean age of the patients and mean GA treatment duration were 41,85±9,05 years and 28,73 months, respectively. The mean number of relapses before and after the treatment were 2.30±1.16 and 0,52±1.24 respectively. The number of relapses reduced in 64 (90,14%, unchanged in 4 (5,63% and increased in 3 (4,23% patients after GA treatment. The mean EDSS scores before and after the treatment were 2,56±1,46 and 2,04±1,68 respectively. Before GA treatment, 63,4% of all patients had EDSS scores three or more. After the treatment 50,6% of all patients had EDSS scores three or more. GA was the first choice immunomodulatory treatment in 71,8% and the second choice in 28,2% of the patients. The treatment discontinued in 8 (11,3% patients and the reason was the severe side effect in only one patient (1,4%. CONCLUSION: Glatiramer acetate decreased the number of relapses and EDSS score with tolerable side effects.

  18. New-onset ascites as a manifestation of virologic relapse in patients with hepatitis C cirrhosis

    Directory of Open Access Journals (Sweden)

    Chua DL

    2014-01-01

    Full Text Available Deborah Lim Chua, Thomas Hahambis, Samuel H SigalDivision of Gastroenterology, Department of Medicine, New York University School of Medicine, New York, NY, USABackground: Chronic hepatitis C is the most common cause of cirrhosis in industrialized countries. Successful treatment of chronic hepatitis C in patients with advanced fibrosis or cirrhosis has significant benefits, including improvements in inflammation, fibrosis, and portal hypertension, with prevention of esophageal varices and clinical decompensation.Case: In this report, we present two patients with well-compensated hepatitis C cirrhosis who achieved an end-of-treatment response on a direct-acting antiviral therapy-based triple regimen for hepatitis C virus, but subsequently presented with new-onset ascites associated with virologic relapse.Conclusion: We propose that the development of ascites in this setting is due to the adverse impact of inflammation of the virologic relapse on portal hypertension. Our observation that ascites formation can be a manifestation of virologic relapse has potentially important clinical implications, as it highlights not only the importance of close monitoring of cirrhotic patients after achieving end-of-treatment response but also the impact of active inflammation on the severity of portal hypertension.Keywords: chronic hepatitis C, cirrhosis, virologic relapse, portal hypertension, ascites

  19. relapse in adiposity of type 2 diabetes patients following withdrawa

    African Journals Online (AJOL)

    user

    In order to achieve optimum health status, Type 2 Diabetes (T2D) patients are usually encouraged to undergo ... This study investigated whether the gains of exercises on adiposity ..... the likelihood of morbidity, and prevention of weight gain.

  20. Fingolimod Treatment in Relapsing-Remitting Multiple Sclerosis Patients: A Prospective Observational Multicenter Postmarketing Study

    Directory of Open Access Journals (Sweden)

    Rocco Totaro

    2015-01-01

    Full Text Available Objective. The aim of this prospective observational multicenter postmarketing study was to evaluate fingolimod efficacy in a real world clinical setting. Methods. One hundred forty-two subjects with relapsing-remitting multiple sclerosis (RRMS were enrolled in three multiple sclerosis centers throughout Central and Southern Italy between January 2011 and September 2013. After enrollment, regular visits and EDSS assessment were scheduled every 3 months, and MRI scan was obtained every 12 months. Patients were followed up from 1 to 33 months (mean 14.95 ± 9.15 months. The main efficacy endpoints included the proportion of patients free from clinical relapses, from disability progression, from magnetic resonance imaging activity, and from any disease activity. Results. Out of 142 patients enrolled in the study, 88.1% were free from clinical relapse and 69.0% were free from disability progression; 68.5% of patients remained free from new or newly enlarging T2 lesions and 81.7% of patients were free from gadolinium enhancing lesions. Overall the proportion of patients free from any disease activity was 41.9%. Conclusions. Our data in a real world cohort are consistent with previous findings that yield convincing evidence for the efficacy of fingolimod in patients with RRMS.

  1. Phonological Fluency Strategy of Switching Differentiates Relapsing-Remitting and Secondary Progressive Multiple Sclerosis Patients

    OpenAIRE

    Messinis, L.; Kosmidis, M. H.; Vlahou, C.; Malegiannaki, A. C.; Gatzounis, G.; Dimisianos, N.; Karra, A.; Kiosseoglou, G.; Gourzis, P.; Papathanasopoulos, P.

    2013-01-01

    The strategies used to perform a verbal fluency task appear to be reflective of cognitive abilities necessary for successful daily functioning. In the present study, we explored potential differences in verbal fluency strategies (switching and clustering) used to maximize word production by patients with relapsing-remitting multiple sclerosis (RRMS) versus patients with secondary progressive multiple sclerosis (SPMS). We further assessed impairment rates and potential differences in the sensi...

  2. Causal Attributions about Disease-Onset and Relapse in Patients with Systemic Vasculitis

    Science.gov (United States)

    Grayson, Peter C.; Amudala, Naomi A.; McAlear, Carol A.; Leduc, Renée L.; Shereff, Denise; Richesson, Rachel; Fraenkel, Liana; Merkel, Peter A.

    2014-01-01

    Objectives Patients vary in their beliefs related to the cause of serious illness. The impact of these beliefs among patients with systemic vasculitis is not known. This study aimed to describe causal attributions about disease-onset and relapse in systemic vasculitis and to examine whether causal beliefs a) differ by type of vasculitis; and b) are associated with negative health outcomes. Methods Patients with vasculitis were recruited to complete an online questionnaire. Categories of causal beliefs were assessed with the Revised Illness Perception Questionnaire (IPQ-R). Differences in beliefs about disease-onset versus relapse were compared across different forms of vasculitis. Causal beliefs were assessed in association with several health outcomes including fatigue, functional impairments, and personal understanding of the condition. Results 692 patients representing 9 forms of vasculitis completed the questionnaire. The majority (90%) of patients had beliefs about the cause of their illness. Causal attributions were highly variable, but altered immunity and stress were the most commonly agreed upon causal beliefs. Frequencies of causal beliefs were strikingly similar across different forms of vasculitis, with few notable exceptions primarily in Behçet’s disease. Beliefs differed about causes of disease-onset versus relapse. Specific beliefs about disease-onset and relapse were weakly associated with fatigue, functional impairments, and understanding of the condition. Conclusion Patient beliefs related to the cause of systemic vasculitis are highly variable. Patterns of causal beliefs are associated with important negative health outcomes. Clinicians who care for patients with vasculitis should be mindful of these associations and consider asking about patients’ causal beliefs. PMID:24634202

  3. Possible Association between Serum Matrix Metalloproteinase-9 (MMP-9) Levels and Relapse in Depressed Patients following Electroconvulsive Therapy (ECT).

    Science.gov (United States)

    Shibasaki, Chiyo; Itagaki, Kei; Abe, Hiromi; Kajitani, Naoto; Okada-Tsuchioka, Mami; Takebayashi, Minoru

    2018-03-01

    Matrix metalloproteinases are involved in neuroinflammatory processes, which could underlie depression. Serum levels of MMP-9 and MMP-2 in depressed patients are significantly altered following electroconvulsive therapy, but an association between altered matrix metalloproteinases after successful ECT and possible relapse has yet to be investigated. Serum was obtained twice, before and immediately after a course of electroconvulsive therapy, from 38 depressed patients. Serum was also collected, once, from two groups of age- and gender-matched healthy controls, 40 volunteers in each group. Possible associations between levels of matrix metalloproteinases and relapse during a 1-year follow-up period were analyzed. Excluding patients who did not respond to electroconvulsive therapy and patients lost to follow-up, data from 28 patients were evaluated. Eighteen of the patients (64.3%) relapsed within 1 year. In the group that did not relapse, serum levels of MMP-9 were significantly decreased after a course of electroconvulsive therapy, but not in the group that relapsed. No association between MMP-2 and relapse was observed. The degree of change in serum MMP-9 change could be associated with relapse following electroconvulsive therapy in depressed patients. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  4. Patterns of relapse and outcome of elderly multiple myeloma patients treated as front-line therapy with novel agents combinations

    Directory of Open Access Journals (Sweden)

    Aurelio Lopez

    2015-01-01

    Full Text Available We report the characteristics of relapse, treatment response, and outcomes of 145 elderly patients with multiple myeloma in first relapse after front-line treatment with VMP or VTP. Reappearance of CRAB symptoms (113 patients and more aggressive forms of disease (32 patients were the most common patterns of relapse. After second-line therapy, 75 (51.7% patients achieved at partial response and 16 (11% complete response (CR. Overall survival was longer among patients receiving VMP as front-line induction (21.4 vs. 14.4 months, P=0.037, in patients achieving CR (28.3 vs. 14.8 months; P=0.04, and in patients without aggressive relapse (28.6 vs. 7.6 months; P=0.0007.

  5. Patterns of relapse and outcome of elderly multiple myeloma patients treated as front-line therapy with novel agents combinations☆

    Science.gov (United States)

    Lopez, Aurelio; Mateos, Maria-Victoria; Oriol, Albert; Valero, Marta; Martínez, Joaquín; Lorenzo, Jose Ignacio; Perez, Montserrat; Martinez, Rafael; de Paz, Raquel; Granell, Miguel; De Arriba, Felipe; Blanchard, M. Jesús; Peñalver, Francisco Javier; Bello, Jose Luis; Martin, Maria Luisa; Bargay, Joan; Blade, Joan; Lahuerta, Juan Jose; San Miguel, Jesús F.; de la Rubia, Javier

    2015-01-01

    We report the characteristics of relapse, treatment response, and outcomes of 145 elderly patients with multiple myeloma in first relapse after front-line treatment with VMP or VTP. Reappearance of CRAB symptoms (113 patients) and more aggressive forms of disease (32 patients) were the most common patterns of relapse. After second-line therapy, 75 (51.7%) patients achieved at partial response and 16 (11%) complete response (CR). Overall survival was longer among patients receiving VMP as front-line induction (21.4 vs. 14.4 months, P=0.037), in patients achieving CR (28.3 vs. 14.8 months; P=0.04), and in patients without aggressive relapse (28.6 vs. 7.6 months; P=0.0007). PMID:26500850

  6. External-beam boost prior to total-body irradiation in relapsed NHL transplant patients

    Energy Technology Data Exchange (ETDEWEB)

    Monson, Jedidiah M; Neuberg, Donna; Freedman, Arnold S; Tarbell, Nancy J; Nadler, Lee M; Mauch, Peter

    1995-07-01

    PURPOSE: To determine the impact of an external beam boost (EBB) on the outcome, relapse pattern and normal tissue toxicities of patients undergoing total-body irradiation (TBI) prior to bone marrow transplantation (BMT) for relapsed NHL. MATERIALS AND METHODS: Between 1982 and 1994, 299 patients at our institution underwent BMT for relapsed NHL. Patients underwent induction chemotherapy (CT) followed by conditioning with cyclophosphamide and 12 Gy TBI delivered in 6 fractions over 3 days. A total of 77 patients had persistent gross disease, defined as 2 cm or greater, after induction CT and received an EBB prior to BMT (EBB cohort). The median EBB dose was 28.8 Gy (range, 5-63), the median field size was 13 cm{sup 2} (range, 5-29.4) and the median time from EBB to BMT was 3 weeks (range, 1-20). A total of 222 patients were free of measurable disease or had disease measuring <2cm after CT and did not receive EBB (no-EBB cohort). To assess normal tissue toxicity, patients' simulation films and/or treatment records were reviewed for all 77 patients treated with local EBB and estimates were made of the percentage lung, heart and kidney in the radiation field. RESULTS: A total of 79 of 222 patients (36%) in the no-EBB cohort have relapsed; 33 of 77 patients (43%) in the EBB cohort have relapsed (p=0.28, by Fisher exact test). Median time to relapse after BMT was 54 months for the no-EBB cohort and 38 months for the EBB cohort (p=0.26, by log-rank test). The 3-year actuarial freedom from relapse (deaths in remission censored) was 59% for the no-EBB cohort (90% CI: 52-66%) and 51% for the EBB cohort (90% CI: 40-62%). Data on site of relapse was available for 101 of the 112 relapses (75 no-EBB, 26 EBB). For the no-EBB cohort 33 of 75 relapses (44%) were in sites of prior nodal disease only. For the EBB cohort, 12 of 26 relapses (46%) were in sites of prior nodal disease only, of these, only 6 (23%) were within the EBB treatment field. A total of 26 patients had thoracic

  7. Immunotoxin – a new treatment option in patients with relapsed and refractory Hodgkin lymphoma

    Science.gov (United States)

    Novakovic, Barbara Jezersek

    2015-01-01

    Background Even though Hodgkin lymphoma is a highly curable disease, some of the patients have either a refractory disease or experience a relapse following a successful primary therapy. Durable responses and remissions in patients with relapsed or refractory disease may be achieved in approximately one-half with salvage chemotherapy followed by high dose chemotherapy (HDT) and autologous hematopoietic cell rescue (SCT). On the other hand, patients who relapse after HDT and autologous SCT or those who have failed at least two prior multi-agent chemotherapy regimens and are not candidates for HDT have limited treatment options. Conclusions A new treatment option in this population is an immunotoxin Brentuximab vedotin composed of a CD30 directed antibody linked to the antitubulin agent monomethyl auristatin E. It has demonstrated a substantial effectiveness and an acceptable toxicity. In the pivotal study, the overall response rate was 75% with 34% of complete remissions. The median durations of response were 20.5 and 6.7 months for those with complete remission and all responding patients, respectively. The median overall survival was 40.5 months (3-years overall survival 54%) and the median progression-free survival 9.3 months. The most common non-hematologic toxicities were peripheral sensory neuropathy, nausea, and fatigue while the most common severe side effects were neutropenia, thrombocytopenia, anemia, and peripheral sensory neuropathy. PMID:26834516

  8. Economic evaluation of therapies for patients suffering from relapsed-refractory multiple myeloma in Greece

    Directory of Open Access Journals (Sweden)

    Fragoulakis V

    2013-04-01

    Full Text Available V Fragoulakis,1 E Kastritis,2 T Psaltopoulou,3 N Maniadakis1 1National School of Public Health, Athens, Greece; 2Department of Clinical Therapeutics, Alexandra Hospital, University of Athens, School of Medicine, Athens, Greece; 3Department of Hygiene, Epidemiology and Medical Statistics, University of Athens, School of Medicine, Athens, Greece Background: Multiple myeloma is a hematologic malignancy that incurs a substantial economic burden in care management. Since most patients with multiple myeloma eventually relapse or become refractory to current therapies (rrMM, the aim of this study was to assess the cost-effectiveness of the combination of lenalidomide–dexamethasone, relative to bortezomib alone, in patients suffering from rrMM in Greece. Methods: An international discrete event simulation model was locally adapted to estimate differences in overall survival and treatment costs associated with the two alternative treatment options. The efficacy data utilized came from three international trials (MM-009, MM-010, APEX. Quality of life data were extracted from the published literature. Data on resource use and prices came from relevant local sources and referred to 2012. The perspective of the analysis was that of public providers. Total costs for monitoring and administration of therapy to patients, management of adverse events, and cost of medication were captured. A 3.5% discount rate was used for costs and health outcomes. A Monte Carlo simulation was used to estimate probabilistic results with 95% uncertainty intervals (UI and a cost-effectiveness acceptability curve. Results: The mean number of quality-adjusted life years (QALYs was 3.01 (95% UI 2.81–3.20 and 2.22 (95% UI 2.02–2.41 for lenalidomide–dexamethasone and bortezomib, respectively, giving an incremental gain of 0.79 (95% UI 0.49–1.06 QALYs in favor of lenalidomide–dexamethasone. The mean cost of therapy per patient was estimated at €77,670 (95% UI €76,509

  9. Psychotic relapse and associated factors among patients attending health services in Southwest Ethiopia: a cross-sectional study.

    Science.gov (United States)

    Fikreyesus, Mahlet; Soboka, Matiwos; Feyissa, Garumma Tolu

    2016-10-20

    Psychotic relapse leads to repeated hospitalization and negatively affects the clinical prognosis of the patients. Information on prevalence of relapse among patients with psychotic disorders in Ethiopian setting is scarce. This study aimed to assess the prevalence of relapse among patients with psychotic disorders attending services in Jimma University Specialized Hospital (JUSH). Data were collected using interviewer administered questionnaire. We used medication adherence rating scale (MARS) to assess compliance to medication and abnormal involuntary movement scale (AIMS) to detect medication side effects. Logistic regression analysis was used to identify independent predictors of psychotic relapse. All variables with P-value value higher when compared to those who have never experienced medication side effects (aOR = 1.83, 95 % CI = 1.01, 3.31). The high prevalence of relapse among patients with psychotic disorder needs special attention. Clinicians need to pay attention to medication side effects the patient faces. Intervening noncompliance to medication and appropriately managing medication side effects may help in preventing psychotic relapse that may result because of non-compliance. The provision of counseling, psycho education, psycho social support may help patients in improving compliance to medication and reducing psychotic relapse. Developing and strengthening community based rehabilitation services should be emphasized as part of mental healthcare services.

  10. Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia

    DEFF Research Database (Denmark)

    Craddock, Charles; Labopin, Myriam; Robin, Marie

    2016-01-01

    Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic...... syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65). Sixty-nine patients...... conclude that azacitidine represents an important new therapy in selected patients with acute myeloid leukemia/myelodysplastic syndromes who relapse after allogeneic stem cell transplantation. Prospective studies to confirm optimal treatment options in this challenging patient population are required....

  11. Usefulness of a rapid faecal calprotectin test to predict relapse in Crohn's disease patients on maintenance treatment with adalimumab.

    Science.gov (United States)

    Ferreiro-Iglesias, Rocio; Barreiro-de Acosta, Manuel; Lorenzo-Gonzalez, Aurelio; Dominguez-Muñoz, Juan Enrique

    2016-01-01

    Predicting relapse in Crohn's disease (CD) patients by measuring non-invasive biomarkers could allow for early changes of treatment. Data are scarce regarding the utility of monitoring calprotectin to predict relapse. The aim of the study was to evaluate the predictive value of a rapid test of faecal calprotectin (FC) to predict for flares in CD patients on maintenance treatment with adalimumab (ADA). A prospective, observational cohort study was designed. Inclusion criteria were CD patients in clinical remission on a standard dose of ADA therapy. Fresh FC was measured using a rapid test. Thirty patients were included (median age 38 years, 56.7% female). After the 4 months follow-up, 70.0% patients remained in clinical remission and 30.0% had a relapse. FC concentration at inclusion was significantly higher in those patients who relapsed during the follow-up (625 μg/g) compared to those who stayed in remission (45 μg/g). The optimal cut-off for FC to predict relapse was 204 μg/g. The area under the receiver-operating characteristic curve was 0.968. Sensitivity, specificity, positive, and negative predictive value of FC to predict relapse were 100%, 85.7%, 74.1%, and 100%, respectively. In CD patients on ADA maintenance therapy, FC levels measured with a rapid test allow relapse over the following months to be predicted with high accuracy. Low FC levels exclude relapse within at least 4 months after testing, whereas high levels are associated with relapse in three out of every four patients.

  12. Different cognitive profiles of Brazilian patients with relapsing-remitting and primary progressive multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Dóra-Neide Rodrigues

    2011-08-01

    Full Text Available Cognitive impairment is a symptom of multiple sclerosis (MS. Different clinical forms of multiple sclerosis have different cognitive profiles, according to findings of previous studies which used extensive batteries of neuropsychological tests. OBJECTIVE: To investigate cognitive profiles of Brazilian patients with relapsing-remitting multiple sclerosis (RRMS and primary progressive multiple sclerosis (PPMS by using a brief battery of neuropsychological tests. METHOD: Sixty-six patients, within 18-65 of age and 3-18 years of education, were paired with healthy control subjects, regarding gender, age, and education level. RESULTS: On Symbol Digit Modalities Test and Hooper Visual Organization Test, cognition was affected in 50% in RRMS and 69% in PPMS. Fluency of "F" was impaired in 24% of RRMS and 81% of PPMS. Immediate recall was affected in 32% of RRMS and in 63% of PPMS; whereas late recall, in 46% of relapsing-remitting and in 69% of primary progressive. CONCLUSION: Cognitive profiles of relapsing-remitting and primary progressive patients are different

  13. A Chinese patient with relapsed and refractory Hodgkin lymphoma treated with brentuximab vedotin

    Institute of Scientific and Technical Information of China (English)

    Zhi-Gang Cao; Hong-Wei Zhou; Chao-Jin Peng; Mo Liu; Yu Du; Qing-Ming Yang

    2013-01-01

    At present, approximately 20% of Hodgkin lymphomas (HL) are relapsed and refractory, and therapeutic methods including chemotherapy, radiotherapy, and even stem cell transplantation are unsatisfactory. Brentuximab vedotin, composed of CD30 antibody and a chemotherapeutic agent, is a new targeted drug that eradicates tumor cel s by binding to the CD30 antigen on their surface. In clinical trials, the response rate and complete remission rate of this drug were 73% and 40%, respectively, for relapsed and refractory HL. Here we report a case of CD30-positive relapsed and refractory HL that was treated with brentuximab. Before the treatment with brentuximab, the patient underwent chemotherapy, radiotherapy, and autologous stem cell transplantation. However, the disease continued to progress, affecting multiple organs and prompting symptoms such as persistent fever. After the treatment with brentuximab, the patient′s condition improved. Body temperature returned to normal after 4 days. Lung nodules were reduced in size and number after a single course of treatment, and PET/CT showed partial remission and complete remission after 3 and 6 courses of treatment, respectively. The entire treatment process progressed smoothly, though the patient experienced some symptoms due to chemotherapy, including peripheral neuritis of the limbs, irritating dry cough, and mild increase in aminotransferase. No serious adverse effects were observed. The current general condition of the patient is good;the continuous complete remission has amounted to 6 months.

  14. A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

    Science.gov (United States)

    Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

    2011-06-01

    A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

  15. Work Participation and Executive Abilities in Patients with Relapsing-Remitting Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Karin van der Hiele

    Full Text Available The majority of patients with Multiple Sclerosis (MS are unable to retain employment within 10 years from disease onset. Executive abilities, such as planning, working memory, attention, problem solving, inhibition and mental flexibility may have a direct impact on the ability to maintain a job. This study investigated differences in subjective and objective executive abilities between relapsing-remitting MS patients with and without a paid job. We included 55 relapsing-remitting MS patients from a community-based sample (47 females; mean age: 47 years; 36% employed. Patients underwent neurological, cognitive and psychological assessments at their homes, including an extensive executive test battery. We found that unemployed patients had a longer disease duration (t(53=2.76, p=0.008 and reported more organising and planning problems (χ2(1=6.3, p=0.012, higher distractibility (Kendall's tau-b= -0.24, p=0.03 and more cognitive fatigue (U=205.0, p=0.028, r=-0.30 than employed patients. Unemployed patients completed slightly less categories on the Wisconsin Card Sorting Test (U=243.5, p=0.042, r=-0.28. Possible influential factors such as age, educational level, physical functioning, depression and anxiety did not differ between groups. In conclusion, while relapsing-remitting MS patients without a paid job reported more executive problems and cognitive fatigue than patients with a paid job, little differences were found in objective executive abilities. Further research is needed to examine possible causal relations.

  16. Work Participation and Executive Abilities in Patients with Relapsing-Remitting Multiple Sclerosis.

    Science.gov (United States)

    van der Hiele, Karin; van Gorp, Dennis; Ruimschotel, Rob; Kamminga, Noëlle; Visser, Leo; Middelkoop, Huub

    2015-01-01

    The majority of patients with Multiple Sclerosis (MS) are unable to retain employment within 10 years from disease onset. Executive abilities, such as planning, working memory, attention, problem solving, inhibition and mental flexibility may have a direct impact on the ability to maintain a job. This study investigated differences in subjective and objective executive abilities between relapsing-remitting MS patients with and without a paid job. We included 55 relapsing-remitting MS patients from a community-based sample (47 females; mean age: 47 years; 36% employed). Patients underwent neurological, cognitive and psychological assessments at their homes, including an extensive executive test battery. We found that unemployed patients had a longer disease duration (t(53)=2.76, p=0.008) and reported more organising and planning problems (χ2(1)=6.3, p=0.012), higher distractibility (Kendall's tau-b= -0.24, p=0.03) and more cognitive fatigue (U=205.0, p=0.028, r=-0.30) than employed patients. Unemployed patients completed slightly less categories on the Wisconsin Card Sorting Test (U=243.5, p=0.042, r=-0.28). Possible influential factors such as age, educational level, physical functioning, depression and anxiety did not differ between groups. In conclusion, while relapsing-remitting MS patients without a paid job reported more executive problems and cognitive fatigue than patients with a paid job, little differences were found in objective executive abilities. Further research is needed to examine possible causal relations.

  17. [Neuropsychology of mildly disabled patients with relapsing-remitting multiple sclerosis].

    Science.gov (United States)

    Santiago Rolanía, Olga; Guàrdia Olmos, Joan; Arbizu Urdiain, Txomin

    2006-02-01

    Previous papers have mainly demonstrated the presence of cognitive impairment in patients with multiple sclerosis (MS), these changes have been traditionally associated with the later stages of the disease. In the current study, a comprehensive neuropsychological battery was administered to 216 relapsing-remitting MS patients with mild clinical disability (EDSSreproduction visual memory; and long term verbal memory of texts, and information processing speed. We also observed greeter incidence of depressive symptoms in patients. And a little relation of the cognitive deficits with the clinical variables in these phase of the disease.

  18. Comparison of two doses of intravenous temsirolimus in patients with relapsed/refractory mantle cell lymphoma.

    Science.gov (United States)

    Jurczak, Wojciech; Ramanathan, Sundra; Giri, Pratyush; Romano, Alessandra; Mocikova, Heidi; Clancy, Jill; Lechuga, Mariajose; Casey, Michelle; Boni, Joseph; Giza, Agnieszka; Hess, Georg

    2018-03-01

    Temsirolimus 175 mg once-weekly for 3 weeks, followed by 75 mg once-weekly intravenously dosed (175/75 mg) is approved in the European Union for treatment of relapsed/refractory mantle cell lymphoma (MCL). A phase IV study explored whether similar efficacy, but improved safety could be achieved with 75 mg without 175 mg loading doses (ClinicaTrials.gov: NCT01180049). Patients with relapsed/refractory MCL were randomized to once-weekly temsirolimus 175/75 mg (n = 47) or 75 mg (n = 42). Treatment continued until objective disease progression. Primary endpoint: progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AEs). Median PFS was 4.3 versus 4.5 months (hazard ratio [HR] 0.731; 80% confidence interval [CI], 0.520-1.027), and median OS 18.7 versus 11.0 months (HR 0.681; 80% CI, 0.472-0.982) with 175/75 mg versus 75 mg. There were fewer patients with serious AEs, dose reduction, or death with 175/75 mg (57.4%, 48.9%, and 48.9%) versus 75 mg (73.8%, 64.3%, and 65.1%). Temsirolimus 175/75 mg remains the preferred dosing regimen for relapsed/refractory MCL.

  19. Vorinostat in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma

    International Nuclear Information System (INIS)

    Siegel, D S; Richardson, P; Dimopoulos, M; Moreau, P; Mitsiades, C; Weber, D; Houp, J; Gause, C; Vuocolo, S; Eid, J; Graef, T; Anderson, K C

    2014-01-01

    The addition of vorinostat to lenalidomide/dexamethasone represents a novel combination therapy in multiple myeloma (MM), informed by laboratory studies suggesting synergy. This was a phase I, multicenter, open-label, non-randomized, dose-escalating study in patients with relapsed or relapsed and refractory MM. Clinical evaluation, electrocardiogram, laboratory studies and adverse events were obtained and assessed. The maximum-tolerated dose was not reached owing to a non-occurrence of two dose-limiting toxicities per six patients tested at any of the dosing levels. Patients tolerated the highest dose tested (Level 5) and this was considered the maximum administered dose: at 400 mg vorinostat on days 1–7 and 15–21, 25 mg lenalidomide on days 1–21 and 40 mg dexamethasone on days 1, 8, 15 and 22, per 28-day cycle. Drug-related adverse events were reported in 90% of patients serious adverse experiences were reported in 45% of the patients and 22% of all patients had adverse experiences considered, possibly related to study drug by the investigators. A confirmed partial response or better was reported for 14/30 patients (47%) evaluable for efficacy, including 31% of patients previously treated with lenalidomide. Vorinostat in combination with lenalidomide and dexamethasone proved tolerable with appropriate supportive care, with encouraging activity observed

  20. Reinduction with certolizumab pegol in patients with relapsed Crohn's disease: results from the PRECiSE 4 Study

    DEFF Research Database (Denmark)

    Sandborn, William J; Schreiber, Stefan; Hanauer, Stephen B

    2010-01-01

    We sought to determine the efficacy of certolizumab pegol reinduction in patients with active Crohn's disease who respond to induction therapy with certolizumab pegol and then relapse during continuous or interrupted maintenance therapy....

  1. Ibrutinib efficacy and tolerability in patients with relapsed chronic lymphocytic leukemia following allogeneic HCT.

    Science.gov (United States)

    Ryan, Christine E; Sahaf, Bita; Logan, Aaron C; O'Brien, Susan; Byrd, John C; Hillmen, Peter; Brown, Jennifer R; Dyer, Martin J S; Mato, Anthony R; Keating, Michael J; Jaglowski, Samantha; Clow, Fong; Rezvani, Andrew R; Styles, Lori; Coutre, Steven E; Miklos, David B

    2016-12-22

    Ibrutinib, a potent and irreversible small-molecule inhibitor of both Bruton's tyrosine kinase and interleukin-2 inducible kinase (ITK), has been used to treat relapsed/refractory chronic lymphocytic leukemia (CLL) with prolongation of progression-free and overall survival. Here, we present 27 patients with relapsed CLL following allogeneic hematopoietic cell transplant (HCT) who subsequently received ibrutinib salvage therapy. Sixteen of these patients were part of multi-institutional clinical trials and achieved an overall response rate of 87.5%. An additional 11 patients were treated at Stanford University following US Food and Drug Administration approval of ibrutinib; 7 (64%) achieved a complete response, and 3 (27%) achieved a partial response. Of the 9 patients treated at Stanford who had mixed chimerism-associated CLL relapse, 4 (44%) converted to full donor chimerism following ibrutinib initiation, in association with disease response. Four of 11 (36%) patients evaluated by ClonoSeq achieved minimal residual disease negativity with CLL ibrutinib was discontinued, in 1 case even after 26 months. None of the 27 patients developed graft-versus-host-disease (GVHD) following ibrutinib initiation. We postulate that ibrutinib augments the graft-versus-leukemia (GVL) benefit through a T-cell-mediated effect, most likely due to ITK inhibition. To investigate the immune modulatory effects of ibrutinib, we completed comprehensive immune phenotype characterization of peripheral B and T cells from treated patients. Our results show that ibrutinib selectively targets pre-germinal B cells and depletes Th2 helper cells. Furthermore, these effects persisted after drug discontinuation. In total, our results provide evidence that ibrutinib effectively augments GVL without causing GVHD. © 2016 by The American Society of Hematology.

  2. Treatment strategies in patients with AML or high-risk myelodysplastic syndrome relapsed after Allo-SCT.

    Science.gov (United States)

    Sauer, T; Silling, G; Groth, C; Rosenow, F; Krug, U; Görlich, D; Evers, G; Albring, J; Besoke, R; Mesters, R M; Müller-Tidow, C; Kessler, T; Büchner, T; Berdel, W E; Stelljes, M

    2015-04-01

    Non-relapse mortality after Allo-SCT has significantly decreased over the last years. Nevertheless, relapse remains a major cause for post SCT mortality in patients with AML and high-risk myelodysplastic syndrome (MDS). In this retrospective single-center analysis, we have analyzed the treatment outcomes of 108 patients with AML or MDS, who relapsed after Allo-SCT. Seventy of these patients (65%) were treated with salvage therapies containing chemotherapy alone, allogeneic cell-based treatment or the combination of both. Thirty-eight patients (35%) received palliative treatment. Median OS after diagnosis of relapse was 130 days. Compared with patients who received chemotherapy alone, response to salvage therapy was significantly improved in patients treated with a combination of chemo- and allogeneic cell-based therapy (CR rate 57% vs 13%, P=0.002). Among risk factors concerning pretreatment characteristics, disease status before first Allo-SCT, and details of transplantation, only the time interval from Allo-SCT to relapse was an independent predictor of response to salvage therapy and OS. These data confirmed that time to relapse after transplantation is an important prognostic factor. Up to now, only patients eligible for treatment regimens containing allogeneic cell-based interventions achieved relevant response rates.

  3. Risk of venous thromboembolism in neuromyelitis optica patients hospitalized for acute relapse.

    Science.gov (United States)

    Farber, Rebecca Straus; Gross, Robert; Zakin, Elina; Fabian, Michelle

    2017-06-01

    Neuromyelitis optica spectrum disorder (NMOSD) patients may be at increased risk of venous thromboembolism (VTE) not only due to ambulatory disability but also due to systemic autoimmune and inflammatory mechanisms altering the hemostatic balance. To compare the risk of VTE in NMOSD versus multiple sclerosis (MS) patients hospitalized for acute relapses. Hospital admissions for MS or NMOSD exacerbations were retrospectively identified. Demographics and medical history were recorded. The relationship between visit diagnosis and presence of VTE within 6 weeks of relapse onset was assessed by univariate logistic regression. A multivariate model evaluated the relationship between diagnosis, age, race, gender, body mass index (BMI), disease modifying therapy use, oral corticosteroid use, oral contraceptive use, smoking, length of stay (LOS), and ambulatory status on VTE risk. A total of 30 NMOSD patients had 55 hospitalizations; 179 MS patients had 264 hospitalizations. Six NMOSD patients and one MS patient had VTE. NMOSD visits compared to MS visits had an odds ratio (OR) of VTE of 32.2 ( p = 0.002). NMOSD was more likely to be associated with VTE (OR = 17.4; p = 0.01) controlling for age, LOS, and ambulatory disability. NMOSD may be a risk factor for VTE. Larger prospective studies are required to confirm this risk and determine implications for prophylaxis.

  4. Serum biomarkers in patients with relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss.

    Directory of Open Access Journals (Sweden)

    Christian Dejaco

    Full Text Available Previous studies suggest a role for eotaxin-3, TARC/CCL17 and IgG4 in newly-diagnosed patients with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss with highly active disease. The role of these biomarkers in relapsing disease is unclear.Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio were determined in serum samples from a longitudinal cohort of patients with EGPA (105 visits of 25 patients. Epidemiological, clinical and laboratory data were available for all visits.At the first visit, 80% of patients were using glucocorticoids and 68% additional immunosuppressive drugs. Disease flares were seen at 18 visits. The median BVAS and BVAS/WG scores at time of relapse were 4 and 2, respectively. None of the biomarkers tested were useful to discriminate between active disease and remission. Patients treated with prednisone had lower eotaxin-3 and eosinophil levels compared to patients not taking glucocorticoids irrespective of disease activity. Use of immunosuppressive agents was not associated with biomarker levels.Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio do not clearly differentiate active and inactive disease in established EGPA. Defining biomarkers in EGPA remains a challenge especially during times of glucocorticoid use.

  5. Botulinum toxin as a therapeutic agent to prevent relapse in deep bite patients.

    Science.gov (United States)

    Mücke, Thomas; Löffel, Anja; Kanatas, Anastasios; Karnezi, Sandy; Rana, Majeed; Fichter, Andreas; Haarmann, Stephan; Wolff, Klaus-Dietrich; Loeffelbein, Denys John

    2016-05-01

    The etiology of deep bite is multifactorial. One of the causes is increased muscular activity. This makes the treatment of deep bite malocclusions difficult and often results in relapse in many cases. In this work we compared patients with surgical orthognathic treatment only and surgical orthognathic treatment with additional injections of botulinum toxin after mandibular advancement for class II division 2 malocclusion. This is a prospective study. Adult patients were assessed pretreatment (T1), posttreatment (T2), and long-term after 1 year (T3). In total, 32 patients (mean age, 30.7 years; 23 women and 9 men) reached the study end point (T3); 24 patients were treated without botulinum toxin and 8 patients received preoperative injections of botulinum toxin. Significant differences between both groups were observed, with a more stable result for the experimental group treated with botulinum toxin. In a selective group of adult patients with a class II division II incisor relationship and with a class II skeletal base, botulinum toxin injections can effectively prevent relapse. This may present an alternative to a conventional myotomy. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  6. Incidence, clinical features, laboratory findings and outcome of patients with multiple myeloma presenting with extramedullary relapse.

    Science.gov (United States)

    Papanikolaou, Xenofon; Repousis, Panagiotis; Tzenou, Tatiana; Maltezas, Dimitris; Kotsopoulou, Maria; Megalakaki, Katerina; Angelopoulou, Maria; Dimitrakoloulou, Elektra; Koulieris, Efstathios; Bartzis, Vassiliki; Pangalis, Gerasimos; Panayotidis, Panagiotis; Kyrtsonis, Marie-Christine

    2013-07-01

    Extramedullary plasmacytomas constitute a rare and not well studied subset of multiple myeloma (MM) relapses. We report the incidence, clinical-laboratory features and outcome of patients with MM and extramedullary relapse (ExMeR). A total of 303 patients with symptomatic MM were recorded in a 13-year period in two institutions. Twenty-eight cases of ExMeR (9%) were recorded. There was an increased frequency of elevated lactate dehydrogenase (LDH) (p = 0.026), bone plasmacytomas (p = 0.001) and fractures (p = 0.002) at diagnosis, in patients with ExMeR compared to the others. ExMeR was associated with an ominous outcome, high LDH, constitutional symptoms and a statistically significant decrease of monoclonal paraprotein compared to levels at diagnosis (p = 0.009). Prior treatment with bortezomib was associated with a decreased hazard of ExMeR (p = 0.041). Overall survival (OS) was decreased in patients with ExMeR compared to the others (38 vs. 59 months, p = 0.006). Patients with MM with ExMeR have a lower OS and their clinical and laboratory features differ from those without.

  7. Role of routine imaging in detecting recurrent lymphoma; a review of 258 patients with relapsed aggressive non-Hodgkin and Hodgkin lymphoma

    DEFF Research Database (Denmark)

    El-Galaly, Tarec Christoffer; Mylam, Karen Juul; Bøgsted, Martin

    2014-01-01

    After first-line therapy, patients with Hodgkin and aggressive non-Hodgkin lymphomas are followed closely for early signs of relapse. The current follow-up practice with frequent use of surveillance imaging is highly controversial and warrants a critical evaluation. Therefore a retrospective...... multicenter study of relapsed Hodgkin and aggressive non-Hodgkin lymphomas (nodal T-cell and diffuse large B-cell lymphomas) was conducted. All included patients had been diagnosed during the period 2002-2011 and relapsed after achieving complete remission on first-line therapy. Characteristics and outcome...... of imaging-detected relapses were compared to other relapses. A total of 258 patients with recurrent lymphoma were included in the study. Relapse investigations were initiated outside preplanned visits in 52% of the patients. Relapse detection could be attributed to patient-reported symptoms alone...

  8. Factors of risk for relapse of pulmonary tuberculosis in-patient of the Hospital Santa Clara from Bogota 1992/2000

    International Nuclear Information System (INIS)

    Hidalgo Martinez, Patricia; Awad Garcia, Carlos; Pavia Albor, Jacqueline

    2002-01-01

    Pulmonary tuberculosis relapse is defined as these patients that make recurrence of tuberculosis after complete an adequate treatment, and these patients are again diagnosed bacteriologically with tuberculosis. We tried to identify the risk factors for relapse among adults, through an analytical study of cases and controls, with eighty patients among the tuberculosis programmed of Santa Clara Hospital between 1992-2000 with relapse diagnosis which meet criterion of case and eighty patients which meet criterion of control. We did a bivariate analysis with confidence intervals and univariate calculation with logistic regression analysis to predict the development of relapse for the different variables. Diabetes mellitus, chronic renal failure, silicosis are associated with relapse, but in our study we found another factors which are joined to relapse and we suggest that if we find these factors among tuberculosis patients would indicate the chance of relapse and this would create the necessity of use a larger number of doses of antituberculosis medicaments

  9. IIVP salvage regimen induces high response rates in patients with relapsed lymphoma before autologous stem cell transplantation.

    Science.gov (United States)

    Abali, Huseyin; Oyan, Basak; Koc, Yener; Kars, Ayse; Barista, Ibrahim; Uner, Aysegul; Turker, Alev; Demirkazik, Figen; Tekin, Fatma; Tekuzman, Gulten; Kansu, Emin

    2005-06-01

    Patients with relapsed lymphoma can be cured with high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). New therapeutic approaches with better cytoreductive capacity are needed for relapsed patients to keep their chance for cure with transplantation. We report 30 patients with relapsed lymphoma, median age 43 years, treated with IIVP salvage regimen consisting of ifosfamide, mesna, idarubicin, and etoposide for 2 or 3 cycles. Seventeen patients had non-Hodgkin lymphoma (NHL) and 13 patients had Hodgkin disease (HD). Fourteen (47%) patients were at their first relapse. Overall response rate was 86.6% (n = 26) with 19 patients (63.3%) achieving complete response. Overall response rate was 92% in patients with HD and 82% in NHL. The most frequent side effects observed were grade III-IV neutropenia (87%) and thrombocytopenia (73%). IIVP regimen is a highly effective salvage therapy for patients with relapsed HD or NHL who are candidates for autologous HSCT. Close follow up is necessary because of the high incidence of grade III-IV hematologic toxicity.

  10. A Phase I Trial of DFMO Targeting Polyamine Addiction in Patients with Relapsed/Refractory Neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Giselle L Saulnier Sholler

    Full Text Available Neuroblastoma (NB is the most common cancer in infancy and most frequent cause of death from extracranial solid tumors in children. Ornithine decarboxylase (ODC expression is an independent indicator of poor prognosis in NB patients. This study investigated safety, response, pharmacokinetics, genetic and metabolic factors associated with ODC in a clinical trial of the ODC inhibitor difluoromethylornithine (DFMO ± etoposide for patients with relapsed or refractory NB.Twenty-one patients participated in a phase I study of daily oral DFMO alone for three weeks, followed by additional three-week cycles of DFMO plus daily oral etoposide. No dose limiting toxicities (DLTs were identified in patients taking doses of DFMO between 500-1500 mg/m2 orally twice a day. DFMO pharmacokinetics, single nucleotide polymorphisms (SNPs in the ODC gene and urinary levels of substrates for the tissue polyamine exporter were measured. Urinary polyamine levels varied among patients at baseline. Patients with the minor T-allele at rs2302616 of the ODC gene had higher baseline levels (p=0.02 of, and larger decreases in, total urinary polyamines during the first cycle of DFMO therapy (p=0.003 and had median progression free survival (PFS that was over three times longer, compared to patients with the major G allele at this locus although this last result was not statistically significant (p=0.07. Six of 18 evaluable patients were progression free during the trial period with three patients continuing progression free at 663, 1559 and 1573 days after initiating treatment. Median progression-free survival was less among patients having increased urinary polyamines, especially diacetylspermine, although this result was not statistically significant (p=0.056.DFMO doses of 500-1500 mg/m2/day are safe and well tolerated in children with relapsed NB. Children with the minor T allele at rs2302616 of the ODC gene with relapsed or refractory NB had higher levels of urinary

  11. The Effect of Body Mass Index on Relapse of Pilonidal Sinus Disease in Adult Patients

    Directory of Open Access Journals (Sweden)

    Jalal Poorghasem

    2012-04-01

    Full Text Available Background: Pilonidal disease occurs either as a secreting sinus or in the form of an acute abscess in the coccygeal area and is an underlying cyst associated with granulomatous and fibrosis tissue which commonly contains heaps of hair, for which inherited and acquisitive hypotheses are proposed. Body mass index (BMI is the objective indicator of obesity according to height and weight. This study aims to examine the relationship between BMI and the role of obesity in development and relapse of pilonidal cyst disease.Materials and Methods: This retrospective cross-sectional study examined 126 patients with primary or recurrent pilonidal sinus within a year. A separate questionnaire was formed and recorded in the computer for each patient based on the disease type and body mass index.Results: One hundred out of 126 studied patients (79.4% underwent primary Pilonidal Sinus surgery and 26 patients (20.6 had recurrent Pilonidal sinus surgery. 36 patients (28.6 were female and 90 patients (71.4% were male. Among patients with recurrent Pilonidal sinus, 18 patients (69.2% had BMI above 30 and 8 patients (30.8% had BMI of 25 to 30 kg/m2. The patients whose BMI was estimated to be 20 to 25 or less than 20 kg/ m2 per square meter, had no recurrence of disease. Conclusion: In this study, high BMI was associated with relapse of pilonidal sinus disease. Supporting the previous studies, the incidence of disease in this study was also higher in young adults.

  12. Phase I trial of verubulin (MPC-6827) plus carboplatin in patients with relapsed glioblastoma multiforme.

    Science.gov (United States)

    Grossmann, Kenneth F; Colman, Howard; Akerley, Wallace A; Glantz, Michael; Matsuoko, Yuko; Beelen, Andrew P; Yu, Margaret; De Groot, John F; Aiken, Robert D; Olson, Jeffrey J; Olsen, Jeffery J; Evans, Brent A; Jensen, Randy L

    2012-11-01

    Verubulin (MPC-6827) is a microtubule-destabilizing agent that achieves high concentrations in the brain. Verubulin disrupts newly formed blood vessels in xenografts. We determined the safety and tolerability of verubulin administered in combination with carboplatin in patients with relapsed glioblastoma multiforme (GBM). Three pre-selected doses of verubulin were tested: 2.1, 2.7, and 3.3 mg/m(2) in a standard "3+3" design. Verubulin was given every second week of a 6-week cycle in the 2.1 mg/m(2) cohort or weekly for 3 weeks of a 4-week cycle in subsequent cohorts. Carboplatin was administered intravenously at an area under the curve (AUC) dosage 4 every 2 weeks for the 2.1 mg/m(2) cohort or on day 1 of each 4-week cycle in subsequent cohorts. Nineteen patients with GBM in first or second relapse were enrolled. Four patients (21 %) experienced a grade 3 or greater verubulin- or carboplatin-related adverse event, including hypesthesia, cerebral ischemia, anemia, and thrombocytopenia. The mean plasma half life of verubulin was 3.2 h (SD = 0.82). Two patients achieved at least a partial response by Macdonald criteria. One of these patients remains progression free and off treatment more than 24 months beyond his initiation of verubulin. Five patients had stable disease. Median progression-free survival (PFS) across all patients was 8 weeks, and the 6-month PFS rate was 21 %. The combination of verubulin at the previously determined single-agent maximum tolerated dose of 3.3 mg/m(2) with carboplatin in patients with recurrent/refractory GBM is safe and well tolerated. In this patient population with a highly vascularized tumor, no cerebral hemorrhage was observed.

  13. Isolation of Trypanosoma brucei gambiense from cured and relapsed sleeping sickness patients and adaptation to laboratory mice.

    Directory of Open Access Journals (Sweden)

    Patient Pati Pyana

    Full Text Available BACKGROUND: Sleeping sickness due to Trypanosoma brucei (T.b. gambiense is still a major public health problem in some central African countries. Historically, relapse rates around 5% have been observed for treatment with melarsoprol, widely used to treat second stage patients. Later, relapse rates of up to 50% have been recorded in some isolated foci in Angola, Sudan, Uganda and Democratic Republic of the Congo (DRC. Previous investigations are not conclusive on whether decreased sensitivity to melarsoprol is responsible for these high relapse rates. Therefore we aimed to establish a parasite collection isolated from cured as well as from relapsed patients for downstream comparative drug sensitivity profiling. A major constraint for this type of investigation is that T.b. gambiense is particularly difficult to isolate and adapt to classical laboratory rodents. METHODOLOGY/PRINCIPAL FINDINGS: From 360 patients treated in Dipumba hospital, Mbuji-Mayi, D.R. Congo, blood and cerebrospinal fluid (CSF was collected before treatment. From patients relapsing during the 24 months follow-up, the same specimens were collected. Specimens with confirmed parasite presence were frozen in liquid nitrogen in a mixture of Triladyl, egg yolk and phosphate buffered glucose solution. Isolation was achieved by inoculation of the cryopreserved specimens in Grammomys surdaster, Mastomys natalensis and SCID mice. Thus, 85 strains were isolated from blood and CSF of 55 patients. Isolation success was highest in Grammomys surdaster. Forty strains were adapted to mice. From 12 patients, matched strains were isolated before treatment and after relapse. All strains belong to T.b. gambiense type I. CONCLUSIONS AND SIGNIFICANCE: We established a unique collection of T.b. gambiense from cured and relapsed patients, isolated in the same disease focus and within a limited period. This collection is available for genotypic and phenotypic characterisation to investigate the

  14. Psychotic relapse and associated factors among patients attending health services in Southwest Ethiopia: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Mahlet Fikreyesus

    2016-10-01

    Full Text Available Abstract Background Psychotic relapse leads to repeated hospitalization and negatively affects the clinical prognosis of the patients. Information on prevalence of relapse among patients with psychotic disorders in Ethiopian setting is scarce. This study aimed to assess the prevalence of relapse among patients with psychotic disorders attending services in Jimma University Specialized Hospital (JUSH. Methods Data were collected using interviewer administered questionnaire. We used medication adherence rating scale (MARS to assess compliance to medication and abnormal involuntary movement scale (AIMS to detect medication side effects. Logistic regression analysis was used to identify independent predictors of psychotic relapse. All variables with P-value <0.25 in the bivariate analyses were entered into multivariate logistic regression and variables with P-value < 0.05 in the final model were declared to be significantly associated with the outcome variable. Results The prevalence of relapse among patients with psychotic disorder was 24.6 % (n = 95. Of this, 25.4 and 22.4 % were males and females respectively. The odds of developing psychotic relapse among patients living with family was 72 % lower than that of patients living alone (aOR = 0.28, 95 % CI = 0.08, 0.93. The odds of developing psychotic relapse among patients compliant to medication was 69 % lower than that of patients who were not compliant to medications (aOR = 0.31, 95 % CI = 0.12, 0.80. The odds of developing psychotic relapse among patients having high score on social support score was 48 % lower than that of patients who were compliant to medications (aOR = 0.52, 95 % CI = 0.28, 0.95. The odds of developing psychotic relapse among patients reporting to have sought religious support was 45 % lower than that of patients who have not sought religious support (aOR = 0.55, 95 % CI = 0.31, 0.96. On the other hand, the odds of developing

  15. A Prospective Study to Investigate Predictors of Relapse among Patients with Opioid Use Disorder Treated with Methadone

    Directory of Open Access Journals (Sweden)

    Leen Naji

    2016-01-01

    Full Text Available Introduction Concomitant opioid abuse is a serious problem among patients receiving methadone maintenance treatment (MMT for opioid use disorder. This is an exploratory study that aims to identify predictors of the length of time a patient receiving MMT for opioid use disorder remains abstinent (relapse-free. Methods Data were collected from 250 MMT patients enrolled in addiction treatment clinics across Southern Ontario. The impact of certain clinical and socio-demographic factors on the outcome (time until opioid relapse was determined using a Cox proportional hazard model. Results History of injecting drug use behavior (hazard ratio (HR: 2.26, P = 0.042, illicit benzodiazepine consumption (HR: 1.07, P = 0.002, and the age of onset of opioid abuse (HR: 1.10, P < 0.0001 are important indicators of accelerated relapse among MMT patients. Conversely, current age is positively associated with duration of abstinence from illicit opioid use, serving as a protective factor against relapse (HR: 0.93, P = 0.003. Conclusion This study helps to identify patients at increased risk of relapse during MMT, allowing health care providers to target more aggressive adjunct therapies toward high-risk patients.

  16. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Clinicians Publications for Your Patients MS Navigator Program Programs and Services for Your Patients Contact Us Clinical Fellows ... Relapsing-remitting MS (RRMS) Relapsing-remitting ...

  17. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... for You and Your Practice Publications for Clinicians Publications for Your Patients MS Navigator Program Programs and Services for Your Patients ... Relapsing-remitting MS (RRMS) Relapsing-remitting MS ( ...

  18. Role of regulatory T cells in acute myeloid leukemia patients undergoing relapse-preventive immunotherapy.

    Science.gov (United States)

    Sander, Frida Ewald; Nilsson, Malin; Rydström, Anna; Aurelius, Johan; Riise, Rebecca E; Movitz, Charlotta; Bernson, Elin; Kiffin, Roberta; Ståhlberg, Anders; Brune, Mats; Foà, Robin; Hellstrand, Kristoffer; Thorén, Fredrik B; Martner, Anna

    2017-11-01

    Regulatory T cells (T regs ) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov ) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3 + CD25 high CD4 + T regs during immunotherapy and to determine the potential impact of T regs on relapse risk and survival. We observed a pronounced increase in T reg counts in peripheral blood during initial cycles of HDC/IL-2. The accumulating T regs resembled thymic-derived natural T regs (nT regs ), showed augmented expression of CTLA-4 and suppressed the cell cycle proliferation of conventional T cells ex vivo. Relapse of AML was not prognosticated by T reg counts at onset of treatment or after the first cycle of immunotherapy. However, the magnitude of T reg induction was diminished in subsequent treatment cycles. Exploratory analyses implied that a reduced expansion of T regs in later treatment cycles and a short T reg telomere length were significantly associated with a favorable clinical outcome. Our results suggest that immunotherapy with HDC/IL-2 in AML entails induction of immunosuppressive T regs that may be targeted for improved anti-leukemic efficiency.

  19. Regional homogeneity changes between heroin relapse and non-relapse patients under methadone maintenance treatment: a resting-state fMRI study

    OpenAIRE

    Chang, Haifeng; Li, Wei; Li, Qiang; Chen, Jiajie; Zhu, Jia; Ye, Jianjun; Liu, Jierong; Li, Zhe; Li, Yongbin; Shi, Ming; Wang, Yarong; Wang, Wei

    2016-01-01

    Background Methadone maintenance treatment (MMT) is recognized as one of the most effective treatments for heroin addiction but its effect is dimmed by the high incidence of heroin relapse. However, underlying neurobiology mechanism of heroin relapse under MMT is still largely unknown. Here, we took advantage of a resting-state fMRI technique by analysis of regional homogeneity (ReHo), and tried to explore the difference of brain function between heroin relapsers and non-relapsers in MMT. Met...

  20. Relapsing bronchiolitis obliterans organising pneumonia and chronic sarcoidosis in an atopic asthmatic patient.

    Science.gov (United States)

    Carbonelli, C; Roggeri, A; Cavazza, A; Zompatori, M; Zucchi, L

    2008-03-01

    Asthma is thought to be a Th2 disease while sarcoidosis is considered a Th1 granulomatous disorder. Organising pneumonia is a histologic pattern of lung injury. When it has no recognisable cause it is defined as cryptogenic organising pneumonia. We herein report the case of a patient with recurrent and steroid sensitive organising pneumonia associated with chronic sarcoidosis in an atopic, moderate persistent asthmatic patient. Each disease has been documented with transbronchial biopsies and recurrence of organising pneumonia was suggested by clinical features and by follow up HRCT which shows distinctive signs even in associated disease. Steroids are the mainstay of therapy for these disorders and especially for the consolidated processes typical of organising pneumonia but prognostic indices for relapse and progression are lacking.

  1. Daratumumab in combination with lenalidomide and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma

    DEFF Research Database (Denmark)

    Plesner, T.; Arkenau, H. T.; Gimsing, Peter

    2015-01-01

    %), muscle spasms (44%), cough (38%), diarrhea (34%), fatigue and hypertension (28% each). Only 1 (3%) patient experienced febrile neutropenia (grade 1). Neutropenia was the most frequently (>25%) reported grade 3 or 4 TEAE (75%). Eighteen (56%) patients had IRRs and these were generally mild to moderate...... treatment due to either disease progression (n = 3), treatment-emergent adverse events (TEAE; 1 patient with gastric adenocarcinoma and 1 patient with laryngeal edema that was a grade 3 infusion-related reaction [IRR]), or physician decision (n = 1). The most common (>25%) TEAEs included neutropenia (81...

  2. Influence of Disease and Patient Characteristics on Daratumumab Exposure and Clinical Outcomes in Relapsed or Refractory Multiple Myeloma

    DEFF Research Database (Denmark)

    Yan, Xiaoyu; Clemens, Pamela L; Puchalski, Thomas

    2018-01-01

    OBJECTIVE: The aim of this study was to understand the influence of disease and patient characteristics on exposure to daratumumab, an immunoglobulin Gκ (IgGκ) monoclonal antibody, and clinical outcomes in relapsed or refractory multiple myeloma (MM). PATIENTS AND METHODS: Baseline myeloma type, ...

  3. Neurophysiological correlates of response inhibition predict relapse in detoxified alcoholic patients: some preliminary evidence from event-related potentials

    Directory of Open Access Journals (Sweden)

    Petit G

    2014-06-01

    Full Text Available Géraldine Petit, Agnieszka Cimochowska, Charles Kornreich, Catherine Hanak, Paul Verbanck, Salvatore CampanellaLaboratory of Psychological Medicine and Addictology, ULB Neuroscience Institute (UNI, Université Libre de Bruxelles (ULB, Brussels, BelgiumBackground: Alcohol dependence is a chronic relapsing disease. The impairment of response inhibition and alcohol-cue reactivity are the main cognitive mechanisms that trigger relapse. Despite the interaction suggested between the two processes, they have long been investigated as two different lines of research. The present study aimed to investigate the interaction between response inhibition and alcohol-cue reactivity and their potential link with relapse.Materials and methods: Event-related potentials were recorded during a variant of a “go/no-go” task. Frequent and rare stimuli (to be inhibited were superimposed on neutral, nonalcohol-related, and alcohol-related contexts. The task was administered following a 3-week detoxification course. Relapse outcome was measured after 3 months, using self-reported abstinence. There were 27 controls (seven females and 27 patients (seven females, among whom 13 relapsed during the 3-month follow-up period. The no-go N2, no-go P3, and the “difference” wave (P3d were examined with the aim of linking neural correlates of response inhibition on alcohol-related contexts to the observed relapse rate.Results: Results showed that 1 at the behavioral level, alcohol-dependent patients made significantly more commission errors than controls (P<0.001, independently of context; 2 through the subtraction no-go P3 minus go P3, this inhibition deficit was neurophysiologically indexed in patients with greater P3d amplitudes (P=0.034; and 3 within the patient group, increased P3d amplitude enabled us to differentiate between future relapsers and nonrelapsers (P=0.026.Conclusion: Our findings suggest that recently detoxified alcoholics are characterized by poorer

  4. Outcomes following autologous hematopoietic stem cell transplant for patients with relapsed Wilms’ Tumor: A CIBMTR retrospective analysis

    Science.gov (United States)

    Malogolowkin, Marcio H.; Hemmer, Michael T.; Le-Rademacher, Jennifer; Hale, Gregory A; Metha, Parinda A.; Smith, Angela R.; Kitko, Carrie; Abraham, Allistair; Abdel-Azim, Hisham; Dandoy, Christopher; Diaz, Miguel Angel; Gale, Robert Peter; Guilcher, Greg; Hayashi, Robert; Jodele, Sonata; Kasow, Kimberly A.; MacMillian, Margaret L.; Thakar, Monica; Wirk, Baldeep M.; Woolfrey, Ann; Thiel, E L

    2017-01-01

    Despite the dramatic improvement in the overall survival for patients diagnosed with Wilms’ tumor (WT), the outcomes for those that experience relapse have remained disappointing. We describe the outcomes of 253 patients with relapsed WT who received high-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplant (HCT) between 1990 and 2013, and reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR). The 5-year estimates for event free survival (EFS) and overall survival (OS) were 36% (95% CI; 29 – 43%) and 45% (95% CI; 38 – 51%) respectively. Relapse of primary disease was the cause of death in 81% of the population. EFS, OS, relapse and transplant-related mortality (TRM) showed no significant differences when broken down by disease status at transplant, time from diagnosis to transplant, year of transplant or conditioning regimen. Our data suggest that HDT followed by autologous HCT for relapsed WT is well tolerated and outcomes are similar to those reported in the literature. Since attempts to conduct a randomized trial comparing maintenance chemotherapy with consolidation versus high-dose chemotherapy followed by stem cell transplant have failed, one should balance the potential benefits with the yet unknown long-term risks. Since disease recurrence continues to be the most common cause of death, future research should focus on the development of consolidation therapies for those patients achieving complete response to therapy. PMID:28869618

  5. Baseline ultrasound examination as possible predictor of relapse in patients affected by juvenile idiopathic arthritis (JIA).

    Science.gov (United States)

    De Lucia, Orazio; Ravagnani, Viviana; Pregnolato, Francesca; Hila, Arvena; Pontikaki, Irene; Gattinara, Maurizio; Romano, Micol; Gerloni, Valeria; Pieropan, Sara; Murgo, Antonella; Rossini, Maurizio; Cimaz, Rolando; Meroni, Pier Luigi

    2018-02-06

    To define the correlation between joint ultrasonography and clinical examination in patients with juvenile idiopathic arthritis (JIA) and to assess whether synovitis detected by ultrasonography in clinically inactive patients predicts arthritis flares. 88 consecutive patients with JIA-46 (52%) with persistent oligoarthritis, 15 (17%) with extended oligoarthritis, 15 (17%) with rheumatoid factor-negative polyarthritis and 12 (14%) with other forms of JIA, all clinically inactive for a minimum of 3 months-underwent ultrasound (US) assessment of 44 joints. Joints were scanned at study entry for synovial hyperplasia, joint effusion and power Doppler (PD) signal. Patients were followed clinically for 4 years. US was abnormal in 20/88 (22.7%) patients and in 38/3872 (0.98%) joints. Extended oligoarthritis and rheumatoid factor-negative polyarthritis were more frequent in US-positive than in US-negative patients (35.0% vs 11.8% and 30.0% vs 13.2%, respectively; P=0.005). During 4 years of follow-up, 41/88 (46.6%) patients displayed a flare; 26/68 (38.2%) were US-negative and 15/20 (75%) were US-positive at baseline. Abnormality on US examination, after correction for therapy modification, significantly increased the risk of flare (OR=3.8, 95% CI 1.2 to 11.5). The combination of grey scale and PD abnormalities displayed a much higher predictive value of relapse (65%, 13/20) than grey scale alone (33%, 6/18). US abnormalities are a strong predictor of relapse at individual patient level. Irrespective of treatment, the risk of flare in US-positive versus US-negative patients was almost four times higher. In case of US abnormalities, patients should be carefully followed regardless of both the International League of Associations for Rheumatology and Wallace categories. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. Arthroscintigraphy in diagnosis of relapses after early synovectomy of the knee joints in patients with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Zubovski, G.A.; Abasov, Eh.Sh.; Smirnov, Yu.N.

    1980-01-01

    The authors studied differential diagnostic possibilities of scintigraphy with the use of sup(99m)Tc-pyrophosphate to reveal relapses after early synovectomy of the knee joints in 40 patients with rheumatoid arthritis. High informativeness of the method was established. The authors succeded in diagnosing the subclinical variant of rheumatoid synovitis in the operated joints by means of scintigraphy. The computer-arthroscintigraphy method with sup(99m)Tc-pyrophosphate is recommended for a wide use in arthrological practice to ensure an objective assessment of the condition of the operated joints in patients with rheumatoid arthritis and to conduct timely adequate therapy for the prevention of the relapses

  7. Clinical Implications of Complex Pharmacokinetics for Daratumumab Dose Regimen in Patients With Relapsed/Refractory Multiple Myeloma

    DEFF Research Database (Denmark)

    Xu, Xu Steven; Yan, Xiaoyu; Puchalski, Thomas

    2017-01-01

    New therapeutic strategies are urgently needed to improve clinical outcomes in patients with multiple myeloma (MM). Daratumumab is a first-in-class, CD38 human immunoglobulin G1κ monoclonal antibody approved for treatment of relapsed or refractory MM. Identification of an appropriate dose regimen...... for daratumumab is challenging due to its target-mediated drug disposition, leading to time- and concentration-dependent pharmacokinetics. We describe a thorough evaluation of the recommended dose regimen for daratumumab in patients with relapsed or refractory MM. This article is protected by copyright. All...

  8. Mounting resistance of uropathogens to antimicrobial agents: A retrospective study in patients with chronic bacterial prostatitis relapse.

    Science.gov (United States)

    Stamatiou, Konstantinos; Pierris, Nikolaos

    2017-07-01

    Despite recent progress in the management of chronic bacterial prostatitis (CBP), many cases relapse. Increased drug resistance patterns of responsible bacteria have been proposed as the most probable causative factor. Driven by the limited number of previous studies addressing this topic, we aimed to study whether antibiotic resistance increases in patients with CBP when relapse occurs. A secondary aim of this study was to determine the resistance patterns of responsible bacteria from patients with CBP. The study material consisted of bacterial isolates from urine and/or prostatic secretions obtained from patients with CBP. Bacterial identification was performed by using the Vitek 2 Compact system and susceptibility testing was performed by disc diffusion and/or the Vitek 2 system. Interpretation of susceptibility results was based on Clinical and Laboratory Standards Institute guidelines. A total of 253 samples from patients diagnosed with CBP for the first time (group A) and 137 samples from relapsing patients with a history of CBP and previous antibiotic treatment (group B) were analyzed. A significant reduction in bacterial resistance to the less used antibiotics (TMP-SMX, tetracyclines, aminoglycosides, penicillins, and macrolides) was noted. An increase in resistance to quinolones of many bacteria that cause CBP was also noted with the increase in resistance of enterococcus strains being alarming. Comparison of the resistance profile of CBP-responsible bacteria between samples from first-time-diagnosed patients and samples from relapsing patients revealed notable differences that could be attributed to previous antibiotic treatment.

  9. Safety and tolerability of ibrutinib monotherapy in Japanese patients with relapsed/refractory B cell malignancies.

    Science.gov (United States)

    Tobinai, Kensei; Ogura, Michinori; Ishizawa, Kenichi; Suzuki, Tatsuya; Munakata, Wataru; Uchida, Toshiki; Aoki, Tomohiro; Morishita, Takanobu; Ushijima, Yoko; Takahara, Satoko

    2016-01-01

    In this phase I dose-escalation study we evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK, in Japanese patients with relapsed/refractory B cell malignancies (RRBCM). Fifteen patients aged 42-78 years were enrolled to one of three cohorts. Cohort 1 (n = 3) consisted of two phases, a single-dose (140 and 280 mg) phase and a multiple-dose (420 mg) phase of ibrutinib; cohort 2 (n = 6) included multiple doses of ibrutinib 560 mg; and cohort 3 (n = 6) included only patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) dosed at ibrutinib 420 mg. One patient (CLL/SLL cohort) experienced grade 3 pneumonia and sepsis, which were considered dose-limiting toxicities. No deaths were reported. The most common (≥ 20% patients) adverse events were neutropenia, anemia, nasopharyngitis, increased bilirubin, and rash. Dose-dependent increase in maximum plasma concentration and area under the concentration from 0 to the last quantifiable time was observed, while time to reach maximum plasma concentration and elimination half-life was similar between doses. The overall response rate was 73.3% (11/15) for all cohorts combined. Overall, ibrutinib (420 and 560 mg) was tolerable with acceptable safety profiles and effective for Japanese patients with RRBCM including CLL/SLL. NCT01704963.

  10. Integrity of Literature on Expressed Emotion and Relapse in Patients with Schizophrenia Verified by a p-Curve Analysis.

    Science.gov (United States)

    Weintraub, Marc J; Hall, Daniel L; Carbonella, Julia Y; Weisman de Mamani, Amy; Hooley, Jill M

    2017-06-01

    There is growing concern that much published research may have questionable validity due to phenomena such as publication bias and p-hacking. Within the psychiatric literature, the construct of expressed emotion (EE) is widely assumed to be a reliable predictor of relapse across a range of mental illnesses. EE is an index of the family climate, measuring how critical, hostile, and overinvolved a family member is toward a mentally ill patient. No study to date has examined the evidential value of this body of research as a whole. That is to say, although many studies have shown a link between EE and symptom relapse, the integrity of the literature from which this claim is derived has not been tested. In an effort to confirm the integrity of the literature of EE predicting psychiatric relapse in patients with schizophrenia, we conducted a p-curve analysis on all known studies examining EE (using the Camberwell Family Interview) to predict psychiatric relapse over a 9- to 12-month follow-up period. Results suggest that the body of literature on EE is unbiased and has integrity, as there was a significant right skew of p-values, a nonsignificant left skew of p-values, and a nonsignificant test of flatness. We conclude that EE is a robust and valuable predictor of symptom relapse in schizophrenia. © 2016 Family Process Institute.

  11. Late relapse of progressive multifocal leucoencephalopathy postallogenic transplant in a young patient with CLL.

    Science.gov (United States)

    Sanchez-Quintana, Ana; Breña-Atienza, Joaquín; Marrero-Santos, Carmen; Alvarez-Acosta, Luis

    2013-08-05

    We describe a case of progressive multifocal leucoencephalopathy (PML) in a 39-year-old patient diagnosed with chronic lymphocytic leukaemia (CLL) who underwent two allogenic matched-sibling stem cell transplantations. PML was confirmed just after the first transplantation with cerebral MRI and by PCR in the cerebrospinal fluid. After immunosuppression withdrawal and cidofovir treatment, he achieved a reversal of clinical symptoms, John Cunningham (JC) virus positivity and MRI lesions regression. He remained asymptomatic for 5 years with no signs of infection activity, even though he received three new chemotherapy regimens due to a CLL relapse. However, after the second stem cell transplantation, new neurological symptoms began and a reactivation of the JC virus infection was detected. This time, treatment with mefloquine was started, but he experienced a progressive neurological deterioration and died 1 month after the symptoms began.

  12. Intracortical excitability in patients with relapsing-remitting and secondary progressive multiple sclerosis.

    Science.gov (United States)

    Conte, A; Lenzi, D; Frasca, V; Gilio, F; Giacomelli, E; Gabriele, M; Bettolo, C Marini; Iacovelli, E; Pantano, P; Pozzilli, C; Inghilleri, M

    2009-06-01

    We designed this study to investigate possible correlations between variables measuring primary motor cortex excitability detected by single and paired-pulse transcranial magnetic stimulation (TMS) and the severity of clinical manifestations in patients with multiple sclerosis (MS). Thirty patients with MS in remission, 16 with relapsing-remitting (RR), 14 with secondary progressive disease (SP) and 17 healthy subjects participated in the study. In each subject, the central motor conduction time (CMCT) was calculated, and single-pulse and paired-pulse TMS at 3 and 10 ms interstimulus intervals was delivered over the primary motor cortex of the dominant hemisphere to measure the amplitude of motor-evoked potentials (MEPs), motor threshold (MTh), intracortical inhibition (ICI) and facilitation (ICF). Correlations were determined between the patients' TMS findings and magnetic resonance imaging (MRI) (lesion load) and clinical features (expanded disability status scale, EDSS score). EDSS scores were significantly higher in SPMS than in RRMS patients. The MTh was significantly higher, and the MEP was significantly smaller in SPMS patients than in RRMS patients and control subjects. All patients had longer CMCTs than healthy subjects. In all patients, paired-pulse TMS elicited an inhibited test MEP at the 3-ms ISI and a facilitated test MEP at the 10 ms ISI. Post hoc analysis showed that ICI was significantly lower in SPMS patients than in those with RRMS and healthy subjects. EDSS scores correlated significantly with TMS measures (MEP, ICI, CMCT and MTh), but not with MRI lesion load. It was found that intracortical excitability as measured with TMS differs according to the clinical course of MS; it remains normal in patients with low EDSS scores and is altered in patients with high EDSS scores.

  13. Risk factors associated with gastroesophageal reflux disease relapse in primary care patients successfully treated with a proton pump inhibitor.

    Science.gov (United States)

    López-Colombo, A; Pacio-Quiterio, M S; Jesús-Mejenes, L Y; Rodríguez-Aguilar, J E G; López-Guevara, M; Montiel-Jarquín, A J; López-Alvarenga, J C; Morales-Hernández, E R; Ortiz-Juárez, V R; Ávila-Jiménez, L

    There are no studies on the factors associated with gastroesophageal reflux disease (GERD) relapse in primary care patients. To identify the risk factors associated with GERD relapse in primary care patients that responded adequately to short-term treatment with a proton pump inhibitor. A cohort study was conducted that included GERD incident cases. The patients received treatment with omeprazole for 4 weeks. The ReQuest questionnaire and a risk factor questionnaire were applied. The therapeutic success rate and relapse rate were determined at 4 and 12 weeks after treatment suspension. A logistic regression analysis of the possible risk factors for GERD relapse was carried out. Of the 83 patient total, 74 (89.16%) responded to treatment. Symptoms recurred in 36 patients (48.64%) at 4 weeks and in 13 patients (17.57%) at 12 weeks, with an overall relapse rate of 66.21%. The OR multivariate analysis (95% CI) showed the increases in the possibility of GERD relapse for the following factors at 12 weeks after treatment suspension: basic educational level or lower, 24.95 (1.92-323.79); overweight, 1.76 (0.22-13.64); obesity, 0.25 (0.01-3.46); smoking, 0.51 (0.06-3.88); and the consumption of 4-12 cups of coffee per month, 1.00 (0.12-7.84); citrus fruits, 14.76 (1.90-114.57); NSAIDs, 27.77 (1.12-686.11); chocolate, 0.86 (0.18-4.06); ASA 1.63 (0.12-21.63); carbonated beverages, 4.24 (0.32-55.05); spicy food 7-16 times/month, 1.39 (0.17-11.17); and spicy food ≥ 20 times/month, 4.06 (0.47-34.59). The relapse rate after short-term treatment with omeprazole was high. The consumption of citrus fruits and NSAIDs increased the possibility of GERD relapse. Copyright © 2016 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  14. Phonological fluency strategy of switching differentiates relapsing-remitting and secondary progressive multiple sclerosis patients.

    Science.gov (United States)

    Messinis, L; Kosmidis, M H; Vlahou, C; Malegiannaki, A C; Gatzounis, G; Dimisianos, N; Karra, A; Kiosseoglou, G; Gourzis, P; Papathanasopoulos, P

    2013-01-01

    The strategies used to perform a verbal fluency task appear to be reflective of cognitive abilities necessary for successful daily functioning. In the present study, we explored potential differences in verbal fluency strategies (switching and clustering) used to maximize word production by patients with relapsing-remitting multiple sclerosis (RRMS) versus patients with secondary progressive multiple sclerosis (SPMS). We further assessed impairment rates and potential differences in the sensitivity and specificity of phonological versus semantic verbal fluency tasks in discriminating between those with a diagnosis of MS and healthy adults. We found that the overall rate of impaired verbal fluency in our MS sample was consistent with that in other studies. However, we found no differences between types of MS (SPMS, RRMS), on semantic or phonological fluency word production, or the strategies used to maximize semantic fluency. In contrast, we found that the number of switches differed significantly in the phonological fluency task between the SPMS and RRMS subtypes. The clinical utility of semantic versus phonological fluency in discriminating MS patients from healthy controls did not indicate any significant differences. Further, the strategies used to maximize performance did not differentiate MS subgroups or MS patients from healthy controls.

  15. Quantifying risk of early relapse in patients with first demyelinating events: Prediction in clinical practice.

    Science.gov (United States)

    Spelman, Tim; Meyniel, Claire; Rojas, Juan Ignacio; Lugaresi, Alessandra; Izquierdo, Guillermo; Grand'Maison, Francois; Boz, Cavit; Alroughani, Raed; Havrdova, Eva; Horakova, Dana; Iuliano, Gerardo; Duquette, Pierre; Terzi, Murat; Grammond, Pierre; Hupperts, Raymond; Lechner-Scott, Jeannette; Oreja-Guevara, Celia; Pucci, Eugenio; Verheul, Freek; Fiol, Marcela; Van Pesch, Vincent; Cristiano, Edgardo; Petersen, Thor; Moore, Fraser; Kalincik, Tomas; Jokubaitis, Vilija; Trojano, Maria; Butzkueven, Helmut

    2017-09-01

    Characteristics at clinically isolated syndrome (CIS) examination assist in identification of patient at highest risk of early second attack and could benefit the most from early disease-modifying drugs (DMDs). To examine determinants of second attack and validate a prognostic nomogram for individualised risk assessment of clinical conversion. Patients with CIS were prospectively followed up in the MSBase Incident Study. Predictors of clinical conversion were analysed using Cox proportional hazards regression. Prognostic nomograms were derived to calculate conversion probability and validated using concordance indices. A total of 3296 patients from 50 clinics in 22 countries were followed up for a median (inter-quartile range (IQR)) of 1.92 years (0.90, 3.71). In all, 1953 (59.3%) patients recorded a second attack. Higher Expanded Disability Status Scale (EDSS) at baseline, first symptom location, oligoclonal bands and various brain and spinal magnetic resonance imaging (MRI) metrics were all predictors of conversion. Conversely, older age and DMD exposure post-CIS were associated with reduced rates. Prognostic nomograms demonstrated high concordance between estimated and observed conversion probabilities. This multinational study shows that age at CIS onset, DMD exposure, EDSS, multiple brain and spinal MRI criteria and oligoclonal bands are associated with shorter time to relapse. Nomogram assessment may be useful in clinical practice for estimating future clinical conversion.

  16. Reduced GABA levels correlate with cognitive impairment in patients with relapsing-remitting multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Guanmei; Gao, Fei; Gong, Tao; Wang, Guangbin; Zhao, Bin [Shandong University, Shandong Medical Imaging Research Institute, Jinan (China); Edden, Richard A.E. [The Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Kennedy Krieger Institute, FM Kirby Center for Functional Brain Imaging, Baltimore, MD (United States); Li, Hao [Air Force General Hospital PLA, Beijing (China); Chen, Weibo [Philips Healthcare, Shanghai (China); Liu, Xiaohui [Shandong Provincial Hospital Affiliated to Shandong University, Department of Neurology, Jinan (China)

    2018-03-15

    To investigate if brain gamma-aminobutyric acid (GABA) levels in patients with relapsing-remitting multiple sclerosis (RRMS) are abnormal compared with healthy controls, and their relationship to cognitive function in RRMS. Twenty-eight RRMS patients and twenty-six healthy controls underwent magnetic resonance spectroscopy (MRS) at 3-T to detect GABA signals from posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC) and left hippocampus using the 'MEGAPoint Resolved Spectroscopy Sequence' (MEGA-PRESS) technique. All subjects also underwent a cognitive assessment. In RRMS patients, GABA+ were lower in the PCC (p = 0.036) and left hippocampus (p = 0.039) compared with controls, decreased GABA+ in the PCC and left hippocampus were associated with specific cognitive functions (r = -0.452, p = 0.016 and r = 0.451, p = 0.016 respectively); GABA+ in the mPFC were not significantly decreased or related to any cognitive scores (p > 0.05). This study demonstrates that abnormalities of the GABAergic system may be present in the pathogenesis of RRMS and suggests a potential link between regional GABA levels and cognitive impairment in patients with RRMS. (orig.)

  17. Reduced GABA levels correlate with cognitive impairment in patients with relapsing-remitting multiple sclerosis

    International Nuclear Information System (INIS)

    Cao, Guanmei; Gao, Fei; Gong, Tao; Wang, Guangbin; Zhao, Bin; Edden, Richard A.E.; Li, Hao; Chen, Weibo; Liu, Xiaohui

    2018-01-01

    To investigate if brain gamma-aminobutyric acid (GABA) levels in patients with relapsing-remitting multiple sclerosis (RRMS) are abnormal compared with healthy controls, and their relationship to cognitive function in RRMS. Twenty-eight RRMS patients and twenty-six healthy controls underwent magnetic resonance spectroscopy (MRS) at 3-T to detect GABA signals from posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC) and left hippocampus using the 'MEGAPoint Resolved Spectroscopy Sequence' (MEGA-PRESS) technique. All subjects also underwent a cognitive assessment. In RRMS patients, GABA+ were lower in the PCC (p = 0.036) and left hippocampus (p = 0.039) compared with controls, decreased GABA+ in the PCC and left hippocampus were associated with specific cognitive functions (r = -0.452, p = 0.016 and r = 0.451, p = 0.016 respectively); GABA+ in the mPFC were not significantly decreased or related to any cognitive scores (p > 0.05). This study demonstrates that abnormalities of the GABAergic system may be present in the pathogenesis of RRMS and suggests a potential link between regional GABA levels and cognitive impairment in patients with RRMS. (orig.)

  18. Recurrent bleeding after arterial embolization in patients with hemoptysis : Comparison of angiographic findings and relapsing period

    International Nuclear Information System (INIS)

    Park, Sung Keun; Choi, Seok Jin; Choi, Gi Bok; Kim, Hae Yeon; Park, Auh Whan; Juhn, Jae Ryang; Cha, Seong Sook

    2001-01-01

    To describe the angiographic findings of patients with recurrent hemoptysis after bronchial artery embolization (BAE) according to the point at which relapse occurred. From 125 patients who underwent BAE due to hemoptysis between 1996 and 2000, we selected 18 of 23 who underwent additional BAE due to recurrent bleeding after initial BAE. Depending on the point at which relapse occurred, they were divided into two groups (I and ll, according to whether additional BAE was performed within two weeks of initial BAE or more than two weeks after this) We retrospectively compared the two groups in terms of angiographic findings, number of embolized arteries, and character of feeding arteries at initial and additional BAE. Nine patients in group I (additional BAE: n=10) and nine in group ll (additional BAE: n=13) were admitted for recurrent hemoptysis within two weeks of initial BAE and more than two weeks after this, respectively. In group I (n=29) and ll(n=31), angiography demonstrated two direct and 27 indirect, and two direct and 29 indirect signs of hemorrhage, respectiveIy. No statistically significant differences were observed (x 2 =0.005, ρ=0.945). Among the embolized feeder ressels in group I (n=30) there were 20 bronchial artery and 10 non bronchial systemic collaterals, while for group ll (n=35), the corresponding totals were 21 and 14. Again, no statistically significant differences were encountered(x 2 =0.308; ρ=0.579). In group I, feeders were newly developed in one case(10%), previously embolized in five(50%), and missed in four(40%), while in group two the corresponding figures were none, twelve(92.3%), and one(7.7%) No significant differences were noted, though the incidence of previously embolized feeders in Group ll was very high (x 2 =5.383, ρ=0.068). Among patients in whom hemoptysis after BAE recurred at different times, the angiographic findings and number of embolized arteries were not significantly different, but differences in the nature of the

  19. Autologous stem cell transplantation versus novel drugs or conventional chemotherapy for patients with relapsed multiple myeloma after previous ASCT

    DEFF Research Database (Denmark)

    Grövdal, M; Nahi, H; Gahrton, G

    2015-01-01

    . A second ASCT also resulted in a significantly longer second time to progression and a significantly longer time to next treatment. We conclude that, irrespective of the addition of novel drugs, MM patients in first relapse after ASCT still appear to benefit from a second ASCT. A second ASCT should...

  20. Predictors of Time to Relapse/Recurrence after Electroconvulsive Therapy in Patients with Major Depressive Disorder: A Population-Based Cohort Study

    Directory of Open Access Journals (Sweden)

    Axel Nordenskjöld

    2011-01-01

    Full Text Available Objective. The aim of the study is to define predictors of relapse/recurrence after electroconvulsive therapy, ECT, for patients with major depressive disorder. Methods. A study of all patients (n=486 treated by means of ECT for major depressive disorder was performed. The data were derived from a regional quality register in Sweden. Psychiatric hospitalisation or suicide was used as a marker for relapse/recurrence. Results. The relapse/recurrence rate within one year after ECT was 34%. Factors associated with increased risk of relapse/recurrence included comorbid substance dependence and treatment with benzodiazepines or antipsychotics during the follow-up period. Conclusions. Within the first years after ECT, relapses/recurrences leading to hospitalisation or suicide are common. Treatment with lithium might be beneficial, while benzodiazepines, antipsychotics, or continuation ECT does not seem to significantly reduce the risk of relapse/recurrence.

  1. Comprehensive Safety Analysis of Venetoclax Monotherapy for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Davids, Matthew S; Hallek, Michael; Wierda, William; Roberts, Andrew W; Stilgenbauer, Stephan; Jones, Jeffrey A; Gerecitano, John F; Kim, Su Young; Potluri, Jalaja; Busman, Todd; Best, Andrea; Verdugo, Maria E; Cerri, Elisa; Desai, Monali; Hillmen, Peter; Seymour, John F

    2018-06-12

    The oral BCL-2 inhibitor venetoclax is an effective therapy for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), including disease with high-risk genomic features such as chromosome 17p deletion (del[17p]) or progressive disease following B-cell receptor pathway inhibitors. We conducted a comprehensive analysis of the safety of 400mg daily venetoclax monotherapy in 350 patients with CLL using an integrated dataset from three phase-I/II studies. Median age was 66 years and 60% had del(17p). Patients had received a median of three prior therapies (range: 0-15); 42% previously received ibrutinib or idelalisib. Median duration of exposure to venetoclax was 16 months (0-56). In the pooled analysis, the most common adverse events (AEs) of any grade were diarrhea (41%), neutropenia (40%), nausea (39%), anemia (31%), fatigue (28%), and upper respiratory tract infection (25%). The most common grade 3/4 AEs were neutropenia (37%), anemia (17%), and thrombocytopenia (14%). With the current 5-week ramp-up dosing, the incidence of laboratory TLS was 1.4% (2/166), none had clinical sequelae, and all of these patients were able to ramp-up to a daily dose of 400mg. Grade 3/4 neutropenia was manageable with growth-factor support and dose adjustments; the incidence of serious infections in these patients was 15%. Ten percent of patients discontinued venetoclax due to AEs and 8% died while on study, with the majority of deaths in the setting of disease progression. Venetoclax as a long-term continuous therapy is generally well-tolerated in patients with R/R CLL when initiated with the current treatment algorithm. Copyright ©2018, American Association for Cancer Research.

  2. Management of relapsed/refractory classical Hodgkin lymphoma in transplant-ineligible patients.

    Science.gov (United States)

    Mehta-Shah, Neha; Bartlett, Nancy L

    2018-04-12

    Addition of brentuximab vedotin, a CD30-targeted antibody-drug conjugate, and the programmed death 1 (PD-1) inhibitors nivolumab and pembrolizumab to the armamentarium for transplant-ineligible relapsed/refractory classical Hodgkin lymphoma has resulted in improved outcomes, including the potential for cure in a small minority of patients. For patients who have failed prior transplant or are unsuitable for dose-intense approaches based on age or comorbidities, an individualized approach with sequential use of single agents such as brentuximab vedotin, PD-1 inhibitors, everolimus, lenalidomide, or conventional agents such as gemcitabine or vinorelbine may result in prolonged survival with a minimal or modest effect on quality of life. Participation in clinical trials evaluating new approaches such as combination immune checkpoint inhibition, novel antibody-drug conjugates, or cellular therapies such as Epstein-Barr virus-directed cytotoxic T lymphocytes and chimeric antigen receptor T cells offer additional options for eligible patients. © 2018 by The American Society of Hematology.

  3. Natalizumab Modifies Catecholamines Levels Present in Patients with Relapsing- Remitting Multiple Sclerosis.

    Science.gov (United States)

    Escribano, Begona M; Aguilar-Luque, Macarena; Bahamonde, Carmen; Conde, Cristina; Lillo, Rafael; Sanchez-Lopez, Fernando; Giraldo, Ana I; Cruz, Antonio H; Luque, Evelio; Gascon, Felix; Aguera, Eduardo; Tunez, Isaac

    2016-01-01

    The main aim of this study was to verify the effect of natalizumab on the levels of circulating catecholamines and indolamine and their possible relation with MS. For this purpose, 12 healthy individuals (control group) and 12 relapsing-remitting multiple sclerosis patients (RR-MS) were selected. The patients were treated with 300 mg of natalizumab during 56 weeks (1 dose/4 weeks) (MS-56). This selection was based on the McDonalds revision criterion and scheduled to star treatment with natalizumab. Blood samples were taken before treatment (basal level) and after 56 weeks of using natalizumab. Melatonin was measured in serum and in plasma, catecholamines (dopamine, epinephrine, and norepinephrine), carbonylated proteins, 8-hydroxy-2'deoxyguanosine (8OH-dG) and the ratio reduced glutathione/oxidised glutathione (GSH/GSSG). The epinephrine and dopamine levels diminished in the basal group with respect to the control and did not recover normal levels with the treatment. The melatonin was decreased in RR-MS patients and went back to its normal levels with natalizumab. Norepinephrine was increased in RR-MS and decreased in MS-56 until it equalled the control group. Natalizumab normalizes altered melatonin and norepinephrine levels in MS.

  4. Fecal Calprotectin is an Accurate Tool and Correlated to Seo Index in Prediction of Relapse in Iranian Patients With Ulcerative Colitis.

    Science.gov (United States)

    Hosseini, Seyed Vahid; Jafari, Peyman; Taghavi, Seyed Alireza; Safarpour, Ali Reza; Rezaianzadeh, Abbas; Moini, Maryam; Mehrabi, Manoosh

    2015-02-01

    The natural clinical course of Ulcerative Colitis (UC) is characterized by episodes of relapse and remission. Fecal Calprotectin (FC) is a relatively new marker of intestinal inflammation and is an available, non-expensive tool for predicting relapse of quiescent UC. The Seo colitis activity index is a clinical index for assessment of the severity of UC. The present study aimed to evaluate the accuracy of FC and the Seo colitis activity index and their correlation in prediction of UC exacerbation. In this prospective cohort study, 157 patients with clinical and endoscopic diagnosis of UC selected randomly from 1273 registered patients in Fars province's IBD registry center in Shiraz, Iran, were followed from October 2012 to October 2013 for 12 months or shorter, if they had a relapse. Two patients left the study before completion and one patient had relapse because of discontinuation of drugs. The participants' clinical and serum factors were evaluated every three months. Furthermore, stool samples were collected at the beginning of study and every three months and FC concentration (commercially available enzyme linked immunoassay) and the Seo Index were assessed. Then univariate analysis, multiple variable logistic regression, Receiver Operating Characteristics (ROC) curve analysis, and Pearson's correlation test (r) were used for statistical analysis of data. According to the results, 74 patients (48.1%) relapsed during the follow-up (33 men and 41 women). Mean ± SD of FC was 862.82 ± 655.97 μg/g and 163.19 ± 215.85 μg/g in relapsing and non-relapsing patients, respectively (P Seo index were significant predictors of relapse. ROC curve analysis of FC level and Seo activity index for prediction of relapse demonstrated area under the curve of 0.882 (P Seo index was significant in prediction of relapse (r = 0.63, P Seo activity index in prediction of relapse in the course of quiescent UC in Iranian patients.

  5. Assessment of Pneumatic Balloon Dilation in Patients with Symptomatic Relapse after Failed Heller Myotomy: A Single Center Experience.

    Science.gov (United States)

    Amani, Mohammad; Fazlollahi, Narges; Shirani, Shapour; Malekzadeh, Reza; Mikaeli, Javad

    2016-01-01

    BACKGROUND Although Heller myotomy is one of the most effective treatments for achalasia, it may be associated with early or late symptom relapse in some patients. Therefore, additional treatment is required to achieve better control of symptoms. To evaluate the safety and efficacy of pneumatic balloon dilation (PBD) in patients with symptom relapse after Heller myotomy. METHODS Thirty six post-myotomy patients were evaluated from 1993 to 2013. Six patients were excluded from the analysis because of comorbid diseases or epiphrenic diverticula. Thirty patients were treated with PBD. Primary outcome was defined as a decrease in symptom score to 4 or less and a reduction greater than 80% from the baseline in the volume of barium in timed barium esophagogram in 6 weeks. Achalasia symptom score (ASS) was assessed at 1.5, 3, 6, and 12 months after treatment and then every six months in all patients and PBD was repeated in case of symptom relapse (ASS>4). RESULTS The mean age of the patients was 45.5±13.9 years (range: 21-73). Primary outcome was observed in 25 patients (83%). The mean ASS of the patients dropped from 7.8 before treatment to 1.3±2.0 at 1.5 months after treatment (p=0.0001). The mean volume and height of barium decreased from 43.1±33.4 and 7.1±4.7 to 6.0±17.1 and 1.1±2.2, respectively (p=0.003, p=0.003). The mean duration of follow-up was 11.8±6.3 years. At the end of the study, 21 patients (70%) reported sustained good response. No major complications such as perforation or gross bleeding were seen. CONCLUSION PBD is an effective and safe treatment option for achalasia in patients with symptom relapse after Heller myotomy.

  6. Relapsed acute promyelocytic leukemia in a hemodialysis-dependent patient treated with arsenic trioxide: a case report

    Directory of Open Access Journals (Sweden)

    Emmons Gregory S

    2012-10-01

    Full Text Available Abstract Introduction In the relapsed setting, arsenic trioxide remains the backbone of treatment. Scant literature exists regarding treatment of relapsed acute promyelocytic leukemia in patients with renal failure. To the best of our knowledge we are the first to report a safe and effective means of treatment for relapsed acute promyelocytic leukemia in the setting of advanced renal failure, employing titration of arsenic trioxide based on clinical parameters rather than arsenic trioxide levels. Case presentation A 33-year-old Caucasian man with a history of acute promyelocytic leukemia in remission for 3 years, as well as dialysis-dependent chronic renal failure secondary to a solitary kidney and focal segmental glomerulosclerosis and human immunodeficiency virus infection, receiving highly active antiretroviral therapy presented to our hospital with bone marrow biopsy-confirmed relapsed acute promyelocytic leukemia. Arsenic trioxide was begun at a low dose with dose escalation based only on side effect profile monitoring and not laboratory testing for induction as well as maintenance without undue toxicity. Our patient achieved and remains in complete hematologic and molecular remission as of this writing. Conclusion Arsenic trioxide can be used safely and effectively to treat acute promyelocytic leukemia in patients with advanced renal failure using careful monitoring of side effects rather than blood levels of arsenic to guide therapeutic dosing.

  7. Cost effectiveness of pomalidomide in patients with relapsed and refractory multiple myeloma in Sweden.

    Science.gov (United States)

    Borg, Sixten; Nahi, Hareth; Hansson, Markus; Lee, Dawn; Elvidge, Jamie; Persson, Ulf

    2016-05-01

    Multiple myeloma (MM) patients who have progressed following treatment with both bortezomib and lenalidomide have a poor prognosis. In this late stage, other effective alternatives are limited, and patients in Sweden are often left with best supportive care. Pomalidomide is a new anti-angiogenic and immunomodulatory drug for the treatment of MM. Our objective was to evaluate the cost effectiveness of pomalidomide as an add-on to best supportive care in patients with relapsed and refractory MM in Sweden. We developed a health-economic discrete event simulation model of a patient's course through stable disease and progressive disease, until death. It estimates life expectancy, quality-adjusted life years (QALYs) and costs from a societal perspective. Effectiveness data and utilities were taken from the MM-003 trial comparing pomalidomide plus low-dose dexamethasone with high-dose dexamethasone (HIDEX). Cost data were taken from official Swedish price lists, government sources and literature. The model estimates that, if a patient is treated with HIDEX, life expectancy is 1.12 years and the total cost is SEK 179 976 (€19 100), mainly indirect costs. With pomalidomide plus low-dose dexamethasone, life expectancy is 2.33 years, with a total cost of SEK 767 064 (€81 500), mainly in drug and indirect costs. Compared to HIDEX, pomalidomide treatment gives a QALY gain of 0.7351 and an incremental cost of SEK 587 088 (€62 400) consisting of increased drug costs (59%), incremental indirect costs (33%) and other healthcare costs (8%). The incremental cost-effectiveness ratio is SEK 798 613 (€84 900) per QALY gained. In a model of late-stage MM patients with a poor prognosis in the Swedish setting, pomalidomide is associated with a relatively high incremental cost per QALY gained. This model was accepted by the national Swedish reimbursement authority TLV, and pomalidomide was granted reimbursement in Sweden.

  8. Reduction in relapse rate of radioiodine therapy in patients of toxic multinodular goiter: A quality improvement project

    OpenAIRE

    Mitra, Sujata; Muthu, Sonai G

    2012-01-01

    Introduction: Radioiodine (I-131) therapy is the definitive treatment of toxic multinodular goiter (TMNG). Treatment failure may result in relapse after I-131 therapy. The present study was undertaken to reduce treatment failure rate of I-131 therapy in TMNG patients. Materials and Methods: Multiple causes may have lead to treatment failure of I-131 in TMNG patients making it difficult to establish a direct cause?effect relationship and take corrective action. Therefore, the JURAN methodology...

  9. Relapsing and Progressive Tumefactive Demyelinating Form of Central Nervous System Involvement in a Patient with Progressive Systemic Sclerosis

    International Nuclear Information System (INIS)

    Kim, Ho Kyun; Lee, Hui Joong

    2013-01-01

    White matter hyper intensities (WMHI) on MRI are not rare in patients with progressive systemic sclerosis (PSS). In this presentation, WMHI were developed in both middle cerebellar peduncles and temporal white matter in a patient with PSS, and regressed after medication of high dose steroid. However, new lesions were developed in the subcortices of both precentral gyri, and progressed rapidly to tumefactive hyperintensity on MRI. We report an unusual relapsing and progressive tumefactive demyelinating form of central nervous system involvement in PSS.

  10. Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Sorensen, Per Soelberg; Ross, Christian; Clemmesen, Katja Maria

    2003-01-01

    Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis, but the drug can induce neutralising antibodies against itself, which might reduce effectiveness. We aimed to assess the clinical effect of neutralising antibodies....

  11. Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients

    Science.gov (United States)

    Hirase, Satoshi; Saitoh, Atsuro; Hartomo, Tri Budi; Kozaki, Aiko; Yanai, Tomoko; Hasegawa, Daiichiro; Kawasaki, Keiichiro; Kosaka, Yoshiyuki; Matsuo, Masafumi; Yamamoto, Nobuyuki; Mori, Takeshi; Hayakawa, Akira; Iijima, Kazumoto; Nishio, Hisahide; Nishimura, Noriyuki

    2016-01-01

    Neuroblastoma is an aggressive pediatric tumor accounting for ~15% of cancer-associated mortalities in children. Despite the current intensive therapy, >50% of high-risk patients experience tumor relapse or regrowth caused by the activation of minimal residual disease (MRD). Although several MRD detection protocols using various reverse transcription-quantitative polymerase chain reaction (RT-qPCR) markers have been reported to evaluate the therapeutic response and disease status of neuroblastoma patients, their clinical significance remains elusive. The present study reports two high-risk neuroblastoma patients, whose MRD was consecutively monitored using 11 RT-qPCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) during their course of treatment. The two patients initially responded to the induction therapy and reached MRD-negative status. The patients' MRD subsequently became positive with no elevation of their urinary homovanillic acid, urinary vanillylmandelic acid and serum neuron-specific enolase levels at 13 or 19 weeks prior to the clinical diagnosis of tumor relapse or regrowth. The present cases highlight the possibility of consecutive MRD monitoring using 11 markers to enable an early detection of tumor relapse or regrowth in high-risk neuroblastoma patients. PMID:27446404

  12. Mounting resistance of uropathogens to antimicrobial agents: A retrospective study in patients with chronic bacterial prostatitis relapse

    Directory of Open Access Journals (Sweden)

    Konstantinos Stamatiou

    2017-07-01

    Full Text Available Purpose: Despite recent progress in the management of chronic bacterial prostatitis (CBP, many cases relapse. Increased drug resistance patterns of responsible bacteria have been proposed as the most probable causative factor. Driven by the limited number of previous studies addressing this topic, we aimed to study whether antibiotic resistance increases in patients with CBP when relapse occurs. A secondary aim of this study was to determine the resistance patterns of responsible bacteria from patients with CBP. Materials and Methods: The study material consisted of bacterial isolates from urine and/or prostatic secretions obtained from patients with CBP. Bacterial identification was performed by using the Vitek 2 Compact system and susceptibility testing was performed by disc diffusion and/or the Vitek 2 system. Interpretation of susceptibility results was based on Clinical and Laboratory Standards Institute guidelines. Results: A total of 253 samples from patients diagnosed with CBP for the first time (group A and 137 samples from relapsing patients with a history of CBP and previous antibiotic treatment (group B were analyzed. A significant reduction in bacterial resistance to the less used antibiotics (TMP-SMX, tetracyclines, aminoglycosides, penicillins, and macrolides was noted. An increase in resistance to quinolones of many bacteria that cause CBP was also noted with the increase in resistance of enterococcus strains being alarming. Conclusions: Comparison of the resistance profile of CBP-responsible bacteria between samples from first-time-diagnosed patients and samples from relapsing patients revealed notable differences that could be attributed to previous antibiotic treatment.

  13. CA-125–indicated asymptomatic relapse confers survival benefit to ovarian cancer patients who underwent secondary cytoreduction surgery

    Directory of Open Access Journals (Sweden)

    Wang Fang

    2013-02-01

    Full Text Available Abstract Background There is no consensus regarding the management of ovarian cancer patients, who have shown complete clinical response (CCR to primary therapy and have rising cancer antigen CA-125 levels but have no symptoms of recurrent disease. The present study aims to determine whether follow-up CA-125 levels can be used to identify the need for imaging studies and secondary cytoreductive surgery (CRS. Methods We identified 410 ovarian cancer patients treated at The University of Texas MD Anderson Cancer Center between 1984 and 2011. These patients had shown CCR to primary therapy. Follow-up was conducted based on the surveillance protocol of the MD Anderson Cancer Center. We used the Cox proportional hazards model and log-rank test to assess the associations between the follow-up CA-125 levels and secondary CRS and survival duration. Results The CA-125 level of 1.68 × nadir was defined as the indicator of recurrent disease (p  1.68 × nadir at relapse (55.7 and 10.4 months; p = 0.04 and 0.01, respectively. The overall and progression free survival duration of patients with asymptomatic relapse and underwent a secondary CRS was longer than that of patients with symptomatic relapse (p = 0.02 and 0.04 respectively. Conclusions The increase of serum CA-125 levels is an early warning of clinical relapse in ovarian cancer. Using CA-125 levels in guiding the treatment of patients with asymptomatic recurrent ovarian cancer, who have shown CCR to primary therapy, can facilitate optimal secondary CRS and extend the survival duration of the patients.

  14. Clinical trial: factors associated with freedom from relapse of heartburn in patients with healed reflux oesophagitis--results from the maintenance phase of the EXPO study.

    Science.gov (United States)

    Labenz, J; Armstrong, D; Zetterstrand, S; Eklund, S; Leodolter, A

    2009-06-01

    Ability to predict freedom from heartburn relapse during maintenance therapy for healed reflux oesophagitis may facilitate optimal treatment choices for individual patients. To determine factors predicting freedom from heartburn relapse during maintenance proton pump inhibitor therapy in patients with healed reflux oesophagitis. This post-hoc analysis used data from the maintenance phase of the EXPO study (AstraZeneca study code: SH-NEG-0008); 2766 patients with healed reflux oesophagitis and resolved heartburn received once-daily esomeprazole 20 mg or pantoprazole 20 mg for 6 months. Multiple logistic regression analysis determined factors associated with freedom from heartburn relapse. Heartburn relapse rates were lower with esomeprazole than pantoprazole in all subgroups analysed. Esomeprazole treatment was the factor most strongly associated with freedom from heartburn relapse (odds ratio 2.08; P heartburn relapse were Helicobacter pylori infection, greater age, non-obesity, absence of epigastric pain at baseline, pre-treatment nonsevere heartburn and GERD symptom duration heartburn relapse during maintenance proton pump inhibitor therapy for healed reflux oesophagitis, the strongest being choice of proton pump inhibitor. These findings outline the importance of optimizing acid control and identifying predictors of relapse for effective long-term symptom management in reflux oesophagitis patients.

  15. Successful Control of Disseminated Intravascular Coagulation by Recombinant Thrombomodulin during Arsenic Trioxide Treatment in Relapsed Patient with Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Motohiro Shindo

    2012-01-01

    Full Text Available Disseminated intravascular coagulation (DIC frequently occurs in patients with acute promyelocytic leukemia (APL. With the induction of therapy in APL using all-trans retinoic acid (ATRA, DIC can be controlled in most cases as ATRA usually shows immediate improvement of the APL. However, arsenic trioxide (ATO which has been used for the treatment of relapse in APL patients has shown to take time to suppress APL cells, therefore the control of DIC in APL with ATO treatment is a major problem. Recently, the recombinant soluble thrombomodulin fragment has received a lot of attention as the novel drug for the treatment of DIC with high efficacy. Here, we present a relapsed patient with APL in whom DIC was successfully and safely controlled by rTM during treatment with ATO.

  16. Cinacalcet in treatment of the secondary hyperparathyroidism relapse in patients on dialysis

    Directory of Open Access Journals (Sweden)

    Olga Vetchinnikova

    2012-06-01

    Full Text Available The incidence of the secondary hyperparathyroidism (HPT after parathyroidectomy (PTE in dialysis patients accounts for 10-80%. We present a case of the successful cinacalcet treatment of a female hemodialysis (HD patient with HPT relapse. A female patient (aged 40 years with the diabetes mellitus I (since 11 years of age has been undergoing substitution therapy on continuous ambulatory peritoneal dialysis (CAPD since October 2004. Insulin and erythropoietin treatment has been continued as well as taking phosphate binders with calcium and calcitriol analogs (with intervals due to hyperphosphatemia. Нb=117 g/L, Са=2.2, Р=1.8 mmoles/L, PTH=272 pg/ml, total alkaline phosphatase (AlP=69 U/L (normal level 31-115, and Нb1С=9.2%. Since December 2007, the patient has been treated with HD (due to inadequacy of the CAPD ultrafiltration; in 2009, her left leg was amputated (gangrene. Taking into account unconntrolled HPT developed in the patient (PTH=2058 pg/ml, Са=2.4, Р=2.7 mmoles/L, and AlP=290 U/L, PTE was carried out in October 2007: enlarged (∅ 12 mm right inferior parathyroid gland was removed, other glands weren’t revealed. Patient’s condition in postoperative period was satisfactory (PTH 70–120 pg/ml, Са=1.5-1.9, Р=1.3–1.5 mmoles/L, and AlP=145-68 U/L. Since 2009, the signs of the secondary HPT recurrence: PTH 1436 pg/ml., Са=2.4, Р=2.3 mmoles/L, and AlP=184 U/L. Increasing the dose of calcitriol analogs caused hypercalcemia and hyperphosphatemia. Ultrasound investigation and scintigraphy with 99mТс-technetril also have not revealed parathyroid glands. The negative dynamics was detected by the DEXA scanning shown by the T-scores at the hip, spine and left forearm. Cinacalcet treatment was started: the initial dose 30 mg/day, in a month − 60 mg/day, and in 6 months and till now − 45 mg/day. The sought-for values of the mineral-osseous metabolism have been achieved. Bone mineral density stabilized in the

  17. [Relapse: causes and consequences].

    Science.gov (United States)

    Thomas, P

    2013-09-01

    Relapse after a first episode of schizophrenia is the recurrence of acute symptoms after a period of partial or complete remission. Due to its variable aspects, there is no operational definition of relapse able to modelise the outcome of schizophrenia and measure how the treatment modifies the disease. Follow-up studies based on proxys such as hospital admission revealed that 7 of 10 patients relapsed after a first episode of schizophrenia. The effectiveness of antipsychotic medications on relapse prevention has been widely demonstrated. Recent studies claim for the advantages of atypical over first generation antipsychotic medication. Non-adherence to antipsychotic represents with addictions the main causes of relapse long before some non-consensual factors such as premorbid functioning, duration of untreated psychosis and associated personality disorders. The consequences of relapse are multiple, psychological, biological and social. Pharmaco-clinical studies have demonstrated that the treatment response decreases with each relapse. Relapse, even the first one, will contribute to worsen the outcome of the disease and reduce the capacity in general functionning. Accepting the idea of continuing treatment is a complex decision in which the psychiatrist plays a central role besides patients and their families. The development of integrated actions on modifiable risk factors such as psychosocial support, addictive comorbidities, access to care and the therapeutic alliance should be promoted. Relapse prevention is a major goal of the treatment of first-episode schizophrenia. It is based on adherence to the maintenance treatment, identification of prodromes, family active information and patient therapeutical education. Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

  18. [Louse-borne-relapsing-fever in refugees from the Horn of Africa; a case series of 25 patients].

    Science.gov (United States)

    Seilmaier, M; Guggemos, W; Wieser, A; Fingerle, V; Balzer, L; Fenzl, T; Hoch, M; von Both, U; Schmidt, H U; Wendtner, C M; Strobel, E

    2016-07-01

    Background | Relapsing fever is divided into tick borne relapsing fever (TBRF) and louse borne relapsing fever (LBRF). This report describes 25 refugees from East Africa who were diagnosed to suffer from LBRF within a period of 6 month only at a single hospital in Munich / Germany. Material & Methods | The aim was to point out common clinical features as well as laboratory findings and clinical symptoms before and after initiation of treatment in 25 patients with louse borne relapsing fever (LBRF) who were diagnosed and treated at Klinikum München Schwabing from August 2015 to January 2016. To the best of our knowledge this is the largest case series of LBRF in the western world for decades. Main focus of the investigation was put on clinical aspects. Results | All 25 patients suffered from acute onset of high fever with chills, headache and severe prostration. Laboratory analysis showed high CRP and a marked thrombocytopenia. A Giemsa blood stain was procured immediately in order to look for malaria. In the blood smear spirochetes with typical shape and aspect of borrelia species could be detected.The further PCR analysis confirmed infection with Borrelia recurrentis. Treatment with Doxycycline was started forthwith. The condition improved already on the second day after treatment was started and all were restored to health in less than a week. Apart from a mild to moderate Jarisch-Herxheimer-reaction we didn`t see any side effects of the therapy. Conclusion | LBRF has to be taken into account in feverish patients who come as refugees from East-Africa. It seems that our patients belong to a cluster which probably has its origin in Libya and more patients are to be expected in the near future. As LBRF might cause outbreaks in refugee camps it is pivotal to be aware of this emerging infectious disease in refugees from East-Africa. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Do polymorphisms in MDR1 and CYP3A5 genes influence the risk of cytogenetic relapse in patients with chronic myeloid leukemia on imatinib therapy?

    Science.gov (United States)

    Harivenkatesh, Natarajan; Kumar, Lalit; Bakhshi, Sameer; Sharma, Atul; Kabra, Madhulika; Velpandian, Thirumurthy; Gogia, Ajay; Shastri, Shivaram S; Gupta, Yogendra Kumar

    2017-09-01

    Influence of polymorphisms in the genes coding for imatinib transporters and metabolizing enzymes on cytogenetic relapse in patients with chronic myeloid leukemia (CML) is not known. One hundred and four patients (52 cases with cytogenetic relapse and 52 controls without relapse) with chronic-phase CML on imatinib therapy and have completed 5 years of follow-up were enrolled. The following single nucleotide polymorphisms (SNPs) were genotyped; C1236T, C3435T, G2677T/A in MDR1 gene and A6986G in CYP3A5 gene, using PCR-RFLP method and validated by direct gene sequencing. Imatinib trough levels were measured using LC-MS/MS. Patients with CC genotype for MDR1-C1236T polymorphism were at significantly higher risk for cytogenetic relapse [OR =4.382, 95% CI (1.145, 16.774), p = .022], while those with TT genotype for MDR1-C3435T polymorphism had significantly lower risk of relapse [OR =0.309, 95% CI (0.134, 0.708), p = .005]. Imatinib trough levels were lower in patients with relapse compared to those without relapse (1551.4 ± 1324.1 vs. 2154.2 ± 1358.3 ng/mL; p = .041). MDR1-C3435T genotype [adjusted-OR: 0.266; 95% CI (0.111, 0.636); p = .003] and trough levels (p = .014) were independent predictors of relapse in multivariate analysis. To conclude, C1236T and C3435T polymorphisms in MDR1 gene and trough levels significantly influence the risk of cytogenetic relapse. MDR1-C3435T genotype might emerge as a potential biomarker to predict the risk of cytogenetic relapse in patients with CML.

  20. DNA Superresolution Structure of Reed-Sternberg Cells Differs Between Long-Lasting Remission Versus Relapsing Hodgkin's Lymphoma Patients.

    Science.gov (United States)

    Righolt, Christiaan H; Knecht, Hans; Mai, Sabine

    2016-07-01

    Recent developments in microscopy have led to superresolution microscopy images of cells. Structured illumination microscopy was used before to reveal new details in the DNA structure and the structure of the DNA-free space in the DAPI-stained cell nuclei of the Hodgkin's lymphoma HDLM-2 cell line. This study extends this technology to primary pre-treatment classical Hodgkin's lymphoma samples of ten patients. Significant differences in both the DNA structure and the structure of the DNA-free space were detected between lymphocytes and malignant cells. Both types of structures were similar for lymphocytes of different patients. When the patients were un-blinded and grouped based on their clinical outcome, either non-relapsed or relapsed, a significant difference in the DNA structure of their Reed-Sternberg (RS) cells was found. Since, RS cells develop from mono-nucleated Hodgkin (H) cells, these data suggest distinct architectural restructuring of nuclei during RS cell formation in patients going to long-lasting remission versus relapse. J. Cell. Biochem. 117: 1633-1637, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  1. Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the CONFIRM study.

    LENUS (Irish Health Repository)

    Hutchinson, Michael

    2013-09-01

    In the phase 3, randomized, placebo-controlled and active reference (glatiramer acetate) comparator CONFIRM study in patients with relapsing-remitting multiple sclerosis, oral BG-12 (dimethyl fumarate) reduced the annualized relapse rate (ARR; primary endpoint), as well as the proportion of patients relapsed, magnetic resonance imaging lesion activity, and confirmed disability progression, compared with placebo. We investigated the clinical efficacy of BG-12 240 mg twice daily (BID) and three times daily (TID) in patient subgroups stratified according to baseline demographic and disease characteristics including gender, age, relapse history, McDonald criteria, treatment history, Expanded Disability Status Scale score, T2 lesion volume, and gadolinium-enhancing lesions. BG-12 treatment demonstrated generally consistent benefits on relapse-related outcomes across patient subgroups, reflecting the positive findings in the overall CONFIRM study population. Treatment with BG-12 BID and TID reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in all subgroups analyzed. Reductions in ARR with BG-12 BID versus placebo ranged from 34% [rate ratio 0.664 (95% confidence interval 0.422-1.043)] to 53% [0.466 (0.313-0.694)] and from 13% [0.870 (0.551-1.373)] to 67% [0.334 (0.226-0.493)] with BG-12 TID versus placebo. Treatment with glatiramer acetate reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in most patient subgroups. The results of these analyses indicate that treatment with BG-12 is effective on relapses across a broad range of patients with relapsing-remitting multiple sclerosis with varied demographic and disease characteristics.

  2. Prognostic Factors and Patterns of Relapse in Ewing Sarcoma Patients Treated With Chemotherapy and R0 Resection

    International Nuclear Information System (INIS)

    Pan, Hubert Y.; Morani, Ajaykumar; Wang, Wei-Lien; Hess, Kenneth R.; Paulino, Arnold C.; Ludwig, Joseph A.; Lin, Patrick P.; Daw, Najat C.; Mahajan, Anita

    2015-01-01

    Purpose: To identify prognostic factors and patterns of relapse for patients with Ewing sarcoma who underwent chemotherapy and R0 resection without radiation therapy (RT). Methods and Materials: We reviewed the medical records of patients who underwent surgical resection at our institution between 2000 and 2013 for an initial diagnosis of Ewing sarcoma. The associations of demographic and clinical factors with local control (LC) and patient outcome were determined by Cox regression. Time to events was measured from the time of surgery. Survival curves were estimated by the Kaplan-Meier method and compared by the log-rank test. Results: A total of 66 patients (median age 19 years, range 4-55 years) met the study criteria. The median follow-up was 5.6 years for living patients. In 43 patients (65%) for whom imaging studies were available, the median tumor volume reduction was 73%, and at least partial response by Response Evaluation Criteria in Solid Tumors was achieved in 17 patients (40%). At 5 years, LC was 78%, progression-free survival (PFS) was 59%, and overall survival (OS) was 65%. Poor histologic response (necrosis ≤95%) was an independent predictor of LC (hazard ratio [HR] 6.8, P=.004), PFS (HR 5.2, P=.008), and OS (HR 5.0, P=.008). Metastasis on presentation was also an independent predictor of LC (HR 6.3, P=.011), PFS (HR 6.8, P=.002), and OS (HR 6.7, P=.002). Radiologic partial response was a predictor of PFS (HR 0.26, P=.012), and postchemotherapy tumor volume was associated with OS (HR 1.06, P=.015). All deaths were preceded by distant relapse. Of the 8 initial local-only relapses, 5 (63%) were soon followed by distant relapse. Predictors of poor postrecurrence survival were time to recurrence <1 year (HR 11.5, P=.002) and simultaneous local and distant relapse (HR 16.8, P=.001). Conclusions: Histologic and radiologic response to chemotherapy were independent predictors of outcome. Additional study is needed to determine the role of adjuvant

  3. Irinotecan in patients with relapsed or cisplatin-refractory germ cell cancer: a phase II study of the German Testicular Cancer Study Group

    OpenAIRE

    Kollmannsberger, C; Rick, O; Klaproth, H; Kubin, T; Sayer, H G; Hentrich, M; Welslau, M; Mayer, F; Kuczyk, M; Spott, C; Kanz, L; Bokemeyer, C

    2002-01-01

    Despite generally high cure rates in patients with metastatic germ cell cancer, patients with progressive disease on first-line cisplatin-based chemotherapy or with relapsed disease following high-dose salvage therapy exhibit a very poor prognosis. Irinotecan has shown antitumour activity in human testicular tumour xenografts in nude mice. We have performed a phase II study examining the single agent activity of irinotecan in patients with metastatic relapsed or cisplatin-refractory germ cell...

  4. Will black holes eventually engulf the Universe?

    International Nuclear Information System (INIS)

    Martin-Moruno, Prado; Jimenez Madrid, Jose A.; Gonzalez-Diaz, Pedro F.

    2006-01-01

    The Babichev-Dokuchaev-Eroshenko model for the accretion of dark energy onto black holes has been extended to deal with black holes with non-static metrics. The possibility that for an asymptotic observer a black hole with large mass will rapidly increase and eventually engulf the Universe at a finite time in the future has been studied by using reasonable values for astronomical parameters. It is concluded that such a phenomenon is forbidden for all black holes in quintessential cosmological models

  5. Long lasting second remission and quality of life following brachytherapy of relapsing cancer in preirradiated regions. Experience in 108 patients

    International Nuclear Information System (INIS)

    Schmidt, B.F.; Kwiatkowski, J.

    1996-01-01

    Introduction: In patients with unresectable relapsing malignant tumor following external beam radiotherapy retreatment by brachytherapy gives a second chance of good palliation and even cure. But regardless the great number of tumor relapse reirradiation is given only to few patients due to the impending risks of severe radiation sequelae. Material and method: From January 1st 1992 to December 31st 1995 overall 108 patients with histologically proven local tumor relapses in preirradiated regions were reirradiated by interstitial or intraluminal brachytherapy (192-Iridium sources). The preirradiation dose was 40 to 70 Gray (Gy) in conventional fractionation. The brachytherapy retreatment dose was 30 to 40 Gy at the individually shaped reference isodose shell. In high dose-rate technique (about two third of all patients) mostly single doses of 5 Gy were applied once or twice a week. If low dose-rate techniques were used, a maximum dose of 60 Gy was applied. In some cases a second course of external beam radiotherapy was added. The sites of reirradiation were: ear-nose-throat-yaw areas 76, large airways 24, soft tissues 7, scalp 1. Results: In (23(108)) patients (21 %) complete or partial remission could be achieved lasting at least one year. In (8(23)) patients (overall 7,4 %) the second remission lasted longer than two years. The quality of life in the long time survivors was felt to be good or at least acceptable. Local necroses, not life threatening, occurred in about 20 %. No fatal complication was to be observed. Altogether in about 85 % the reirradiation resulted in effective palliation and was well tolerated. Discussion and conclusion: Retreatment by brachytherapy yields valuable palliation to the vast majority of patients and gives a second chance of long time good quality survival to about 10 % of all retreated patients. Careful selection of patients and experienced realisation of brachytherapy is essential to avoid severe complications

  6. Are old-old patients with major depression more likely to relapse than young-old patients during continuation treatment with escitalopram?

    Directory of Open Access Journals (Sweden)

    Katona Cornelius

    2011-01-01

    Full Text Available Abstract Background Escitalopram has shown efficacy and tolerability in the prevention of relapse in elderly patients with major depressive disorder (MDD. This post-hoc analysis compared time to relapse for young-old patients (n = 197 to that for old-old patients (n = 108. Method Relapse prevention: after 12-weeks open-label treatment, remitters (MADRS ≤12 were randomised to double-blind treatment with escitalopram or placebo and followed over 24-weeks. Patients were outpatients with MDD from 46 European centers aged ≥75 years (old-old or 65-74 years of age (young-old, treated with escitalopram 10-20mg/day. Efficacy was assessed using the Montgomery Åsberg Depression Rating Scale (MADRS. Results After open-label escitalopram treatment, a similar proportion of young-old patients (78% and old-old patients (72% achieved remission. In the analysis of time to relapse based on the Cox model (proportional hazards regression, with treatment and age group as covariates, the hazard ratio was 4.4 for placebo versus escitalopram (χ2-test, df = 1, χ2= 22.5, p old-old versus young-old (χ2-test, df = 1, χ2 = 0.41, p = 0.520. Escitalopram was well tolerated in both age groups with adverse events reported by 53.1% of young-old patients and 58.3% of old-old patients. There was no significant difference in withdrawal rates due to AEs between age groups (χ2-test, χ2 = 1.669, df = 1, p = 0.196. Conclusions Young-old and old-old patients with MDD had comparable rates of remission after open-label escitalopram, and both age groups had much lower rates of relapse on escitalopram than on placebo.

  7. Reduction in relapse rate of radioiodine therapy in patients of toxic multinodular goiter: a quality improvement project

    International Nuclear Information System (INIS)

    Mitra, Sujata; Muthu, Sonai G.

    2012-01-01

    Radioiodine ( 131 I) therapy is the definitive treatment of toxic multinodular goiter (TMNG). Treatment failure may result in relapse after 131 I therapy. The present study was undertaken to reduce treatment failure rate of 131 I therapy in TMNG patients. Multiple causes may have lead to treatment failure of 131 I in TMNG patients making it difficult to establish a direct cause-effect relationship and take corrective action. Therefore, the JURAN methodology of quality improvement was applied. The treatment failure rate in 80 TMNG patients treated with 131 I in the period 2003-06 was 29%. The root cause analysis identified delay in decision to radioablate and concomitant antithyroid drugs (ATD) with 131 I therapy as factors leading to relapse. In 2007, a change in management was introduced with decision to radioablate all TMNG patients not remitting at 1 year of ATD and to withdraw ATD for 2 weeks prior to 131 I therapy. A total of 63 patients of TMNG followed the changed protocol between 2007 and 2009. Further analysis showed that one of the factors identified in the initial brainstorming (high iodide pool in the patient) had not been addressed in the protocol currently followed. The protocol was modified to include patient preparation and implemented after standardization. The post- 131 I relapse rate in patients treated after implementation of the new protocol from 2007 to 2009 was 18% which further reduced to 16% in 2011 after modification of the protocol. The failure rate of 131 I therapy in TMNG reduced from 29% to 16% through standardization of the treatment procedure achieved by the use of Juran Methodology that helped to identify process-related defects. (author)

  8. Reduction in relapse rate of radioiodine therapy in patients of toxic multinodular goiter: a quality improvement project

    Energy Technology Data Exchange (ETDEWEB)

    Mitra, Sujata; Muthu, Sonai G., E-mail: sujatamitra@tatasteel.com [Department of Nuclear Medicine, Tata Main Hospital, Jamshedpur (India)

    2012-01-15

    Radioiodine ({sup 131}I) therapy is the definitive treatment of toxic multinodular goiter (TMNG). Treatment failure may result in relapse after {sup 131}I therapy. The present study was undertaken to reduce treatment failure rate of {sup 131}I therapy in TMNG patients. Multiple causes may have lead to treatment failure of {sup 131}I in TMNG patients making it difficult to establish a direct cause-effect relationship and take corrective action. Therefore, the JURAN methodology of quality improvement was applied. The treatment failure rate in 80 TMNG patients treated with {sup 131}I in the period 2003-06 was 29%. The root cause analysis identified delay in decision to radioablate and concomitant antithyroid drugs (ATD) with {sup 131}I therapy as factors leading to relapse. In 2007, a change in management was introduced with decision to radioablate all TMNG patients not remitting at 1 year of ATD and to withdraw ATD for 2 weeks prior to {sup 131}I therapy. A total of 63 patients of TMNG followed the changed protocol between 2007 and 2009. Further analysis showed that one of the factors identified in the initial brainstorming (high iodide pool in the patient) had not been addressed in the protocol currently followed. The protocol was modified to include patient preparation and implemented after standardization. The post-{sup 131}I relapse rate in patients treated after implementation of the new protocol from 2007 to 2009 was 18% which further reduced to 16% in 2011 after modification of the protocol. The failure rate of {sup 131}I therapy in TMNG reduced from 29% to 16% through standardization of the treatment procedure achieved by the use of Juran Methodology that helped to identify process-related defects. (author)

  9. Substance Abuse, Relapse, and Treatment Program Evaluation in Malaysia: Perspective of Rehab Patients and Staff Using the Mixed Method Approach

    Science.gov (United States)

    Chie, Qiu Ting; Tam, Cai Lian; Bonn, Gregory; Dang, Hoang Minh; Khairuddin, Rozainee

    2016-01-01

    This study examined reasons for substance abuse and evaluated the effectiveness of substance treatment programs in Malaysia through interviews with rehab patients and staff. Substance rehab patients (aged 18–69 years; n = 30) and staff (ages 30–72 years; n = 10) participated in semi-structured interviews covering a range of topics, including family and peer relationships, substance use and treatment history, factors for substance use and relapse, motivation for entering treatment, work experience, job satisfaction, treatment evaluation, and patient satisfaction. Most patients did not demonstrate the substance progression trend and had normal family relationships. Most patients reported having peers from normal family backgrounds as well. Various environmental and personal factors was cited as contributing to substance abuse and relapse. There was no significant difference between patient and staff program evaluation scores although the mean score for patients was lower. A holistic treatment approach with a combination of cognitive–behavioral, medical, social, and spiritual components was favored by patients. Suggestions for improving existing programs include better tailoring treatment to individual needs, and providing more post-treatment group support. PMID:27303313

  10. Accuracy of Consecutive Fecal Calprotectin Measurements to Predict Relapse in Inflammatory Bowel Disease Patients Under Maintenance With Anti-TNF Therapy: A Prospective Longitudinal Cohort Study.

    Science.gov (United States)

    Ferreiro-Iglesias, Rocio; Barreiro-de Acosta, Manuel; Lorenzo-Gonzalez, Aurelio; Dominguez-Muñoz, Juan E

    2018-03-01

    Predicting relapse in inflammatory bowel disease (IBD) patients could allow early changes in therapy. We aimed at evaluating the accuracy of consecutive fecal calprotectin (FC) measurements to predict flares in IBD patients under maintenance treatment with anti-tumor necrosis factor (TNF) drugs. A prospective longitudinal cohort study with 16-month follow-up period was designed. IBD patients in clinical remission for at least 6 months under anti-TNF therapy were included. FC was quantified at 4-month intervals for 1 year, and patients were clinically evaluated for relapse at 2-month intervals. Diagnostic accuracy of FC for predicting relapse was evaluated by receiver-operating characteristic curve analysis. In total, 95 of 106 included patients finalized the study and were analyzed (median age 44 y, 50.5% female, 75% with Crohn's disease). A total of 30 patients (31.6%) had a relapse over follow-up. FC concentration was significantly higher in patients who relapsed (477 μg/g) than in patients who maintained in remission (65 μg/g) (Ppredict remission was 130 μg/g (negative predictive value of 100%), and 300 μg/g to predict relapse (positive predictive value of 78.3%). FC is a good predictor of clinical relapse and a particularly good predictor of remission over the following 4 months in patients with IBD on maintenance therapy with anti-TNF drugs. FC levels 300 μg/g allow predicting relapse with a high probability at any time over the following 4 months.

  11. Medication withdrawal may be an option for a select group of patients in relapsing-remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Guilherme Sciascia do Olival

    2013-08-01

    Full Text Available This article describes the clinical and radiological evolution of a stable group of patients with relapsing-remitting multiple sclerosis that had their disease-modifying therapy (DMT withdrawn. Forty patients, which had made continuous use of one immunomodulator and had remained free of disease for at least 5 years, had their DMT withdrawn and were observed from 13 to 86 months. Out of the followed patients, 4 (10% patients presented with new attacks. In addition to these patients, 2 (5% patients had new lesions revealed by magnetic resonance imaging that did not correspond to clinical attacks. Despite these results, the difficult decision to withdraw medication requires careful analysis. Withdrawal, however, should not be viewed as simply the suspension of treatment because these patients should be evaluated periodically, and the immunomodulators should be readily reintroduced if new attacks occur. Nonetheless, medication withdrawal is an option for a select group of patients.

  12. Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    von Stackelberg, Arend; Locatelli, Franco; Zugmaier, Gerhard; Handgretinger, Rupert; Trippett, Tanya M; Rizzari, Carmelo; Bader, Peter; O'Brien, Maureen M; Brethon, Benoît; Bhojwani, Deepa; Schlegel, Paul Gerhardt; Borkhardt, Arndt; Rheingold, Susan R; Cooper, Todd Michael; Zwaan, Christian M; Barnette, Phillip; Messina, Chiara; Michel, Gérard; DuBois, Steven G; Hu, Kuolung; Zhu, Min; Whitlock, James A; Gore, Lia

    2016-12-20

    Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II). Results We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 µg/m 2 /d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 µg/m 2 /d for the first 7 days, followed by 15 µg/m 2 /d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade ≥ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures. Conclusion This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new treatment option in this setting, requiring further investigation in curative indications.

  13. Retreatment with peg-interferon and ribavirin in patients with chronic hepatitis C virus genotype 2 or 3 infection with prior relapse

    DEFF Research Database (Denmark)

    Lagging, Martin; Rembeck, Karolina; Rauning Buhl, Mads

    2013-01-01

    Uncertainty remains regarding the efficacy of retreatment with current standard-of-care peg-interferon (peg-IFN) and ribavirin among patients infected with hepatitis C virus (HCV) genotypes 2 or 3 with relapse after prior therapy.......Uncertainty remains regarding the efficacy of retreatment with current standard-of-care peg-interferon (peg-IFN) and ribavirin among patients infected with hepatitis C virus (HCV) genotypes 2 or 3 with relapse after prior therapy....

  14. Phase 1 study of clofarabine in pediatric patients with relapsed/refractory acute lymphoblastic leukemia in Japan.

    Science.gov (United States)

    Koh, Katsuyoshi; Ogawa, Chitose; Okamoto, Yasuhiro; Kudo, Kazuko; Inagaki, Jiro; Morimoto, Tsuyoshi; Mizukami, Hideya; Ecstein-Fraisse, Evelyne; Kikuta, Atsushi

    2016-08-01

    A phase 1 study was conducted to evaluate the safety, pharmacokinetics (PK), efficacy and pharmacogenetic characteristics of clofarabine in seven Japanese pediatric patients with relapsed/refractory acute lymphoblastic leukemia (ALL). Patients in Cohort 1 received clofarabine 30 mg/m(2)/day for 5 days, followed by 52 mg/m(2)/day for 5 days in subsequent cycles. Cohort 2 patients were consistently treated with 52 mg/m(2)/day for 5 days. No more than six cycles were performed. Every patient had at least one ≥Grade 3 adverse event (AE). AEs (≥Grade 3) related to clofarabine were anaemia, neutropenia, febrile neutropenia, thrombocytopenia, alanine aminotransferase increased, aspartate aminotransferase increased, haemoglobin decreased, and platelet (PLT) count decreased. C max and AUC of clofarabine increased in a dose-dependent fashion, but its elimination half-life (T 1/2) did not appear to be dependent on dose or duration of treatment. Clofarabine at 52 mg/m(2)/day shows similarly tolerable safety and PK profiles compared to those in previous studies. No complete remission (CR), CR without PLT recovery, or partial remission was observed. Since clofarabine is already used as a key drug for relapsed/refractory ALL patients in many countries, the efficacy of clofarabine in Japanese pediatric patients should be evaluated in larger study including more patients, such as by post-marketing surveillance.

  15. Efficacy and Safety of Ibrutinib in Indian Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma: Cases from a Named Patient Program.

    Science.gov (United States)

    Agarwal, Mohan B; Bhurani, Dinesh; Shah, Chirag; Sood, Nitin; Singhal, Manish; Kamat, Anil; Chezhian, Subash; Mishra, Suryaprakash; Nagrale, Dinesh

    2017-01-01

    This named patient program evaluated the safety and efficacy of ibrutinib, a selective inhibitor of Bruton's tyrosine kinase in Indian patients with relapsed/refractory chronic lymphocytic leukemia (CLL, with/without chromosome 17 deletion [del17p]) and mantle cell lymphoma (MCL). The eight enrolled patients (relapsed/refractory CLL: n = 6 [4/6 patients with del17p] and relapsed/refractory MCL: n = 2) had median age of 55 years (range, 52-60) and had received a median of 3 (CLL patients) and 4 (MCL patients) prior therapies. Patients received once-daily dose of ibrutinib (420 mg: CLL, 560 mg: MCL). In CLL patients, the median time to response was 3 months (range, 0.5-7) and five of six patients had partial response (PR) whereas one achieved complete response (CR). Median time on treatment was 11.5 months (range, 8-14); five patients continued treatment and one was recommended stem cell transplantation (SCT). Of the two MCL patients, one achieved PR and one showed CR and advanced to SCT. In CLL patients, the median (range) hemoglobin level improved from 9.8 g/dL (7.2-11) at baseline to 12.0 g/dL (9.5-13.2) and median (range) platelet count improved from 150,000 cells/μL (21,000-195,000) at baseline to 190,350 cells/μL (130,000-394,000) at the time of analysis (July 2016). Most adverse events (AEs) reported were infections ( n = 2). No Grade 3-4 or serious AEs, dose reductions, or treatment discontinuation due to AEs were reported. In this first real-world experience in Indian patients, ibrutinib demonstrated therapeutic efficacy in relapsed/refractory CLL (with/without del17p) and MCL. Safety results were consistent with the current known profile of ibrutinib.

  16. Investigating the Relationship Between Selective Attention and Cognitive Flexibility With Balance in Patients With Relapsing-Remitting Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Vali Shiri

    2018-01-01

    Conclusion A significant relationship between selective attentions to balance demonstrates that appropriately designed interventions to repair the attention, can decrease the balance problem in patients with MS. One of the possible reasons for this relationship can be found in the brain system that attention circuits are interacting with equilibrium systems, and any defect in selective attention leads to a loss of balance. Patients with MS experience constant imbalance due to cerebral plaques and relapsing-remitting periods, and in addition to rehabilitation of the balance system, cognitive systems such as attention should be treated.

  17. A phase I study of vorinostat combined with bortezomib in Japanese patients with relapsed or refractory multiple myeloma.

    Science.gov (United States)

    Ogawa, Yoshiaki; Ogura, Michinori; Tobinai, Kensei; Ando, Kiyoshi; Suzuki, Tatsuya; Watanabe, Takashi; Ohmachi, Ken; Uchida, Toshiki; Hanson, Mary E; Tanaka, Yoshinobu; Koh, Yasuhiro; Shimamoto, Takashi; Hotta, Tomomitsu

    2016-01-01

    This study was undertaken to evaluate safety and pharmacokinetics and to determine treatment doses of vorinostat plus bortezomib in Japanese patients with relapsed or refractory multiple myeloma (MM). Of 9 originally enrolled patients, 2 were refractory to bortezomib, and both experienced dose-limiting toxicity (DLT), prompting a protocol amendment to exclude bortezomib-refractory individuals. Patients not considered bortezomib refractory (N = 7) received 21-day cycles of 1.3 mg/m(2) intravenous bortezomib (Days 1, 4, 8, and 11) and oral vorinostat 400 mg (Days 1 through 14) and were further evaluated. Vorinostat and bortezomib treatment doses were determined by DLT and safety, tolerability, and treatment response were assessed. Of 7 enrolled patients, 6 were evaluated, and one developed DLTs. The most common adverse events were leukopenia, neutropenia, thrombocytopenia, diarrhea, nausea, decreased appetite, and vomiting. Combination of vorinostat plus bortezomib did not increase vorinostat exposure at Day 11 [AUC0-24 h ratio (95% CI) = 1.08 (0.80, 1.45)]; geometric mean AUC0-24 h ratio for bortezomib (90% CI) was 1.96 (1.24-3.12). Objective therapeutic response occurred in 3 patients, including 1 complete response and 2 partial responses. Vorinostat 400 mg plus bortezomib 1.3 mg/m(2) was safe and well-tolerated in Japanese patients with relapsed or refractory MM not considered bortezomib refractory (NCT00858234).

  18. Factors Influencing Suicidal Tendencies of Patients with Diagnosis of Attempted Suicide in Medical History and Potential Prevention of Relapse Prevention.

    Science.gov (United States)

    Kotrbová, Kvetoslava; Dóci, Ivan; Hamplová, Lidmila; Dvořák, Vít; Selingerová, Šárka; Růžičková, Veronika; Chmelařová, Šárka

    2017-12-01

    The authors researched the incidence of suicidal thoughts and related factors in 123 patients of the psychiatric ward of the Hospital of České Budějovice with diagnosed attempted suicide in their medical history for the period from January 2013 – June 2015. The research was carried out in two stages. At the beginning of the hospitalization, quantitative data collection was implemented using a semi-structured questionnaire, followed by qualitative research conducted with semi-structured phone conversation, based on previous patient's written consent. The research data were statistically processed to obtain information about the character of relations among individual characteristics. To quantify them, the Bayesian Network (BN) was constructed, and to identify relations among individual characteristics, the Hill-Climbing algorithm was used. Before deriving the network, variables were discretized. The network parameters were set based on a data matrix using the maximal plausibility method. The results of analysed set show that the probability of suicidal thoughts is high, achieving a value of 0.750 (0.781 for women and 0.724 for men). If the patient visits a contact centre for drug-addicted persons, the probability of suicidal thoughts decreases to 0.683. If the patient visits a psychotherapist, the values of 0.736 are achieved. If a daily care centre is visited, the estimated risk rises to 0.832 and the probability of the patient repetitively attempting suicide is 0.606. If the interviewed person regularly consumes alcohol, the probable relapse amounts to 0.616. But if the person consumes alcohol from time to time, the probability rises to 0.701. In case of abstinence, the probable relapse decreases to 0.565. The incidence of suicidal thoughts in observed patients was high, and the amount of risk was influenced by gender, by visiting follow-up care facilities, psychotherapy, and particularly by the frequency of alcohol consumption. Intermittent alcohol

  19. The Singapore Liver Cancer Recurrence (SLICER Score for relapse prediction in patients with surgically resected hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Soo Fan Ang

    Full Text Available Surgery is the primary curative option in patients with hepatocellular carcinoma (HCC. Current prognostic models for HCC are developed on datasets of primarily patients with advanced cancer, and may be less relevant to resectable HCC. We developed a postoperative nomogram, the Singapore Liver Cancer Recurrence (SLICER Score, to predict outcomes of HCC patients who have undergone surgical resection.Records for 544 consecutive patients undergoing first-line curative surgery for HCC in one institution from 1992-2007 were reviewed, with 405 local patients selected for analysis. Freedom from relapse (FFR was the primary outcome measure. An outcome-blinded modeling strategy including clustering, data reduction and transformation was used. We compared the performance of SLICER in estimating FFR with other HCC prognostic models using concordance-indices and likelihood analysis.A nomogram predicting FFR was developed, incorporating non-neoplastic liver cirrhosis, multifocality, preoperative alpha-fetoprotein level, Child-Pugh score, vascular invasion, tumor size, surgical margin and symptoms at presentation. Our nomogram outperformed other HCC prognostic models in predicting FFR by means of log-likelihood ratio statistics with good calibration demonstrated at 3 and 5 years post-resection and a concordance index of 0.69. Using decision curve analysis, SLICER also demonstrated superior net benefit at higher threshold probabilities.The SLICER score enables well-calibrated individualized predictions of relapse following curative HCC resection, and may represent a novel tool for biomarker research and individual counseling.

  20. The outbreak fingolimod cardiovascular side effects in relapsing-remitting multiple sclerosis patient: A longitudinal study in an Iranian population

    Directory of Open Access Journals (Sweden)

    Morteza Abdar

    2017-03-01

    Full Text Available BACKGROUND: Fingolimod (FTY-720 has shown efficacy in relapsing multiple sclerosis (MS, while some side effects of this drug have been recognized that the most important is cardiovascular side effects. The aim of this study was to evaluate the cardiovascular side effects of FTY-720. However, the effect of fingolimod on cardiac has not been well recognized. This study was designed to evaluate the cardiovascular side effects of fingolimod in relapsing-remitting multiple sclerosis (RRMS patient in an Iranian population. METHODS: This prospective clinical trial study was performed on 200 RRMS patients. The patients received a single daily oral dose of fingolimod 0.5 mg. During the first 6 hours after the first fingolimod dose, the patients’ vital signs and electrocardiographic traces were continuously monitored. Moreover, the patients followed up over 6 months after receiving fingolimod. RESULTS: The results showed that pulse rate (P < 0.001, systolic blood pressure (BP (P < 0.001, and diastolic BP (P < 0.001 were decreased significantly during 6 hours after receiving the first dose of fingolimod. The most reduction in vital sign was observed in 3 hours. Arrhythmia, bradycardia, and dizziness were the other complications of fingolimod, which were detected in our study. CONCLUSION: All the side effects such as hypotension and bradycardia were happened in first 3 hours after receiving the fingolimod. Indeed, we advise clinicians to monitor the patients for first 6 hours after initiation of fingolimod to decrease worse side effects. 

  1. Tandem autologous-allo-SCT is feasible in patients with high-risk relapsed non-Hodgkin's lymphoma.

    Science.gov (United States)

    Crocchiolo, R; Castagna, L; Fürst, S; El-Cheikh, J; Faucher, C; Oudin, C; Granata, A; Bouabdallah, R; Coso, D; Chabannon, C; Balzarotti, M; Santoro, A; Blaise, D

    2013-02-01

    Allo-SCT is used to exploit GVL effect in high-risk relapsed non-Hodgkin's lymphoma (NHL). Here, we retrospectively analyzed 34 high-risk NHL patients who underwent auto-SCT followed closely by reduced-intensity allo-SCT ('tandem auto-allo') from January 2002 to November 2010. The search for an allogeneic donor was started at the beginning of salvage regimen. Median patients' age was 47 (27-68) years; histotypes were: diffuse large B-cell n=5, follicular n=14, transformed follicular n=4, mantle-cell n=5, plasmocytoid lymphoma n=1, anaplastic large T-cell n=2, peripheral T-cell n=3. Donors were HLA-identical siblings (n=29) or 10/10-matched unrelated individuals (n=5). Median interval between auto-SCT and allo-SCT was 77 days (36-197). At a median follow-up of 46 (8-108) months since allo-SCT, 5-year OS is 77% (61-93) and PFS is 68% (51-85). Disease relapse or progression occurred in six patients, 100-day TRM was 0%, 2-year TRM incidence was 6%. In conclusion, tandem transplantation is feasible in high-risk NHL patients having a HLA-identical donor. This approach could represent a suitable therapeutic option for those patients with high-risk NHL potentially benefitting from further therapy after auto-SCT. Donor searches should be started promptly whenever such an approach is chosen.

  2. Improved survival of multiple myeloma patients with late relapse after high-dose treatment and stem cell support, a population-based study of 348 patients in Denmark in 1994-2004

    DEFF Research Database (Denmark)

    Vangsted, Annette Juul; Klausen, Tobias W; Andersen, Niels F

    2010-01-01

    To analyse if patients with early relapse after high-dose chemotherapy with stem cell support (HDT) benefit from new treatment strategies in a population-based setting.......To analyse if patients with early relapse after high-dose chemotherapy with stem cell support (HDT) benefit from new treatment strategies in a population-based setting....

  3. When can real-time quantitative RT-PCR effectively define molecular relapse in acute promyelocytic leukemia patients? (Results of the French Belgian Swiss APL Group).

    Science.gov (United States)

    Cassinat, Bruno; de Botton, Stéphane; Kelaidi, Charikleia; Ades, Lionel; Zassadowski, Fabien; Guillemot, Isabelle; Schlageter, Marie-Helene; Raffoux, Emmanuel; Harousseau, Jean-Luc; Legrand, Olivier; Escoffre-Barbe, Martine; Reman, Oumedaly; Gardembas, Martine; Himberlin, Chantal; Cahn, Jean Yves; Guyotat, Denis; Bouscary, Didier; Parry, Anne; Rousselot, Philippe; Baruchel, Andre; Dombret, Hervé; Chevret, Sylvie; Fenaux, Pierre; Chomienne, Christine

    2009-09-01

    10-20% of APL patients relapse and the challenge remains to early identify these patients to improve survival rate. We report PML-RARalpha transcript detection by RQ-PCR in 260 consecutive APL patients (n = 970 samples). 223 patients with samples of sufficient RNA quality to demonstrate they reached molecular remission were monitored for MRD. During follow-up, 38 of these patients were tested positive for PML-RARalpha mRNA. 13 out of the 38 patients (34%) effectively developed hematological relapse. In the first positive sample, specific PML-RARalpha NCN thresholds over which, or under which, patients could effectively be predicted to relapse or not, were identified and subsequently validated in a second cohort.

  4. Survival analysis of patients with clinical stages I or II Hodgkin's disease who have relapsed after initial treatment with radiotherapy alone

    DEFF Research Database (Denmark)

    Horwich, A.; Specht, L.; Ashley, S.

    1997-01-01

    relapse included initial stage, age, sex, histology, number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, alkaline phosphatase, serum albumin and haemoglobin. As well as presentation variables, we analysed the disease-free interval after initial......To aid treatment choice in early stage of Hodgkin's disease, we analysed patients registered in the IDHD Database with clinical stages I or II Hodgkin's disease who were not staged with laparotomy and whose initial treatment was with radiotherapy alone. The factors analysed for outcome after first...... radiotherapy and the extent of disease at relapse. A total of 1364 patients with clinical stage I or II Hodgkin's disease were treated with initial radiotherapy, of whom 473 relapsed. The probability of survival 10 years after relapse was 63%. For cause-specific survival (CSS), both multivariate and univariate...

  5. Zoledronic acid as compared with observation in multiple myeloma patients at biochemical relapse: results of the randomized AZABACHE Spanish trial

    Science.gov (United States)

    García-Sanz, Ramón; Oriol, Albert; Moreno, María J.; de la Rubia, Javier; Payer, Angel R.; Hernández, Miguel T.; Palomera, Luis; Teruel, Ana I.; Blanchard, María J.; Gironella, Mercedes; Ribas, Paz; Bargay, Joan; Abellá, Eugenia; Granell, Miquel; Ocio, Enrique M.; Ribera, Josep M.; San Miguel, Jesús F.; Mateos, María V.

    2015-01-01

    This study analyzed the anti-myeloma effect of zoledronic acid monotherapy by investigating patients at the time of asymptomatic biochemical relapse. One hundred patients were randomized to receive either zoledronic acid (4 mg iv/4 weeks, 12 doses) (n=51) or not (n=49). Experimental and control groups were well balanced for disease and prognostic features. Zoledronic acid did not show an antitumor effect according to changes in M-component. However, there were fewer symptomatic progressions in the experimental group than in the control group (34 versus 41, respectively; P=0.05) resulting in a median time to symptoms of 16 versus 10 months (P=0.161). The median time to next therapy was also slightly longer for the treated group than the untreated, control group (13.4 versus 10.1 months), although the difference was not statistically significant (P=0.360). The pattern of relapses was different for treated versus control patients: progressive bone disease (8 versus 20), anemia (24 versus 18), renal dysfunction (1 versus 2), and plasmacytomas (1 versus 1, respectively). This concurred with fewer skeletal-related events in the treated group than in the control group (2 versus 14), with a projected 4-year event proportion of 6% versus 40% (P<0.001). In summary, zoledronic acid monotherapy does not show an antitumor effect on biochemical relapses in multiple myeloma, but does reduce the risk of progression with symptomatic bone disease and skeletal complications. This trial was registered in the ClinicalTrials.gov database with code NCT01087008 PMID:26069291

  6. High-dose therapy and autologous bone marrow transplantation for Hodgkin's disease patients with relapses potentially treatable by radical radiation therapy

    International Nuclear Information System (INIS)

    Pezner, Richard D.; Nademanee, Auayporn; Forman, Stephen J.

    1995-01-01

    Purpose: A retrospective review evaluated the results of autologous bone marrow transplantation (A-BMT) for patients with relapsed Hodgkin's disease (HD) who were potentially treatable by radical radiation therapy (RRT). Methods and Materials: Evaluated patient cases met the following criteria: initial treatment with chemotherapy (with or without involved field radiation therapy 20 Gy to spinal cord); HD at time of salvage therapy limited to lymph nodes, Waldeyer's ring, liver, spleen, direct extension sites, and/or one lung. Results: There were 23 A-BMT patients treated between 1986 and 1991 who fulfilled the criteria. Three (13%) patients died from treatment-related complications and eight (35%) developed nonfatal Grade 3-4 complications. The 3-year actuarial disease-free survival rate was 61%. The 3-year disease-free survival rate was 55% for the nine patients with at least one prior disease-free interval (DFI) > 12 months, 67% for nine patients with DFI 0.10). These results are comparable to retrospective studies of RRT results in selected relapsed HD patients. Conclusions: Long-term disease-free survival is frequently possible with either A-BMT or RRT appropriately selected relapsed HD patients. In considering treatment options, important prognostic factors include initial stage of disease, number of prior relapses, DFI, and extent of relapsed disease

  7. Relapse outcomes, safety, and treatment patterns in patients diagnosed with relapsing-remitting multiple sclerosis and initiated on subcutaneous interferon β-1a or dimethyl fumarate: a real-world study.

    Science.gov (United States)

    Ernst, Frank R; Barr, Peri; Elmor, Riad; Wong, Schiffon L

    2017-12-01

    To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) β-1a (Rebif) vs dimethyl fumarate (DMF; Tecfidera), to treat relapsing-remitting multiple sclerosis (RRMS). A US retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN β-1a (n = 143) or DMF (n = 307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN β-1a or DMF, or (b) previously treated, switching to sc IFN β-1a or DMF. Two years' follow-up data were captured. Patient characteristics, persistence, and adverse events between treatment groups were compared using t-tests or Chi-square tests. Kaplan-Meier curves with log-rank tests and Cox proportional hazards models were used to compare time to, and risk of non-persistence. Annualized Relapse Rates (ARR) were calculated using a robust variance Poisson model adjusting for covariates. Propensity scores were used to address possible selection bias. One hundred and twelve patients became non-persistent, most commonly due to an adverse event (n = 37). No difference was observed in time to overall non-persistence between sc IFN β-1a and DMF patients. Among treatment-naïve patients, those receiving DMF had 2.4-times the risk (HR = 2.439, 95% CI = 1.007-5.917, p = .0483) of experiencing a discontinuation than patients receiving sc IFN β-1a. Non-persistent patients receiving DMF had 2.3-times the risk (HR = 2.311, 95% CI = 1.350-3.958, p = .0023) of experiencing an adverse event at a given time point than patients prescribed sc IFN β-1a. No differences in relapse risk or ARR between sc IFN β-1a- and DMF-treated patients were observed. sc IFN β-1a-treated patients had comparable persistence and relapse outcomes, and better safety outcomes vs DMF-treated patients across 2 years.

  8. Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20(+) Indolent B-Cell Non-Hodgkin Lymphoma

    DEFF Research Database (Denmark)

    Sehn, L. H.; Goy, A.; Offner, F. C.

    2015-01-01

    Purpose Obinutuzumab (GA101), a novel glycoengineered type II anti-CD20 monoclonal antibody, demonstrated responses in single-arm studies of patients with relapsed/refractory non-Hodgkin lymphoma. This is the first prospective, randomized study comparing safety and efficacy of obinutuzumab...... with rituximab in relapsed indolent lymphoma. The primary end point of this study was the overall response rate (ORR) in patients with follicular lymphoma after induction and safety in patients with indolent lymphoma. Patients and Methods A total of 175 patients with relapsed CD20(+) indolent lymphoma requiring...... maintenance therapy every 2 months for up to 2 years. Results Among patients with follicular lymphoma (n = 149), ORR seemed higher for obinutuzumab than rituximab (44.6% v 33.3%; P = .08). This observation was also demonstrated by a blinded independent review panel that measured a higher ORR for obinutuzumab...

  9. Multiple sclerosis-associated retrovirus, Epstein-Barr virus, and vitamin D status in patients with relapsing remitting multiple sclerosis.

    Science.gov (United States)

    Mostafa, Aliehossadat; Jalilvand, Somayeh; Shoja, Zabihollah; Nejati, Ahmad; Shahmahmoodi, Shohreh; Sahraian, Mohammad Ali; Marashi, Sayed Mahdi

    2017-07-01

    The relationship between infections and autoimmune diseases is complex and there are several reports highlighting the role of human endogenous retroviruses (HERVs) in these patients. The levels of multiple sclerosis-associated retrovirus (MSRV)-type DNA of Env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (RRMS) and 40 healthy controls using specific quantitative PCR (qPCR) analysis. Furthermore, we analyzed the status of HERV-W/MSRV in these patients with regards to both EBV (DNA load and anti-EBNA1 IgG antibody) and vitamin D concentration. MSRV DNA copy number were significantly higher in RRMS patients than healthy controls (P < 0.0001). Interestingly, an inverse correlation was found between MSRV DNA copy number and serum vitamin D concentration (P < 0.01), but not for EBV load or anti-EBNA-1 IgG antibody. © 2017 Wiley Periodicals, Inc.

  10. Classical Hodgkin's lymphoma: the Lymphoma Study Association guidelines for relapsed and refractory adult patients eligible for transplant.

    Science.gov (United States)

    Van Den Neste, Eric; Casasnovas, Olivier; André, Marc; Touati, Mohamed; Senecal, Delphine; Edeline, Véronique; Stamatoullas, Aspasia; Fornecker, Luc; Deau, Bénédicte; Gastinne, Thomas; Reman, Oumédaly; Gaillard, Isabelle; Borel, Cécile; Brice, Pauline; Fermé, Christophe

    2013-08-01

    The Hodgkin's Lymphoma Committee of the Lymphoma Study Association (LYSA) gathered in 2012 to prepare guidelines on the management of transplant-eligible patients with relapsing or refractory Hodgkin's lymphoma. The working group is made up of a multidisciplinary panel of experts with a significant background in Hodgkin's lymphoma. Each member of the panel of experts provided an interpretation of the evidence and a systematic approach to obtain consensus was used. Grades of recommendation were not required since levels of evidence are mainly based on phase II trials or standard practice. Data arising from randomized trials are emphasized. The final version was endorsed by the scientific council of the LYSA. The expert panel recommends a risk-adapted strategy (conventional treatment, or single/double transplantation and/or radiotherapy) based on three risk factors at progression (primary refractory disease, remission duration < 1 year, stage III/IV), and an early evaluation of salvage chemosensitivity, including (18)fluorodeoxy glucose-positron emission tomography interpreted according to the Deauville scoring system. Most relapsed or refractory Hodgkin's lymphoma patients chemosensitive to salvage should receive high-dose therapy and autologous stem-cell transplantation as standard. Efforts should be made to increase the proportion of chemosensitive patients by alternating non-cross-resistant chemotherapy lines or exploring the role of novel drugs.

  11. Estimated medical cost reductions for paliperidone palmitate vs placebo in a randomized, double-blind relapse-prevention trial of patients with schizoaffective disorder.

    Science.gov (United States)

    Joshi, K; Lin, J; Lingohr-Smith, M; Fu, D J

    2015-01-01

    The objective of this economic model was to estimate the difference in medical costs among patients treated with paliperidone palmitate once-monthly injectable antipsychotic (PP1M) vs placebo, based on clinical event rates reported in the 15-month randomized, double-blind, placebo-controlled, parallel-group study of paliperidone palmitate evaluating time to relapse in subjects with schizoaffective disorder. Rates of psychotic, depressive, and/or manic relapses and serious and non-serious treatment-emergent adverse events (TEAEs) were obtained from the long-term paliperidone palmitate vs placebo relapse prevention study. The total annual medical cost for a relapse from a US payer perspective was obtained from published literature and the costs for serious and non-serious TEAEs were based on Common Procedure Terminology codes. Total annual medical cost differences for patients treated with PP1M vs placebo were then estimated. Additionally, one-way and Monte Carlo sensitivity analyses were conducted. Lower rates of relapse (-18.3%) and serious TEAEs (-3.9%) were associated with use of PP1M vs placebo as reported in the long-term paliperidone palmitate vs placebo relapse prevention study. As a result of the reduction in these clinical event rates, the total annual medical cost was reduced by $7140 per patient treated with PP1M vs placebo. One-way sensitivity analysis showed that variations in relapse rates had the greatest impact on the estimated medical cost differences (range: -$9786, -$4670). Of the 10,000 random cycles of Monte Carlo simulations, 100% showed a medical cost difference schizoaffective disorder was associated with a significantly lower rate of relapse and a reduction in medical costs compared to placebo. Further evaluation in the real-world setting is warranted.

  12. Pattern of occult nodal relapse diagnosed with 18F-fluoro-choline PET/CT in prostate cancer patients with biochemical failure after prostate-only radiotherapy

    International Nuclear Information System (INIS)

    Lépinoy, Alexis; Cochet, Alexandre; Cueff, Adèle; Cormier, Luc; Martin, Etienne; Maingon, Philippe; Bosset, Jean François; Brunotte, François; Créhange, Gilles

    2014-01-01

    Introduction: The purpose of this study was to describe the pattern of nodal relapse with 18 F-fluoro-choline (FCH) Positron Emission Tomography/Computerized Tomography (PET/CT) in prostate cancer patients after radiotherapy. Materials and methods: Eighty-three patients had a FCH PET/CT at time of biochemical failure. Of 65 patients with positive findings, 33 had positive nodes. This analysis included 31 patients who had undergone prior prostate-only radiotherapy with or without a prior radical prostatectomy. Each FCH positive node was assigned to a lymph node station with respect to the CTV defined by the RTOG guidelines (CTV RTOG ). 3D mapping was performed after each node was manually placed in a reference planning CT scan after automatic co-registration of the two scans based on bone anatomy. Eighteen patients (58%) underwent focal salvage FCH PET-guided stereotactic radiotherapy with no hormones. Results: Fourteen patients (45.2%) had a relapse outside the CTV RTOG . Of the 17 patients with a positive node inside the CTV RTOG , 15 had a single node (88.2%) while seven patients out of the 13 evaluable patients (53.9%) who had a relapse outside the CTV RTOG had ⩾2 positive nodes on FCH PET/CT (OR = 8.75, [95% CI: 1.38–54.80], p = 0.020). Relapses that occurred outside the CTV RTOG involved the proximal common iliac (19.3%) and lower periaortic nodes (19.3%) up to L2–L3. Conclusion: 3D mapping of nodal relapses evaluated with FCH PET/CT suggests that with IMRT the upper field limit of pelvic radiotherapy could be extended to L2–L3 safely to cover 95% of nodal stations at risk of an occult relapse

  13. Development of a Virtual Reality Coping Skills Game to Prevent Post-Hospitalization Smoking Relapse in Tobacco Dependent Cancer Patients.

    Science.gov (United States)

    Krebs, Paul; Burkhalter, Jack; Lewis, Shireen; Hendrickson, Tinesha; Chiu, Ophelia; Fearn, Paul; Perchick, Wendy; Ostroff, Jamie

    2009-08-01

    Many hospitalized smokers return to smoking after hospital discharge even though continued smoking can compromise treatment effectiveness, reduce survival, increase risk of disease recurrence, and impair quality of life. After leaving a smoke-free hospital, patients encounter smoking cues at home, such as family members who smoke or emotional triggers such as stress, which can elicit powerful urges to smoke and lead to smoking relapse. Enabling smokers to experience such urges in a controlled setting while providing the ability to practice coping skills may be a useful strategy for building quitting self-efficacy. We are developing a virtual reality coping skills (VRCS) game to help hospitalized smokers practice coping strategies to manage these triggers in preparation for returning home after hospitalization. Our multidisciplinary team developed a prototype VRCS game using Second Life, a platform that allowed rapid construction of a virtual reality environment. The prototype contains virtual home spaces (e.g., living room, kitchen) populated with common triggers to smoke and a "toolkit" with scripted actions that enable the avatar to rehearse various coping strategies. Since eliciting and managing urges to smoke is essential to the game's utility as an intervention, we assessed the ability of the prototype virtual environment to engage former smokers in these scenarios. We recruited eight former smokers with a recent history of hospitalization and guided each through a VRCS scenario during which we asked the patient to evaluate the strength of smoking urges and usefulness of coping strategies. Initial data indicate that patients report high urges to smoke (mean = 8.8 on a 10 point scale) when their avatar confronted virtual triggers such as drinking coffee. Patients rated virtual practice of coping strategies, such as drinking water or watching TV, as very helpful (mean = 8.4 on a 10 point scale) in reducing these urges. With further development, this VRCS game

  14. A randomized controlled trial to compare cure and relapse rate of paucibacillary multidrug therapy with monthly rifampicin, ofloxacin, and minocycline among paucibacillary leprosy patients in Agra District, India

    Directory of Open Access Journals (Sweden)

    Anil Kumar

    2015-01-01

    Full Text Available Objectives: To study cure rate and relapse rate of standard World Health Organization paucibacillary multidrug therapy (PB-MDT with monthly rifampicin, ofloxacin, and minocycline for six months (ROM-6 among paucibacillary leprosy patients. Methods: A total of 268 patients, detected during active search in Agra district during 2001-2004, who had paucibacillary (PB leprosy having 1-5 skin lesions and/or one nerve thickening/tenderness, were allocated, using random number tables, to two treatment groups; PB-MDT and ROM-6. On the first day of the month, dose of PB-MDT and of the ROM were given under supervision for 6 months. After completion of drug therapy, patients were followed every 6 months for first 5 years and later annually for next 3 years for monitoring disease status, cure rates, reactions and relapses. Cηi σθuαρε test was used to compare relapse rates. Results: The cure rate at 2 years was 99% in ROM-6 and 97.0% in PB-MDT group, of those who completed treatment and the difference was statistically not significant. At 5 years, only 88 patients in PB-MDT group and 90 patients in ROM-6 group could be followed; all were observed to be cured. However, during the period of 5-8 years, 3 of 67 patients in PB-MDT group and 1 of 73 in ROM-6 group were observed to have relapsed. In all, 10 relapses were noted (3 in ROM-6 and 7 in PB-MDT group giving a relapse rate of 1.10/100 person years in PB-MDT and 0.435/100 person years in ROM groups (P = 0.053 ; statistically not significant. Of the 10 relapses, 5 occurred within 5 years (3 in PB-MDT group and 2 in ROM-6, 4 during 5-8 years (3 in PB-MDT and 1 in ROM-6, and 1 occurred in MDT group after 8 years. Limitation: A number of patients were lost to follow up after release from treatment and thus actual number of relapses in the study could not be assessed. Additionally, diagnosis was purely clinical and histology could not be done for reasons related to functional difficulties in the field

  15. PD-1hiTIM-3+ T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation

    International Nuclear Information System (INIS)

    Kong, Y; Zhang, J; Claxton, D F; Ehmann, W C; Rybka, W B; Zhu, L; Zeng, H; Schell, T D; Zheng, H

    2015-01-01

    Prognosis of leukemia relapse post allogeneic stem cell transplantation (alloSCT) is poor and effective new treatments are urgently needed. T cells are pivotal in eradicating leukemia through a graft versus leukemia (GVL) effect and leukemia relapse is considered a failure of GVL. T-cell exhaustion is a state of T-cell dysfunction mediated by inhibitory molecules including programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3). To evaluate whether T-cell exhaustion and inhibitory pathways are involved in leukemia relapse post alloSCT, we performed phenotypic and functional studies on T cells from peripheral blood of acute myeloid leukemia patients receiving alloSCT. Here we report that PD-1 hi TIM-3 + cells are strongly associated with leukemia relapse post transplantation. Consistent with exhaustion, PD-1 hi TIM-3 + T cells are functionally deficient manifested by reduced production of interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). In addition, these cells demonstrate a phenotype consistent with exhausted antigen-experienced T cells by losing T N and T EMRA subsets. Importantly, increase of PD-1 hi TIM-3 + cells occurs before clinical diagnosis of leukemia relapse, suggesting their predictive value. Results of our study provide an early diagnostic approach and a therapeutic target for leukemia relapse post transplantation

  16. Efficacy and safety of bortezomib-based retreatment at the first relapse in multiple myeloma patients: A retrospective study.

    Science.gov (United States)

    Oriol, Albert; Giraldo, Pilar; Kotsianidis, Ioannis; Couturier, Catherine; Olie, Robert; Angermund, Ralf; Corso, Alessandro

    2015-08-01

    Multiple myeloma remains incurable and retreatment with available therapies is of substantial interest. This retrospective observational study included data from 35 patients treated initially and at the first relapse with bortezomib-containing regimens. Bortezomib retreatment provided a similar depth and time to response as first-line therapy; however, as could be expected, the duration of response was shorter with retreatment. The tolerability profile was similar with bortezomib as the first- and second-line therapy, with no evidence of cumulative toxicity. These findings support bortezomib retreatment after a treatment-free interval of ≥6 months in patients who achieved at least a partial response to the first-line bortezomib-based therapy.

  17. Effectiveness of Relapse Prevention Cognitive-Behavioral Model in Opioid-Dependent Patients Participating in the Methadone Maintenance Treatment in Iran.

    Science.gov (United States)

    Pashaei, Tahereh; Shojaeizadeh, Davoud; Rahimi Foroushani, Abbas; Ghazitabatabae, Mahmoud; Moeeni, Maryam; Rajati, Fatemeh; M Razzaghi, Emran

    2013-08-01

    To evaluate the effectiveness of a relapse prevention cognitive-behavioral model, based on Marlatt treatment approach, in Opioid-dependent patients participating in the Methadone Maintenance Treatment (MMT) in Iran. The study consisted of 92 individuals treated with methadone in Iranian National Center of Addiction Studies (INCAS). Participants were randomized into two groups: educational intervention group (N=46) and control group (N=46). The intervention was comprised of 10 weekly 90 minute sessions, done during a period of 2.5 months based on the most high risk situations determined using Inventory Drug Taking Situation instrument. Relapse was defined as not showing up for MMT, drug use for at least 5 continuous days, and a positive urinary morphine test. While, only 36.4% of the intervention group relapsed into drug use, 63.6% of the control group relapsed. The result of the logistic regressions showed that the odd ratio of the variable of intervention program for the entire follow up period was 0.43 (P<0.01). Further, the odd ratio of this variable in one month, three months, and 195 days after the therapy were 0.48 (P<.03), 0.31 (P<.02), and 0.13 (P<.02) respectively that revealed that on average, the probability of relapse among individuals in the intervention group was lower than patients in control group. Relapse prevention model based on Marlatt treatment approach has an effective role in decreasing relapse rate. This model can be introduced as a complementary therapy in patients treated with methadone maintenance.

  18. Rates and Durability of Response to Salvage Radiation Therapy Among Patients With Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma

    International Nuclear Information System (INIS)

    Tseng, Yolanda D.; Chen, Yu-Hui; Catalano, Paul J.; Ng, Andrea

    2015-01-01

    Purpose: To evaluate the response rate (RR) and time to local recurrence (TTLR) among patients who received salvage radiation therapy for relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) and investigate whether RR and TTLR differed according to disease characteristics. Methods and Materials: A retrospective review was performed for all patients who completed a course of salvage radiation therapy between January 2001 and May 2011 at Brigham and Women's Hospital/Dana-Farber Cancer Institute. Separate analyses were conducted for patients treated with palliative and curative intent. Predictors of RR for each subgroup were assessed using a generalized estimating equation model. For patients treated with curative intent, local control (LC) and progression-free survival were estimated with the Kaplan-Meier method; predictors for TTLR were evaluated using a Cox proportional hazards regression model. Results: Salvage radiation therapy was used to treat 110 patients to 121 sites (76 curative, 45 palliative). Salvage radiation therapy was given as part of consolidation in 18% of patients treated with curative intent. Median dose was 37.8 Gy, with 58% and 36% of curative and palliative patients, respectively, receiving 39.6 Gy or higher. The RR was high (86% curative, 84% palliative). With a median follow-up of 4.8 years among living patients, 5-year LC and progression-free survival for curative patients were 66% and 34%, respectively. Refractory disease (hazard ratio 3.3; P=.024) and lack of response to initial chemotherapy (hazard ratio 4.3; P=.007) but not dose (P=.93) were associated with shorter TTLR. Despite doses of 39.6 Gy or higher, 2-year LC was only 61% for definitive patients with refractory disease or disease that did not respond to initial chemotherapy. Conclusions: Relapsed or refractory aggressive NHL is responsive to salvage radiation therapy, and durable LC can be achieved in some cases. However, refractory disease is associated with a

  19. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Coiffier, Bertrand; Lepretre, Stéphane; Pedersen, Lars Møller

    2008-01-01

    Safety and efficacy of the fully human anti-CD20 monoclonal antibody, ofatumumab, was analyzed in a multicenter dose-escalating study including 33 patients with relapsed or refractory chronic lymphocytic leukemia. Three cohorts of 3 (A), 3 (B), and 27 (C) patients received 4, once weekly, infusio...

  20. Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Shirani, Afsaneh; Zhao, Yinshan; Karim, Mohammad Ehsanul; Evans, Charity; Kingwell, Elaine; van der Kop, Mia L; Oger, Joel; Gustafson, Paul; Petkau, John; Tremlett, Helen

    2012-07-18

    Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0

  1. Effects of needs-assessment-based psycho-education of schizophrenic patients' families on the severity of symptoms and relapse rate of patients.

    Science.gov (United States)

    Kheirabadi, Gholam Reza; Rafizadeh, Mahnaz; Omranifard, Victoria; Yari, Azam; Maracy, Mohammad Reza; Mehrabi, Tayebe; Sadri, Sima

    2014-11-01

    Family psycho-education is one of the most effective interventions for preventing relapse in patients with schizophrenia. We evaluated the efficacy of a needs-assessment-based educational program in comparison with a current program (textbook based) in the treatment of schizophrenia. Patients with schizophrenia and their families (N = 60) were allocated to needs-assessment-based education (treatment) and textbook-based (control) programs; both included 10 sessions of education within about 6 months. Symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS) prior to intervention and every 3 months for a total of 18 months. A 25% decrease or increase in total PANSS score was considered as response or relapse, respectively. Forty-two cases completed the study. The total PANSS score was significantly decreased in both groups with more reduction in the treatment group. Positive and negative scale scores were reduced in the treatment group, but not significantly in the control group. Response rate was higher in the treatment group and relapse rate was lower (15% vs. 27.2%, P = 0.279). In logistic regression analysis, needs-assessment-based psycho-education was associated with more treatment response. Needs-assessment-based psycho-education is more effective than textbook-based education for treating schizophrenia. We recommend psychiatric care centers to conduct needs-assessment and develop their own program for family psycho-education.

  2. Prognostic analysis of patients with epilepsy according to time of relapse after withdrawal of antiepileptic drugs following four seizure-free years.

    Science.gov (United States)

    Park, Soochul; Lee, Dong Hyun; Kim, Seung Woo; Roh, Yun Ho

    2017-01-01

    We performed a retrospective, prognostic analysis of a cohort of patients with epilepsy according to time of relapse after four seizure-free years. Planned withdrawal of antiepileptic drugs (AEDs) and at least 3 years of follow-up after AED discontinuation were performed. The following two groups were assessed: (1) an early relapse (ER) group of patients who experienced recurrence during AED withdrawal and (2) a late relapse (LR) group of patients who experienced recurrence after completion of the AED discontinuation process. After dichotomization, the relapse rate, prognostic factors, and their impacts for each group were compared with those of a group of patients who continued to be seizure-free after AED withdrawal (SF group) using multiple logistic regression analysis. The AED intake mode was also analyzed. Two hundred seventeen (64.6%) of the 336 total patients experienced relapse. One hundred thirty-nine patients (41.4%) and 78 patients (23.2%) were included in the LR and ER groups, respectively. Symptom duration >120 months showed the strongest negative prognostic impact as demonstrated by the 4.7-fold higher risk of recurrence in the ER group compared with the SF group. Additional factors with a negative prognostic impact included an age at epilepsy onset of ≤20 years and the presence of localization-related epilepsy. No reliable predictor between the SF and LR groups was revealed. After exclusion of the SF group, post hoc analysis according to age at epilepsy onset and symptom duration showed that the above-mentioned negative prognostic factors significantly affected the relapse patterns of the LR and ER groups. The results suggest that longer symptom duration, which could be associated with intrinsic reactivation of epilepsy, is the strongest negative prognostic factor for relapse. Relapse after AED withdrawal in prolonged follow-up of seizure-free patients is one aspect of the natural history of epilepsy. © 2016 The Authors. Epilepsia published by

  3. Cost analysis of glatiramer acetate versus interferon-β for relapsing-remitting multiple sclerosis in patients with spasticity: the Escala study.

    Science.gov (United States)

    Sánchez-de la Rosa, Rainel; García-Bujalance, Laura; Meca-Lallana, José

    2015-12-01

    The Escala Study evidenced that the administration of glatiramer acetate for relapsing-remitting multiple sclerosis improved the spasticity of patients previously treated with interferon-β. However, whether such an improvement was translated into cost savings remained unclear. We therefore conducted a cost analysis of glatiramer acetate versus interferon-β in these patients with multiple sclerosis and spasticity. This cost analysis encompassed data from the observational Escala Study, which included patients with relapsing-remitting multiple sclerosis and spasticity whose treatment had been switched from interferon-β to glatiramer acetate. Costs prior to starting glatiramer acetate (interferon-β period) were compared to the subsequent six months on glatiramer acetate (glatiramer acetate period). The analysis was carried out following the recommendations for conducting pharmacoeconomic studies and from the Spanish National Health System perspective. Costs associated with multiple sclerosis treatment, spasticity treatment and relapse management were expressed in 2014 euros (€); a 7.5 % discount was applied-when needed-as stipulated in Spanish law. The management of relapsing-remitting multiple sclerosis, spasticity and relapses accounted for a 6-month cost per patient of 7,078.02€ when using interferon-β and 4,671.31€ when using glatiramer acetate. Switching from interferon-β to glatiramer acetate therefore represented a cost saving of 2,406.72€ per patient in favour of glatiramer acetate, which resulted from savings in treatment costs, relapse management and spasticity treatment of 1,890.02€, 430.48€ and 86.21€, respectively. The ratio of the costs during interferon-β was 1.5 times the costs during glatiramer acetate; thus, a fixed budget of 5,000,000€ would enable 1,070 patients to be treated with glatiramer acetate and only 706 patients with interferon-β. The treatment of relapsing-remitting multiple sclerosis with glatiramer acetate

  4. Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study.

    Science.gov (United States)

    Giovannoni, Gavin; Soelberg Sorensen, Per; Cook, Stuart; Rammohan, Kottil W; Rieckmann, Peter; Comi, Giancarlo; Dangond, Fernando; Hicking, Christine; Vermersch, Patrick

    2018-04-01

    In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis. Describe two clinically relevant definitions for patients with high disease activity (HDA) at baseline of the CLARITY study (utility verified in patients receiving placebo) and assess the treatment effects of Cladribine Tablets 3.5 mg/kg compared with the overall study population. Outcomes of patients randomised to Cladribine Tablets 3.5 mg/kg or placebo were analysed for subgroups using HDA definitions based on high relapse activity (HRA; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not) or HRA plus disease activity on treatment (HRA + DAT; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not, PLUS patients with ⩾1 relapse during the year prior to study entry while on therapy with other DMDs and ⩾1 T1 Gd+ or ⩾9 T2 lesions). In the overall population, Cladribine Tablets 3.5 mg/kg reduced the risk of 6-month-confirmed Expanded Disability Status Scale (EDSS) worsening by 47% vs placebo. A risk reduction of 82% vs placebo was seen in both the HRA and HRA + DAT subgroups (vs 19% for non-HRA and 18% for non-HRA + DAT), indicating greater responsiveness to Cladribine Tablets 3.5 mg/kg in patients with HDA. There were consistent results for other efficacy endpoints. The safety profile in HDA patients was consistent with the overall CLARITY population. Patients with HDA showed clinical and MRI responses to Cladribine Tablets 3.5 mg/kg that were generally better than, or at least comparable with, the outcomes seen in the overall CLARITY population.

  5. QualiCOP: real-world effectiveness, tolerability, and quality of life in patients with relapsing-remitting multiple sclerosis treated with glatiramer acetate, treatment-naïve patients, and previously treated patients.

    Science.gov (United States)

    Ziemssen, Tjalf; Calabrese, Pasquale; Penner, Iris-Katharina; Apfel, Rainer

    2016-04-01

    Treatment of symptoms and signs beyond the expanded disability status scale remains a major target in multiple sclerosis. QualiCOP was an observational, non-interventional, open-label study conducted at 170 sites in Germany. Of the 754 enrolled patients, 96 % had relapsing-remitting multiple sclerosis (MS) and were either disease-modifying therapy naïve (de novo, n = 481) or previously treated (n = 237) with once-daily, subcutaneous 20-mg/mL glatiramer acetate (GA). Assessments of relapse rate, disease progression, overall functioning, quality of life (QoL), cognition, fatigue, and depression were performed over 24 months. GA treatment over 24 months was associated with reduced annual relapse rate for previously treated (from 0.98 to 0.54 relapses) and de novo (from 0.81 to 0.48 relapses) patients. Multiple Sclerosis Functional Composite scores showed slight improvement in both cohorts (all p Multiple Sclerosis Inventory Cognition scale scores showed robust improvement in cognition among previously treated and de novo cohorts (all p treatment in important QoL parameters beyond standard measures of relapse and disease severity.

  6. Lack of CD4+ T cell percent decrease in alemtuzumab-treated multiple sclerosis patients with persistent relapses.

    Science.gov (United States)

    Rolla, Simona; De Mercanti, Stefania Federica; Bardina, Valentina; Horakova, Dana; Habek, Mario; Adamec, Ivan; Cocco, Eleonora; Annovazzi, Pietro; Vladic, Anton; Novelli, Francesco; Durelli, Luca; Clerico, Marinella

    2017-12-15

    Alemtuzumab, a highly effective treatment for relapsing remitting multiple sclerosis (RRMS), induces lymphopenia especially of CD4+ T cells. Here, we report the atypical CD4+ T population behaviour of two patients with persistent disease activity despite repeated alemtuzumab treatments. Whereas lymphocytes count decreased and fluctuated accordingly to alemtuzumab administration, their CD4+ cell percentage was not or just mildly affected and was slightly below the lowest normal limit already before alemtuzumab. These cases anticipate further studies aimed to investigate whether the evaluation of the CD4+ cell percentage could represent a helpful tool to address the individual clinical response to alemtuzumab. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Gemcitabine, dexamethasone, and cisplatin (GDP) as salvage chemotherapy for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified.

    Science.gov (United States)

    Qi, Fei; Dong, Mei; He, Xiaohui; Li, Yexiong; Wang, Weihu; Liu, Peng; Yang, Jianliang; Gui, Lin; Zhang, Changgong; Yang, Sheng; Zhou, Shengyu; Shi, Yuankai

    2017-02-01

    Standard therapeutic options for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) remain unclear. There are few large cohort studies specifically focused on gemcitabine-based chemotherapy for PTCL-NOS. We retrospectively reviewed patients with relapsed or refractory PTCL-NOS who received salvage GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, from May 2008 to August 2014. Twenty-five patients were enrolled and analyzed. The median number of cycles of GDP chemotherapy per patient was four (range, 2-8 cycles). Overall response rate was 64.0% (16/25) with five achieved complete remission or complete remission unconfirmed. After a median follow-up of 9 months, median overall survival (OS) and progression-free survival after relapse or progression (second-PFS) were 9.3 and 5.4 months. One-year PFS rate and 1-year OS rate were 27.4% and 43.9%, respectively. Median second-PFS was significantly longer in patients sensitive to GDP than the ones resistant to the treatment (10.3 vs. 2.8 months, p GDP including neutropenia (8/25), thrombocytopenia (5/25), and anemia (4/25). Taken together, our study suggests that GDP is an effective and optional salvage regimen for relapsed or refractory PTCL-NOS.

  8. Leishmania Antigenuria to Predict Initial Treatment Failure and Relapse in Visceral Leishmaniasis/HIV Coinfected Patients: An Exploratory Study Nested Within a Clinical Trial in Ethiopia.

    Science.gov (United States)

    van Griensven, Johan; Mengesha, Bewketu; Mekonnen, Tigist; Fikre, Helina; Takele, Yegnasew; Adem, Emebet; Mohammed, Rezika; Ritmeijer, Koert; Vogt, Florian; Adriaensen, Wim; Diro, Ermias

    2018-01-01

    Background: Biomarkers predicting the risk of VL treatment failure and relapse in VL/HIV coinfected patients are needed. Nested within a two-site clinical trial in Ethiopia (2011-2015), we conducted an exploratory study to assess whether (1) levels of Leishmania antigenuria measured at VL diagnosis were associated with initial treatment failure and (2) levels of Leishmania antigenuria at the end of treatment (parasitologically-confirmed cure) were associated with subsequent relapse. Methods: Leishmania antigenuria at VL diagnosis and cure was determined using KAtex urine antigen test and graded as negative (0), weak/moderate (grade 1+/2+) or strongly-positive (3+). Logistic regression and Kaplan-Meier methods were used to assess the association between antigenuria and (1) initial treatment failure, and (2) relapse over the 12 months after cure, respectively. Results: The analysis to predict initial treatment failure included sixty-three coinfected adults [median age: 30 years interquartile range (IQR) 27-35], median CD4 count: 56 cells/μL (IQR 38-113). KAtex results at VL diagnosis were negative in 11 (17%), weak/moderate in 17 (27%) and strongly-positive in 35 (36%). Twenty (32%) patients had parasitologically-confirmed treatment failure, with a risk of failure of 9% (1/11) with KAtex-negative results, 0% (0/17) for KAtex 1+/2+ and 54% (19/35) for KAtex 3+ results. Compared to KAtex-negative patients, KAtex 3+ patients were at increased risk of treatment failure [odds ratio 11.9 (95% CI 1.4-103.0); P : 0.025]. Forty-four patients were included in the analysis to predict relapse [median age: 31 years (IQR 28-35), median CD4 count: 116 cells/μL (IQR 95-181)]. When achieving VL cure, KAtex results were negative in 19 (43%), weak/moderate (1+/2+) in 10 (23%), and strongly positive (3+) in 15 patients (34%). Over the subsequent 12 months, eight out of 44 patients (18%) relapsed. The predicted 1-year relapse risk was 6% for KAtex-negative results, 14% for KAtex 1

  9. Visceral leishmaniasis relapse hazard is linked to reduced miltefosine exposure in patients from Eastern Africa: a population pharmacokinetic/pharmacodynamic study.

    Science.gov (United States)

    Dorlo, Thomas P C; Kip, Anke E; Younis, Brima M; Ellis, Sally J; Alves, Fabiana; Beijnen, Jos H; Njenga, Simon; Kirigi, George; Hailu, Asrat; Olobo, Joseph; Musa, Ahmed M; Balasegaram, Manica; Wasunna, Monique; Karlsson, Mats O; Khalil, Eltahir A G

    2017-11-01

    Low efficacy of miltefosine in the treatment of visceral leishmaniasis was recently observed in Eastern Africa. To describe the pharmacokinetics and establish a pharmacokinetic/pharmacodynamic relationship for miltefosine in Eastern African patients with visceral leishmaniasis, using a time-to-event approach to model relapse of disease. Miltefosine plasma concentrations from 95 patients (48 monotherapy versus 47 combination therapy) were included in the population pharmacokinetic model using non-linear mixed effects modelling. Subsequently a time-to-event model was developed to model the time of clinical relapse. Various summary pharmacokinetic parameters (various AUCs, Time > EC50, Time > EC90), normalized within each treatment arm to allow simultaneous analysis, were evaluated as relapse hazard-changing covariates. A two-compartment population model with first-order absorption fitted the miltefosine pharmacokinetic data adequately. Relative bioavailability was reduced (-74%, relative standard error 4.7%) during the first week of treatment of the monotherapy arm but only the first day of the shorter combination regimen. Time to the relapse of infection could be described using a constant baseline hazard (baseline 1.8 relapses/year, relative standard error 72.7%). Miltefosine Time > EC90 improved the model significantly when added in a maximum effect function on the baseline hazard (half maximal effect with Time > EC90 6.97 days for monotherapy). Miltefosine drug exposure was found to be decreased in Eastern African patients with visceral leishmaniasis, due to a (transient) initial lower bioavailability. Relapse hazard was inversely linked to miltefosine exposure. Significantly lower miltefosine exposure was observed in children compared with adults, further urging the need for implementation of dose adaptations for children. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  10. Ibrutinib versus previous standard of care: an adjusted comparison in patients with relapsed/refractory chronic lymphocytic leukaemia.

    Science.gov (United States)

    Hansson, Lotta; Asklid, Anna; Diels, Joris; Eketorp-Sylvan, Sandra; Repits, Johanna; Søltoft, Frans; Jäger, Ulrich; Österborg, Anders

    2017-10-01

    This study explored the relative efficacy of ibrutinib versus previous standard-of-care treatments in relapsed/refractory patients with chronic lymphocytic leukaemia (CLL), using multivariate regression modelling to adjust for baseline prognostic factors. Individual patient data were collected from an observational Stockholm cohort of consecutive patients (n = 144) diagnosed with CLL between 2002 and 2013 who had received at least second-line treatment. Data were compared with results of the RESONATE clinical trial. A multivariate Cox proportional hazards regression model was used which estimated the hazard ratio (HR) of ibrutinib versus previous standard of care. The adjusted HR of ibrutinib versus the previous standard-of-care cohort was 0.15 (p ibrutinib in the RESONATE study were significantly longer than with previous standard-of-care regimens used in second or later lines in routine healthcare. The approach used, which must be interpreted with caution, compares patient-level data from a clinical trial with outcomes observed in a daily clinical practice and may complement results from randomised trials or provide preliminary wider comparative information until phase 3 data exist.

  11. Survival and breast relapse in 3834 patients with T1-T2 breast cancer after conserving surgery and adjuvant treatment

    International Nuclear Information System (INIS)

    Livi, Lorenzo; Paiar, Fabiola; Saieva, Calogero; Scoccianti, Silvia; Dicosmo, Dora; Borghesi, Simona; Agresti, Benedetta; Nosi, Fabiano; Orzalesi, Lorenzo; Santini, Roberto; Barca, Raffaella; Biti, Giampaolo P.

    2007-01-01

    Purpose: The aim of the present analysis is to determine the long-term results in terms of breast relapse and specific survival in patients treated with conserving surgery and adjuvant treatment for early breast cancer. Methods: From January 1980 to December 2001, 3834 patients with pT1-T2 breast cancer were treated consecutively at the University of Florence. The median age of the patient population was 55 years (range 30-80). All patients were followed for a median of 7.4 years (range 0.6 year to 22.5 years). The crude probability of survival (or local recurrence) was estimated by using Kaplan-Meier method, and survival (or local recurrence) comparisons were carried out using Cox proportional hazard regression models. Results: The Cox regression model by stepwise selection showed some parameters, such as chemotherapy (HR 1.53; CI 1.19-1.95), pT status (HR 1.62, CI 1.31-2.01), positive axillary lymph nodes (HR 1.92, CI 1.66-2.22), and local recurrence (HR 4.58; CI 3.66-5.73), as independent prognostic factors for breast cancer death. Moreover, we found lower rate survival among patients treated before 1991 in comparison to women treated after 1991 (p = 0.0001) probably due to inadequate treatment. For local disease free survival, age at presentation (HR 0.47; CI 0.35-0.63), use of tamoxifen (HR 0.42; CI 0.25-0.71), surgical margins (HR 2.00; CI 1.21-3.30), and chemotherapy (HR 0.53; CI 0.31-0.91) emerged by multivariate analyses as significant breast relapse predictors. Conclusion: In our experience breast conserving surgery followed by adjuvant radiotherapy treatment gives high rates of local control in women with early breast cancer. The use of routinely adjuvant chemotherapy and hormone therapy lowered the local recurrence and probably the modification of therapeutic approach in the last decades also improved the specific survival

  12. Development and Pilot Evaluation of an Online Relapse-Prevention Program Based on Acceptance and Commitment Therapy for Chronic Pain Patients

    NARCIS (Netherlands)

    Fledderus, M.; Schreurs, Karlein Maria Gertrudis; Bohlmeijer, Ernst Thomas; Vollenbroek-Hutten, Miriam Marie Rosé

    2015-01-01

    Background: A significant number of chronic pain patients experience a decline in therapeutic effects after rehabilitation. As face-to-face contacts with health care professionals are not always feasible after treatment, new, innovative, fully automated relapse-prevention programs are highly needed.

  13. Accelerated Total Lymphoid Irradiation-containing Salvage Regimen for Patients With Refractory and Relapsed Hodgkin Lymphoma: 20 Years of Experience

    Energy Technology Data Exchange (ETDEWEB)

    Rimner, Andreas; Lovie, Shona [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Hsu, Meier [Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Chelius, Monica [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Chau, Karen [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Moskowitz, Alison J.; Matasar, Matthew; Moskowitz, Craig H. [Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Yahalom, Joachim, E-mail: yahalomj@mskcc.org [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States)

    2017-04-01

    Purpose: We report the long-term results of integrated accelerated involved field radiation therapy (IFRT) followed by total lymphoid irradiation (TLI) as part of the high-dose salvage regimen followed by autologous bone marrow transplantation or autologous stem cell transplantation in patients with relapsed or refractory Hodgkin lymphoma (HL). Methods and Materials: From November 1985 to July 2008, 186 previously unirradiated patients with relapsed or refractory HL underwent salvage therapy on 4 consecutive institutional review board–approved protocols. All patients had biopsy-proven primary refractory or relapsed HL. After standard-dose salvage chemotherapy (SC), accelerated IFRT (18-20 Gy) was given to relapsed or refractory sites, followed by TLI (15-18 Gy) and high-dose chemotherapy. Overall survival (OS) and event-free survival (EFS) were analyzed by Cox analysis and disease-specific survival (DSS) by competing-risk regression. Results: With a median follow-up period of 57 months among survivors, 5- and 10-year OS rates were 68% and 56%, respectively; 5- and 10-year EFS rates were 62% and 56%, respectively; and 5- and 10-year cumulative incidences of HL-related deaths were 21% and 29%, respectively. On multivariate analysis, complete response to SC was independently associated with improved OS and EFS. Primary refractory disease and extranodal disease were independently associated with poor DSS. Eight patients had grade 3 or higher cardiac toxicity, with 3 deaths. Second malignancies developed in 10 patients, 5 of whom died. Conclusions: Accelerated IFRT followed by TLI and high-dose chemotherapy is an effective, feasible, and safe salvage strategy for patients with relapsed or refractory HL with excellent long-term OS, EFS, and DSS. Complete response to SC is the most important prognostic factor.

  14. Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group.

    Science.gov (United States)

    Oriol, Albert; Vives, Susana; Hernández-Rivas, Jesús-María; Tormo, Mar; Heras, Inmaculada; Rivas, Concepción; Bethencourt, Concepción; Moscardó, Federico; Bueno, Javier; Grande, Carlos; del Potro, Eloy; Guardia, Ramon; Brunet, Salut; Bergua, Juan; Bernal, Teresa; Moreno, Maria-José; Calvo, Carlota; Bastida, Pilar; Feliu, Evarist; Ribera, Josep-Maria

    2010-04-01

    About one half of adults with acute lymphoblastic leukemia are not cured of the disease and ultimately die. The objective of this study was to explore the factors influencing the outcome of adult patients with relapsed acute lymphoblastic leukemia. We analyzed the characteristics, the outcome and the prognostic factors for survival after first relapse in a series of 263 adult patients with acute lymphoblastic leukemia (excluding those with mature B-cell acute lymphoblastic leukemia) prospectively enrolled in four consecutive risk-adapted PETHEMA trials. The median overall survival after relapse was 4.5 months (95% CI, 4-5 months) with a 5-year overall survival of 10% (95% CI, 8%-12%); 45% of patients receiving intensive second-line treatment achieved a second complete remission and 22% (95% CI, 14%-30%) of them remained disease free at 5 years. Factors predicting a good outcome after rescue therapy were age less than 30 years (2-year overall survival of 21% versus 10% for those over 30 years old; P<0.022) and a first remission lasting more than 2 years (2-year overall survival of 36% versus 17% among those with a shorter first remission; P<0.001). Patients under 30 years old whose first complete remission lasted longer than 2 years had a 5-year overall survival of 38% (95% CI, 23%-53%) and a 5-year disease-free survival of 53% (95% CI, 34%-72%). The prognosis of adult patients with acute lymphoblastic leukemia who relapse is poor. Those aged less than 30 years with a first complete remission lasting longer than 2 years have reasonable possibilities of becoming long-term survivors while patients over this age or those who relapse early cannot be successfully rescued using the therapies currently available.

  15. Accelerated Total Lymphoid Irradiation-containing Salvage Regimen for Patients With Refractory and Relapsed Hodgkin Lymphoma: 20 Years of Experience

    International Nuclear Information System (INIS)

    Rimner, Andreas; Lovie, Shona; Hsu, Meier; Chelius, Monica; Zhang, Zhigang; Chau, Karen; Moskowitz, Alison J.; Matasar, Matthew; Moskowitz, Craig H.; Yahalom, Joachim

    2017-01-01

    Purpose: We report the long-term results of integrated accelerated involved field radiation therapy (IFRT) followed by total lymphoid irradiation (TLI) as part of the high-dose salvage regimen followed by autologous bone marrow transplantation or autologous stem cell transplantation in patients with relapsed or refractory Hodgkin lymphoma (HL). Methods and Materials: From November 1985 to July 2008, 186 previously unirradiated patients with relapsed or refractory HL underwent salvage therapy on 4 consecutive institutional review board–approved protocols. All patients had biopsy-proven primary refractory or relapsed HL. After standard-dose salvage chemotherapy (SC), accelerated IFRT (18-20 Gy) was given to relapsed or refractory sites, followed by TLI (15-18 Gy) and high-dose chemotherapy. Overall survival (OS) and event-free survival (EFS) were analyzed by Cox analysis and disease-specific survival (DSS) by competing-risk regression. Results: With a median follow-up period of 57 months among survivors, 5- and 10-year OS rates were 68% and 56%, respectively; 5- and 10-year EFS rates were 62% and 56%, respectively; and 5- and 10-year cumulative incidences of HL-related deaths were 21% and 29%, respectively. On multivariate analysis, complete response to SC was independently associated with improved OS and EFS. Primary refractory disease and extranodal disease were independently associated with poor DSS. Eight patients had grade 3 or higher cardiac toxicity, with 3 deaths. Second malignancies developed in 10 patients, 5 of whom died. Conclusions: Accelerated IFRT followed by TLI and high-dose chemotherapy is an effective, feasible, and safe salvage strategy for patients with relapsed or refractory HL with excellent long-term OS, EFS, and DSS. Complete response to SC is the most important prognostic factor.

  16. Being 40 or younger is an independent risk factor for relapse in operable breast cancer patients: The Saudi Arabia experience

    International Nuclear Information System (INIS)

    Elkum, Naser; Al-Tweigeri, Taher; Dermime, Said; Ajarim, Dahish; Al-Zahrani, Ali; Alsayed, Adher; Tulbah, Asma; Al Malik, Osama; Alshabanah, Mohamed; Ezzat, Adnan

    2007-01-01

    Breast cancer in young Saudi women is a crucial problem. According to the 2002 annual report of Saudi National Cancer Registry, breast cancers that developed before the age of 40 comprise 26.4% of all female breast cancers comparing to 6.5% in the USA. Breast cancer in young patients is often associated with a poorer prognosis, but there has been a scarcity of published data in the Middle East population. Total of 867 breast cancer patients seen at King Faisal Specialist Hospital & Research Centre (KFSH&RC) between 1986 and 2002 were reviewed. Patients were divided in two age groups: ≤ 40 years and above 40 years. The clinicopathological characteristics and treatment outcomes were compared between younger and older age groups. Median age at presentation was 45 years. A total of 288 (33.2%) patients were aged ≤ 40 years. Hormone receptors were positive in 69% of patients 40 and 78.2% of patients above 40 (p = 0.009). There was a significantly higher incidence of grade III tumor in younger patients compared to older patients (p = 0.0006). Stage, tumor size, lymphatic/vascular invasion, number of nodes and axillary lymph node status, did not differ significantly between the two age groups. Younger patients had a greater probability of recurrence at all time periods (p = 0.035). Young age had a negative impact on survival of patients with positive axillary lymph nodes (p = 0.030) but not on survival of patients with negative lymph nodes (p = 0.695). Stage, tumor size, nodal status and hormonal receptors had negative impact on survival. Adjuvant chemotherapy was administered to 87.9% of younger and 65.6% of older patients (p < 0.0001). In terms of hormone therapy, the proportion of tamoxifen treated patients was significantly lower in young age group (p < 0.0001). No significant difference in radiation therapy between the two groups. Young age (≤ 40) is an independent risk factor for relapse in operable Saudi breast cancer patients. The fundamental biology of

  17. Raltitrexed (Tomudex administration in patients with relapsed metastatic colorectal cancer after weekly irinotecan/5-Fluorouracil/Leucovorin chemotherapy

    Directory of Open Access Journals (Sweden)

    Vadiaka Maria

    2002-01-01

    Full Text Available Abstract Purpose The present study aimed at evaluating the efficacy of Raltitrexed, a specific thymidilate synthase inhibitor, in patients with advanced colorectal cancer (ACC in relapse (>8 weeks after a prior response or disease stabilization to first-line chemotherapy combination with lrinotecan+5-Fluorouracil (5-FU+Leucovorin (LV. Methods Twenty-five patients with metastatic ACC entered; 17 males/8 females, median age 61 (range: 47–70, median Karnovsky PS: 80 (70–90, and sites of metastases; liver: 21, lung: 4, lymph nodes: 7, peritoneal: 5 and a life expectancy of at least 3 months, were entered in the present pilot study. All patients had progressed after prior chemotherapy with lrinotecan+5-FU+LV. Raltitrexed was administered at a dose of 3 mg/m2 i.v. every 21 days. Results Three patients (12% achieved a partial response (PR, 8 (32% had stable disease (SD, and the remaining 14 (56% developed progressive disease (PD. Median time-to-progression (TTP was 5.5 months (range, 2–8.5, and median overall survival (OS 8 months (range, 4.0–12.5. Toxicity was generally mild; it consisted mainly of myelosuppression; neutropenia grade 1–2: 52%-grade 3: 28%, and anemia grade 1–2 only: 36%. Mild mucositis grade 1–2 occured in 13.5% of patients and was the principal non-hematologic toxicity. Conclusion Response to treatment with Raltitrexed is limited in patients with ACC failing after an initial response or non-progression to the weekly lrinotecan+5-FU+LV combination. However, it appears that a limited number of patients with PR/SD may derive clinical benefit, but final proof would require a randomized study.

  18. Amrubicin for relapsed small-cell lung cancer: a systematic review and meta-analysis of 803 patients

    Science.gov (United States)

    Horita, Nobuyuki; Yamamoto, Masaki; Sato, Takashi; Tsukahara, Toshinori; Nagakura, Hideyuki; Tashiro, Ken; Shibata, Yuji; Watanabe, Hiroki; Nagai, Kenjiro; Nakashima, Kentaro; Ushio, Ryota; Ikeda, Misako; Kobayashi, Nobuaki; Shinkai, Masaharu; Kudo, Makoto; Kaneko, Takeshi

    2016-01-01

    Currently, amrubicin is permitted for relapsed small-cell lung carcinoma (SCLC) only in Japan. The efficacy and adverse effects of amrubicin as reported by previous studies varied greatly. The inclusion criterion was a prospective study that was able to provide data for efficacy and safety by the AMR single agent regimen as second-line chemotherapy for a patient with SCLC. Binary data were meta-analyzed with the random-model generic inverse variance method. We included nine articles consisted of 803 patients. The pooled three-, six-, and nine-month progression-free survival were 63% (95% CI 57–69%, I2 = 53%), 28% (95% CI 21–35%, I2 = 71%), and 10% (95% CI 6–14%, I2 = 41%), respectively. The pooled six-, 12-, and 18-month overall survival were 69% (95% CI 61–78%, I2 = 83%), 36% (95% CI 28–44%, I2 = 80%), and 15% (95% CI 8–21%, I2 = 81%), respectively. Amrubicin seemed much more beneficial for Japanese patients. However, compared to the efficacy of topotecan presented in a previous meta-analysis, amrubicin may be a better treatment option than topotecan for both Japanese and Euro-American. Adverse effects by amrubicin were almost exclusively observed to be hematological. Notably, grade III/IV neutropenia incidence was 70% and febrile neutropenia incidence was 12%. PMID:26750506

  19. Symptoms and Association with Health Outcomes in Relapsing-Remitting Multiple Sclerosis: Results of a US Patient Survey

    Directory of Open Access Journals (Sweden)

    Angela E. Williams

    2014-01-01

    Full Text Available Background. A variety of symptoms have been reported, but the prevalence of specific symptoms in relapsing-remitting multiple sclerosis (RRMS, how they are related to one another, and their impact on patient reported outcomes is not well understood. Objective. To describe how symptoms of RRMS cooccur and their impact on patient-reported outcomes. Methods. Individuals who reported a physician diagnosis of RRMS in a large general health survey in the United States indicated the symptoms they experience because of RRMS and completed validated scales, including the work productivity and activity impairment questionnaire and either the SF-12v2 or SF-36v2. Symptom clusters were identified through hierarchical cluster analysis, and the relationship between clusters and outcomes was assessed through regression. Results. Fatigue, difficulty walking, and numbness were the most commonly reported symptoms. Seven symptom clusters were identified, and several were significantly related to patient reported outcomes. Pain, muscle spasms, and stiffness formed a cluster strongly related to physical quality of life; depression was strongly related to mental quality of life and cognitive difficulty was associated with work impairment. Conclusions. Symptoms in RRMS show a strong relationship with quality of life and should be taken into consideration in treatment decisions and evaluation of treatment success.

  20. Elevated body temperature is linked to fatigue in an Italian sample of relapsing-remitting multiple sclerosis patients.

    Science.gov (United States)

    Leavitt, V M; De Meo, E; Riccitelli, G; Rocca, M A; Comi, G; Filippi, M; Sumowski, J F

    2015-11-01

    Elevated body temperature was recently reported for the first time in patients with relapsing-remitting multiple sclerosis (RRMS) relative to healthy controls. In addition, warmer body temperature was associated with worse fatigue. These findings are highly novel, may indicate a novel pathophysiology for MS fatigue, and therefore warrant replication in a geographically separate sample. Here, we investigated body temperature and its association to fatigue in an Italian sample of 44 RRMS patients and 44 age- and sex-matched healthy controls. Consistent with our original report, we found elevated body temperature in the RRMS sample compared to healthy controls. Warmer body temperature was associated with worse fatigue, thereby supporting the notion of endogenous temperature elevations in patients with RRMS as a novel pathophysiological factor underlying fatigue. Our findings highlight a paradigm shift in our understanding of the effect of heat in RRMS, from exogenous (i.e., Uhthoff's phenomenon) to endogenous. Although randomized controlled trials of cooling treatments (i.e., aspirin, cooling garments) to reduce fatigue in RRMS have been successful, consideration of endogenously elevated body temperature as the underlying target will enhance our development of novel treatments.

  1. Salvage radiotherapy for patients with P.S.A. relapse after radical prostatectomy: comparisons among Astro and Phoenix biochemical failure definitions

    International Nuclear Information System (INIS)

    Quero, L.; Hennequin, V.; Maylin, C.; Hennequin, C.; Ravery, V.; Mongiat-Artus, P.; Desgrandchamps, F.

    2009-01-01

    Purpose Study about the efficacy of salvage radiotherapy (R.T.), in terms of biochemical disease free survival (b.D.F.S.), according to Astro and Phoenix (nadir + 2) definitions, for persistent or rising P.S.A. after radical prostatectomy. Patients and methods Retrospective analysis of 59 patients who underwent R.T. between 1990 and 2003 for P.S.A. recurrence after radical prostatectomy. Patients received a median of 66 Gy to the prostate bed with 3D or 2D R.T.. The main end point was b.D.F.S. according to Astro and Phoenix (nadir + 2) definitions. Different criterion sets were analysed to calculate b.D.F.S. and pretreatment factors that might predict biochemical relapse were sought for each. Results After a 38-month median follow-up, the 3-year b.D.F.S. rates were: 60 and 72% for Astro and Phoenix (nadir + 2 ng/ml) definitions respectively. According to univariate analysis, pre-R.T. P.S.A. = 1 ng/ml and seminal vesicle involvement were associated with biochemical relapse. Multivariate analysis retained only pre-R.T. P.S.A. = 1 ng/ml as an independent predictor of biochemical relapse for the two definitions. Conclusion Salvage R.T. is an effective treatment after radical prostatectomy according to Astro or Phoenix definitions. Only pre-R.T. P.S.A. = 1 ng/ml predicted relapse. (authors)

  2. The personality pattern of duodenal ulcer patients in relation to spontaneous ulcer healing and relapse

    DEFF Research Database (Denmark)

    Jess, P; von der Lieth, L; Matzen, Peter

    1989-01-01

    stressful life events before entrance to the study (P less than 0.05) and, like the neurotic patients, they had lower ego-strength to cope with such events (P less than 0.05). The results indicate that personality assessments make it possible to distinguish between subgroups of duodenal ulcer patients......One hundred consecutive out-patients with duodenal ulceration from a hospital and a gastroenterological clinic were tested with the Minnesota Multiphasic Personality Inventory (MMPI). This was carried out in order to investigate whether neuroticism or other personality disorders were...... characteristics of duodenal ulcer patients, and whether the presence of such possible personality disorders might influence the prognosis of the disease. Neuroticism occurred in 53% of the patients, but only in 5% of controls (P less than 0.0001). Overall, personality disorders were present in 69% of the patients...

  3. Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function.

    Science.gov (United States)

    Li, Yan; Wang, Xiaomin; O'Mara, Edward; Dimopoulos, Meletios A; Sonneveld, Pieter; Weisel, Katja C; Matous, Jeffrey; Siegel, David S; Shah, Jatin J; Kueenburg, Elisabeth; Sternas, Lars; Cavanaugh, Chloe; Zaki, Mohamed; Palmisano, Maria; Zhou, Simon

    2017-01-01

    Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide concentration data collected on dialysis days from both the withdrawal (arterial) side and from the returning (venous) side of the dialyzer, from rrMM patients with severely impaired renal function requiring dialysis, were used to assess the extent to which dialysis contributes to the removal of pomalidomide from blood circulation. PPK analyses demonstrated that moderate to severe renal impairment not requiring dialysis has no influence on pomalidomide clearance or plasma exposure, as compared to those patients with normal renal function, while pomalidomide exposure increased approximately 35% in patients with severe renal impairment requiring dialysis on nondialysis days. In addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12 L/h, indicating that dialysis will significantly remove pomalidomide from the blood circulation. Thus, pomalidomide should be administered post-dialysis on the days of dialysis.

  4. Melarsoprol sensitivity profile of Trypanosoma brucei gambiense isolates from cured and relapsed sleeping sickness patients from the Democratic Republic of the Congo.

    Directory of Open Access Journals (Sweden)

    Patient Pyana Pati

    2014-10-01

    Full Text Available Sleeping sickness caused by Trypanosoma brucei (T.b. gambiense constitutes a serious health problem in sub-Sahara Africa. In some foci, alarmingly high relapse rates were observed in patients treated with melarsoprol, which used to be the first line treatment for patients in the neurological disease stage. Particularly problematic was the situation in Mbuji-Mayi, East Kasai Province in the Democratic Republic of the Congo with a 57% relapse rate compared to a 5% relapse rate in Masi-Manimba, Bandundu Province. The present study aimed at investigating the mechanisms underlying the high relapse rate in Mbuji-Mayi using an extended collection of recently isolated T.b. gambiense strains from Mbuji-Mayi and from Masi-Manimba.Forty five T.b. gambiense strains were used. Forty one were isolated from patients that were cured or relapsed after melarsoprol treatment in Mbuji-Mayi. In vivo drug sensitivity tests provide evidence of reduced melarsoprol sensitivity in these strains. This reduced melarsoprol sensitivity was not attributable to mutations in TbAT1. However, in all these strains, irrespective of the patient treatment outcome, the two aquaglyceroporin (AQP 2 and 3 genes are replaced by chimeric AQP2/3 genes that may be associated with resistance to pentamidine and melarsoprol. The 4 T.b. gambiense strains isolated in Masi-Manimba contain both wild-type AQP2 and a different chimeric AQP2/3. These findings suggest that the reduced in vivo melarsoprol sensitivity of the Mbuji-Mayi strains and the high relapse rates in that sleeping sickness focus are caused by mutations in the AQP2/AQP3 locus and not by mutations in TbAT1.We conclude that mutations in the TbAQP2/3 locus of the local T.b. gambiense strains may explain the high melarsoprol relapse rates in the Mbuji-Mayi focus but other factors must also be involved in the treatment outcome of individual patients.

  5. Twice-daily versus once-daily applications of pimecrolimus cream 1% for the prevention of disease relapse in pediatric patients with atopic dermatitis.

    Science.gov (United States)

    Ruer-Mulard, Mireille; Aberer, Werner; Gunstone, Anthony; Kekki, Outi-Maria; López Estebaranz, Jose Luis; Vertruyen, André; Guettner, Achim; Hultsch, Thomas

    2009-01-01

    The aim of this study is to compare twice-daily and once-daily applications of pimecrolimus cream 1% for prevention of atopic dermatitis relapses in pediatric patients. This multicenter trial enrolled 300 outpatients aged 2 to 17 years, with mild-to-severe atopic dermatitis. The patients were initially treated with twice-daily topical pimecrolimus until complete clearance or for up to 6 weeks (open-label period). Those who achieved a decrease of at least 1 point in the Investigator's Global Assessment score were then randomized to double-blind treatment with pimecrolimus cream 1% either twice daily or once daily for up to 16 weeks. Study medication was discontinued during periods of disease remission (Investigator's Global Assessment = 0). The primary efficacy end point of the double-blind phase was disease relapse (worsening requiring topical corticosteroids or additional/alternative therapy and confirmed by Investigator's Global Assessment score > or = 3 and pruritus score > or = 2). Of the 300 patients enrolled in the study, 268 were randomized to treatment with pimecrolimus cream 1% either twice daily or once daily (n = 134 in each group). The relapse rate was lower in the twice-daily dose group (9.9%) than that in the once-daily dose group (14.7%), but analysis of the time to disease relapse, using a Cox proportional model to adjust for confounding variables, did not show a statistically significant difference between treatment arms (hazard ratio: 0.64; 95% CI: 0.31-1.30). Treatment of active atopic dermatitis lesions with pimecrolimus cream 1% twice daily, followed by the once-daily dosing regimen, was sufficient to prevent subsequent atopic dermatitis relapses over 16 weeks in pediatric patients.

  6. Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma.

    Science.gov (United States)

    Vogl, Dan T; Stadtmauer, Edward A; Tan, Kay-See; Heitjan, Daniel F; Davis, Lisa E; Pontiggia, Laura; Rangwala, Reshma; Piao, Shengfu; Chang, Yunyoung C; Scott, Emma C; Paul, Thomas M; Nichols, Charles W; Porter, David L; Kaplan, Janeen; Mallon, Gayle; Bradner, James E; Amaravadi, Ravi K

    2014-08-01

    The efficacy of proteasome inhibition for myeloma is limited by therapeutic resistance, which may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation. Preclinical studies demonstrate that autophagy inhibition with hydroxychloroquine augments the antimyeloma efficacy of the proteasome inhibitor bortezomib. We conducted a phase I trial combining bortezomib and hydroxychloroquine for relapsed or refractory myeloma. We enrolled 25 patients, including 11 (44%) refractory to prior bortezomib. No protocol-defined dose-limiting toxicities occurred, and we identified a recommended phase 2 dose of hydroxychloroquine 600 mg twice daily with standard doses of bortezomib, at which we observed dose-related gastrointestinal toxicity and cytopenias. Of 22 patients evaluable for response, 3 (14%) had very good partial responses, 3 (14%) had minor responses, and 10 (45%) had a period of stable disease. Electron micrographs of bone marrow plasma cells collected at baseline, after a hydroxychloroquine run-in, and after combined therapy showed therapy-associated increases in autophagic vacuoles, consistent with the combined effects of increased trafficking of misfolded proteins to autophagic vacuoles and inhibition of their degradative capacity. Combined targeting of proteasomal and autophagic protein degradation using bortezomib and hydroxychloroquine is therefore feasible and a potentially useful strategy for improving outcomes in myeloma therapy.

  7. Potent anti-leukemia activities of humanized CD19-targeted CAR-T cells in patients with relapsed/refractory acute lymphoblastic leukemia.

    Science.gov (United States)

    Cao, Jiang; Wang, Gang; Cheng, Hai; Wei, Chen; Qi, Kunming; Sang, Wei; Zhenyu, Li; Shi, Ming; Li, Huizhong; Qiao, Jianlin; Pan, Bin; Zhao, Jing; Wu, Qingyun; Zeng, Lingyu; Niu, Mingshan; Jing, Guangjun; Zheng, Junnian; Xu, Kailin

    2018-04-10

    Chimeric antigen receptor T (CAR-T) cell therapy has shown promising results for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). The immune response induced by murine single-chain variable fragment (scFv) of the CAR may limit CAR-T cell persistence and thus increases the risk of leukemia relapse. In this study, we developed a novel humanized scFv from the murine FMC63 antibody. A total of 18 R/R ALL patients with or without prior murine CD19 CAR-T therapy were treated with humanized CD19-targeted CAR-T cells (hCART19s). After lymphodepletion chemotherapy with cyclophosphamide and fludarabine, the patients received a single dose (1 × 10 6 /kg) of autologous hCART19s infusion. Among the 14 patients without previous CAR-T therapy, 13 (92.9%) achieved complete remission (CR) or CR with incomplete count recovery (CRi) on day 30, whereas 1 of the 3 patients who failed a second murine CAR-T infusion achieved CR after hCART19s infusion. At day 180, the overall and leukemia-free survival rates were 65.8% and 71.4%, respectively. The cumulative incidence of relapse was 22.6%, and the non-relapse mortality rate was 7.1%. During treatment, 13 patients developed grade 1-2 cytokine release syndrome (CRS), 4 patients developed grade 3-5 CRS, and 1 patient experienced reversible neurotoxicity. These results indicated that hCART19s could induce remission in patients with R/R B-ALL, especially in patients who received a reinfusion of murine CAR-T. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  8. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies.

    Science.gov (United States)

    Advani, Ranjana H; Buggy, Joseph J; Sharman, Jeff P; Smith, Sonali M; Boyd, Thomas E; Grant, Barbara; Kolibaba, Kathryn S; Furman, Richard R; Rodriguez, Sara; Chang, Betty Y; Sukbuntherng, Juthamas; Izumi, Raquel; Hamdy, Ahmed; Hedrick, Eric; Fowler, Nathan H

    2013-01-01

    Survival and progression of mature B-cell malignancies depend on signals from the B-cell antigen receptor, and Bruton tyrosine kinase (BTK) is a critical signaling kinase in this pathway. We evaluated ibrutinib (PCI-32765), a small-molecule irreversible inhibitor of BTK, in patients with B-cell malignancies. Patients with relapsed or refractory B-cell lymphoma and chronic lymphocytic leukemia received escalating oral doses of ibrutinib. Two schedules were evaluated: one, 28 days on, 7 days off; and two, once-daily continuous dosing. Occupancy of BTK by ibrutinib in peripheral blood was monitored using a fluorescent affinity probe. Dose escalation proceeded until either the maximum-tolerated dose (MTD) was achieved or, in the absence of MTD, until three dose levels above full BTK occupancy by ibrutinib. Response was evaluated every two cycles. Fifty-six patients with a variety of B-cell malignancies were treated over seven cohorts. Most adverse events were grade 1 and 2 in severity and self-limited. Dose-limiting events were not observed, even with prolonged dosing. Full occupancy of the BTK active site occurred at 2.5 mg/kg per day, and dose escalation continued to 12.5 mg/kg per day without reaching MTD. Pharmacokinetic data indicated rapid absorption and elimination, yet BTK occupancy was maintained for at least 24 hours, consistent with the irreversible mechanism. Objective response rate in 50 evaluable patients was 60%, including complete response of 16%. Median progression-free survival in all patients was 13.6 months. Ibrutinib, a novel BTK-targeting inhibitor, is well tolerated, with substantial activity across B-cell histologies.

  9. Contribution of SPECT/CT for sentinel node localization in patients with ipsilateral breast cancer relapse

    Energy Technology Data Exchange (ETDEWEB)

    Borrelli, Pablo [Antoni Van Leeuwenhoek Hospital, Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam (Netherlands); Hospital La Fe, Nuclear Medicine, Medical Imaging Clinical Area, Valencia (Spain); Donswijk, Maarten L.; Stokkel, Marcel P.; Teixeira, Suzana C. [Antoni Van Leeuwenhoek Hospital, Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam (Netherlands); Tinteren, Harm van [Antoni Van Leeuwenhoek Hospital, Department of Biometrics, The Netherlands Cancer Institute, Amsterdam (Netherlands); Rutgers, Emiel J.T. [Antoni Van Leeuwenhoek Hospital, Department of Surgery, The Netherlands Cancer Institute, Amsterdam (Netherlands); Valdes Olmos, Renato A. [Antoni Van Leeuwenhoek Hospital, Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam (Netherlands); Leiden University Medical Centre, Nuclear Medicine Section and Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden (Netherlands)

    2017-04-15

    In recent years repeat sentinel node (SN) biopsy has been proven to be feasible in local breast cancer recurrence (LBCR). However, in these patients SNs outside the ipsilateral axilla are frequently observed. This study evaluates the contribution of SPECT/CT for SN localization and surgical adjustment in LBCR patients. SN biopsy was performed in 122 LBCR patients (median age 60.5 years, range 24-87), enrolled from August 2006 to July 2015. Median disease-free time lapse was 109.5 months (range 9-365). Axillary lymph node dissection (ALND) had previously been performed in 55 patients, SN biopsy in 44, both techniques in 13 and fine-needle aspiration in 10. Primary breast cancer treatment included radiotherapy in 104 patients (85.3 %) and chemotherapy in 40 (32.8 %). Preoperative lymphatic mapping, using planar scintigraphy (PS) and SPECT/CT included report of SN location according to lymph node territory. In case of a territorial PS-SPECT/CT mismatch, surgery was adjusted according to SPECT/CT findings. SPECT/CT SN visualization rate was higher than PS (53.3 % vs. 43.4 %, p n.s.) with, in total, 19 additional SN (118 vs. 99, p n.s.). PS-SPECT/CT territory mismatch, found in 60 % (39/65) of patients with SN visualization, led to surgical adjustment in 21.3 % (26/122) of patients. The SN procedure was finally performed in 104 patients resulting in a 65.7 % surgical retrieval rate with a total of 132 removed SNs (1.86/patient). SN metastases were found in 17/71 patients (23.9 %), in 16 of them (94 %) in ipsilateral basins outside the axilla or in the contralateral axilla. Using SPECT/CT there is a trend to visualize more SNs in LBCR, providing at the same time important anatomical information to adjust intraoperative SN procedures. The addition of SPECT/CT to the standard imaging protocol may lead to better staging mainly in patients presenting drainage outside the ipsilateral axilla. (orig.)

  10. Prolonged Survival of a Refractory Acute Myeloid Leukemia Patient after a Third Hematopoietic Stem Cell Transplantation with Umbilical Cord Blood following a Second Relapse

    Directory of Open Access Journals (Sweden)

    Suk-young Lee

    2014-01-01

    Full Text Available Although hematopoietic stem cell transplantation (HSCT has been considered to be the only way for potential cure of relapsed acute myeloid leukemia (AML, there has been no report on a third HSCT in patients with multiple relapsed AML. Here, we report a case of 53-year-old female who received a successful third allogeneic HSCT after relapse of AML following a second allogeneic HSCT. She was treated with a toxicity reduced conditioning regimen and received direct intrabone cord blood transplantation (CBT using a single unit of 5/6 HLA-matched cord blood as a graft source. Graft-versus-host disease prophylaxis was performed with a single agent of tacrolimus to increase graft-versus-leukemia effect. She is in remission for 8 months since the direct intrabone CBT. This report highlights not only the importance of individually adjusted approach but also the need for further investigation on the role of HSCT as a treatment modality in patients with refractory or multiple relapsed AML.

  11. The personality pattern of duodenal ulcer patients in relation to spontaneous ulcer healing and relapse

    DEFF Research Database (Denmark)

    Jess, P; von der Lieth, L; Matzen, Peter

    1989-01-01

    One hundred consecutive out-patients with duodenal ulceration from a hospital and a gastroenterological clinic were tested with the Minnesota Multiphasic Personality Inventory (MMPI). This was carried out in order to investigate whether neuroticism or other personality disorders were characterist......One hundred consecutive out-patients with duodenal ulceration from a hospital and a gastroenterological clinic were tested with the Minnesota Multiphasic Personality Inventory (MMPI). This was carried out in order to investigate whether neuroticism or other personality disorders were...

  12. Time perception and illness acceptance among remitting-relapsing multiple sclerosis patients under treatment.

    Science.gov (United States)

    Król, Joanna; Szcześniak, Małgorzata; Koziarska, Dorota; Rzepa, Teresa

    2015-01-01

    The aim of the study was to determine temporal orientation in patients diagnosed with RR-MS as compared with that of healthy individuals; to analyse self-evaluated acceptance levels in terms of physical and psychological condition and self-reliance; an attempt to identify factors of illness acceptance in patients with RR-MS including temporal perspective. Acceptance of Illness Scale (AIS, adapted into Polish by Z. Juczyński), Zimbardo Time Perspective Inventory (ZTPI, adapted into Polish by M. Mażewski), and original interview aimed to assess socio-demographic data and self-evaluated physical as well as psychological condition and self-reliance of patients with MS (referred to the neurological testing according to the EDSS). Patients with RR-MS focus on fatalistic and hedonistic present more than healthy individuals. They also tend to reflect on their negative past experience. Acceptance of illness correlated positively with subjective assessment of physical and psychological condition as well as self-reliance, and negatively with objective disability score (measured with the use of EDSS) and a factor considering time of disease duration. Avoiding contemplation of negative past and concentrating on hedonistic future constitute significant predictors of illness acceptance. These results may be of importance in terms of holistic approach to treatment of RR-MS patients. In the initial stage of the disease progression, patients might benefit from psychological support due to change in temporal orientation.

  13. Andrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: a 12-month double-blind placebo-controlled pilot study.

    Science.gov (United States)

    Bertoglio, J C; Baumgartner, M; Palma, R; Ciampi, E; Carcamo, C; Cáceres, D D; Acosta-Jamett, G; Hancke, J L; Burgos, R A

    2016-05-23

    Andrographis paniculata (A. paniculata), a medicinal plant, has shown anti-inflammatory, neuroprotective and antifibrotic effects in animal models as well as clinical efficacy in different studies, including an anti-fatigue effect in autoimmune diseases such as rheumatoid arthritis. In multiple sclerosis (MS), fatigue is rated as one of the most common and disabling symptoms. In the present trial, we investigated the effect of A. paniculata on relapse rate and fatigue in relapsing-remitting MS (RRMS) patients receiving interferon beta. A randomised double-blind placebo-controlled trial assessed the effects of 170 mg of A. paniculata dried extract tablet b.i.d. p.o. on relapse rate and fatigue using the Fatigue Severity Scores (FSS) over 12 months in RRMS patients receiving interferon. The Expanded Disability Status Scale (EDSS) score, inflammatory parameters and radiological findings were also investigated. Twenty-five patients were enrolled, and twenty-two patients were ultimately analysed and randomised to the active or placebo group. Patients treated with A. paniculata showed a significant reduction in their FSS score as compared to the placebo, equivalent to a 44 % reduction at 12 months. No statistically significant differences were observed for relapse rate, EDSS or inflammatory parameters, with a trend in reducing new lesions among the A. paniculata group. One patient in the A. paniculata group presented with a mild and transient skin rash, which was alleviated with anti-histamine treatment for three weeks. A. paniculata was well tolerated in patients and no changes in clinical parameters were observed. A. paniculata significantly reduces fatigue in patients with RRMS receiving interferon beta in comparison to placebo and only interferon beta treatment. ClinicalTrials.gov Identifier: NCT02280876 ; Trial registration date: 20.10.2014.

  14. Factors associated with failure to achieve remission and with relapse after remission in patients with major depressive disorder in the PERFORM study.

    Science.gov (United States)

    Saragoussi, Delphine; Touya, Maëlys; Haro, Josep Maria; Jönsson, Bengt; Knapp, Martin; Botrel, Bastien; Florea, Ioana; Loft, Henrik; Rive, Benoît

    2017-01-01

    The Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder (PERFORM) study has been initiated to better understand the course of a depressive episode and its impact on patient functioning. This analysis aimed to identify sociodemographic and clinical factors associated with failure to achieve remission at month 2 after initiating or switching antidepressant monotherapy and with subsequent relapse at month 6 for patients in remission at month 2. This was a 2-year observational cohort study in 1,159 outpatients aged 18-65 years with major depressive disorder initiating or undergoing the first switch of antidepressant monotherapy. Factors with P 8 weeks (OR 0.51), being in psychotherapy (OR 0.51), sexual dysfunction (OR 0.62), and severity of depression (OR 0.87). Factors significantly associated with relapse at month 6 were male sex (OR 2.47), being married or living as a couple (OR 2.73), residual patient-reported cognitive symptoms at 2 months (OR 1.12 per additional unit of Perceived Deficit Questionnaire-5 score) and residual depressive symptoms at 2 months (OR 1.27 per additional unit of Patient Health Questionnaire-9 score). Different factors appear to be associated with failure to achieve remission in patients with major depressive disorder and with subsequent relapse in patients who do achieve remission. Patient-reported cognitive dysfunction is an easily measurable and treatable characteristic that may be associated with an increased likelihood of relapse at 6 months in patients who have achieved remission.

  15. Optimising the treatment of the partially platinum-sensitive relapsed ovarian cancer patient

    Directory of Open Access Journals (Sweden)

    Nicoletta Colombo

    2014-12-01

    Full Text Available The choice of second-line chemotherapy in patients with recurrent ovarian cancer (ROC is complex, with several factors to be considered, the most important of which is the length of the platinum-free treatment interval (PFI. Recently ROC patients have been further stratified into platinum sensitive (PS, partially platinum sensitive (PPS and platinum resistant (PR subgroups depending on the length of the PFI. Response to second-line therapy, progression-free survival (PFS and overall survival (OS are linked to the PFI, all of them improving as the PFI increases. Consequently, there is increasing interest in PFI extension strategies with platinum-free therapeutic options. Such strategies are currently being studied in patients with partially platinum-sensitive disease (PFI 6-12 months, as the treatment of these patients remains clinically challenging. A non-platinum option, trabectedin + pegylated liposomal doxorubicin (PLD combination, has been evaluated in ROC patients in the pivotal phase III OVA-301 study. The OVA-301 study differed from previous trials in the same setting as it included only patients who were not expected to benefit from or who were ineligible for or who were unwilling to receive re-treatment with platinum-based chemotherapy, including those with PPS and PR disease. Subset analysis of patients with PPS disease in OVA-301 showed that the trabectedin + PLD combination significantly improved PFS compared with PLD alone; median PFS 7.4 versus 5.5 months, p=0.0152. Final survival data from the same subset of patients, showed that trabectedin + PLD also achieved a significant 36% decrease in the risk of death compared with PLD alone (HR=0.64; 95% CI, 0.47–0.88; p=0.0027. Median overall survival (OS was 22.4 months in the trabectedin + PLD arm versus 16.4 months in the PLD arm. This represents a statistically significant 6-month improvement in median OS in patients treated with trabectedin + PLD compared to those treated with PLD

  16. Short-term stress, but not mucosal healing nor depression was predictive for the risk of relapse in patients with ulcerative colitis: a prospective 12-month follow-up study.

    Science.gov (United States)

    Langhorst, Jost; Hofstetter, Anna; Wolfe, Fred; Häuser, Winfried

    2013-10-01

    Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. Psychological factors such as depression and stress are under debate to contribute to the risk of relapse. The impact of mucosal healing to reduce the risk of relapse had not been studied prospectively. The aim of this study was to identify whether depression and stress increase and mucosal healing reduces the risk of clinical relapse in patients with UC in clinical remission. Patients in clinical remission were followed prospectively for 1 year, or less if they relapsed. Endoscopy and histology score and long-term perceived stress (Perceived Stress Questionnaire) were measured at baseline. Mucosal healing was defined by a Mayo Endoscopy score of 0-1. Depression (Hospital Anxiety and Depression Scale) and acute perceived stress (Cohen Perceived Stress Scale) were measured at baseline and after 1, 3, 6, 9, and 12 months. A time-dependent multivariate Cox regression model determined the predictors of time to relapse. Seventy-five patients were included into final analysis, of which 28 (37.3%) relapsed. Short-term stress at the last visit before relapse (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 1.01-1.10) and male gender (HR = 2.38, 95% CI = 1.01-5.61), but not baseline mucosal healing (HR = 0.86, 95% CI = 0.35-2.11), baseline long-term stress (HR = 0.20, 95% CI = 0.01-3.31), and depression at the last visit before relapse (HR = 1.08, 95% CI = 0.95-1.22) were predictive for a relapse. Short-term stress but not depression nor mucosal healing was predictive for the risk of relapse in patients with UC in clinical remission. Larger multicentre studies are necessary to confirm our findings.

  17. Serum uric acid levels and leukocyte nitric oxide production in multiple sclerosis patients outside relapses

    NARCIS (Netherlands)

    Mostert, JP; Ramsaransing, GSM; Heerserna, DJ; Heerings, M; Wilczak, N; De Keyser, J

    2005-01-01

    Background: A number of studies found that patients with multiple sclerosis (MS) have low serum levels of uric acid. It is unclear whether this represents a primary deficit or secondary effect. Uric acid is a scavenger of peroxynitrite, which is the product of nitric oxide (NO) and superoxide.

  18. Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Cohen, Jeffrey A; Coles, Alasdair J

    2016-01-01

    .0300); improvement in MSFC scores with alemtuzumab was primarily driven by the upper limb coordination and dexterity domain. Alemtuzumab-treated patients had more favorable changes from baseline in SLCLA (2.5% contrast) scores (p = 0.0014) and MSFC + SLCLA composite scores (p = 0.0097) than SC IFN-β-1a...

  19. Concomitant NSAID use during antipsychotic treatment and risk of 2-year relapse - a population-based study of 16,253 incident patients with schizophrenia

    DEFF Research Database (Denmark)

    Köhler, Karl Ole; Petersen, Liselotte; Benros, Michael Eriksen

    2016-01-01

    OBJECTIVE: Clinical trials have indicated antipsychotic effects of non-steroidal anti-inflammatory drugs (NSAIDs) among incident patients with schizophrenia. We aimed to study, in a population-based setting, whether concomitant use of NSAIDs or paracetamol, changed 2-year relapse risk...... for schizophrenia. METHODS: We identified all incident patients with schizophrenia in Denmark diagnosed 1996-2012 initiating antipsychotic treatment within the year after diagnosis. We calculated concomitant treatment intervals for antipsychotic and NSAID or paracetamol use. Hazard rate ratios (HRR) were estimated...... using Cox regression adjusted for important covariates. MAIN OUTCOME MEASURES: 2-year relapse, i.e. (re)-hospitalizations with schizophrenia. RESULTS: Among 16,235 incident patients with schizophrenia using antipsychotics, 1480 (9.1%) used NSAIDs and 767 (4.7%) paracetamol. Concomitant use of NSAIDs...

  20. Risk Factors for Regional Nodal Relapse in Breast Cancer Patients With One to Three Positive Axillary Nodes

    Energy Technology Data Exchange (ETDEWEB)

    Yates, Lucy, E-mail: lucy.yates@gstt.nhs.uk [Guy' s, King' s, St Thomas' Cancer Centre, Guy' s Hospital, London (United Kingdom); Kirby, Anna [Guy' s, King' s, St Thomas' Cancer Centre, Guy' s Hospital, London (United Kingdom); Department of Clinical Oncology, Royal Marsden Hospital, Sutton (United Kingdom); Crichton, Siobhan [Department of Statistics, Kings College London (United Kingdom); Gillett, Cheryl [Breast Pathology, Kings College London (United Kingdom); Cane, Paul [Department of Histopathology, Guy' s and St Thomas' Foundation Trust, London (United Kingdom); Fentiman, Ian; Sawyer, Elinor [Guy' s, King' s, St Thomas' Cancer Centre, Guy' s Hospital, London (United Kingdom)

    2012-04-01

    Purpose: In many centers, supraclavicular fossa radiotherapy (SCF RT) is not routinely offered to breast cancer patients with one to three positive lymph nodes. We aimed to identify a subgroup of these patients who are at high risk of supra or infraclavicular fossa relapse (SCFR) such that they can be offered SCFRT at the time of diagnosis to improve long term locoregional control. Methods and Materials: We performed a retrospective analysis of the pathological features of 1,065 cases of invasive breast cancer with one to three positive axillary lymph nodes. Patients underwent radical breast conserving surgery or mastectomy. A total of 45% of patients received adjuvant chest wall/breast RT. No patients received adjuvant SCFRT. The primary outcome was SCFR. Secondary outcomes were chest wall/breast recurrence, distant metastasis, all death, and breast-cancer specific death. Kaplan-Meier estimates were used to calculate actuarial event rates and survival functions compared using log-rank tests. Multivariate analyses (MVA) of factors associated with outcome were conducted using Cox proportional hazards models. Results: Median follow-up was 9.7 years. SCFR rate was 9.2%. Median time from primary diagnosis to SCFR was 3.4 years (range, 0.7-14.4 years). SCFR was associated with significantly lower 10-year survival (18% vs. 65%; p < 0.001). Higher grade and number of positive lymph nodes were the most significant predictors of SCFR on MVA (p < 0.001). 10 year SCFR rates were less than 1% in all patients with Grade 1 cancers compared with 30% in those having Grade 3 cancers with three positive lymph nodes. Additional factors associated with SCFR on univariate analysis but not on MVA included larger nodal deposits (p = 0.002) and proportion of positive nodes (p = 0.003). Conclusions: Breast cancer patients with one to three positive lymph nodes have a heterogenous risk of SCFR. Patients with two to three positive axillary nodes and/or high-grade disease may warrant

  1. Diagnosis and operatory treatment of the patients with failed back surgery caused by herniated disk relapse.

    Science.gov (United States)

    Bodiu, A

    2014-01-01

    THE OBJECT OF STUDY: Analysis of surgical treatment results in patients with recurrent lumbar disc herniation by transforaminal lumbar interbody fusion (TLIF) and repeated laminotomy and discectomy for the improvement of pain and disability. Data analysis was performed on a complex diagnosis and treatment of 56 patients with recurrent lumbar disc herniation who had previously underwent 1-3 lumbar disc surgeries. An MRI investigation with paramagnetic contrast agent (gadolinium) was used for the diagnosis and differentiation of epidural fibrosis, and a dynamic lateral X-ray investigation was carried out for the identification of segmental instability. The evolution period after the previous surgery was between 1 and 3 years after the index surgery. Pain expression degree and dynamics were assessed with the pain visual analog scale (VAS) in early and late postoperative periods. Postoperative success was assessed by using a modified MacNab scale. The follow-up recording period after the last operation was of at least 1 year, ranging from 1 to 4 years. The surgical treatment was effective in most cases, recording a reduction in pain expression level from 7.2-7.7 points on the VAS scale to 1.7-2.1 in the early period and 2.2-2.6 in the late period (1 year). Repeated surgery was effective in 21 of 30 (70%) cases who underwent decompression surgery without fusion and in 20 of 26 (76.9%) cases who underwent repeated surgery with transforaminal lumbar interbody fusion (TLIF). Overall, postoperative success was assessed by using a modified MacNab scale. Repeated surgery is a viable option for patients who have clinical manifestations of recurrent disc herniation. Investigation with contrast agent by MRI allows differentiating disk herniation recurrences from epidural fibrosis. Supplementing repeated discectomies and decompression with intervertebral transforaminal fusion provide superior clinical outcomes, especially in patients with clinical and radiological signs of lumbar

  2. Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lao, Louis [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Auckland City Hospital, Auckland (New Zealand); Hope, Andrew J. [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Maganti, Manjula [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Brade, Anthony; Bezjak, Andrea; Saibishkumar, Elantholi P.; Giuliani, Meredith; Sun, Alexander [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Cho, B. C. John, E-mail: john.cho@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada)

    2014-09-01

    Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses at the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT.

  3. Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

    International Nuclear Information System (INIS)

    Lao, Louis; Hope, Andrew J.; Maganti, Manjula; Brade, Anthony; Bezjak, Andrea; Saibishkumar, Elantholi P.; Giuliani, Meredith; Sun, Alexander; Cho, B. C. John

    2014-01-01

    Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses at the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT

  4. Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls.

    Directory of Open Access Journals (Sweden)

    Andreas Keller

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory demyelinating disease of the central nervous system, which is heterogenous with respect to clinical manifestations and response to therapy. Identification of biomarkers appears desirable for an improved diagnosis of MS as well as for monitoring of disease activity and treatment response. MicroRNAs (miRNAs are short non-coding RNAs, which have been shown to have the potential to serve as biomarkers for different human diseases, most notably cancer. Here, we analyzed the expression profiles of 866 human miRNAs. In detail, we investigated the miRNA expression in blood cells of 20 patients with relapsing-remitting MS (RRMS and 19 healthy controls using a human miRNA microarray and the Geniom Real Time Analyzer (GRTA platform. We identified 165 miRNAs that were significantly up- or downregulated in patients with RRMS as compared to healthy controls. The best single miRNA marker, hsa-miR-145, allowed discriminating MS from controls with a specificity of 89.5%, a sensitivity of 90.0%, and an accuracy of 89.7%. A set of 48 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 95%, a sensitivity of 97.6%, and an accuracy of 96.3%. While 43 of the 165 miRNAs deregulated in patients with MS have previously been related to other human diseases, the remaining 122 miRNAs are so far exclusively associated with MS. The implications of our study are twofold. The miRNA expression profiles in blood cells may serve as a biomarker for MS, and deregulation of miRNA expression may play a role in the pathogenesis of MS.

  5. Pathological Assessment of Brain White Matter in Relapsing-Remitting MS Patients using Quantitative Magnetization Transfer Imaging

    Directory of Open Access Journals (Sweden)

    Khodarahm Pahlevan

    2011-09-01

    Full Text Available Introduction: Multiple sclerosis (MS is characterized by lesions in the white matter (WM of the central nervous system. Magnetic resonance imaging is the most specific and sensitive method for diagnosis of multiple sclerosis. However, the ability of conventional MRI to show histopathologic heterogeneity of MS lesions is insufficient. Quantitative magnetization transfer imaging (qMTI is a relatively new method to investigate pathologic processes of the brain tissue occurring in MS patients. Material and Methods: Voxel-based analyses allow regional comparisons between groups to be made for the whole brain in a single analysis. This is done by coregistering data from all individual subjects to a reference brain, generally referred to as the "standard space", and then comparing them on a voxel-by-voxel basis. This study aimed to analyze whole-brain quantitative T1 maps, not to find global changes or changes in selected regions, but specifically to investigate the spatial distribution throughout the brain of T1 increases in MS WM with respect to control WM. In this study, 11 healthy controls, 10 relapsing-remitting (RR MS patients and 13 CIS patients were studied using MT-MRI imaging. MT parameters, including magnetization transfer ratio (MTR, magnetization transfer rate between free protons and restricted macromolecular protons, Ksat and longitudinal relaxation times (with and without MT saturation pulse, T1sat and T1free values were evaluated. Results: The results showed that, at a group level, there is widespread involvement of WM throughout the brain in CIS MS and especially in RRMS, where a significant T1 increase was found in 15.58% of WM voxels (normals < RR. Discussion and Conclusion: This study demonstrates that WM in large parts of the brain is susceptible to disease processes in RR and CIS MS

  6. Mindfulness-based cognitive therapy is effective as relapse prevention for patients with recurrent depression in Scandinavian primary health care.

    Science.gov (United States)

    Lilja, Josefine L; Zelleroth, Clara; Axberg, Ulf; Norlander, Torsten

    2016-10-01

    This study examined the effectiveness of mindfulness-based cognitive therapy (MBCT) in primary care for patients with recurrent depression (major depressive disorder: MDD). According to the World Health Organization (WHO), MDD is now the leading cause of disease burden in middle- and high-income countries. Patients (N = 45) with three or more previous depressive episodes were recruited to participate in MBCT as a preventative intervention. Using a benchmarking approach, outcome data was compared with data from a recent efficacy study. The methodology is a rigorous approach to assessing effectiveness when evidence-based UK protocols are transferred into the existing Scandinavian service delivery. Additionally, a person-centred methodological approach was used to assess clinical significance on the Reliable Change Index (RCI). The analysis revealed comparable or larger effects from pre-test to post-test in reduced psychiatric symptoms, increased quality of life and level of mindfulness, and the effects were maintained over 14 months. Analysis of the relapse rate in the current study (16%) compared to the TAU in the efficacy study (68%) yielded an h value of 0.78, a moderate effect size. Only 13% dropped out of the treatment. According to the RCI findings, 65% to 67% of participants in the clinical group improved, no individual worsened, and women showed a significantly greater improvement of depression and anxiety than men. Therapeutic alliance and motivation had no impact on the outcome. The overall result suggests that MBCT can be implemented successfully in Scandinavian primary health care as a preventive intervention for patients with recurrent depression. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  7. A cytogenetic model predicts relapse risk and survival in patients with acute myeloid leukemia undergoing hematopoietic stem cell transplantation in morphologic complete remission.

    Science.gov (United States)

    Rashidi, Armin; Cashen, Amanda F

    2015-01-01

    Up to 30% of patients with acute myeloid leukemia (AML) and abnormal cytogenetics have persistent cytogenetic abnormalities (pCytAbnl) at morphologic complete remission (mCR). We hypothesized that the prognostic significance of pCytAbnl in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) in mCR varies with cytogenetic risk group. We analyzed the data on 118 patients with AML and abnormal cytogenetics who underwent HSCT in mCR, and developed a risk stratification model based on pCytAbnl and cytogenetic risk group. The model distinguished three groups of patients (Pcytogenetics (n=25) had the shortest median time to relapse (TTR; 5 months), relapse-free survival (RFS; 3 months), and overall survival (OS; 7 months). The group with favorable/intermediate risk cytogenetics and without pCytAbnl (n=43) had the longest median TTR (not reached), RFS (57 months), and OS (57 months). The group with pCytAbnl and favorable/intermediate risk cytogenetics, or, without pCytAbnl but with unfavorable risk cytogenetics (n=50) experienced intermediate TTR (18 months), RFS (9 months), and OS (18 months). In conclusion, a cytogenetic risk model identifies patients with AML in mCR with distinct rates of relapse and survival following HSCT. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Technetium uptake predicts remission and relapse in Grave's disease patients on antithyroid drugs for at least 1 year in South Indian subjects

    Directory of Open Access Journals (Sweden)

    Neha Singhal

    2016-01-01

    Full Text Available Context: Most of the information on remission related factors in Grave's disease are derived from Western literature. It is likely that there may be additional prognostic factors and differences in the postdrug treatment course of Grave's disease in India. Aim: To study factors which predict remission/relapse in Grave's disease patients from South India. Also to establish if technetium (Tc uptake has a role in predicting remission. Subjects and Methods: Records of 174 patients with clinical, biochemical, and scintigraphic criteria consistent with Grave's disease, seen in our Institution between January 2006 and 2014 were analyzed. Patient factors, drug-related factors, Tc-99m uptake and other clinical factors were compared between the remission and nonremission groups. Statistical Analysis Used: Mann–Whitney U-test and Chi-square tests were used when appropriate to compare the groups. Results: Fifty-seven (32.7% patients attained remission after at least 1 year of thionamide therapy. Of these, 11 (19.2% patients relapsed within 1 year. Age, gender, goiter, and presence of extrathyroidal manifestations were not associated with remission. Higher values of Tc uptake were positively associated with remission (P- 0.02. Time to achievement of normal thyroid function and composite dose: Time scores were significantly associated with remission (P - 0.05 and P - 0.01, respectively. Patients with lower FT4 at presentation had a higher chance of remission (P - 0.01. The relapse rates were lower than previously reported in the literature. A higher Tc uptake was found to be significantly associated with relapse also (P - 0.009. Conclusion: The prognostic factors associated with remission in Graves's disease in this South Indian study are not the same as that reported in Western literature. Tc scintigraphy may have an additional role in identifying people who are likely to undergo remission and thus predict the outcome of Grave's disease.

  9. Technetium uptake predicts remission and relapse in Grave's disease patients on antithyroid drugs for at least 1 year in South Indian subjects.

    Science.gov (United States)

    Singhal, Neha; Praveen, V P; Bhavani, Nisha; Menon, Arun S; Menon, Usha; Abraham, Nithya; Kumar, Harish; JayKumar, R V; Nair, Vasantha; Sundaram, Shanmugha; Sundaram, Padma

    2016-01-01

    Most of the information on remission related factors in Grave's disease are derived from Western literature. It is likely that there may be additional prognostic factors and differences in the postdrug treatment course of Grave's disease in India. To study factors which predict remission/relapse in Grave's disease patients from South India. Also to establish if technetium (Tc) uptake has a role in predicting remission. Records of 174 patients with clinical, biochemical, and scintigraphic criteria consistent with Grave's disease, seen in our Institution between January 2006 and 2014 were analyzed. Patient factors, drug-related factors, Tc-99m uptake and other clinical factors were compared between the remission and nonremission groups. Mann-Whitney U-test and Chi-square tests were used when appropriate to compare the groups. Fifty-seven (32.7%) patients attained remission after at least 1 year of thionamide therapy. Of these, 11 (19.2%) patients relapsed within 1 year. Age, gender, goiter, and presence of extrathyroidal manifestations were not associated with remission. Higher values of Tc uptake were positively associated with remission (P- 0.02). Time to achievement of normal thyroid function and composite dose: Time scores were significantly associated with remission (P - 0.05 and P - 0.01, respectively). Patients with lower FT4 at presentation had a higher chance of remission (P - 0.01). The relapse rates were lower than previously reported in the literature. A higher Tc uptake was found to be significantly associated with relapse also (P - 0.009). The prognostic factors associated with remission in Graves's disease in this South Indian study are not the same as that reported in Western literature. Tc scintigraphy may have an additional role in identifying people who are likely to undergo remission and thus predict the outcome of Grave's disease.

  10. Proteasome subunit expression analysis and chemosensitivity in relapsed paediatric acute leukaemia patients receiving bortezomib-containing chemotherapy

    Directory of Open Access Journals (Sweden)

    Denise Niewerth

    2016-09-01

    Full Text Available Abstract Background Drug combinations of the proteasome inhibitor bortezomib with cytotoxic chemotherapy are currently evaluated in phase 2 and 3 trials for the treatment of paediatric acute myeloid leukaemia (AML and acute lymphocytic leukaemia (ALL. Methods We investigated whether expression ratios of immunoproteasome to constitutive proteasome in leukaemic cells correlated with response to bortezomib-containing re-induction chemotherapy in patients with relapsed and refractory acute leukaemia, enrolled in two Children’s Oncology Group phase 2 trials of bortezomib for ALL (COG-AALL07P1 and AML (COG-AAML07P1. Expression of proteasome subunits was examined in 72 patient samples (ALL n = 60, AML n = 12 obtained before start of therapy. Statistical significance between groups was determined by Mann-Whitney U test. Results Ratios of immunoproteasome to constitutive proteasome subunit expression were significantly higher in pre-B ALL cells than in AML cells for both β5i/β5 and β1i/β1 subunits (p = 0.004 and p < 0.001. These ratios correlated with therapy response in AML patients; β1i/β1 ratios were significantly higher (p = 0.028 between patients who did (n = 4 and did not reach complete remission (CR (n = 8, although for β5i/β5 ratios, this did not reach significance. For ALL patients, the subunit ratios were also higher for patients who showed a good early response to therapy but this relation was not statistically significant. Overall, for this study, the patients were treated with combination therapy, so response was not only attributed to proteasome inhibition. Moreover, the leukaemic blast cells were not purified for these samples. Conclusions These first ex vivo results encourage further studies into relative proteasome subunit expression to improve proteasome inhibition-containing therapy and as a potential indicator of bortezomib response in acute leukaemia.

  11. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma

    DEFF Research Database (Denmark)

    San-Miguel, Jesús F; Hungria, Vânia T M; Yoon, Sung-Soo

    2014-01-01

    with bortezomib (1·3 mg/m(2) on days 1, 4, 8, 11, intravenously) and dexamethasone (20 mg on days 1, 2, 4, 5, 8, 9, 11, 12, orally). Patients, physicians, and the investigators who did the data analysis were masked to treatment allocation; crossover was not permitted. The primary endpoint was progression...

  12. Impact of a second FDG PET scan before adjuvant therapy for the early detection of residual/relapsing tumours in high-risk patients with oral cavity cancer and pathological extracapsular spread

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Chun-Ta; Huang, Shiang-Fu; Chen, I-How; Kang, Chung-Jan [Chang Gung Memorial Hospital and Chang Gung University, Department of Otorhinolaryngology, Head and Neck Surgery, Taoyuan (China); Chang Gung Memorial Hospital and Chang Gung University, Head and Neck Oncology Group, Taoyuan (China); Fan, Kang-Hsing; Lin, Chien-Yu [Chang Gung Memorial Hospital and Chang Gung University, Head and Neck Oncology Group, Taoyuan (China); Chang Gung Memorial Hospital and Chang Gung University, Department of Radiation Oncology, Taoyuan (China); Wang, Hung-Ming [Chang Gung Memorial Hospital and Chang Gung University, Head and Neck Oncology Group, Taoyuan (China); Chang Gung Memorial Hospital and Chang Gung University, Department of Medical Oncology, Taoyuan (China); Ng, Shu-Hang [Chang Gung Memorial Hospital and Chang Gung University, Head and Neck Oncology Group, Taoyuan (China); Chang Gung Memorial Hospital and Chang Gung University, Department of Diagnostic Radiology, Taoyuan (China); Hsueh, Chuen; Lee, Li-Yu [Chang Gung Memorial Hospital and Chang Gung University, Head and Neck Oncology Group, Taoyuan (China); Chang Gung Memorial Hospital and Chang Gung University, Department of Pathology, Taoyuan (China); Lin, Chih-Hung [Chang Gung Memorial Hospital and Chang Gung University, Head and Neck Oncology Group, Taoyuan (China); Chang Gung Memorial Hospital and Chang Gung University, Department of Plastic and Reconstructive Surgery, Taoyuan (China); Yen, Tzu-Chen [Chang Gung Memorial Hospital and Chang Gung University, Head and Neck Oncology Group, Taoyuan (China); Chang Gung Memorial Hospital and Chang Gung University, Department of Nuclear Medicine and Molecular Imaging Center, Taoyuan (China)

    2012-06-15

    Extracapsular spread (ECS) to the cervical lymph nodes is a major adverse prognostic factor in oral cavity squamous cell carcinoma (OSCC). We prospectively examined the value of FDG PET immediately before postoperative radiotherapy/concurrent chemoradiotherapy (pre-RT/CCRT PET) to detect residual/relapsing disease in the early postsurgical follow-up period in high-risk OSCC patients with ECS. We examined 183 high-risk OSCC patients with ECS who underwent preoperative FDG PET/CT for staging purposes. Of these patients, 29 underwent a second pre-RT/CCRT FDG PET/CT scan. The clinical utility of the second FDG PET/CT was examined using Kaplan-Meier curve analysis. Patients who underwent the second FDG PET/CT scan had baseline clinicopathological characteristics similar to those who did not undergo a second scan. Of the patients who underwent the second scan, seven (24 %) had unexpected, newly discovered lesions. Five eventually died of the disease, and two had no evidence of recurrence after a change in RT field and dose. In an event-based analysis at 2 months, rates of neck control (6/29 vs. 6/154, p = 0.001), distant metastases (3/29 vs. 4/154, p = 0.046), and disease-free survival (7/29 vs. 10/154, p = 0.003) were significantly higher in patients who received a second PET scan than in those who did not. The second pre-RT/CCRT PET scan was of particular benefit for detecting new lesions in OSCC patients with both ECS and lymph node standardized uptake value (SUV) of {>=}5.2 in the first PET scan. The present findings support the clinical value of pre-RT/CCRT FDG PET for defining treatment strategy in OSCC patients with both ECS and high nodal SUV, even when FDG PET had already been performed during the initial staging work-up. (orig.)

  13. VALVULAR BRONCHIAL BLOCKING IN TREATMENT OF RELAPSING SPONTANEOUS PHEUMOTHORAX IN THE PATIENT WITH PARASEPTAL PULMONARY EMPHYSEMA

    Directory of Open Access Journals (Sweden)

    O. V. Lovacheva

    2014-01-01

    Full Text Available Spontaneous pneumothorax was treated by placing two endobronchial valves during rigid bronchoscopy under anesthesia in a patient with severe end-stage chronic obstructive pulmonary disease (an emphysematous phenotype and overall paraseptal emphysema in the presence of grade III respiratory failure, with complicated spontaneous pneumothorax recurring manifold even after surgical treatment for spontaneous pneumothorax. This gave rise to the expansion of the lung that had collapsed within 18 months, to healing of bronchopleural fistula, and to return to normal life.The duration of a follow-up was 1 year with the valves being present in the bronchi and another year after their removal; there was no recurrence of spontaneous pneumothorax. Examination of respiratory function established significant positive changes (forced expiratory volume, vital capacity, and forced vital capacity after one year, then after removal of endobronchial valves. There were more significant positive changes in blood gas composition: normalization of blood oxygen saturation was achieved. 

  14. Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function

    Directory of Open Access Journals (Sweden)

    Li Y

    2017-11-01

    Full Text Available Yan Li,1 Xiaomin Wang,2 Edward O’Mara,1 Meletios A Dimopoulos,3 Pieter Sonneveld,4 Katja C Weisel,5 Jeffrey Matous,6 David S Siegel,7 Jatin J Shah,8 Elisabeth Kueenburg,9 Lars Sternas,9 Chloe Cavanaugh,9 Mohamed Zaki,9 Maria Palmisano,1 Simon Zhou1 1Translational Development and Clinical Pharmacology, Celgene Corporation, Summit, NJ, USA; 2Non-Clinical Development and Drug Metabolism and Pharmacokinetics, Celgene Corporation, Summit, NJ, USA; 3Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece; 4Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; 5Department of Hematology, University Hospital Tübingen, Tübingen, Germany; 6Department of Hematology/Oncology, Colorado Blood Cancer Institute, Denver, CO, USA; 7Myeloma Division, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA; 8Department of Lymphoma/Myeloma, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX, USA; 9Global Clinical R&D, Celgene Corporation, Summit, NJ, USA Abstract: Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide

  15. Dosimetric analysis of 177Lu-DOTA-rituximab in patients with relapsed/refractory non-Hodgkin's lymphoma.

    Science.gov (United States)

    Yadav, Madhav P; Singla, Suhas; Thakral, Parul; Ballal, Sanjana; Bal, Chandrasekhar

    2016-07-01

    Radioimmunotherapy targeting CD20 receptors in lymphoma using radiolabeled chimeric antibodies may lead to better therapeutic responses than cold anti-CD20 antibodies. This study aimed to assess the biodistribution and present reasonable estimates of normal organ doses, including red marrow using Lu-DOTA-rituximab. Patients with relapsed/refractory CD20+ B-cell non-Hodgkin's lymphoma were recruited into this prospective study. In-house labeling of Lu-DOTA-rituximab was performed and administered after quality assurance. Rituximab (375 mg/m), followed by 50 mCi (1850 MBq) of Lu-DOTA-rituximab was administered as a slow intravenous infusion and emission images were acquired. Regions of interest were drawn for kidney, liver, heart, bladder, spleen, and tumor lesions on both anterior and posterior images. Internal dose estimation was performed using OLINDA v1.0 software. The mean age of the 10 patients (eight men and two women) was 52±13 years. The uptake of radiolabeled antibody was visualized within 30 min of administration in the liver, kidneys, heart, spleen, and bladder. The coefficient of determination (R) was greater than 0.95 for organs and the whole body in all patients. The effective half-life of radioimmunoconjugate was 100±28 h (42-126 h). The critical organ in our study was the red marrow. The average total body dose, effective dose, and effective dose equivalent calculated in all 10 patients were 0.13±0.02, 0.15±0.03, and 0.22±0.04 mGy/MBq, respectively. There may be considerable interindividual differences in absorbed doses of organs and generalization or extrapolation of doses in the clinical setting at present is not feasible with Lu-DOTA-rituximab in non-Hodgkin's lymphoma patients. Patient-specific dosimetry is thus recommended to eliminate the variations and reduce the possibility of dose-limiting toxicity.

  16. The experience of transitioning from relapsing remitting to secondary progressive multiple sclerosis: views of patients and health professionals.

    Science.gov (United States)

    O'Loughlin, Emer; Hourihan, Susan; Chataway, Jeremy; Playford, E Diane; Riazi, Afsane

    2017-09-01

    The majority of people with multiple sclerosis (pwMS) initially present with discreet periods of relapses followed by partial remission of symptoms (RRMS). Over time, most pwMS transition to secondary progressive MS (SPMS), characterized by a gradual accumulation of disability. This study aimed to explore the experiences, coping and needs associated with transitioning from RRMS to SPMS. Data were collected via semi-structured interviews with nine pwMS and seven specialist MS health professionals (HPs). Thematic analysis was used to analyze the data. Four major themes were identified: "Is this really happening?"; "Becoming a reality"; "A life of struggle"; and "Brushing oneself off and moving on." Findings suggested a process of moving from uncertainty towards confirmation of one's diagnostic label. Being reclassified with SPMS served as a turning point for many, and was accompanied by a range of cognitive, emotional and behavioral responses. The value of adequate information and support surrounding the transition, and the potential benefit of education and support for health professionals in relation to the transition were indicated. Understanding pwMS' experiences of the transition is essential if clinicians are to provide pwMS with appropriate support during the transition. Implications for Rehabilitation The timing and delivery of preparatory education for patients about the transition to SPMS should be carefully considered. Sufficient information and follow-up support following the reclassification of SPMS is crucial but sometimes lacking. The importance of sensitive communication of the reclassification of SPMS was highlighted. MS Specialist health professionals may potentially benefit from training and support around communication of the reclassification of SPMS. Given the potential negative psychological impact of the transition, the psychological wellbeing of the patients during the transition to SPMS should be monitored and responded to appropriately.

  17. Relapse (number of detoxifications) in abstinent male alcohol-dependent patients as related to personality traits and types of tolerance to frustration.

    Science.gov (United States)

    Baars, Melanie Y; Müller, Matthias J; Gallhofer, Bernd; Netter, Petra

    2013-01-01

    Personality traits like depression on the one hand and aggression and impulsivity on the other are assumed to be predisposing factors for different types of alcohol dependence. Both types are associated with sensitivity to frustration, but this may be different for the two types of personality according to whether they are confronted with frustrations caused by withdrawal from positive or infliction of negative events. It has not been shown so far if both types of personality factors and the two different sources of frustration are differently relevant for the propensity of relapse. This was investigated here in a study on 60 abstinent male alcohol-dependent patients. Correlations between the number of previous detoxifications reflecting liability to relapse and questionnaire scores on personality factors and on reactions to frustration were computed. Bonferroni-corrected correlations yielded significant relationships between the number of detoxifications and the personality factor of aggression as well as pronounced depressive reactions to frustrating conditions of non-reward caused by humans. Controlling for impulsivity, aggression and depression revealed that depressive reactions to frustration are genuine predictors for probability of relapse independent of underlying personality factors. Persons particularly sensitive to frustrations from human denial of positive reinforcers are liable to relapse which fits the theory of sensitivity to reward in drug-addicted individuals. Results demonstrate that relapse is clearly more related to aggression than to impulsivity, depression and anxiety and may be facilitated if persons are sensitive to frustrating conditions of non-reward caused by social partners. Copyright © 2013 S. Karger AG, Basel.

  18. [The influence of age and illness duration on cognitive impairment in aging patients with relapsing-remitting multiple sclerosis (RR-MS)].

    Science.gov (United States)

    Leclercq, Eugénie; Cabaret, Maryline; Guilbert, Alma; Jougleux, Caroline; Vermersch, Patrick; Moroni, Christine

    2014-09-01

    The aim of this study was to dissociate age and duration of illness effects on cognitive impairment of patients with relapsing-remitting multiple sclerosis. Cognitive impairment among patients with multiple sclerosis (MS) is well known. However, few studies were devoted to assess the respective role of disease duration and age on cognitive functions in MS patients. Therefore, two studies were carried out on relapsing-remitting MS (RR-MS) patients using some tests of the BCcogSEP--a French test battery evaluating cognitive functions in MS. The cognitive deficits of RR-MS patients aged 50 years and over and whose symptoms had been present for more than 20 years were more severe than those of MS patients with a shorter illness duration (less than 10 years) or matched-age control participants. The more impaired cognitive functions were information-processing speed, episodic memory, verbal fluency and attention. On the other hand, cognitive performances of young RR-MS patients were similar to those of older RR-MS patients when all patients had the same illness duration (8 years in this study). Older patients even achieved better performance than younger ones on verbal fluency. This can be partly explained by the theory of cognitive reserve, as reported in previous cognitive aging studies. In RR-MS patients, the influence of illness duration seems to be a predominant factor in the development of cognitive impairment.

  19. Impact of cytomegalovirus reactivation on relapse and survival in patients with acute leukemia who received allogeneic hematopoietic stem cell transplantation in first remission

    OpenAIRE

    Yoon, Jae-Ho; Lee, Seok; Kim, Hee-Je; Jeon, Young-Woo; Lee, Sung-Eun; Cho, Byung-Sik; Lee, Dong-Gun; Eom, Ki-Seong; Kim, Yoo-Jin; Min, Chang-Ki; Cho, Seok-Goo; Min, Woo-Sung; Lee, Jong Wook

    2016-01-01

    Cytomegalovirus (CMV)-reactivation is associated with graft-vs-leukemia (GVL) effect by stimulating natural-killer or T-cells, which showed leukemia relapse prevention after hematopoietic stem cell transplantation (HSCT). We enrolled patients with acute myeloid leukemia (n = 197) and acute lymphoid leukemia (n = 192) who underwent allogeneic-HSCT in first remission. We measured RQ-PCR weekly to detect CMV-reactivation and preemptively used ganciclovir (GCV) when the titer increased twice cons...

  20. Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal survival, frequency of relapse, and outcomes compared to single-seropositive patients.

    Science.gov (United States)

    McAdoo, Stephen P; Tanna, Anisha; Hrušková, Zdenka; Holm, Lisa; Weiner, Maria; Arulkumaran, Nishkantha; Kang, Amy; Satrapová, Veronika; Levy, Jeremy; Ohlsson, Sophie; Tesar, Vladimir; Segelmark, Mårten; Pusey, Charles D

    2017-09-01

    Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such 'double-positive' cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients with ANCA-associated vasculitis, 41 patients with anti-GBM disease, and 37 double-positive patients with ANCA and anti-GBM disease from four European centers. Double-positive patients shared characteristics of ANCA-associated vasculitis (AAV), such as older age distribution and longer symptom duration before diagnosis, and features of anti-GBM disease, such as severe renal disease and high frequency of lung hemorrhage at presentation. Despite having more evidence of chronic injury on renal biopsy compared to patients with anti-GBM disease, double-positive patients had a greater tendency to recover from being dialysis-dependent after treatment and had intermediate long-term renal survival compared to the single-positive patients. However, overall patient survival was similar in all three groups. Predictors of poor patient survival included advanced age, severe renal failure, and lung hemorrhage at presentation. No single-positive anti-GBM patients experienced disease relapse, whereas approximately half of surviving patients with AAV and double-positive patients had recurrent disease during a median follow-up of 4.8 years. Thus, double-positive patients have a truly hybrid disease phenotype, requiring aggressive early treatment for anti-GBM disease, and careful long-term follow-up and consideration for maintenance immunosuppression for AAV. Since double-positivity appears common, further work is required to define the underlying mechanisms of this association and define optimum treatment strategies. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  1. Anti-IgE Monoclonal Antibody (Omalizumab) in Refractory and Relapsing Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss): Data on Seventeen Patients.

    Science.gov (United States)

    Jachiet, Marie; Samson, Maxime; Cottin, Vincent; Kahn, Jean-Emmanuel; Le Guenno, Guillaume; Bonniaud, Philippe; Devilliers, Hervé; Bouillet, Laurence; Gondouin, Anne; Makhlouf, Fatma; Meaux-Ruault, Nadine; Gil, Helder; Bienvenu, Boris; Coste, André; Groh, Matthieu; Giraud, Violaine; Dominique, Stéphane; Godeau, Bertrand; Puéchal, Xavier; Khouatra, Chahera; Ruivard, Marc; Le Jeunne, Claire; Mouthon, Luc; Guillevin, Loïc; Terrier, Benjamin

    2016-09-01

    To describe the efficacy and safety of omalizumab, an anti-IgE monoclonal antibody, in patients with refractory and/or relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA). We conducted a nationwide retrospective study including EGPA patients who received omalizumab. Response was defined as the absence of asthma and/or sinonasal exacerbations with a prednisone dosage of ≤7.5 mg/day (complete response) or >7.5 mg/day (partial response). Seventeen patients (median age 45 years) received omalizumab for severe steroid-dependent asthma (88%) and/or sinonasal involvement (18%). After a median follow-up of 22 months, 6 patients (35%) achieved a complete response, 5 patients (30%) achieved a partial response, and 6 patients (35%) had no improvement. The median Birmingham Vasculitis Activity Score decreased from 2.5 at baseline to 0.5 at 12 months. The median number of exacerbations per month decreased from 1 at baseline to 0 at 12 months, and the median forced expiratory volume in 1 second increased from 63% of the percent predicted at baseline to 85% of the percent predicted at 12 months. The median prednisone dosage decreased from 16 mg/day at baseline to 11 mg/day at 6 months and 9 mg/day at 12 months. Omalizumab was discontinued in 8 patients (47%) during follow-up, because of remission (12.5%), adverse event despite disease remission (12.5%), refractory disease (25%), or relapse (50%). Relapses included retrobulbar optic neuritis attributable to EGPA in 2 patients and severe asthma flare in 2 others. The results of this study suggest that omalizumab may have a corticosteroid-sparing effect in EGPA patients with asthmatic and/or sinonasal manifestations, but reducing the corticosteroid dose may also increase the risk of severe EGPA flares, which raises the question of the safety of omalizumab in patients with EGPA. © 2016, American College of Rheumatology.

  2. ASSESSMENT OF ALCOHOL USE CONTRIBUTING TO RELAPSE AND MAINTENANCE OF ABSTINENCE IN PATIENTS UNDERGOING ALCOHOL DE-ADDICTION AT A TERTIARY CARE CENTRE, HUBLI

    Directory of Open Access Journals (Sweden)

    Arunkumar C

    2017-11-01

    Full Text Available BACKGROUND Alcohol de-addiction is a cornerstone in the treatment of alcohol dependence syndrome. Following de-addiction therapy many patients relapse and only few patients maintain abstinence. The clinical, demographic variables have been reported to play an important role in the dynamics of relapse and abstinence after de-addiction in many studies, but there is no clear cut association between the variables and outcome till date, so the present study was planned. MATERIALS AND METHODS Initially, all study subjects in the study were subjected to alcohol detoxification and later to alcohol de-addiction therapy. After de-addiction patients were recalled for evaluation for period of three months. The sociodemographic data and details of clinical variables related to alcohol use were obtained in a pre-structured pro forma prepared in the Department for the purpose of the study. Severity of Alcohol Dependence Questionnaire (SADQ-C was used in the study to assess the severity of alcohol dependence in the study subjects. RESULTS There was no statistical significance result observed in relation to any demographic variables, clinical variables and outcome (relapse/abstinence to alcohol. CONCLUSION In this study, no significant association was found between sociodemographic variables, clinical variables and the outcome.

  3. Network meta-analysis of randomized trials in multiple myeloma: efficacy and safety in relapsed/refractory patients.

    Science.gov (United States)

    Botta, Cirino; Ciliberto, Domenico; Rossi, Marco; Staropoli, Nicoletta; Cucè, Maria; Galeano, Teresa; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

    2017-02-28

    Despite major therapeutic advancements, multiple myeloma (MM) is still incurable and relapsed/refractory multiple myeloma (RRMM) remains a challenge; the rational choice of the most appropriate regimen in this setting is currently undefined. We performed a systematic review and 2 standard pairwise meta-analyses to evaluate the efficacy of regimens that have been directly compared with bortezomib or immunomodulatory imide drugs (IMiDs) in head-to-head clinical trials and a network meta-analysis (NMA) to determine the relevance of each regimen on the basis of all the available direct and indirect evidence. Sixteen trials were included in the pairwise meta-analyses, and 18 trials were included in the NMA. Pairwise meta-analyses showed that a 3-drug regimen (bortezomib- or IMiD-based) was superior to a 2-drug regimen in progression-free-survival (PFS) and overall response rate (ORR). NMA showed that an IMiD backbone associated with anti-MM monoclonal antibodies (mAbs) (preferably) or proteasome inhibitors had the highest probability of being the most effective regimen with the lowest toxicity. The combination of daratumumab, lenalidomide, and dexamethasone ranked as the first regimen in terms of activity, efficacy, and tolerability according to the average value between surface under the cumulative ranking curve of PFS, overall survival, ORR, complete response rate, and safety. This is the first NMA comparing all currently available regimens evaluated in published randomized trials for the treatment of RRMM, but our results need to be interpreted taking into account differences in their patient populations. Our analysis suggests that IMiDs plus new anti-MM mAb-containing regimens are the most active therapeutic option in RRMM.

  4. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study.

    Science.gov (United States)

    Dreyling, Martin; Jurczak, Wojciech; Jerkeman, Mats; Silva, Rodrigo Santucci; Rusconi, Chiara; Trneny, Marek; Offner, Fritz; Caballero, Dolores; Joao, Cristina; Witzens-Harig, Mathias; Hess, Georg; Bence-Bruckler, Isabelle; Cho, Seok-Goo; Bothos, John; Goldberg, Jenna D; Enny, Christopher; Traina, Shana; Balasubramanian, Sriram; Bandyopadhyay, Nibedita; Sun, Steven; Vermeulen, Jessica; Rizo, Aleksandra; Rule, Simon

    2016-02-20

    Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma. This randomised, open-label, multicentre, phase 3 clinical trial enrolled patients with relapsed or refractory mantle-cell lymphoma confirmed by central pathology in 21 countries who had received one or more rituximab-containing treatments. Patients were stratified by previous therapy and simplified mantle-cell lymphoma international prognostic index score, and were randomly assigned with a computer-generated randomisation schedule to receive daily oral ibrutinib 560 mg or intravenous temsirolimus (175 mg on days 1, 8, and 15 of cycle 1; 75 mg on days 1, 8, and 15 of subsequent 21-day cycles). Randomisation was balanced by using randomly permuted blocks. The primary efficacy endpoint was progression-free survival assessed by a masked independent review committee with the primary hypothesis that ibrutinib compared with temsirolimus significantly improves progression-free survival. The analysis followed the intention-to-treat principle. The trial is ongoing and is registered with ClinicalTrials.gov (number NCT01646021) and with the EU Clinical Trials Register, EudraCT (number 2012-000601-74). Between Dec 10, 2012, and Nov 26, 2013, 280 patients were randomised to ibrutinib (n=139) or temsirolimus (n=141). Primary efficacy analysis showed significant improvement in progression-free survival (pibrutinib versus temsirolimus (hazard ratio 0·43 [95% CI 0·32-0·58]; median progression-free survival 14·6 months [95% CI 10·4-not estimable] vs 6·2 months [4·2-7·9], respectively). Ibrutinib was better tolerated than temsirolimus, with grade 3 or higher treatment-emergent adverse events reported for 94 (68%) versus 121 (87

  5. Patients with primary diffuse large B-cell lymphoma of female genital tract have high risk of central nervous system relapse.

    Science.gov (United States)

    Cao, Xin-xin; Li, Jian; Zhang, Wei; Duan, Ming-hui; Shen, Ti; Zhou, Dao-bin

    2014-06-01

    The objective of this study was to evaluate retrospectively the clinical characteristics, treatments, and outcomes of patients with primary diffuse large B-cell lymphoma (DLBCL) of the female genital tract. The basic characteristics, treatments, and outcomes of six patients diagnosed with primary DLBCL of the female genital tract, including the ovary, uterine cervix, and vagina, treated in our hospital between 2000 and 2012, were analyzed retrospectively. Seven of 323 (2.2 %) newly diagnosed DLBCLs were diagnosed as primary female genital tract DLBCL. Six patients with complete medical data were included in the analysis. The median age at diagnosis was 52.5 years (range 20-65). The presenting symptoms included abnormal vaginal bleeding, increased vaginal discharge, abdominal fullness, and abdominal pain. Two patients had stage IE disease and four patients had stage IIE disease. Treatment included chemotherapy only in five patients, and combined chemotherapy and localized radiation in one patient. After a median follow-up of 58 months, four patients showed relapse in the central nervous system and two had died from progressive disease. The median progression-free survival was 27 months and the median overall survival for this group has not been reached. Patients with primary female genital tract DLBCL may have poor outcomes and a high risk of central nervous system relapse. Central nervous system prophylaxis might be considered in addition to systemic chemotherapy for DLBCL of the female genital tract.

  6. Depression relapse and ethological measures

    NARCIS (Netherlands)

    Hale, WWH; Jansen, JHC; Bouhuys, AL; vandenHoofdakker, RH

    1997-01-01

    Within the framework of interactional theories on depression, the question is raised whether depression relapse can be predicted by observable behavior of remitted patients and their interviewer during an interaction (i.e. discharge interview). Thirty-four patients were interviewed at hospital

  7. Circulating Tyrosinase and MART-1 mRNA does not Independently Predict Relapse or Survival in Patients with AJCC Stage I–II Melanoma

    DEFF Research Database (Denmark)

    Schmidt, Henrik; Sørensen, Boe S; Sjoegren, Pia

    2006-01-01

    The detection of melanoma cells in peripheral blood has been proposed to select patients with a high risk of relapse. In this study, tyrosinase and melanoma antigen recognized by T cells 1 (MART-1) mRNA expression was evaluated in serial samples obtained before definitive surgery and during follow......-up in patients with American Joint Committee on Cancer stage I-II melanoma. Serial samples (n=2,262) were collected from 236 patients from 1997 to 2002. Analyses of the RNA samples were performed with a calibrated reverse transcriptase-PCR assay. Gender, age, primary tumor site, ulceration, thickness, Clark...

  8. Serum YKL-40 Predicts Relapse-Free and Overall Survival in Patients With American Joint Committee on Cancer Stage I and II Melanoma

    DEFF Research Database (Denmark)

    Schmidt, Henrik; Johansen, Julia S; Sjoegren, Pia

    2006-01-01

    level has been associated with poor prognosis in patients with several cancer types. PATIENTS AND METHODS: Serum samples from 234 patients with stage I (n = 162) and II (n = 72) melanoma were analyzed for YKL-40 by enzyme-linked immunosorbent assay. Serial samples were obtained before definitive primary...... surgery and during follow-up. RESULTS: After a median follow-up period of 66 months (range, 1 to 97 months), 41 relapses (18%) and 39 deaths (17%) were observed. Serum YKL-40 treated as an updated continuous covariate were analyzed together with the covariates sex, age, primary tumor site, ulceration...

  9. Clinical features and relapse rates after surgery in type 1 autoimmune pancreatitis differ from type 2: a study of 114 surgically treated European patients.

    Science.gov (United States)

    Detlefsen, Sönke; Zamboni, Giuseppe; Frulloni, Luca; Feyerabend, Bernd; Braun, Felix; Gerke, Oke; Schlitter, Anna Melissa; Esposito, Irene; Klöppel, Günter

    2012-01-01

    At the recent consensus conference on autoimmune pancreatitis (AIP) in Honolulu, we presented preliminary data from our study of surgically treated AIP patients. Our data strongly supported the separation of AIP into type 1 and type 2. Our study is based on a total of 114 surgically treated European AIP patients. Our aims were to elucidate serum IgG4 elevation, other organ involvement, relapse of disease, steroid treatment and diabetes after surgery in 114 surgically treated European AIP patients. 88 pancreaticoduodenectomies, 22 left-sided resections and 4 total pancreatectomies were examined. All cases were graded for granulocytic epithelial lesions, IgG4-positive cells, storiform fibrosis, phlebitis and eosinophilic granulocytes. Follow-up data were obtained from 102/114 patients, mean follow-up was 5.3 years. Histologically, 63 (55.3%) of the 114 patients fulfilled the criteria of type 1 AIP, while 51 (44.7%) patients fulfilled the criteria of type 2 AIP. Type 1 AIP patients were older and more often males than type 2 AIP patients. Elevation of serum IgG4, involvement of extrapancreatic organs, disease relapse, systemic steroid treatment and diabetes after surgery were noted more often in type 1 AIP, while inflammatory bowel disease (IBD) was observed mainly in type 2 AIP. Histological typing of AIP is clinically important because type 1 AIP is part of the IgG4-related disease and type 2 AIP is associated with IBD. Our data also show that relapse of disease and steroid treatment after surgery occur more frequently in type 1 than in type 2 AIP. Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  10. Progression of a series of patients with relapsing-remitting multiple sclerosis treated for 7 years with natalizumab using the "no evidence of disease activity" parameter.

    Science.gov (United States)

    Pato Pato, A; Costa Arpín, E; Rodríguez Regal, A; Rodríguez Constenla, I; Cimas Hernando, I; Muñoz Pousa, I; Naya Ríos, L; Lorenzo González, J R; Amigo Jorrín, M C; Prieto González, J M

    2018-05-10

    The safety and effectiveness of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in clinical trials. However, due to the limitations of these trials, it is important to know how the condition behaves under long-term clinical practice conditions. To determine the long-term effectiveness of natalizumab in patients with RRMS by means of annual evaluation of the "no evidence of disease activity" (NEDA) parameter, which includes number of relapses, disability (measured with the Expanded Disability Status Scale), and brain MRI parameters. We performed a retrospective study of patients with RRMS from 3 centres who were treated with one or more doses of natalizumab. Each year, we evaluated NEDA status and safety based on the percentage of patients who discontinued treatment with natalizumab and experienced adverse reactions. The study included 89 patients, most of whom received treatment for 2 to 4 years, with a follow-up period of up to 7 years. Natalizumab significantly reduces the radiological and clinical progression of the disease, as well as the annual rate of relapses. The NEDA parameter demonstrates the effectiveness of the drug, with values of 75.28% for year one and 66.67% for year 7. Twenty-five patients (28.1%) dropped out after a median of 4 years. Fourteen of these patients (56%) dropped out due to the appearance of anti-JC virus antibodies, either in isolation or associated with another cause. Four dropouts (16%) were due to treatment ineffectiveness, with one patient dying due to progressive multifocal leukoencephalopathy. Natalizumab is highly effective as measured by the NEDA long-term remission parameter. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. The MS@Work study: a 3-year prospective observational study on factors involved with work participation in patients with relapsing-remitting Multiple Sclerosis.

    Science.gov (United States)

    van der Hiele, Karin; van Gorp, Dennis A M; Heerings, Marco A P; van Lieshout, Irma; Jongen, Peter J; Reneman, Michiel F; van der Klink, Jac J L; Vosman, Frans; Middelkoop, Huub A M; Visser, Leo H

    2015-08-12

    Multiple Sclerosis (MS) is the most common cause of neurological disability in young and middle-aged adults. At this stage in life most people are in the midst of their working career. The majority of MS patients are unable to retain employment within 10 years from disease onset. Leading up to unemployment, many may experience a reduction in hours or work responsibilities and increased time missed from work. The MS@Work study examines various factors that may influence work participation in relapsing-remitting MS patients, including disease-related factors, the working environment and personal factors. The MS@Work study is a multicenter, 3-year prospective observational study on work participation in patients with relapsing-remitting MS. We aim to include 350 patients through 15-18 MS outpatient clinics in the Netherlands. Eligible participants are 18 years and older, and either currently employed or within three years since their last employment. At baseline and after 1, 2 and 3 years, the participants are asked to complete online questionnaires (including questions on work participation, work problems and accommodations, cognitive and physical ability, anxiety, depression, psychosocial stress, quality of life, fatigue, empathy, personality traits and coping strategies) and undergo cognitive and neurological examinations. After six months, patients are requested to only complete online questionnaires. Patient perspectives on maintaining and improving work participation and reasons to stop working are gathered through semi-structured interviews in a sub-group of patients. Prospective studies with long-term follow-up on work participation in MS are rare, or take into account a limited number of factors. The MS@Work study provides a 3-year follow-up on various factors that may influence work participation in patients with relapsing-remitting MS. We aim to identify factors that relate to job loss and to provide information about preventative measures for physicians

  12. Salvage of relapse of patients with Hodgkin's disease in clinical stages I or II who were staged with laparotomy and initially treated with radiotherapy alone. A report from the international database on Hodgkin's disease

    DEFF Research Database (Denmark)

    Specht, L.; Horwich, A.; Ashley, S.

    1994-01-01

    patients in the International Database on Hodgkin's Disease who were initially in clinical Stages I or II, who were staged with laparotomy, and who relapsed after initial treatment with irradiation alone. Factors analyzed for outcome after first relapse included initial stage, age, sex, histology......PURPOSE: To analyze presentation variables that might indicate a high or low likelihood of success of the treatment of patients relapsing after initial radiotherapy of Hodgkin's disease in clinical Stages I or II who were staged with laparotomy. METHODS AND MATERIALS: Data were analyzed on 681...

  13. Flow cytometric minimal residual disease assessment of peripheral blood in acute lymphoblastic leukaemia patients has potential for early detection of relapsed extramedullary disease.

    Science.gov (United States)

    Keegan, Alissa; Charest, Karry; Schmidt, Ryan; Briggs, Debra; Deangelo, Daniel J; Li, Betty; Morgan, Elizabeth A; Pozdnyakova, Olga

    2018-03-27

    To evaluate peripheral blood (PB) for minimal residual disease (MRD) assessment in adults with acute lymphoblastic leukaemia (ALL). We analysed 76 matched bone marrow (BM) aspirate and PB specimens independently for the presence of ALL MRD by six-colour flow cytometry (FC). The overall rate of BM MRD-positivity was 24% (18/76) and PB was also MRD-positive in 22% (4/18) of BM-positive cases. We identified two cases with evidence of leukaemic cells in PB at the time of the extramedullary relapse that were interpreted as MRD-negative in BM. The use of PB MRD as a non-invasive method for monitoring of systemic relapse may have added clinical and diagnostic value in patients with high risk of extramedullary disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Anti-hLAMP2-antibodies and dual positivity for anti-GBM and MPO-ANCA in a patient with relapsing pulmonary-renal syndrome

    Directory of Open Access Journals (Sweden)

    Kistler Thomas

    2011-06-01

    Full Text Available Abstract Background Pulmonary-renal syndrome associated with anti-glomerular basement membrane (GBM antibodies, also known as Goodpasture's syndrome, is a rare but acute and life-threatening condition. One third of patients presenting as anti-GBM antibody positive pulmonary-renal syndrome or rapidly progressive glomerulonephritis are also tested positive for anti-neutrophil cytoplasmic antibodies (ANCA. Whilst anti-GBM disease is considered a non-relapsing condition, the long-term course of double-positive patients is less predictable. Case Presentation We report a patient with such dual positivity, who presented with pulmonary hemorrhage, crescentic glomerulonephritis and membranous nephropathy. Plasmapheresis in combination with immunosuppresive therapy led to a rapid remission but the disease relapsed after two years. The serum of the patient was tested positive for antibodies to human lysosomal membrane protein 2 (hLAMP2, a novel autoantigen in patients with active small-vessel vasculitis (SVV. The anti-hLAMP2 antibody levels correlated positively with clinical disease activity in this patient. Conclusion We hypothesize that this antibody may indicate a clinical course similar to ANCA-associated vasculitis in double-positive patients. However, this needs to be confirmed on comprehensive patient cohorts.

  15. The regulatory BCL2 promoter polymorphism (-938C>A) is associated with relapse and survival of patients with oropharyngeal squamous cell carcinoma.

    Science.gov (United States)

    Lehnerdt, G F; Franz, P; Bankfalvi, A; Grehl, S; Kelava, A; Nückel, H; Lang, S; Schmid, K W; Siffert, W; Bachmann, H S

    2009-06-01

    Expression of the antiapoptotic and antiproliferative protein B-cell lymphoma 2 (Bcl-2) has been repeatedly shown to be associated with better locoregional control and patients' survival in oropharyngeal squamous cell carcinoma (OSCC). A regulatory (-938C>A) single-nucleotide polymorphism (SNP) in the inhibitory P2 BCL2 gene promoter generates significantly different BCL2 promoter activities and has been associated with outcome in different malignancies. The aim of the present study was to analyze the possible influence of the (-938C>A) SNP on survival of patients suffering from OSCC. One hundred and thirty-three patients with primary OSCC were retrospectively investigated. Bcl-2 expression of tumor cells was demonstrated by means of immunohistochemistry. Both the Bcl-2 expression and the (-938C>A) genotypes were correlated with the patients' survival. The (-938C>A) SNP was significantly related to Bcl-2 expression (P = 0.008). Kaplan-Meier curves revealed a significant association of the -938 SNP with relapse-free (P = 0.0283) and overall survival (P = 0.0247). Multiple Cox regression identified the BCL2 (-938CC) genotype as an independent prognostic factor for relapse [hazard ratio (HR) 1.898, P = 0.021] as well as for death in OSCC patients (HR 1.897, P = 0.013). The (-938C>A) SNP represents a potential novel prognostic marker in patients with OSCC that could help to identify a group of patients at high risk for relapse and death.

  16. Changes in brain-derived neurotrophic factor (BDNF) during abstinence could be associated with relapse in cocaine-dependent patients.

    Science.gov (United States)

    Corominas-Roso, Margarida; Roncero, Carlos; Daigre, Constanza; Grau-Lopez, Lara; Ros-Cucurull, Elena; Rodríguez-Cintas, Laia; Sanchez-Mora, Cristina; Lopez, Maria Victoria; Ribases, Marta; Casas, Miguel

    2015-02-28

    Brain-derived neurotrophic factor (BDNF) is involved in cocaine craving in humans and drug seeking in rodents. Based on this, the aim of this study was to explore the possible role of serum BDNF in cocaine relapse in abstinent addicts. Forty cocaine dependent subjects (DSM-IV criteria) were included in an inpatient 2 weeks abstinence program. Organic and psychiatric co-morbidities were excluded. Two serum samples were collected for each subject at baseline and at after 14 abstinence days. After discharge, all cocaine addicts underwent a 22 weeks follow-up, after which they were classified into early relapsers (ER) (resumed during the first 14 days after discharge,) or late relapsers (LR) (resumed beyond 14 days after discharge). The only clinical differences between groups were the number of consumption days during the last month before detoxification. Serum BDNF levels increased significantly across the 12 days of abstinence in the LR group (p=0.02), whereas in the ER group BDNF remained unchanged. In the ER group, the change of serum BDNF during abstinence negatively correlated with the improvement in depressive symptoms (p=0.02). These results suggest that BDNF has a role in relapse to cocaine consumption in abstinent addicts, although the underlying neurobiological mechanisms remain to be clarified. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Towards a Perron--Frobenius Theory for Eventually Positive Operators

    OpenAIRE

    Glück, Jochen

    2016-01-01

    This article is a contribution to the spectral theory of so-called eventually positive operators, i.e.\\ operators $T$ which may not be positive but whose powers $T^n$ become positive for large enough $n$. While the spectral theory of such operators is well understood in finite dimensions, the infinite dimensional case has received much less attention in the literature. We show that several sensible notions of "eventual positivity" can be defined in the infinite dimensional setting, and in con...

  18. Predicting relapse in major depressive disorder using patient-reported outcomes of depressive symptom severity, functioning, and quality of life in the Individual Burden of Illness Index for Depression (IBI-D).

    Science.gov (United States)

    Ishak, Waguih William; Greenberg, Jared M; Cohen, Robert M

    2013-10-01

    Patients with Major Depressive Disorder (MDD) often experience unexpected relapses, despite achieving remission. This study examines the utility of a single multidimensional measure that captures variance in patient-reported Depressive Symptom Severity, Functioning, and Quality of Life (QOL), in predicting MDD relapse. Complete data from remitted patients at the completion of 12 weeks of citalopram in the STAR*D study were used to calculate the Individual Burden of Illness index for Depression (IBI-D), and predict subsequent relapse at six (n=956), nine (n=778), and twelve months (n=479) using generalized linear models. Depressive Symptom Severity, Functioning, and QOL were all predictors of subsequent relapse. Using Akaike information criteria (AIC), the IBI-D provided a good model for relapse even when Depressive Symptom Severity, Functioning, and QOL were combined in a single model. Specifically, an increase of one in the IBI-D increased the odds ratio of relapse by 2.5 at 6 months (β=0.921 ± 0.194, z=4.76, pDepressive Symptom Severity in the IBI-D is useful in assessing the full burden of illness and in adequately predicting relapse, in MDD. © 2013 Elsevier B.V. All rights reserved.

  19. Advanced-stage Hodgkin lymphoma: US/chest radiography for detection of relapse in patients in first complete remission--a randomized trial of routine surveillance imaging procedures.

    Science.gov (United States)

    Picardi, Marco; Pugliese, Novella; Cirillo, Michele; Zeppa, Pio; Cozzolino, Imma; Ciancia, Giuseppe; Pettinato, Guido; Salvatore, Claudia; Quintarelli, Concetta; Pane, Fabrizio

    2014-07-01

    To compare the use of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) with the use of a combination of ultrasonography (US) and chest radiography for systematic follow-up of patients with high-risk Hodgkin lymphoma. Institutional review board approval and informed consent were obtained. In a single center between January 2001 and December 2009, patients with advanced-stage Hodgkin lymphoma who had responded completely to first-line treatment were randomly assigned (1:1) to follow-up with either PET/CT or US/chest radiography. Follow-up included clinical and imaging procedures at 4, 8, 12, 16, 20, 24, 30, 36, 48, 60, 84, and 108 months after treatment discontinuation. When clinical and/or imaging results were positive, recurrence was confirmed histologically. The primary endpoint was to compare the sensitivity of the two follow-up imaging approaches. Secondary endpoints were their specificity, positive and negative predictive values, time to recurrence detection, radiation risks, and costs. A total of 300 patients were randomized into the two arms. The study was closed after a median follow-up time of 60 months, with a relapse rate of 27%. Sensitivity for detection of Hodgkin lymphoma was similar for the two follow-up approaches. All of the relapses (40 of 40) were identified with FDG PET/CT (100%) and 39 of 40 relapses were identified with US/chest radiography (97.5%; P = .0001 for the equivalence test). US/chest radiography showed significantly higher specificity and positive predictive value than did PET/CT (96% [106 of 110] vs 86% [95 of 110], respectively; P = .02; and 91% [39 of 43] vs 73% [40 of 55], respectively; P = .01). Exposure to ionizing radiation was estimated to be 14.5 mSv for one PET/CT examination versus 0.1 mSv for one chest radiographic examination. Estimated cost per relapse diagnosed with routine PET/CT was 10-fold higher compared with that diagnosed with routine US/chest radiography. US and

  20. Relapses in Multiple Sclerosis: Definition, Pathophysiology, Features, Imitators, and Treatment

    Directory of Open Access Journals (Sweden)

    Serhan Sevim

    2016-09-01

    Full Text Available Relapse in multiple sclerosis (MS is defined as a neurologic deficit associated with an acute inflammatory demyelinating event that lasts at least 24 hours in the absence of fever and infection. Myelinoclasis and axonal transection occur in relapses. Diagnosis, prognosis, treatment, and many other features of the disease are directly related to the relapses. MS starts as the relapsing-remitting (RRMS form in 85% of patients. A large number of relapses in the first years, polysymptomatic relapses, and pyramidal system, brain stem, and spinal cord involvement are signs of a poor outcome. The average frequency of relapses is approximately one per year during the first years of RRMS. The frequency of relapses increases during systemic infections, psychological stress, and in the postpartum first 3 months. Seventy-five percent of relapses are monosymptomatic. Pseudo-relapses and paroxysmal symptoms are distinguished from relapses by their sudden onset, sudden termination, and shorter duration. Contrast enhancement is valuable in imaging, but undetectable in most relapses. The regression in the first few weeks of relapses is explained by reduction of the edema, and by remyelination in the following months. Relapses and their features are also among the main determinants of treatment. High-dose methylprednisolone and early treatment with adrenocorticotropic hormone reduce post-relapse disability and shorten the duration of relapses. Plasmapheresis is a good option for patients who do not respond to steroid treatment. Identification of relapses by patients and physicians, distinguishing them from imitators, proper evaluation, treatment when necessary, and monitoring the results are of great importance for patients with MS. The educational levels of patients and physicians regarding these parameters should be increased. Well-designed studies that evaluate the long-term effect of relapse treatment on disability are needed.

  1. INF-β1b therapy modulates L-arginine and nitric oxide metabolism in patients with relapse remittent multiple sclerosis.

    Science.gov (United States)

    Stojanovic, Ivana; Vojinovic, Slobodan; Ljubisavljevic, Srdjan; Pavlovic, Radmila; Basic, Jelena; Pavlovic, Dusica; Ilic, Andjelka; Cvetkovic, Tatjana; Stukalov, Maja

    2012-12-15

    The scope of this study is the examination of NO(2)+NO(3), 3-nitrotyrosine (3-NT), S-nitrosothiols (RSNO), arginase activity and asymmetric (ADMA) and symmetric (SDMA) dimethyl-L-arginine concentrations in plasma of MS patients during interferon-β1b therapy. The study population included 15 (12 women, 3 men) untreated MS patients and 12 (10 women, 2 men) interferon-β1b treated MS patients with clinically definite relapsing MS (McDonalds criteria) for at least 1 year and a baseline EDSS score of 1.0 to 3.5 inclusive. Patients were treated with 250 μg IU interferon-β1b s.c. every second day during 30 months. The disease course was evaluated using correlations between baseline EDSS score and relapse rates in both groups. During interferon-β1b treatment, EDSS scores in treated patients were decreased compared to untreated ones - after 18 and 30 months (p<0.05). In interferon-β1b treated MS patients, NO(2)+NO(3), 3-NT and RSNO plasma concentrations were significantly lower (p<0.05), while arginase activity, ADMA and SDMA levels were significantly increased (p<0.05) during the therapy, compared to the baseline levels in treated patients. The investigated parameters may be the new biomarkers, providing information for the therapeutic approach and valuable in clinical monitoring. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Laryngeal manifestations of relapsing polychondritis and a novel treatment option.

    Science.gov (United States)

    Childs, Lesley F; Rickert, Scott; Wengerman, Oscar C; Lebovics, Robert; Blitzer, Andrew

    2012-09-01

    Laryngotracheal involvement in relapsing polychondritis (RP) is rare. However, it is one of the most common causes of death in this patient population. We present three patients who primarily presented with laryngeal manifestations of RP and a novel treatment option for bamboo nodules. Retrospective chart review and comprehensive review of the literature. Two patients first presented to an otolaryngologist because of hoarseness and chronic cough that eventually progressed to dyspnea upon exertion. Laryngeal examination revealed subglottic stenoses. Upon rheumatologic workup both were diagnosed with RP. After treatment with steroids and immunosuppressive drugs, one of the patient's laryngeal symptoms improved, whereas the other required dilation procedures. Neither patient had classic auricular or nasal symptoms upon initial presentation. The third patient was being treated for spasmodic dysphonia and was noted to have bamboo nodules with accompanying dysphonia. Rheumatologic workup revealed RP and systemic treatment ensued. Unfortunately, her symptoms of hoarseness persisted despite systemic treatment. A pulsed-potassium-titanyl-phosphate (KTP) laser was applied to the bilateral bamboo nodules, which eventually caused resolution of her vocal fold lesions and dysphonia. We present three patients with RP, all of whom sought health care by an otolaryngologist primarily. Awareness of this disease entity and the possibility for early laryngeal involvement is crucial for proper care of those with this life-threatening disease. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  3. Salvage chemotherapy of gemcitabine, dexamethasone, and cisplatin (GDP) for patients with relapsed or refractory peripheral T-cell lymphomas: a consortium for improving survival of lymphoma (CISL) trial.

    Science.gov (United States)

    Park, Byeong-Bae; Kim, Won Seog; Suh, Cheolwon; Shin, Dong-Yeop; Kim, Jeong-A; Kim, Hoon-Gu; Lee, Won Sik

    2015-11-01

    There is no standard salvage chemotherapy for relapsed or refractory peripheral T-cell lymphomas (PTCLs). Gemcitabine combined with cisplatin has been known as an effective regimen for lymphoma treatment in the salvage setting. We investigated the efficacy and toxicity of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory PTCLs in search of a more effective and less toxic therapy. Patients with relapsed or refractory PTCLs with more than one previous regimen were eligible. Treatment consisted of gemcitabine 1000 mg/m(2) intravenously (i.v.) on days 1 and 8, dexamethasone 40 mg orally on days 1-4, and cisplatin 70 mg/m(2) i.v. on day 1, and then every 21 days. Patients could proceed to autologous stem cell transplantation (ASCT) after four cycles of GDP or receive up to six treatment cycles. Twenty-five eligible patients were evaluated for toxicity and response. The diagnoses of participants included 14 cases of PTCL-not otherwise specified (NOS) (56 %) and four cases of angioimmunoblastic T-cell lymphoma (16 %) among others. The median age of the patients was 59 years (range 20-75 years). After treatments with GDP, which delivered a median of four GDP cycles, there were 12 patients with complete responses (CR; 48 %) and six with partial responses (PR; 24 %). The overall response rate (RR) was 72 %. Four patients preceded to ASCT, and three patients finally achieved CR. The median progression free survival was 9.3 months (95 % confidence interval (CI); 4.1-14.6) with a median follow-up duration of 27.1 months. In a total of 86 cycles of GDP, grade 3 or 4 neutropenia and thrombocytopenia occurred in 16.3 and 12.8 % of cycles, respectively. Three patients (3.3 %) experienced febrile neutropenia. GDP is a highly effective and optimal salvage regimen for relapsed or refractory PTCLs and can be administered with acceptable toxicity.

  4. Preoperative [18F]-fluorodeoxyglucose positron emission tomography standardized uptake value of neck lymph nodes may aid in selecting patients with oral cavity squamous cell carcinoma for salvage therapy after relapse

    International Nuclear Information System (INIS)

    Liao, Chun-Ta; Huang, Shiang-Fu; Chen, I. How; Chang, Joseph Tung-Chieh; Wang, Hung-Ming; Ng, Shu-Hang; Hsueh, Chuen; Lee, Li-Yu.; Lin, Chih-Hung; Cheng, Ann-Joy; Yen, Tzu-Chen

    2009-01-01

    Relapse of tumours in patients with oral cavity squamous cell carcinoma (OSCC) is associated with a dismal outcome. In this prospective study, we sought to investigate the clinical significance of the preoperative maximal standardized uptake value (SUVmax) at the neck lymph nodes in selecting patients with OSCC for salvage therapy after relapse. Between 2002 and 2007, 108 patients with early relapse of OSCC (n=75) or late relapse of OSCC (n=33) were identified. Salvage therapy was performed in 47 patients. All patients underwent 2-deoxy-2[ 18 F]-fluoro-d-glucose positron emission tomography during the 2 weeks before surgery and neck dissection. All patients were followed for 12 months or more after surgery or until death. The optimal cut-off value for the neck lymph node SUVmax (SUVnodal-max) was selected according to the 5-year disease-specific survival (DSS) rate. Independent risk factors were identified by Cox regression analysis. The mean follow-up for all patients was 20.3 months (41.1 months for surviving patients). In the early relapse group, several prognostic factors were identified in univariate and multivariate analyses, including a SUVnodal-max value of ≥4.2. A scoring system based on univariate analysis was formulated. Patients with a score of 0 had a better 5-year DSS than those with scores of 1 or higher (58% vs. 5%, p=0.0003). In patients with late relapse, a SUVnodal-max value of ≥4.2 had the highest prognostic value for predicting the 5-year DSS (45% vs. 0%, p=0.0005). Among patients with relapsed OSCC, the SUVnodal-max value may aid in selecting patients for salvage therapy. (orig.)

  5. Tumor relapse present in oncologic nasal repair

    International Nuclear Information System (INIS)

    Galvez Chavez, Julio Cesar; Sanchez Wals, Lenia; Monzon Fernandez, Abel Nicolas; Morales Tirado, Roxana

    2009-01-01

    Tumor relapse is one of the more fearsome complications of the oncologic course and also to obscure the life prognosis, causing the loss of many reconstructions and of exhausting the repairing surgical possibilities. The aim of this study was to determine the relapse frequency, the repercussion on the repair and the subsequent medical course of patients operated on malign nasal tumors

  6. Sacral Myeloid Sarcoma Manifesting as Radiculopathy in a Pediatric Patient: An Unusual Form of Myeloid Leukemia Relapse

    Directory of Open Access Journals (Sweden)

    Joana Ruivo Rodrigues

    2018-01-01

    Full Text Available Myeloid sarcoma (MS, granulocytic sarcoma or chloroma, is defined as a localized extramedullary mass of blasts of granulocytic lineage with or without maturation, occurring outside the bone marrow. MS can be diagnosed concurrently with acute myeloid leukemia (AML or myelodysplastic syndrome (MDS. The authors report a case of sacral MS occurring as a relapse of myeloid leukemia in a 5-year-old girl who was taken to the emergency department with radiculopathy symptoms.

  7. Gemcitabine and treatment of diffuse large B-cell lymphoma in relapsed or refractory elderly patients: A prospective randomized trial in Algeria

    Directory of Open Access Journals (Sweden)

    Aribi Mourad

    2010-01-01

    Full Text Available Context: Support for non-Hodgkin′s lymphoma (NHL with large cells that is refractory or relapsed after first-line chemotherapy poses a greater therapeutic problem with bone marrow transplant therapy or when old age is a contra-indication for high-dose chemotherapy, especially among developing countries such as Algeria. Aim: To show that the regimen, including gemcitabine, could be more effective in treating elderly patients with diffuse large B-cell lymphoma (DLBCL in relapse / refractory, without complete remission, when compared with the ESHAP (etoposide, cisplatine, solumedrol, aracytine regimen. Materials and Methods: Ninety-six patients in the age group of 60-70 years were volunteers for a prospective randomized single-blind study, carried out for three years. Patients were divided into two groups by the drawing of lots. The first group (GA, n = 48, relapse; n = 27 [56.3%], refractory; n = 21 [43.7%] received treatment with ESHAP protocol and the second one (GB, n = 48, relapse; n = 28 [58%], refractory; n = 20 [42%] with GPD (gemcitabine, dexamethasone, cisplatine protocol. Results: The overall response rates and mean survival at three years were significantly higher among patients subjected to GPD treatment compared with those subjected to ESHAP treatment (63% vs. 55%, P = 0.01 and 20.5% [95% CI 16.5-24.5] vs. 11.8% [8.9-14.6], respectively. Additionally, three-year progression-free and event-free survival rates were 20.5% (16.3-24 and 19.7% (15.9-23.5, respectively, for the GPD regimen and 10.9% (8.2-13.7 and 11.1% (95% CI 8.5-13.7, respectively, for the ESHAP regimen. Moreover, the GPD regimen was associated with improving overall survival (RR=2.02, 95% CI 1.59-2.56; P = 0.000, event-free survival (2.03, 1.64-2.52; P < 0.001 and progression-free survival (1.86, 1.46-2.37; P < 0.001. Conclusion: In cases of contra-indication for high-dose chemotherapy for elderly patients with DLBCL, without complete remission, the Gemcitabine

  8. Five-year follow-up of survival and relapse in patients who received cryotherapy during high-dose chemotherapy for stem cell transplantation shows no safety concerns.

    Science.gov (United States)

    Svanberg, A; Ohrn, K; Birgegård, G

    2012-11-01

    We have previously published a randomised controlled study of the efficacy of cryotherapy in preventing acute oral mucositis after high-dose chemotherapy for stem cell transplantation. The present study is a 5-year follow-up safety study of survival in these patients. In the previously published study oral cryotherapy (cooling of the oral cavity) during high-dose chemotherapy significantly reduced mucositis grade and opiate use in the treated group. All patients were followed up for at least 5 years with regard to relapse and death rates. Baseline data, transplant complications and mucositis data were compared. Significantly more patients (25/39) who received oral cryotherapy were alive after 5 years compared to 15/39 in the control group (P= 0.025). Relapse rates were similar. The only baseline difference was a lower proportion of patients in complete remission at transplantation in the control group (6 vs. 13, P= 0.047). This 5-year follow-up study gave no support for safety concerns with cryotherapy. © 2012 Blackwell Publishing Ltd.

  9. Homozygous HLA-C1 is Associated with Reduced Risk of Relapse after HLA-Matched Transplantation in Patients with Myeloid Leukemia.

    Science.gov (United States)

    Arima, Nobuyoshi; Kanda, Junya; Tanaka, Junji; Yabe, Toshio; Morishima, Yasuo; Kim, Sung-Won; Najima, Yuho; Ozawa, Yukiyasu; Eto, Tetsuya; Kanamori, Heiwa; Mori, Takehiko; Kobayashi, Naoki; Kondo, Tadakazu; Nakamae, Hirohisa; Uchida, Naoyuki; Inoue, Masami; Fukuda, Takahiro; Ichinohe, Tatsuo; Atsuta, Yoshiko; Kanda, Yoshinobu

    2018-04-01

    Natural killer (NK) cells assume graft-versus-leukemia alloreactivity after hematopoietic stem cell transplantation (HSCT) through their inhibitory killer cell immunoglobulin-like receptors (KIRs). KIR2D family members recognize HLA-C alleles with Asn80 (HLA-C1) or Lys80 (HLA-C2). The predominance of HLA-C1 over HLA-C2 and the frequent presence of KIR2DL1 are characteristic of Japanese people. We compared clinical outcomes among homozygous HLA-C1 (HLA-C1/C1) patients and heterozygous HLA-C1/C2 patients who underwent HLA-matched HSCT for hematologic malignancies by assessing the data of 10,638 patients from the Japanese national registry. HLA-C1/C1 recipients had a lower rate of relapse than HLA-C1/C2 recipients after transplantation for acute myelogenous leukemia (AML) (hazard ratio [HR], .79; P = .006) and chronic myelogenous leukemia (CML) (HR, .48; P = .025), but not for acute lymphoblastic leukemia (HR, 1.36), lymphoma (HR, .97), or low-grade myelodysplastic syndrome (HR, 1.40). We then grouped AML and CML patients together and divided them into several subgroups. Advantages of HLA-C1/C1 recipients over HLA-C1/C2 recipients regarding relapse were observed irrespective of donor relation (related: HR, .79, P = .069; unrelated: HR, .77, P = .022), preparative regimen (myeloablative: HR, .79, P = .014; reduced intensity: HR, .73, P = .084), and occurrence of acute graft-versus-host disease (yes: HR, .70, P = .122; no, HR .71, P = .026) or cytomegalovirus reactivation (reactivated: HR .67,P = .054; nonreactivated: HR .71, P = .033); however, these advantages were not observed in recipients with a delay in achieving complete chimerism (HR, 1.06). The advantage of decreasing relapse and extending relapse-free survival of C1/1 over C1/2 KIR-ligand status was most pronounced in T cell-depleted HSCT (HR, .27; P < .001 and HR, .30; P = .002, respectively) and in children age <15 years (HR, .29; P < .001 and HR .31; P

  10. Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial

    Directory of Open Access Journals (Sweden)

    Francine Foss

    2016-03-01

    Full Text Available Abstract Background Achievement of durable responses in patients with relapsed/refractory peripheral T cell lymphoma (PTCL is challenging with current therapies, and there are few data regarding the potential benefits of continuing treatment in patients with the best response of stable disease (SD. Histone deacetylase inhibitors are a novel class of drugs with activity in T cell malignancies. Romidepsin was approved by the US Food and Drug Administration for the treatment of relapsed/refractory PTCL based on a pivotal trial demonstrating an objective response rate of 25 % (33/130, including 15 % with confirmed/unconfirmed complete response and a median duration of response of 28 months. Our objective was to further study the clinical benefits of romidepsin in patients that had the best response of SD. Methods Patients with PTCL relapsed/refractory to ≥1 prior therapy were treated with the approved dose of 14 mg/m2 romidepsin on days 1, 8, and 15 of six 28-day cycles; patients with SD or response after cycle 6 were allowed to continue on study until progression. By protocol amendment, patients treated for ≥12 cycles could receive maintenance dosing twice per cycle; after cycle 24, dosing could be further reduced to once per cycle in those who had received maintenance dosing for ≥6 months. Results Of the 32 patients (25 % with the best response of SD, 22 had SD for ≥90 days (SD90; cycle 4 response assessment. The longest SD was >3 years in a patient who received maintenance dosing of 14 mg/m2 on days 1 and 15 beginning in cycle 13. Patients with the best response of SD90 or partial response achieved similar overall and progression-free survival. Prolonged dosing of romidepsin was well tolerated. Conclusions We concluded that patients who achieve SD may consider continuing treatment because the clinical benefits of romidepsin may extend beyond objective responses. Trial registration NCT00426764

  11. Factors associated with failure to achieve remission and with relapse after remission in patients with major depressive disorder in the PERFORM study

    Directory of Open Access Journals (Sweden)

    Saragoussi D

    2017-08-01

    Full Text Available Delphine Saragoussi,1 Maëlys Touya,2 Josep Maria Haro,3 Bengt Jönsson,4 Martin Knapp,5 Bastien Botrel,6 Ioana Florea,7 Henrik Loft,8 Benoît Rive9 1Real-World Evidence and Epidemiology, Lundbeck SAS, Issy-les-Moulineaux, France; 2Health Economics and Outcomes Research, Lundbeck, Deerfield, IL, US; 3Research and Teaching Unit, Parc Sanitari Sant Joan de Deu, CIBERSAM, University of Barcelona, Sant Boi de Llobregat, Barcelona, Spain; 4Department of Economics, Stockholm School of Economics, Stockholm, Sweden; 5Department of Health Policy, London School of Economics and Political Science, London, UK; 6Biostatistics, Inferential, Paris, France; 7Clinical Research Paediatrics, H. Lundbeck A/S, Valby, Denmark; 8Biometrics, H. Lundbeck A/S, Valby, Denmark; 9Global Analytics, Lundbeck SAS, Issy-les-Moulineaux, France Background: The Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder (PERFORM study has been initiated to better understand the course of a depressive episode and its impact on patient functioning. This analysis aimed to identify sociodemographic and clinical factors associated with failure to achieve remission at month 2 after initiating or switching antidepressant monotherapy and with subsequent relapse at month 6 for patients in remission at month 2. Materials and methods: This was a 2-year observational cohort study in 1,159 outpatients aged 18–65 years with major depressive disorder initiating or undergoing the first switch of antidepressant monotherapy. Factors with P<0.20 in univariate logistic regression analyses were combined in a multiple logistic regression model to which backward variable selection was applied (ie, sequential removal of the least significant variable from the model and recomputation of the model until all remaining variables have P<0.05. Results: Baseline factors significantly associated with lower odds of remission at month 2 were body-mass index ≥30 kg/m2 (OR 0

  12. Evaluation of Vascular Endothelial Growth Factor as a Prognostic Marker for Local Relapse in Early-Stage Breast Cancer Patients Treated With Breast-Conserving Therapy

    International Nuclear Information System (INIS)

    Moran, Meena S.; Yang Qifeng; Goyal, Sharad; Harris, Lyndsay; Chung, Gina; Haffty, Bruce G.

    2011-01-01

    Purpose: Vascular endothelial growth factor (VEGF) is an important protein involved in the process of angiogenesis that has been found to correlate with relapse-free and overall survival in breast cancer, predominantly in locally advanced and metastatic disease. A paucity of data is available on the prognostic implications of VEGF in early-stage breast cancer; specifically, its prognostic value for local relapse after breast-conserving therapy (BCT) is largely unknown. The purpose of our study was to assess VEGF expression in a cohort of early-stage breast cancer patients treated with BCT and to correlate the clinical and pathologic features and outcomes with overexpression of VEGF. Methods and Materials: After obtaining institutional review board approval, the paraffin specimens of 368 patients with early-stage breast cancer treated with BCT between 1975 and 2005 were constructed into tissue microarrays with twofold redundancy. The tissue microarrays were stained for VEGF and read by a trained pathologist, who was unaware of the clinical details, as positive or negative according the standard guidelines. The clinical and pathologic data, long-term outcomes, and results of VEGF staining were analyzed. Results: The median follow-up for the entire cohort was 6.5 years. VEGF expression was positive in 56 (15%) of the 368 patients. Although VEGF expression did not correlate with age at diagnosis, tumor size, nodal status, histologic type, family history, estrogen receptor/progesterone receptor status, or HER-2 status, a trend was seen toward increased VEGF expression in the black cohort (26% black vs. 13% white, p = .068). Within the margin-negative cohort, VEGF did not predict for local relapse-free survival (RFS) (96% vs. 95%), nodal RFS (100% vs. 100%), distant metastasis-free survival (91% vs. 92%), overall survival (92% vs. 97%), respectively (all p >.05). Subset analysis revealed that VEGF was highly predictive of local RFS in node-positive, margin

  13. Early Relapse of Unresectable Gallbladder Cancer after Discontinuation of Gemcitabine Monotherapy Administered for 5 Years in a Patient Who Had Complete Response to the Treatment

    Directory of Open Access Journals (Sweden)

    Koichi Suyama

    2013-10-01

    Full Text Available The tumor shrinkage effect of gemcitabine is considered to be limited in cases of advanced gallbladder cancer, and there are few reports of complete response to gemcitabine therapy in patients with this cancer. Therefore, the treatment continuation strategy in these patients, after a complete response has been achieved, still remains to be established. Here, we present the case of a 77-year-old patient with unresectable gallbladder cancer, who after showing complete response to gemcitabine monotherapy administered for 5 years, showed early relapse within only 11 months of discontinuation of the drug. Thus, it is necessary to establish a suitable treatment continuation strategy for patients who show complete response to gemcitabine treatment.

  14. The Combined Quantification and Interpretation of Multiple Quantitative Magnetic Resonance Imaging Metrics Enlightens Longitudinal Changes Compatible with Brain Repair in Relapsing-Remitting Multiple Sclerosis Patients.

    Science.gov (United States)

    Bonnier, Guillaume; Maréchal, Benedicte; Fartaria, Mário João; Falkowskiy, Pavel; Marques, José P; Simioni, Samanta; Schluep, Myriam; Du Pasquier, Renaud; Thiran, Jean-Philippe; Krueger, Gunnar; Granziera, Cristina

    2017-01-01

    Quantitative and semi-quantitative MRI (qMRI) metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration, and repair. Moreover, advanced magnetic resonance imaging (MRI) metrics with overlapping elements amplify the true tissue-related information and limit measurement noise. In this work, we combined multiple advanced MRI parameters to assess focal and diffuse brain changes over 2 years in a group of early-stage relapsing-remitting MS patients. Thirty relapsing-remitting MS patients with less than 5 years disease duration and nine healthy subjects underwent 3T MRI at baseline and after 2 years including T1, T2, T2* relaxometry, and magnetization transfer imaging. To assess longitudinal changes in normal-appearing (NA) tissue and lesions, we used analyses of variance and Bonferroni correction for multiple comparisons. Multivariate linear regression was used to assess the correlation between clinical outcome and multiparametric MRI changes in lesions and NA tissue. In patients, we measured a significant longitudinal decrease of mean T2 relaxation times in NA white matter ( p  = 0.005) and a decrease of T1 relaxation times in the pallidum ( p  decrease in T1 relaxation time ( p -value  0.4, p  < 0.05). In summary, the combination of multiple advanced MRI provided evidence of changes compatible with focal and diffuse brain repair at early MS stages as suggested by histopathological studies.

  15. Reduction in Healthcare and Societal Resource Utilization Associated with Cladribine Tablets in Patients with Relapsing-Remitting Multiple Sclerosis: Analysis of Economic Data from the CLARITY Study

    DEFF Research Database (Denmark)

    Ali, Shehzad; Paracha, Noman; Cook, Stuart

    2012-01-01

    and home visits during each study period. Societal resource use and productivity outcomes included mean number of hours and days of paid assistance, mean patient and carer work days missed, and self-reported productivity. Results: The mean number of hospital days per patient over 96 weeks was lower...... gadolinium-enhancing (Gd+) lesion (n = 413); and ≥2 relapses in the previous year plus ≥1 T1 Gd+ lesion (n = 138). Cladribine tablets were administered in two (3.5 mg/kg group) or four (5.25 mg/kg group) short courses given at 4-week intervals at the start of a 48-week treatment period, followed by another...... burden. Objective: This study aimed to compare health and societal resource use and productivity in patients with relapsing-remitting MS (RRMS) receiving cladribine tablets versus placebo over 96 weeks in the CLARITY study. Methods: The CLARITY study was a 96-week, randomized, double-blind, placebo...

  16. Observational study of lenalidomide in patients with mantle cell lymphoma who relapsed/progressed after or were refractory/intolerant to ibrutinib (MCL-004

    Directory of Open Access Journals (Sweden)

    Michael Wang

    2017-11-01

    Full Text Available Abstract Background The observational MCL-004 study evaluated outcomes in patients with relapsed/refractory mantle cell lymphoma who received lenalidomide-based therapy after ibrutinib failure or intolerance. Methods The primary endpoint was investigator-assessed overall response rate based on the 2007 International Working Group criteria. Results Of 58 enrolled patients (median age, 71 years; range, 50–89, 13 received lenalidomide monotherapy, 11 lenalidomide plus rituximab, and 34 lenalidomide plus other treatment. Most patients (88% had received ≥ 3 prior therapies (median 4; range, 1–13. Median time from last dose of ibrutinib to the start of lenalidomide was 1.3 weeks (range, 0.1–21.7; 45% of patients had partial responses or better to prior ibrutinib. Primary reasons for ibrutinib discontinuation were lack of efficacy (88% and ibrutinib toxicity (9%. After a median of two cycles (range, 0–11 of lenalidomide-based treatment, 17 patients responded (8 complete responses, 9 partial responses, for a 29% overall response rate (95% confidence interval, 18–43% and a median duration of response of 20 weeks (95% confidence interval, 2.9 to not available. Overall response rate to lenalidomide-based therapy was similar for patients with relapsed/progressive disease after previous response to ibrutinib (i.e., ≥PR versus ibrutinib-refractory (i.e., ≤SD patients (30 versus 32%, respectively. The most common all-grade treatment-emergent adverse events after lenalidomide-containing therapy (n = 58 were fatigue (38% and cough, dizziness, dyspnea, nausea, and peripheral edema (19% each. At data cutoff, 28 patients have died, primarily due to mantle cell lymphoma. Conclusion Lenalidomide-based treatment showed clinical activity, with no unexpected toxicities, in patients with relapsed/refractory mantle cell lymphoma who previously failed ibrutinib therapy. Trial registration Clinicaltrials.gov identifier NCT02341781 . Date of

  17. Prognostic significance of metabolic tumor burden by positron emission tomography/computed tomography in patients with relapsed/refractory diffuse large B-cell lymphoma.

    Science.gov (United States)

    Tateishi, Ukihide; Tatsumi, Mitsuaki; Terauchi, Takashi; Ando, Kiyoshi; Niitsu, Nozomi; Kim, Won Seog; Suh, Cheolwon; Ogura, Michinori; Tobinai, Kensei

    2015-02-01

    The aim of the present study was to investigate the feasibility of measuring metabolic tumor burden using [F-18] fluorodeoxyglucose ((18) F-FDG) positron emission tomography/computed tomography (PET/CT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) treated with bendamustine-rituximab. Because the standardized uptake value is a critical parameter of tumor characterization, we carried out a phantom study of (18) F-FDG PET/CT to ensure quality control for 28 machines in the 24 institutions (Japan, 17 institutions; Korea, 7 institutions) participating in our clinical study. Fifty-five patients with relapsed or refractory DLBCL were enrolled. The (18) F-FDG PET/CT was acquired before treatment, after two cycles, and after the last treatment cycle. Treatment response was assessed after two cycles and after the last cycle using the Lugano classification. Using this classification, remission was complete in 15 patients (27%) and incomplete in 40 patients (73%) after two cycles of therapy, and remission was complete in 32 patients (58%) and incomplete in 23 patients (42%) after the last treatment cycle. The percentage change in all PET/CT parameters except for the area under the curve of the cumulative standardized uptake value-volume histogram was significantly greater in complete response patients than in non-complete response patients after two cycles and the last cycle. The Cox proportional hazard model and best subset selection method revealed that the percentage change of the sum of total lesion glycolysis after the last cycle (relative risk, 5.24; P = 0.003) was an independent predictor of progression-free survival. The percent change of sum of total lesion glycolysis, calculated from PET/CT, can be used to quantify the response to treatment and can predict progression-free survival after the last treatment cycle in patients with relapsed or refractory DLBCL treated with bendamustine-rituximab. © 2014 The Authors. Cancer Science

  18. Tumor suppressors BTG1 and IKZF1 cooperate during mouse leukemia development and increase relapse risk in B-cell precursor acute lymphoblastic leukemia patients.

    Science.gov (United States)

    Scheijen, Blanca; Boer, Judith M; Marke, René; Tijchon, Esther; van Ingen Schenau, Dorette; Waanders, Esmé; van Emst, Liesbeth; van der Meer, Laurens T; Pieters, Rob; Escherich, Gabriele; Horstmann, Martin A; Sonneveld, Edwin; Venn, Nicola; Sutton, Rosemary; Dalla-Pozza, Luciano; Kuiper, Roland P; Hoogerbrugge, Peter M; den Boer, Monique L; van Leeuwen, Frank N

    2017-03-01

    Deletions and mutations affecting lymphoid transcription factor IKZF1 (IKAROS) are associated with an increased relapse risk and poor outcome in B-cell precursor acute lymphoblastic leukemia. However, additional genetic events may either enhance or negate the effects of IKZF1 deletions on prognosis. In a large discovery cohort of 533 childhood B-cell precursor acute lymphoblastic leukemia patients, we observed that single-copy losses of BTG1 were significantly enriched in IKZF1 -deleted B-cell precursor acute lymphoblastic leukemia ( P =0.007). While BTG1 deletions alone had no impact on prognosis, the combined presence of BTG1 and IKZF1 deletions was associated with a significantly lower 5-year event-free survival ( P =0.0003) and a higher 5-year cumulative incidence of relapse ( P =0.005), when compared with IKZF1 -deleted cases without BTG1 aberrations. In contrast, other copy number losses commonly observed in B-cell precursor acute lymphoblastic leukemia, such as CDKN2A/B, PAX5, EBF1 or RB1 , did not affect the outcome of IKZF1 -deleted acute lymphoblastic leukemia patients. To establish whether the combined loss of IKZF1 and BTG1 function cooperate in leukemogenesis, Btg1 -deficient mice were crossed onto an Ikzf1 heterozygous background. We observed that loss of Btg1 increased the tumor incidence of Ikzf1 +/- mice in a dose-dependent manner. Moreover, murine B cells deficient for Btg1 and Ikzf1 +/- displayed increased resistance to glucocorticoids, but not to other chemotherapeutic drugs. Together, our results identify BTG1 as a tumor suppressor in leukemia that, when deleted, strongly enhances the risk of relapse in IKZF1 -deleted B-cell precursor acute lymphoblastic leukemia, and augments the glucocorticoid resistance phenotype mediated by the loss of IKZF1 function. Copyright© Ferrata Storti Foundation.

  19. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study.

    Science.gov (United States)

    Ravandi, Farhad; Ritchie, Ellen K; Sayar, Hamid; Lancet, Jeffrey E; Craig, Michael D; Vey, Norbert; Strickland, Stephen A; Schiller, Gary J; Jabbour, Elias; Erba, Harry P; Pigneux, Arnaud; Horst, Heinz-August; Recher, Christian; Klimek, Virginia M; Cortes, Jorge; Roboz, Gail J; Odenike, Olatoyosi; Thomas, Xavier; Havelange, Violaine; Maertens, Johan; Derigs, Hans-Günter; Heuser, Michael; Damon, Lloyd; Powell, Bayard L; Gaidano, Gianluca; Carella, Angelo-Michele; Wei, Andrew; Hogge, Donna; Craig, Adam R; Fox, Judith A; Ward, Renee; Smith, Jennifer A; Acton, Gary; Mehta, Cyrus; Stuart, Robert K; Kantarjian, Hagop M

    2015-09-01

    Safe and effective treatments are urgently needed for patients with relapsed or refractory acute myeloid leukaemia. We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed or refractory acute myeloid leukaemia. This phase 3, double-blind, placebo-controlled trial was undertaken at 101 international sites. Eligible patients with acute myeloid leukaemia were aged 18 years of age or older and had refractory disease or were in first relapse after one or two cycles of previous induction chemotherapy, including at least one cycle of anthracycline (or anthracenedione) plus cytarabine. Patients were randomly assigned 1:1 to vosaroxin (90 mg/m(2) intravenously on days 1 and 4 in a first cycle; 70 mg/m(2) in subsequent cycles) plus cytarabine (1 g/m(2) intravenously on days 1-5) or placebo plus cytarabine through a central interactive voice system with a permuted block procedure stratified by disease status, age, and geographical location. All participants were masked to treatment assignment. The primary efficacy endpoint was overall survival and the primary safety endpoint was 30-day and 60-day all-cause mortality. Efficacy analyses were done by intention to treat; safety analyses included all treated patients. This study is registered with ClinicalTrials.gov, number NCT01191801. Between Dec 17, 2010, and Sept 25, 2013, 711 patients were randomly assigned to vosaroxin plus cytarabine (n=356) or placebo plus cytarabine (n=355). At the final analysis, median overall survival was 7·5 months (95% CI 6·4-8·5) in the vosaroxin plus cytarabine group and 6·1 months (5·2-7·1) in the placebo plus cytarabine group (hazard ratio 0·87, 95% CI 0·73-1·02; unstratified log-rank p=0·061; stratified p=0·024). A higher proportion of patients achieved complete remission in the vosaroxin plus cytarabine group than in the placebo plus cytarabine group (107 [30%] of 356 patients vs 58 [16%] of 355

  20. Model of Management (Mo.Ma) for the patient with schizophrenia: crisis control, maintenance, relapse prevention, and recovery with long-acting injectable antipsychotics (LAIs).

    Science.gov (United States)

    Brugnoli, Roberto; Rapinesi, Chiara; Kotzalidis, Georgios D; Marcellusi, Andrea; Mennini, Francesco S; De Filippis, Sergio; Carrus, Dario; Ballerini, Andrea; Francomano, Antonio; Ducci, Giuseppe; Del Casale, Antonio; Girardi, Paolo

    2016-01-01

    Schizophrenia is a severe mental disease that affects approximately 1% of the population with a relevant chronic impact on social and occupational functioning and daily activities. People with schizophrenia are 2-2.5 times more likely to die early than the general population. Non-adherence to antipsychotic medications, both in chronic and first episode schizophrenia, is one of the most important risk factors for relapse and hospitalization, that consequently contributes to increased costs due to psychiatric hospitalization. Atypical long-acting injectable (LAI) antipsychotics can improve treatment adherence and decrease re-hospitalization rates in patients with schizophrenia since its onset. The primary goals in the management of schizophrenia are directed not only at symptom reduction in the short and long term, but also at maintaining physical and mental functioning, improving quality of life, and promoting patient recovery. To propose a scientific evidence-based integrated model that provides an algorithm for recovery of patients with schizophrenia and to investigate the effectiveness and safety of antipsychotics LAI in the treatment, maintenance, relapse prevention, and recovery of schizophrenia. After an accurate literature review we identified, collected and analyzed the crucial points in taking care schizophrenia patients, through which we defined the steps described in the model of management and the choice of the better treatment option. Results. In the management model we propose, the choice of a second generation long acting antipsychotic, could allow from the earliest stages of illness better patient management, especially for young individuals with schizophrenia onset, a better recovery and significant reductions of relapse and health care costs. LAI formulations of antipsychotics are valuable, because they help patients to remain adherent to their medication through regular contact with healthcare professionals and to prevent covert non-adherence. The

  1. Relapse patterns in WHO 2/3 nasopharyngeal cancer: Is there a difference between ethnic Asian vs. non-Asian patients?

    International Nuclear Information System (INIS)

    Corry, June; Fisher, Richard; Rischin, Danny; Peters, Lester J.

    2006-01-01

    Purpose: The purpose of this study was to assess whether ethnicity is an independent prognostic factor in patients with World Health Organization (WHO) type 2 or 3 nasopharyngeal carcinoma (NPC). Specifically, we examined the patterns of relapse observed in patients classified as 'Asian' (born in southern China or southeast Asia) or 'non-Asian' (born in Australia, Europe, the Middle East, or the Pacific Islands). Methods and Materials: All patients planned for radical treatment at the Peter MacCallum Cancer Centre from April 1985 to December 1999 were included in this study. Pathology was reviewed to confirm WHO type 2 or 3 NPC. Patients were staged using the 1997 International Union Against Cancer (UICC) criteria. Mean potential follow-up time was 9.6 years (range, 1.0-18.5 years) Results: There were 158 patients: 86 Asian and 72 non-Asian. Stage groupings were: I-12 patients; II-32 patients; III-59 patients; and IV-55 patients. A staging computerized tomography was performed in 121 patients, and 53 (34%) also had a staging magnetic resonance imaging (MRI). The Asian patients had significantly more women, more patients aged <45, and more with performance status 0 than the non-Asians. Other putative prognostic factors were not significantly different between the groups. The 5-year rates for freedom from local recurrence (FLR), failure-free survival (FFS), and overall survival (OS) for Asian and non-Asian patients were 74% vs. 82%, 61% vs. 55%, and 75% vs. 63%, respectively. Corresponding 10-year figures were: 62% vs. 82%, 43% vs. 48%, and 58% vs. 49%, respectively. Multifactor analysis showed stage and the use of MRI for staging to be significant prognostic factors for all three endpoints. Age was also significant for FFS and OS. There were no significant differences in FFS or OS between Asian and non-Asian patients. However, the FLR interval was significantly worse in the Asian group (hazard ratio [HR], 2.37; 95% confidence interval [CI], 1.11-5.06), whereas

  2. Phase I study of obinutuzumab (GA101) in Japanese patients with relapsed or refractory B-cell non-Hodgkin lymphoma.

    Science.gov (United States)

    Ogura, Michinori; Tobinai, Kensei; Hatake, Kiyohiko; Uchida, Toshiki; Suzuki, Tatsuya; Kobayashi, Yukio; Mori, Masakazu; Terui, Yasuhito; Yokoyama, Masahiro; Hotta, Tomomitsu

    2013-01-01

    As CD20 has become an established target for treating B-cell malignancies, there is interest in developing anti-CD20 antibodies with different functional activity from rituximab that might translate into improved efficacy. Obinutuzumab (GA101) is a glycoengineered, humanized type II anti-CD20 monoclonal antibody that has demonstrated superior activity to type I antibodies in preclinical studies and is currently being investigated in phase III trials. In this phase I dose-escalating study in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma, the primary endpoint was to characterize the safety of GA101; secondary endpoints were efficacy, pharmacokinetics and pharmacodynamics. Patients received up to nine doses of GA101 with up to 52 weeks' follow up. Most adverse events were grade 1 or 2 infusion-related reactions, and 10 grade 3/4 adverse events occurred. No dose-limiting toxicities were observed and the maximum tolerated dose was not identified. Out of 12 patients, 7 responded (end-of-treatment response rate 58%), with 2 complete responses and 5 partial responses. Responses were observed from low to high doses, and no dose-efficacy relationship was observed. B-cell depletion occurred in all patients after the first infusion and was maintained for the duration of treatment. Serum levels of GA101 increased in a dose-dependent fashion, although there was inter-patient variability. This phase I study demonstrated that GA101 has an acceptable safety profile and offers encouraging activity to Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma. © 2012 Japanese Cancer Association.

  3. Malignant lipogenesis defined by {sup 11}C-acetate PET/CT predicts prostate cancer-specific survival in patients with biochemical relapse after prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Regula, Naresh [Uppsala University, Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala (Sweden); Haeggman, Michael [Uppsala University, Section of Urology, Department of Surgical Sciences, Uppsala (Sweden); Johansson, Silvia [Uppsala University, Section of Oncology, Department of Immunology, Genetics and Pathology, Uppsala (Sweden); Soerensen, Jens [Uppsala University, Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala (Sweden); PET Center Research Department, Uppsala (Sweden)

    2016-11-15

    Malignant de novo lipogenesis is strongly linked to the aggressiveness of prostate cancer (PCa) under experimental conditions. {sup 11}C-Acetate PET/CT is a potential noninvasive biomarker of malignant lipogenesis in PCa, but its prognostic value is not known. The objective of this study was to analyse {sup 11}C-acetate PET/CT image metrics in relation to survival. All patients undergoing {sup 11}C-acetate PET/CT in one university hospital from 2005 to 2011 due to PSA relapse after previous prostatectomy were retrospectively evaluated. Two groups of patients were compared: those who died from PCa and those who were censored. All previously reported findings of local recurrence, regional or distal lymph node metastases and bone metastases were counted and evaluated regarding {sup 11}C-acetate uptake intensity (SUV{sub max}) and tumour volume. Total tumour volume and total lipogenic activity (TLA, summed SUV{sub max} x TV) were calculated. Survival analysis in the entire study population was followed by Cox proportional hazards ratio (HR) analysis. A total of 121 patients were included, and 22 PCa-specific deaths were recorded. The mean PSA level at the time of PET was 2.69 ± 4.35 ng/mL. The median follow-up of the study population was 79 ± 28 months. PET identified at least one PCa lesion in 53 % of patients. Five-year PCa-specific survival after PET was 80 % and 100 % in patients with a positive and a negative PET scan, respectively (p < 0.001). Time-to-death was linearly correlated with highest SUV{sub max} (r = -0.55, p = 0.01) and nonlinearly with TLA (r = -0.75, p < 0.001). Multivariate analysis showed statistical significance for number of bone metastases (HR 1.74, p = 0.01), tertile of TLA (HR 5.63, p = 0.029) and postoperative Gleason score (HR 1.84, p = 0.045). Malignant {sup 11}C-acetate accumulation measured with PET/CT is a strong predictor of survival in the setting of PSA relapse after prostatectomy. The study provides further evidence for a

  4. [Research and control of relapse tuberculosis cases].

    Science.gov (United States)

    Yamagishi, Fumio; Toyota, Makoto

    2009-12-01

    With this symposium, we focused on the relapse of tuberculosis in Japan. Out of 19,893 tuberculosis patients registered in 2007 in Japan, 7.48% were classified as relapse cases. Relapse cases have the risk of acquired drug resistance. But we have few analyses of the proportion of relapse tuberculosis cases with standard short course regimens for six months, factors contributing to tuberculosis relapse and the proportion of drug resistance among relapse TB cases in Japan. Therefore we analyzed the relapse tuberculosis cases in two rural areas and three urban areas. We also analyzed the proportion of drug resistance among relapse cases with the data of drug susceptibility survey of Ryoken. 1. Research of relapse tuberculosis cases: Makoto TOYOTA (Kochi City Public Health Center). To clarify the relapse rate and factors contributing to tuberculosis relapse, we investigated the relapse tuberculosis cases in the municipality where the proportion of elderly tuberculosis patients was high. Out of 902 tuberculosis patients registered in Kochi City Public Health Center during 10 years, 20 pulmonary tuberculosis patients were confirmed relapse cases with initial registered records. Pretreatment cavitations, sputum culture positivity at 2 months, medical miss-management (e.g. number of doses, duration of therapy) and poor adherence were considered to be factors contributing to tuberculosis relapse. Out of 20 relapse cases, 12 cases were detected with symptoms, while only 3 cases were detected by examination in law. 2. A clinical study on relapse cases of pulmonary tuberculosis: Shuichi TAKIKAWA (National Hospital Organization Nishibeppu National Hospital). The relapse of pulmonary tuberculosis was investigated. In the cases with a treatment history before short course chemotherapy, drug resistance rate was high, and thus it needs to be cautious of drug resistance at the time of the retreatment. In the cases with a treatment history of short course chemotherapy, relapse cases

  5. 18F-fluorocholine versus 18F-fluorodeoxyglucose for PET/CT imaging in patients with suspected relapsing or progressive multiple myeloma: a pilot study

    International Nuclear Information System (INIS)

    Cassou-Mounat, Thibaut; Balogova, Sona; Nataf, Valerie; Calzada, Marie; Huchet, Virginie; Kerrou, Khaldoun; Devaux, Jean-Yves; Mohty, Mohamad; Garderet, Laurent; Talbot, Jean-Noel

    2016-01-01

    Hybrid positron emission tomography/computed tomography (PET/CT) has now become available, as well as whole-body, low-dose multidetector row computed tomography (MDCT) or magnetic resonance imaging (MRI). The radioactive glucose analogue 18F-fluorodeoxyglucose (FDG) is the most widely used tracer but has a relatively low sensitivity in detecting multiple myeloma (MM). We compared FDG with a more recent metabolic tracer, 18F-fluorocholine (FCH), for the detection of MM lesions at time of disease relapse or progression. We analyzed the results of FDG and FCH imaging in 21 MM patients undergoing PET/CT for suspected relapsing or progressive MM. For each patient and each tracer, an on-site reader and a masked reader independently determined the number of intraosseous and extraosseous foci of tracer and the intensity of uptake as measured by their SUVmax and the corresponding target/non-target ratio (T/NT). In the skeleton of 21 patients, no foci were found for two cases, uncountable foci were observed in four patients, including some mismatched FCH/FDG foci. In the 15 patients with countable bone foci, the on-site reader detected 72 FDG foci vs. 127 FCH foci (+76 %), whereas the masked reader detected 69 FDG foci vs. 121 FCH foci (+75 %), both differences being significant. Interobserver agreement on the total number of bone foci was very high, with a kappa coefficient of 0.81 for FDG and 0.89 for FCH. Measurement of uptake in the matched foci that took up both tracers revealed a significantly higher median SUVmax and T/NT for FCH vs. FDG. Almost all unmatched foci were FCH-positive FDG-negative (57/59 = 97 % on-site and 56/60 = 93 % on masked reading); they were more frequently observed than matched foci in the head and neck region. These findings suggest that PET/CT performed for suspected relapsing or progressive MM would reveal more lesions when using FCH rather than FDG. (orig.)

  6. 18F-fluorocholine versus 18F-fluorodeoxyglucose for PET/CT imaging in patients with suspected relapsing or progressive multiple myeloma: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Cassou-Mounat, Thibaut [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); AP-HP, Department of Nuclear Medicine, Hopital Saint Antoine, Paris (France); Universite Pierre et Marie Curie (UPMC), Paris (France); Balogova, Sona [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); Comenius University and St. Elisabeth Oncology Institute, Department of Nuclear Medicine, Bratislava (Slovakia); Nataf, Valerie [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); AP-HP, Radiopharmacy, Hopital Tenon, Paris (France); Calzada, Marie [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); AP-HP, Department of Nuclear Medicine, Hopital Saint Antoine, Paris (France); Huchet, Virginie; Kerrou, Khaldoun [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); Devaux, Jean-Yves [AP-HP, Department of Nuclear Medicine, Hopital Saint Antoine, Paris (France); Universite Pierre et Marie Curie (UPMC), Paris (France); Mohty, Mohamad; Garderet, Laurent [Universite Pierre et Marie Curie (UPMC), Paris (France); INSERM, UMRS 938, Proliferation and Differentiation of Stem Cells, Paris (France); AP-HP, Departement d' Hematologie et de Therapie Cellulaire, Hopital Saint Antoine, Paris (France); Talbot, Jean-Noel [AP-HP, Department of Nuclear Medicine, Hopital Tenon, Paris (France); Universite Pierre et Marie Curie (UPMC), Paris (France)

    2016-10-15

    Hybrid positron emission tomography/computed tomography (PET/CT) has now become available, as well as whole-body, low-dose multidetector row computed tomography (MDCT) or magnetic resonance imaging (MRI). The radioactive glucose analogue 18F-fluorodeoxyglucose (FDG) is the most widely used tracer but has a relatively low sensitivity in detecting multiple myeloma (MM). We compared FDG with a more recent metabolic tracer, 18F-fluorocholine (FCH), for the detection of MM lesions at time of disease relapse or progression. We analyzed the results of FDG and FCH imaging in 21 MM patients undergoing PET/CT for suspected relapsing or progressive MM. For each patient and each tracer, an on-site reader and a masked reader independently determined the number of intraosseous and extraosseous foci of tracer and the intensity of uptake as measured by their SUVmax and the corresponding target/non-target ratio (T/NT). In the skeleton of 21 patients, no foci were found for two cases, uncountable foci were observed in four patients, including some mismatched FCH/FDG foci. In the 15 patients with countable bone foci, the on-site reader detected 72 FDG foci vs. 127 FCH foci (+76 %), whereas the masked reader detected 69 FDG foci vs. 121 FCH foci (+75 %), both differences being significant. Interobserver agreement on the total number of bone foci was very high, with a kappa coefficient of 0.81 for FDG and 0.89 for FCH. Measurement of uptake in the matched foci that took up both tracers revealed a significantly higher median SUVmax and T/NT for FCH vs. FDG. Almost all unmatched foci were FCH-positive FDG-negative (57/59 = 97 % on-site and 56/60 = 93 % on masked reading); they were more frequently observed than matched foci in the head and neck region. These findings suggest that PET/CT performed for suspected relapsing or progressive MM would reveal more lesions when using FCH rather than FDG. (orig.)

  7. Safety and efficacy of cladribine tablets in patients with relapsing-remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study.

    Science.gov (United States)

    Giovannoni, Gavin; Soelberg Sorensen, Per; Cook, Stuart; Rammohan, Kottil; Rieckmann, Peter; Comi, Giancarlo; Dangond, Fernando; Adeniji, Abidemi K; Vermersch, Patrick

    2017-08-01

    In the 2-year CLARITY study, cladribine tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis (MS). To assess the safety and efficacy of cladribine treatment in a 2-year Extension study. In this 2-year Extension study, placebo recipients from CLARITY received cladribine 3.5 mg/kg; cladribine recipients were re-randomized 2:1 to cladribine 3.5 mg/kg or placebo, with blind maintained. A total of 806 patients were assigned to treatment. Adverse event rates were generally similar between groups, but lymphopenia Grade ⩾ 3 rates were higher with cladribine than placebo (Grade 4 lymphopenia occurred infrequently). In patients receiving cladribine 3.5 mg/kg in CLARITY and experiencing lymphopenia Grade ⩾ 3 in the Extension, >90% of those treated with cladribine 3.5 mg/kg and all treated with placebo in the Extension, recovered to Grade 0-1 by study end. Cladribine treatment in CLARITY produced efficacy improvements that were maintained in patients treated with placebo in the Extension; in patients treated with cladribine 3.5 mg/kg in CLARITY, approximately 75% remained relapse-free when given placebo during the Extension. Cladribine tablets treatment for 2 years followed by 2 years' placebo treatment produced durable clinical benefits similar to 4 years of cladribine treatment with a low risk of severe lymphopenia or clinical worsening. No clinical improvement in efficacy was apparent following further treatment with cladribine tablets after the initial 2-year treatment period in this trial setting.

  8. Eye movement desensitization and reprocessing therapy versus supportive therapy in affective relapse prevention in bipolar patients with a history of trauma: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Moreno-Alcázar, Ana; Radua, Joaquim; Landín-Romero, Ramon; Blanco, Laura; Madre, Mercè; Reinares, Maria; Comes, Mercè; Jiménez, Esther; Crespo, Jose Manuel; Vieta, Eduard; Pérez, Victor; Novo, Patricia; Doñate, Marta; Cortizo, Romina; Valiente-Gómez, Alicia; Lupo, Walter; McKenna, Peter J; Pomarol-Clotet, Edith; Amann, Benedikt L

    2017-04-04

    Up to 60% of patients with bipolar disorder (BD) have a history of traumatic events, which is associated with greater episode severity, higher risk of comorbidity and higher relapse rates. Trauma-focused treatment strategies for BD are thus necessary but studies are currently scarce. The aim of this study is to examine whether Eye Movement Desensitization and Reprocessing (EMDR) therapy focusing on adherence, insight, de-idealisation of manic symptoms, prodromal symptoms and mood stabilization can reduce episode severity and relapse rates and increase cognitive performance and functioning in patients with BD. This is a single-blind, randomized controlled, multicentre trial in which 82 patients with BD and a history of traumatic events will be recruited and randomly allocated to one of two treatment arms: EMDR therapy or supportive therapy. Patients in both groups will receive 20 psychotherapeutic sessions, 60 min each, during 6 months. The primary outcome is a reduction of affective episodes after 12 and 24 months in favour of the EMDR group. As secondary outcome we postulate a greater reduction in affective symptoms in the EMDR group (as measured by the Bipolar Depression Rating Scale, the Young Mania Rating Scale and the Clinical Global Impression Scale modified for BD), and a better performance in cognitive state, social cognition and functioning (as measured by the Screen for Cognitive Impairment in Psychiatry, The Mayer-Salovey-Caruso Emotional Intelligence Test and the Functioning Assessment Short Test, respectively). Traumatic events will be evaluated by The Holmes-Rahe Life Stress Inventory, the Clinician-administered PTSD Scale and the Impact of Event Scale. The results of this study will provide evidence whether a specific EMDR protocol for patients with BD is effective in reducing affective episodes, affective symptoms and functional, cognitive and trauma symptoms. The trial is registered at ClinicalTrials.gov, identifier: NCT02634372 . Registered on

  9. Eventual Suicide in Interrupted and Uninterrupted Attempters: A Challenge to the Cry-for-Help Hypothesis.

    Science.gov (United States)

    Steer, Robert A.; And Others

    1988-01-01

    Followed patients (N=499) hospitalized for suicide attempts (attempters) between 1970 and 1975 until 1982. Found under six percent eventually committed suicide. Found the interrupted attempters were approximately three times more likely to commit suicide than were the uninterrupted attempters. (Author/ABL)

  10. Report of a Phase II Study of Clofarabine and Cytarabine in De Novo and Relapsed and Refractory AML Patients and in Selected Elderly Patients at High Risk for Anthracycline Toxicity

    Science.gov (United States)

    Cooper, Barry; Holmes, Houston; Vance, Estil; Berryman, Robert Brian; Maisel, Christopher; Li, Sandy; Saracino, Giovanna; Tadic-Ovcina, Mirjana; Fay, Joseph

    2011-01-01

    Purpose. To determine the efficacy and safety of clofarabine and cytarabine (Ara-C) in adult patients with relapsed or refractory acute myeloid leukemia (AML) and in elderly patients with untreated AML and heart disease. Patients and Methods. Patients with relapsed/refractory AML and older patients for whom there was a concern over toxicity from additional anthracyclines received 5 days of clofarabine, 40 mg/m2 per day i.v. over 1 hour, followed 4 hours later by Ara-C, 1,000 mg/m2 per day i.v. over 2 hours. Results. Thirty patients were enrolled. The median age was 67 years (range, 38–82 years) and 18 (60%) had received at least one prior therapy. Eleven (37%) patients had a history of cardiovascular disease and were considered to be at high risk for anthracycline toxicity. High-risk cytogenetic abnormalities were present in 14 (47%) patients. The overall response rate (complete remission [CR] plus partial remission) was 53%, including a CR in 14 patients (47%). Responses were observed in all cytogenetic risk groups and in patients who had received up to five prior therapies. The median disease-free survival interval was 9.5 months. The 30-day mortality rate was 20% (de novo AML, 8%; relapsed/refractory AML, 28%). Of the 14 patients achieving a CR, half were able to proceed to curative hematopoietic stem cell transplantation. Conclusions. Clofarabine in combination with Ara-C is effective in both untreated and previously treated patients with AML. In addition, it represents a useful remission induction strategy to serve as a bridge to transplantation in older patients with AML. PMID:21273514

  11. Ultrasound-detected bone erosion is a relapse risk factor after discontinuation of biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis whose ultrasound power Doppler synovitis activity and clinical disease activity are well controlled.

    Science.gov (United States)

    Kawashiri, Shin-Ya; Fujikawa, Keita; Nishino, Ayako; Okada, Akitomo; Aramaki, Toshiyuki; Shimizu, Toshimasa; Umeda, Masataka; Fukui, Shoichi; Suzuki, Takahisa; Koga, Tomohiro; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Mizokami, Akinari; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Aoyagi, Kiyoshi; Maeda, Takahiro; Kawakami, Atsushi

    2017-05-25

    In the present study, we explored the risk factors for relapse after discontinuation of biologic disease-modifying antirheumatic drug (bDMARD) therapy in patients with rheumatoid arthritis (RA) whose ultrasound power Doppler (PD) synovitis activity and clinical disease activity were well controlled. In this observational study in clinical practice, the inclusion criteria were based on ultrasound disease activity and clinical disease activity, set as low or remission (Disease Activity Score in 28 joints based on erythrocyte sedimentation rate Ultrasound was performed in 22 joints of bilateral hands at discontinuation for evaluating synovitis severity and presence of bone erosion. Patients with a maximum PD score ≤1 in each joint were enrolled. Forty patients with RA were consecutively recruited (November 2010-March 2015) and discontinued bDMARD therapy. Variables at the initiation and discontinuation of bDMARD therapy that were predictive of relapse during the 12 months after discontinuation were assessed. The median patient age was 54.5 years, and the median disease duration was 3.5 years. Nineteen (47.5%) patients relapsed during the 12 months after the discontinuation of bDMARD therapy. Logistic regression analysis revealed that only the presence of bone erosion detected by ultrasound at discontinuation was predictive of relapse (OR 8.35, 95% CI 1.78-53.2, p = 0.006). No clinical characteristics or serologic biomarkers were significantly different between the relapse and nonrelapse patients. The ultrasound synovitis scores did not differ significantly between the groups. Our findings are the first evidence that ultrasound bone erosion may be a relapse risk factor after the discontinuation of bDMARD therapy in patients with RA whose PD synovitis activity and clinical disease activity are well controlled.

  12. Radiotherapy may improve overall survival of patients with T3/T4 transitional cell carcinoma of the renal pelvis or ureter and delay bladder tumour relapse

    Directory of Open Access Journals (Sweden)

    Wu Li-Li

    2011-07-01

    Full Text Available Abstract Background Since transitional cell carcinoma (TCC of the upper urinary tract is a relatively uncommon malignancy, the role of adjuvant radiotherapy is unknown. Methods We treated 133 patients with TCC of the renal pelvis or ureter at our institution between 1998 and 2008. The 67 patients who received external beam radiotherapy (EBRT following surgery were assigned to the radiation group (RT. The clinical target volume included the renal fossa, the course of the ureter to the entire bladder, and the paracaval and para-aortic lymph nodes, which were at risk of harbouring metastatic disease in 53 patients. The tumour bed or residual tumour was targeted in 14 patients. The median radiation dose administered was 50 Gy. The 66 patients who received intravesical chemotherapy were assigned to the non-radiation group (non-RT. Results The overall survival rates for the RT and non-RT groups were not significantly different (p = 0.198. However, there was a significant difference between the survival rates for these groups based on patients with T3/T4 stage cancer. A significant difference was observed in the bladder tumour relapse rate between the irradiated and non-irradiated bladder groups (p = 0.004. Multivariate analysis indicated that improved overall survival was associated with age grade 3 hematologic symptoms also occurred. Conclusion EBRT may improve overall survival for patients with T3/T4 cancer of the renal pelvis or ureter and delay bladder tumour recurrence in all patients.

  13. Clinical factors related to schizophrenia relapse.

    Science.gov (United States)

    Porcelli, Stefano; Bianchini, Oriana; De Girolamo, Giovanni; Aguglia, Eugenio; Crea, Luciana; Serretti, Alessandro

    2016-01-01

    Relapses represent one of the main problems of schizophrenia management. This article reviews the clinical factors associated with schizophrenia relapse. A research of the last 22 years of literature data was performed. Two-hundred nineteen studies have been included. Three main groups of factors are related to relapse: factors associated with pharmacological treatment, add-on psychotherapeutic treatments and general risk factors. Overall, the absence of a maintenance therapy and treatment with first generation antipsychotics has been associated with higher risk of relapse. Further, psychotherapy add-on, particularly with cognitive behaviour therapy and psycho-education for both patients and relatives, has shown a good efficacy for reducing the relapse rate. Among general risk factors, some could be modified, such as the duration of untreated psychosis or the substance misuse, while others could not be modified as male gender or low pre-morbid level of functioning. Several classes of risk factors have been proved to be relevant in the risk of relapse. Thus, a careful assessment of the risk factors here identified should be performed in daily clinical practice in order to individualise the relapse risk for each patient and to provide a targeted treatment in high-risk subjects.

  14. Salvage radiotherapy in patients with prostate cancer and biochemical relapse after radical prostatectomy. Long-term follow-up of a single-center survey

    Energy Technology Data Exchange (ETDEWEB)

    Lohm, Gunnar; Luetcke, Joerg; Hinkelbein, Wolfgang [Charite Universitaetsmedizin Berlin, Department of Radiation Oncology, Berlin (Germany); Jamil, Basil [Klinikum Frankfurt Oder, Praxis fuer Strahlentherapie, Frankfurt Oder (Germany); Hoecht, Stefan [X-Care Praxis fuer Strahlentherapie Saarlouis, Saarlouis (Germany); Neumann, Konrad [Charite Universitaetsmedizin Berlin, Department of Biometry and Clinical Epidemiology, Berlin (Germany); Wiegel, Thomas; Bottke, Dirk [University Hospital Ulm, Department of Radiation Oncology, Ulm (Germany)

    2014-08-15

    In patients with prostate cancer (PC) and biochemical relapse after radical prostatectomy, salvage radiotherapy (SRT) could improve PC-specific survival (PCSS) but the timing for initiation is still under discussion. We have demonstrated a low rate of biochemical relapses in a patient series with very low pre-SRT PSA levels after a median follow-up of 42 months. Here, we present an update of that study. Overall, 151 patients were analyzed. A biochemical relapse after SRT was diagnosed when the PSA exceeded the post-SRT nadir by 0.2 ng/ml with subsequent increase. Parameters with significant impact on biochemical progression-free survival (BPFS), PCSS, and overall survival (OS) in univariate analysis were included in a multiple Cox regression analysis. After a median follow-up of 82 months, 18 patients (12 %) had died with 10 (6.6 %) deaths being PC-related. A biochemical progression was diagnosed in 83 patients (55 %). Univariate analysis revealed a significant impact of pre-SRT PSA level, Gleason score, and PSA doubling time (PSADT) on BPFS and for initial tumor stage and Gleason score on OS. Multivariate analysis confirmed the impact of pre-SRT PSA level, Gleason score, and PSADT on BPFS and tumor stage on OS. In this update, the rate of biochemical relapses increased compared with our previous data. Compared to similar studies, we found a remarkably low rate of PC-related deaths. Our data support early initiation of SRT. However, this treatment strategy, triggered by very low PSA levels, could carry the risk of overtreatment in at least a subset of patients. (orig.) [German] Bei Patienten mit Prostatakarzinom und biochemischem Rezidiv nach radikaler Prostatektomie kann eine Salvage-Strahlentherapie das tumorspezifische Ueberleben verbessern. Der Zeitpunkt des Therapiebeginns wird kontrovers diskutiert. Wir haben in unserer Serie eine geringe Rate biochemischer Rezidive bei Patienten mit sehr niedrigen praeradiotherapeutischen PSA-Werten gezeigt. Die vorliegende

  15. Daily corticosteroids reduce infection-associated relapses in frequently relapsing nephrotic syndrome: a randomized controlled trial.

    Science.gov (United States)

    Gulati, Ashima; Sinha, Aditi; Sreenivas, Vishnubhatla; Math, Aparna; Hari, Pankaj; Bagga, Arvind

    2011-01-01

    Relapses of nephrotic syndrome often follow minor infections, commonly of the upper respiratory tract. Daily administration of maintenance prednisolone during intercurrent infections was examined to determine whether the treatment reduces relapse rates in children with frequently relapsing nephrotic syndrome. In a randomized controlled trial (nonblind, parallel group, tertiary-care hospital), 100 patients with idiopathic, frequently relapsing nephrotic syndrome eligible for therapy with prolonged low-dose, alternate-day prednisolone with or without levamisole were randomized to either receive their usual dose of alternate-day prednisolone daily for 7 days during intercurrent infections (intervention group) or continue alternate-day prednisolone (controls). Primary outcome was assessed by comparing the rates of infection-associated relapses at 12-month follow-up. Secondary outcomes were the frequency of infections and the cumulative amount of prednisolone received in both groups. Patients in the intervention group showed significantly lower infection-associated (rate difference, 0.7 episodes/patient per year; 95% confidence intervals [CI] 0.3, 1.1) and lower total relapse rates (0.9 episodes/patient per year, 95% CI 0.4, 1.4) without increase in steroid toxicity. Poisson regression, adjusted for occurrence of infections, showed that daily administration of prednisolone during infections independently resulted in 59% reduction in frequency of relapses (rate ratio, 0.41; 95% CI 0.3, 0.6). For every six patients receiving this intervention, one showed a reduction of relapse frequency to less than three per year. Daily administration of maintenance doses of prednisolone, during intercurrent infections, significantly reduces relapse rates and the proportion of children with frequently relapsing nephrotic syndrome.

  16. Usefulness of desmopressin testing to predict relapse during long-term follow-up in patients in remission from Cushing’s disease

    Directory of Open Access Journals (Sweden)

    Alberto Giacinto Ambrogio

    2017-11-01

    Full Text Available Recurrence of Cushing’s disease after successful transsphenoidal surgery occurs in some 30% of the patients and the response to desmopressin shortly after surgery has been proposed as a marker for disease recurrence. The aim of the present study was to evaluate the response to desmopressin over time after surgery. We tested 56 patients with Cushing’s disease in remission after transsphenoidal surgery with desmopressin for up to 20 years after surgery. The ACTH and cortisol response to desmopressin over time was evaluated in patients on long-term remission or undergoing relapse; an increase by at least 27 pg/mL in ACTH levels identified responders. The vast majority of patients who underwent successful adenomectomy failed to respond to desmopressin after surgery and this response pattern was maintained over time in patients on long-term remission. Conversely, a response to desmopressin reappeared in patients who subsequently developed a recurrence of Cushing’s disease, even years prior to frank hypercortisolism. It appears therefore that a change in the response pattern to desmopressin proves predictive of recurrence of Cushing’s disease and may indicate which patients require close monitoring.

  17. The European Medicines Agency Review of Panobinostat (Farydak) for the Treatment of Adult Patients with Relapsed and/or Refractory Multiple Myeloma.

    Science.gov (United States)

    Tzogani, Kyriaki; van Hennik, Paula; Walsh, Ita; De Graeff, Pieter; Folin, Annika; Sjöberg, Jan; Salmonson, Tomas; Bergh, Jonas; Laane, Edward; Ludwig, Heinz; Gisselbrecht, Christian; Pignatti, Francesco

    2017-11-30

    On August 28, 2015, a marketing authorization valid through the European Union was issued for panobinostat, in combination with bortezomib and dexamethasone, for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent (IMiD).Panobinostat is an orally available histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDAC proteins at nanomolar concentrations. HDAC proteins catalyze the removal of acetyl groups from the lysine residues of histones and some nonhistone proteins. Inhibition of HDAC activity results in increased acetylation of histone proteins, an epigenetic alteration that results in a relaxing of chromatin, leading to transcriptional activation. The recommended starting dose of panobinostat is 20 mg, taken orally in a cyclical manner for up to 48 weeks.The use of panobinostat in combination with bortezomib and dexamethasone was studied in a randomized, double-blind, placebo-controlled, multicenter phase III study (PANORAMA I) in 768 patients with relapsed or relapsed and refractory multiple myeloma who had received one to three prior lines of therapies. In the subgroup of patients who have received at least two prior regimens including bortezomib and an IMiD, there was a difference of 7.8 months in the progression-free survival in favor of the experimental arm (12.5 months for panobinostat + bortezomib + dexamethasone vs. 4.7 months for placebo + bortezomib + dexamethasone; hazard ratio = 0.47, 95% confidence interal 0.31-0.72; log-rank p value = .0003). The incidence of grade 3-4 adverse events suspected to be related to study drug was 76.9% vs. 51.2%, for the panobinostat and the placebo group, respectively. The most common side effects (grade 3-4) associated with panobinostat included diarrhea (18.9%), fatigue (14.7%), nausea (4.5%), vomiting (5.5%), thrombocytopenia (43.6%), anemia (7

  18. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

    2016-01-01

    Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic...... leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were...

  19. Carfilzomib, lenalidomide, and dexamethasone in patients with relapsed multiple myeloma categorised by age: secondary analysis from the phase 3 ASPIRE study.

    Science.gov (United States)

    Dimopoulos, Meletios A; Stewart, A Keith; Masszi, Tamás; Špička, Ivan; Oriol, Albert; Hájek, Roman; Rosiñol, Laura; Siegel, David; Mihaylov, Georgi G; Goranova-Marinova, Vesselina; Rajnics, Péter; Suvorov, Aleksandr; Niesvizky, Ruben; Jakubowiak, Andrzej; San-Miguel, Jesus; Ludwig, Heinz; Palumbo, Antonio; Obreja, Mihaela; Aggarwal, Sanjay; Moreau, Philippe

    2017-05-01

    A primary analysis of the ASPIRE study found that the addition of carfilzomib to lenalidomide and dexamethasone (carfilzomib group) significantly improved progression-free survival (PFS) compared with lenalidomide and dexamethasone alone (control group) in patients with relapsed multiple myeloma (RMM). This post hoc analysis examined outcomes from ASPIRE in patients categorised by age. In the carfilzomib group, 103/396 patients were ≥70 years old, and in the control group, 115/396 patients were ≥70 years old. Median PFS for patients <70 years old was 28·6 months for the carfilzomib group versus 17·6 months for the control group [hazard ratio (HR), 0·701]. Median PFS for patients ≥70 years old was 23·8 months for the carfilzomib group versus 16·0 months for the control group (HR, 0·753). For patients <70 years the overall response rate (ORR) was 86·0% (carfilzomib group) and 66·9% (control group); for patients ≥70 years old the ORR was 90·3% (carfilzomib group) and 66·1% (control group). Within the carfilzomib group, grade ≥3 cardiovascular adverse events occurred more frequently among patients ≥70 years old compared with patients <70 years old. Carfilzomib-lenalidomide-dexamethasone has a favourable benefit-risk profile for patients with RMM, including elderly patients ≥70 years old. clinicaltrials.gov identifier: NCT01080391. © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

  20. Evaluation of 230 patients with relapsed/refractory deletion 17p chronic lymphocytic leukaemia treated with ibrutinib from 3 clinical trials.

    Science.gov (United States)

    Jones, Jeffrey; Mato, Anthony; Coutre, Steven; Byrd, John C; Furman, Richard R; Hillmen, Peter; Osterborg, Anders; Tam, Constantine; Stilgenbauer, Stephan; Wierda, William G; Heerema, Nyla A; Eckert, Karl; Clow, Fong; Zhou, Cathy; Chu, Alvina D; James, Danelle F; O'Brien, Susan M

    2018-06-05

    Patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) with deletion 17p [del(17p)] have poor outcomes with chemoimmunotherapy. Ibrutinib is indicated for the treatment of CLL/SLL, including del(17p) CLL/SLL, and allows for treatment without chemotherapy. This integrated analysis was performed to evaluate outcomes in 230 patients with relapsed/refractory del(17p) CLL/SLL from three ibrutinib studies. With a median of 2 prior therapies (range, 1-12), 18% and 79% of evaluable patients had del(11q) or unmutated IGHV, respectively. With a median follow-up of 28 months, overall response rate was 85% and estimated 30-month progression-free and overall survival rates were 57% [95% confidence interval (CI) 50-64] and 69% (95% CI 61-75), respectively. Patients with normal lactate dehydrogenase or no bulky disease had the most favourable survival outcomes. Sustained haematological improvements in haemoglobin, platelet count and absolute neutrophil count occurred in 61%, 67% and 70% of patients with baseline cytopenias, respectively. New onset severe cytopenias and infections decreased in frequency over time. Progression-free and overall survival with ibrutinib surpass those of other therapies for patients with del(17p) CLL/SLL. These results provide further evidence of the robust clinical activity of ibrutinib in difficult-to-treat CLL/SLL populations. © 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

  1. A approach for differential diagnosis of primary lung cancer and breast cancer relapse presenting as a solitary pulmonary nodule in patients after breast surgery

    International Nuclear Information System (INIS)

    Fujita, Takashi; Iwata, Hiroharu; Yatabe, Yasushi

    2009-01-01

    The differential diagnosis of primary lung cancer from metastatic breast cancer is crucial in patients presenting with a solitary pulmonary nodule after breast surgery. However definitive diagnosis of these nodules is often difficult due to similar radiological and pathological features in primary lung and metastatic breast cancer nodules. We assessed the feasibility of our diagnostic approach for these nodules by morphopathological and immunohistochemical examination (thyroid transcription factor-1 (TTF-1), surfactant pro-protein B (SPPB), estrogen receptor (ER), mammaglobin-1 (MGB1)), and estimated the frequency of primary lung cancer occurrence in 23 breast cancer patients. Biopsy specimens were obtained using CT-guided needle biopsy (NB) and transbronchial lung biopsy (TBLB) in 21 patients (91.3%). Surgical resection was performed for diagnosis and treatment in two patients. Differential diagnosis was obtained by morphopathological methods alone in 17 patients (73.9%, primary lung cancer: 6 cases, metastatic breast cancer: 11 cases) and by immunohistochemical examination in the remaining 6 (26.1%, primary lung cancer: 1 case, metastatic breast cancer: 5 cases). Our results show the clinical feasibility of our approach to the differential diagnosis of breast cancer relapse and primary lung cancer presenting as a solitary nodule in breast cancer patients. (author)

  2. High rate of complete responses to immune checkpoint inhibitors in patients with relapsed or refractory Hodgkin lymphoma previously exposed to epigenetic therapy

    Directory of Open Access Journals (Sweden)

    Lorenzo Falchi

    2016-11-01

    Full Text Available Abstract Options for patients with relapsed or refractory (R/R classical Hodgkin lymphoma (cHL after brentuximab vedotin (Bv and autologous stem cell transplantation (ASCT are limited. Immune checkpoint inhibitors (ICI are active in this population but rarely induce complete response (CR. Ten patients with R/R cHL after ASCT and Bv received pembrolizumab (n = 8 or nivolumab (n = 2. Five had been previously exposed to 5-azacitidine on a phase 1 study. Among nine evaluable patients, seven (78% achieved CR, one partial response, and one reduction of tumor burden. All five patients who had received 5-azacitidine prior to ICI achieved CR, while only two of four who did not receive prior 5-azacitidine achieved CR. At a median follow-up of 9.9 months [0.5–14.3], eight patients are alive and five are still receiving treatment. We documented an unprecedented CR rate after ICI in patients with R/R cHL. We hypothesize that hypomethylating agents might have an immune priming effect and enhance the efficacy of ICI.

  3. Elotuzumab in combination with thalidomide and low-dose dexamethasone: a phase 2 single-arm safety study in patients with relapsed/refractory multiple myeloma.

    Science.gov (United States)

    Mateos, María-Victoria; Granell, Miguel; Oriol, Albert; Martinez-Lopez, Joaquin; Blade, Joan; Hernandez, Miguel T; Martín, Jesus; Gironella, Mercedes; Lynch, Mark; Bleickardt, Eric; Paliwal, Prashni; Singhal, Anil; San-Miguel, Jesus

    2016-11-01

    Elotuzumab is an immunostimulatory, humanized immunoglobulin G1 monoclonal antibody that selectively targets and kills signalling lymphocytic activation molecule family member 7-expressing myeloma cells. We evaluated the safety and tolerability of elotuzumab 10 mg/kg combined with thalidomide 50-200 mg and dexamethasone 40 mg (with/without cyclophosphamide 50 mg) in patients with relapsed/refractory multiple myeloma (RRMM). The primary endpoint was the proportion of grade ≥3 non-haematological adverse events (AEs); other endpoints included the number of dose reductions/discontinuations and efficacy. Forty patients were treated, who had a median of three previous therapies, including bortezomib (98%) and lenalidomide (73%). Grade ≥3 non-haematological AEs were reported in 63% of patients, most commonly asthenia (35%) and peripheral oedema (25%). Six (15%) patients had an infusion reaction. Twenty-six (65%) patients had ≥1 dose reduction/discontinuation due to an AE, none related to elotuzumab. Overall response rate was 38%; median progression-free survival was 3·9 months. Median overall survival was 16·3 months and the 1-year survival rate was 63%. Minimal incremental toxicity was observed with addition of elotuzumab to thalidomide/dexamethasone with or without cyclophosphamide, and efficacy data suggest clinical benefit in a highly pre-treated population. Elotuzumab combined with thalidomide may provide an additional treatment option for patients with RRMM. © 2016 John Wiley & Sons Ltd.

  4. Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis.

    Science.gov (United States)

    Moreau, Philippe; Dimopoulos, Meletios A; Richardson, Paul G; Siegel, David S; Cavo, Michele; Corradini, Paolo; Weisel, Katja; Delforge, Michel; O'Gorman, Peter; Song, Kevin; Chen, Christine; Bahlis, Nizar; Oriol, Albert; Hansson, Markus; Kaiser, Martin; Anttila, Pekka; Raymakers, Reinier; Joao, Cristina; Cook, Gordon; Sternas, Lars; Biyukov, Tsvetan; Slaughter, Ana; Hong, Kevin; Herring, Jennifer; Yu, Xin; Zaki, Mohamed; San-Miguel, Jesus

    2017-09-01

    Heavily pretreated patients with relapsed and refractory multiple myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs are important to ensure patients continue therapy long enough to receive the best clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to further characterize the safety profile of pomalidomide plus low-dose dexamethasone and AE management. This analysis included 1088 patients who received ≥ 2 prior therapies, including lenalidomide and bortezomib, and progressed ≤ 60 days of last therapy. Patients received 28-day cycles of pomalidomide 4 mg/day on days 1-21 and low-dose dexamethasone 40 mg (20 mg if aged > 75 years) weekly until disease progression or unacceptable toxicity. Thromboprophylaxis was required. The most common grade 3/4 AEs were neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%), which occurred within the first few cycles of treatment. Grade 3/4 infections occurred in 33.7% patients, of whom 13.9% had pneumonia, and 40.3% had neutropenia. Pomalidomide dose reductions or interruptions were reported in 24.2% and 66.0% of patients, respectively. AEs were managed by dose modifications and/or supportive care. Pomalidomide plus low-dose dexamethasone showed an acceptable safety profile, and AEs were well managed according to study protocols and established guidelines. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Detection of lymph node metastasis in patients with nodal prostate cancer relapse using (18)F/(11)C-choline positron emission tomography/computerized tomography.

    Science.gov (United States)

    Jilg, Cordula A; Schultze-Seemann, Wolfgang; Drendel, Vanessa; Vach, Werner; Wieser, Gesche; Krauss, Tobias; Jandausch, Anett; Hölz, Stefanie; Henne, Karl; Reske, Sven N; Grosu, Anca-L; Weber, Wolfgang A; Rischke, H Christian

    2014-07-01

    We evaluated the diagnostic accuracy of choline positron emission tomography/computerized tomography for nodal relapse of prostate cancer according to topographical site and tumor infiltration size in lymph nodes. A total of 72 patients with nodal prostate cancer relapse after primary therapy underwent pelvic and/or retroperitoneal salvage lymph node dissection. Salvage was done after whole body positron emission tomography/computerized tomography with (11)C-choline or (18)F-fluoroethylcholine showed positron emission tomography positive lymph nodes but no other detectable metastasis. Diagnostic accuracy was evaluated in 160 dissected lymph node regions (pelvic left/right and retroperitoneal), 498 subregions (common, external and internal iliac, obturator, presacral, aortic bifurcation, aortal, vena caval and interaortocaval) and 2,122 lymph nodes. Lymph node metastasis was present in 32% of resected lymph nodes (681 of 2,122), resulting in 238 positive subregions and 111 positive regions. Positron emission tomography/computerized tomography was positive for 110 regions and 209 subregions. Sensitivity, specificity, positive and negative predictive values, and accuracy were 91.9%, 83.7%, 92.7%, 82.0% and 89.4% (region based), 80.7%, 93.5%, 91.9%, 84.1% and 87.3% (subregion based), and 57.0%, 98.4%, 94.5%, 82.6% and 84.9% (lesion based), respectively. Of 393 positive lymph node metastases detected by this method 278 (70.7%) were in lymph nodes with a less than 10 mm short axis diameter. Imaging sensitivity was 13.3%, 57.4% and 82.8% for a tumor infiltration depth of 2 or greater to less than 3 mm, 5 or greater to less than 6 mm and 10 or greater to less than 11 mm, respectively. Lymph node metastasis site and the radiotracer ((11)C-choline/(18)F-fluoroethylcholine) had no substantial impact on diagnostic accuracy. Choline positron emission tomography/computerized tomography detects affected lymph node regions (pelvic left/right and retroperitoneal) in patients with

  6. Is Ki-67 Expression Prognostic for Local Relapse in Early-Stage Breast Cancer Patients Treated With Breast Conservation Therapy (BCT)?

    Energy Technology Data Exchange (ETDEWEB)

    Hafeez, Farhaan [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States); Neboori, Hanmanth J. [Drexel Medical College, Philadelphia, Pennsylvania (United States); Harigopal, Malini [Department of Pathology, Yale University School of Medicine, New Haven, Connecticut (United States); Wu, Hao; Haffty, Bruce G. [Department of Radiation Oncology, University of Medicine and Dentistry of New Jersey–Robert Wood Johnson School of Medicine, New Brunswick, New Jersey (United States); Yang, Qifeng [Department of Breast Surgery, Shandong University School of Medicine, Shanghai (China); Schiff, Devora [Department of Radiation Oncology, University of Medicine and Dentistry of New Jersey–Robert Wood Johnson School of Medicine, New Brunswick, New Jersey (United States); Moran, Meena S., E-mail: meena.moran@yale.edu [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States)

    2013-10-01

    Purpose: Ki-67 is a human nuclear protein whose expression is strongly up-regulated in proliferating cells and can be used to determine the growth fraction in clonal cell populations. Although there are some data to suggest that Ki-67 overexpression may be prognostic for endpoints such as survival or postmastectomy recurrence, further elucidation of its prognostic significance is warranted. Specifically after breast conservation therapy (BCT) (defined in this setting as breast-conserving surgery and adjuvant radiation therapy), whether Ki-67 predicts for locoregional recurrence has not been investigated. The purpose of this study was to assess Ki-67 expression in a cohort of early-stage breast cancer patients to determine whether a significant independent association between Ki-67 and locoregional relapse exists. Methods and Materials: Ki-67 staining was conducted on a tissue microarray of 438 patients previously treated with BCT, and expression was analyzed with clinicopathologic features and outcomes from our database. Results: Ki-67 expression was more prevalent in black patients (37% of black patients vs 17% of white patients, P<.01), younger patients (27% of patients aged ≤50 years vs 15% of patients aged >50 years, P<.01), estrogen receptor (ER)–negative tumors (25% of ER-negative tumors vs 17% of ER-positive tumors, P=.04), human epidermal growth factor receptor 2 (HER2)/neu–positive tumors (35% of HER2-positive tumors vs 18% of HER2-negative tumors, P=.01), and larger tumors (26% of T2 tumors vs 16% of T1 tumors, P=.03). On univariate/multivariate analysis, Ki-67 did not predict for overall survival (74.4% vs 72.6%), cause-specific survival (82.9% vs 82.1%), local relapse-free survival (83.6% vs 88.5%), distant metastasis-free survival (76.1% vs 81.4%), recurrence-free survival (65.5% vs 74.6%), and locoregional recurrence-free survival (81.6% vs 84.7%): P>.05 for all. Conclusions: Ki-67 appears to be a surrogate marker for aggressive disease and

  7. Longitudinal study of visual function in patients with relapsing-remitting multiple sclerosis with and without a history of optic neuritis.

    Science.gov (United States)

    González Gómez, A; García-Ben, A; Soler García, A; García-Basterra, I; Padilla Parrado, F; García-Campos, J M

    2017-03-15

    The contrast sensitivity test determines the quality of visual function in patients with multiple sclerosis (MS). The purpose of this study is to analyse changes in visual function in patients with relapsing-remitting MS with and without a history of optic neuritis (ON). We conducted a longitudinal study including 61 patients classified into 3 groups as follows: a) disease-free patients (control group); b) patients with MS and no history of ON; and c) patients with MS and a history of unilateral ON. All patients underwent baseline and 6-year follow-up ophthalmologic examinations, which included visual acuity and monocular and binocular Pelli-Robson contrast sensitivity tests. Monocular contrast sensitivity was significantly lower in MS patients with and without a history of ON than in controls both at baseline (P=.00 and P=.01, respectively) and at 6 years (P=.01 and P=.02). Patients with MS and no history of ON remained stable throughout follow-up whereas those with a history of ON displayed a significant loss of contrast sensitivity (P=.01). Visual acuity and binocular contrast sensitivity at baseline and at 6 years was significantly lower in the group of patients with a history of ON than in the control group (P=.003 and P=.002 vs P=.006 and P=.005) and the group with no history of ON (P=.04 and P=.038 vs P=.008 and P=.01). However, no significant differences were found in follow-up results (P=.1 and P=.5). Monocular Pelli-Robson contrast sensitivity test may be used to detect changes in visual function in patients with ON. Copyright © 2017 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Lebensraum: paradoxically, population growth may eventually end wars.

    Science.gov (United States)

    Simon, J L

    1989-03-01

    Population growth may progressively reduce 1 of the motives for making war. Namely, population growth threatens shortages of resources, and especially land. Impending shortages cause a search for ways to mitigate the shortages. The discoveries eventually produce greater availability of resources than if population growth and pressure on resources had never occurred. The argument runs as follows: 1) Rhetoric about resources scarcity induced by population density has often contributed to international conflict, even if economics has not been the main motive in making war. 2) In the pre-modern era, war to obtain land and other resources may sometimes have been an economically sound policy. 3) Politicians and others in industrially developed nations believe resources may still be a casus belli. 4) Land and other productive resources are no longer worth acquiring at the cost of war.

  9. Two different schedules of irinotecan (CPT-11) in patients with advanced colorectal carcinoma relapsing after a 5-fluorouracil and leucovorin combination. A randomized study.

    Science.gov (United States)

    Tsavaris, N; Ziras, N; Kosmas, C; Giannakakis, T; Gouveris, P; Vadiaka, M; Dimitrakopoulos, A; Karadima, D; Rokana, S; Papalambros, E; Papastratis, G; Margaris, H; Tsipras, H; Polyzos, A

    2003-12-01

    To evaluate the efficacy and safety of irinotecan as second-line treatment in patients with advanced colorectal cancer (ACC) failing or relapsing after 5-fluorouracil (5-FU) plus leucovorin (LV) standard chemotherapy. Irinotecan was randomly administered in two different schedules (once every 3 weeks, and every 10 days) in patients failing prior 5-FU plus LV. Patients were randomized to two treatment groups: group A received irinotecan 350 mg/m2 every 21 days and group B received irinotecan 175 mg/m2 days 1 and 10 every 21 days. Group A comprised 60 patients: 34 male/26 female, median age 64 years (range 48-70 years), and median Karnofsky performance status (PS) 90. Their metastatic sites included liver (n=47), lymph nodes (n=27), lung (n=14), abdomen (n=14), pelvis (n=8), "other" (n=2), and local recurrence (n=12). Group B comprised 60 patients: 36 male/24 female, median age 62 years (46-70 years), and median PS 90. Their metastatic sites included liver (n=49), lymph nodes (n=29), lung (n=17), abdomen (n=16), pelvis (n=11), "other" (n=2), and local recurrence (n=13). Group A showed the following responses: complete response (CR) 2, partial response (PR) 12, stable disease (SD) 21, progressive disease (PD) 26, overall response rate (ORR) 23%, tumor growth control 58%. Group B showed the following responses: CR 1, PR 14, SD 22, PD 23; ORR 25%; tumor growth control 62%. Toxicities included acute cholinergic syndrome (group A 53%, group B 19%; P<0.0001), late-onset diarrhea grade 1/2 (group A 21%, group B 46%) and grade 3/4 (group A 41%, group B 66%; P<0.0001), nausea and vomiting grade 1/2 (group A 34%, group B 59%) and grade 3/4 (group A 30%, group B 12%; P<0.0001), neutropenia grade 3/4 (group A 27%, group B 28%; P<0.03), with febrile neutropenia seen in only four patients in group A, anemia grade more than 2 (group A 28%, group B 12%; P<0.05), asthenia grade more than 3 (group A 24%, group B 18%; P<0.001), and alopecia grade more than 3 (group A 40%, group B 34

  10. The association between body composition and toxicities from the combination of Doxil and trabectedin in patients with advanced relapsed ovarian cancer.

    Science.gov (United States)

    Prado, Carla M M; Baracos, Vickie E; Xiao, Jingjie; Birdsell, Laura; Stuyckens, Kim; Park, Youn Choi; Parekh, Trilok; Sawyer, Michael B

    2014-06-01

    Emerging research suggests that body composition can predict toxicity of certain chemotherapeutic agents. We used data from a clinical study to investigate associations between body composition and combined DOXIL (pegylated liposomal doxorubicin; PLD) and trabectedin (Yondelis) treatment, an effective treatment for ovarian cancer that shows high interpatient variation in toxicity profile. Patients (n = 74) participating in a phase III randomized trial of relapsed advanced ovarian cancer receiving PLD (30 mg/m(2)) and trabectedin (1.1 mg/m(2)) were included. Muscle tissue was measured by analysis of computerized tomography images, and an extrapolation of muscle and adipose tissue to lean body mass (LBM) and fat mass (FM) were employed. Toxicity profile after cycle 1 was used and graded according to the National Cancer Institute Common Toxicity Criteria (version 3). Patients presented with a wide range of body composition. In overweight and obese patients (body mass index (BMI) ≥ 25 kg/m(2), n = 48) toxicity was more prevalent in those with lower BMI (p = 0.028) and a lower FM (n = 43, p = 0.034). Although LBM alone was not predictive of toxicity, a lower FM/LBM ratio was the most powerful variable associated with toxicity (p = 0.006). A different pattern emerged among normal weight patients (n = 26) where toxicity was rare among patients with smaller BMI (body weight, with a lower ratio predicting higher exposure and risk for toxicity.

  11. The predictive value of 2-year posttreatment biopsy after prostate cancer radiotherapy for eventual biochemical outcome

    International Nuclear Information System (INIS)

    Vance, Waseet; Tucker, Susan L.; Crevoisier, Renaud de; Kuban, Deborah A.; Cheung, M. Rex

    2007-01-01

    Purpose: To determine the value of a 2-year post-radiotherapy (RT) prostate biopsy for predicting eventual biochemical failure in patients who were treated for localized prostate cancer. Methods and Materials: This study comprised 164 patients who underwent a planned 2-year post-RT prostate biopsy. The independent prognostic value of the biopsy results for forecasting eventual biochemical outcome and overall survival was tested with other factors (the Gleason score, 1992 American Joint Committee on Cancer tumor stage, pretreatment prostate-specific antigen level, risk group, and RT dose) in a multivariate analysis. The current nadir + 2 (CN + 2) definition of biochemical failure was used. Patients with rising prostate-specific antigen (PSA) or suspicious digital rectal examination before the biopsy were excluded. Results: The biopsy results were normal in 78 patients, scant atypical and malignant cells in 30, carcinoma with treatment effect in 43, and carcinoma without treatment effect in 13. Using the CN + 2 definition, we found a significant association between biopsy results and eventual biochemical failure. We also found that the biopsy status provides predictive information independent of the PSA status at the time of biopsy. Conclusion: A 2-year post-RT prostate biopsy may be useful for forecasting CN + 2 biochemical failure. Posttreatment prostate biopsy may be useful for identifying patients for aggressive salvage therapy

  12. Ability of the rhTSH stimulation test to predict relapse in patients with differentiated thyroid carcinoma, after long-term follow-up

    Science.gov (United States)

    MARCELINO, MAFALDA; LOPES, ANA FILIPA; MADUREIRA, DEOLINDA; FERREIRA, TERESA C.; LIMBERT, EDWARD; LEITE, VALERIANO

    2015-01-01

    The analysis of serum thyroglobulin (Tg) following thyroid-stimulating hormone (TSH) stimulation (sTg) has been recommended in the follow-up of differentiated thyroid carcinoma (DTC) patients, however, its routine use remains controversial. The aim of the current study was to evaluate the accuracy of sTg testing following recombinant human (rh) TSH stimulation in DTC patients, with a follow-up of 12.4 years. Retrospective studies were conducted of 125 DTC patients, who underwent rhTSH stimulation testing between 1999 and 2002. The exclusion criteria were: Patients with anti-Tg antibodies, Tg levels >1 ng/ml under TSH suppression and the absence of radioactive iodine (RAI) ablation therapy following surgery. In total, 49 patients were included in the study and all had been previously treated with total or near total thyroidectomy (with or without central neck dissection) and RAI, postoperatively. The Tg functional sensitivity was 1.0 ng/ml. The follow-up for patients was performed annually. During the median follow-up of 12.4 years after the rhTSH stimulation test, nine patients exhibited recurrence (18.4%). Of the nine patients, six exhibited sTg levels >2 ng/ml (positive result) and three exhibited levels <2 ng/ml (negative result). Relapse occurred at a mean of 5.9 years following the rhTSH stimulation test. The positive predictive value and negative predictive value (NPV) of positive sTg were 50 and 91.9%, respectively, with a sensitivity of 66.6% and a specificity of 85.0%. The rhTSH-stimulated Tg levels have a high NPV, allowing the identification of the patients who are free of the tumour. These results are consistent with the previously published data; however, to the best of our knowledge, this is the study with the longest follow-up duration after rhTSH stimulation. PMID:25663898

  13. Factors associated with relapse in schizophrenia | Kazadi | South ...

    African Journals Online (AJOL)

    Aim. Early identification and prevention of relapse in patients with schizophrenia has significant therapeutic and socioeconomic implications. The aim of this study was to determine the factors, if any, that may be associated with relapse in a group of patients in Johannesburg. Method. Patients were recruited from mental ...

  14. Quantitative detection of epstein-barr virus DNA in cerebrospinal fluid and blood samples of patients with relapsing-remitting multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Clementina E Cocuzza

    Full Text Available The presence of Epstein-Barr Virus (EBV DNA in cerebrospinal fluid (CSF and peripheral blood (PB samples collected from 55 patients with clinical and radiologically-active relapsing-remitting MS (RRMS and 51 subjects with other neurological diseases was determined using standardized commercially available kits for viral nucleic acid extraction and quantitative EBV DNA detection. Both cell-free and cell-associated CSF and PB fractions were analyzed, to distinguish latent from lytic EBV infection. EBV DNA was detected in 5.5% and 18.2% of cell-free and cell-associated CSF fractions of patients with RRMS as compared to 7.8% and 7.8% of controls; plasma and peripheral blood mononuclear cells (PBMC positivity rates were 7.3% and 47.3% versus 5.8% and 31.4%, respectively. No significant difference in median EBV viral loads of positive samples was found between RRMS and control patients in all tested samples. Absence of statistically significant differences in EBV positivity rates between RRMS and control patients, despite the use of highly sensitive standardized methods, points to the lack of association between EBV and MS disease activity.

  15. Daclizumab high-yield process reduced the evolution of new gadolinium-enhancing lesions to T1 black holes in patients with relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Radue, E-W; Sprenger, T; Vollmer, T; Giovannoni, G; Gold, R; Havrdova, E; Selmaj, K; Stefoski, D; You, X; Elkins, J

    2016-02-01

    In the SELECT study, treatment with daclizumab high-yield process (DAC HYP) versus placebo reduced the frequency of gadolinium-enhancing (Gd(+) ) lesions in patients with relapsing-remitting multiple sclerosis (RRMS). The objective of this post hoc analysis of SELECT was to evaluate the effect of DAC HYP on the evolution of new Gd(+) lesions to T1 hypointense lesions (T1 black holes). SELECT was a randomized double-blind study of subcutaneous DAC HYP 150 or 300 mg or placebo every 4 weeks. Magnetic resonance imaging (MRI) scans were performed at baseline and weeks 24, 36 and 52 in all patients and monthly between weeks 4 and 20 in a subset of patients. MRI scans were evaluated for new Gd(+) lesions that evolved to T1 black holes at week 52. Data for the DAC HYP groups were pooled for analysis. Daclizumab high-yield process reduced the number of new Gd(+) lesions present at week 24 (P = 0.005) or between weeks 4 and 20 (P = 0.014) that evolved into T1 black holes at week 52 versus placebo. DAC HYP treatment also reduced the percentage of patients with Gd(+) lesions evolving to T1 black holes versus placebo. Treatment with DAC HYP reduced the evolution of Gd(+) lesions to T1 black holes versus placebo, suggesting that inflammatory lesions that evolved during DAC HYP treatment are less destructive than those evolving during placebo treatment. © 2016 EAN.

  16. Health-related quality of life in relapsing remitting multiple sclerosis patients during treatment with glatiramer acetate: a prospective, observational, international, multi-centre study

    Directory of Open Access Journals (Sweden)

    Fredrikson Sten

    2010-11-01

    Full Text Available Abstract Background Glatiramer acetate (GA and interferon-beta (INFb are first-line disease modifying drugs for relapsing remitting multiple sclerosis (RRMS. Treatment with INFb is associated with a significant increase in health-related quality of life (HR-QoL in the first 12 months. It is not known whether HR-QoL increases during treatment with GA. Methods 197 RRMS patients, 106 without and 91 with prior immunomodulation/immunosuppression, were studied for HR-QoL (Leeds Multiple Sclerosis-QoL [LMS-QoL] scale, score range 0 - 32, fatigue (Fatigue Impact Scale [FIS] and depressed mood (Beck Depression Inventory-Short Form [BDI-SF] at baseline and 6 and 12 months after start of GA treatment. Results At 6 and 12 months mean LMS-QoL scores were significantly increased in the treatment-naive patient group (p Conclusions In RRMS patients without prior immunomodulation/immunosuppression treatment with GA was associated with an increase in HR-QoL in the first 6 months, that was sustained at 12 months. In 4 out of 10 patients HR-QoL improved. Increase in HR-QoL was associated with decrease in fatigue.

  17. Cost-effectiveness of carfilzomib plus dexamethasone compared with bortezomib plus dexamethasone for patients with relapsed or refractory multiple myeloma in the United States.

    Science.gov (United States)

    Jakubowiak, Andrzej J; Houisse, Ivan; Májer, István; Benedict, Ágnes; Campioni, Marco; Panjabi, Sumeet; Ailawadhi, Sikander

    2017-12-01

    We assessed the economic value of carfilzomib 56 mg/m 2 and dexamethasone (Kd56) vs. bortezomib and dexamethasone (Vd) for relapsed/refractory multiple myeloma (R/RMM) using ENDEAVOR trial results. Cost-effectiveness of Kd56 vs. Vd was assessed using a partitioned survival model by estimating progression-free survival, overall survival, and direct costs over a lifetime horizon. Surveillance Epidemiology and End Results (SEER) survival data were extrapolated after matching registry and ENDEAVOR patients. Utilities were sourced from the literature and mapped from patient-reported quality of life in ENDEAVOR to estimate quality-adjusted life-years (QALYs) from life-years (LYs). The model predicted an average gain of 1.66 LYs and 1.50 QALYs with Kd56 vs. Vd, and lifetime additional costs of $182,699, resulting in an incremental cost-effectiveness ratio (ICER) of $121,828/QALY gained. The ICER was $114,793/QALY in patients with 1 prior treatment; $99,263/QALY in those not transplanted, and discount in bortezomib price. Kd56 is cost-effective for patients with R/RMM at a willingness-to-pay threshold of $150,000/QALY. Trial data in the model may limit generalizability; however, SEER registry data mitigates this challenge. Kd56 provides additional value in key subgroups, and remains cost-effective after steep comparator discounts.

  18. [Combination of etoposide, cisplatin and ifosfamide (VPH) in the salvage chemotherapy of relapsing or refractory aggressive malignant lymphoma. Study of 51 patients].

    Science.gov (United States)

    Eghbali, H; Catry-Thomas, I; Soubeyran, P; Bonnel, C; Hoerni, B

    1994-09-01

    Fifty-one patients with non-Hodgkin's lymphoma refractory or relapsing after CHOP-like regimen, underwent a salvage chemotherapy by VPH: etoposide 100 mg/m2/d, D1 to D3, cisplatin 20 mg/m2/d, D1 to D5, ifosfamide 1 g/m2/d D1 to D5, mesna 1.2 g/m2/d D1 to D5, every 4 weeks. Among 46 evaluable patients for efficacy, 21 (45.6%) achieved complete or partial response according to WHO criteria and 25 (54.3%) failed, while five cases (9.8% of all patients) were not evaluable (two initial complete remission before VPH, two early toxic deaths and one confusional syndrome). Thirty-five patients (68.6%) died of lymphoma, three (5.8%) of acute toxicity and 13 (25.5%) are alive: five in complete remission. The toxicity is mainly myelo-suppression, digestive and renal but could be managed as usually. Although the follow-up is short, this regimen appears effective in these circumstances after CHOP failure but it should be used early, before overt chemoresistance. It does not hinder a bone marrow transplantation programme.

  19. Using mental visual imagery to improve autobiographical memory and episodic future thinking in relapsing-remitting multiple sclerosis patients: A randomised-controlled trial study.

    Science.gov (United States)

    Ernst, Alexandra; Blanc, Frédéric; De Seze, Jérôme; Manning, Liliann

    2015-01-01

    The co-occurrence of autobiographical memory (AM) and episodic future thinking (EFT) impairment has been documented in relapsing-remitting multiple sclerosis (RR-MS) patients. On these bases, we aimed at probing the efficacy of a mental visual imagery (MVI)-based facilitation programme on AM and EFT functioning in the context of a randomised-controlled trial study in RR-MS patients. Using the Autobiographical Interview (AI), 40 patients presenting with an AM/EFT impairment were randomly assigned in three groups: (i) the experimental (n = 17), who followed the MVI programme, (ii) the verbal control (n = 10), who followed a sham verbal programme, and (iii) the stability groups (n = 13), who underwent the AM/EFT test twice, with no intervention in between. AI's second assessment scores showed a significant improvement of AM and EFT performance only for the experimental group, with a long-term robustness of treatment benefits. The control and stability groups' results ruled out nursing and test learning effects as explanations of AM/EFT improvement. These benefits were corroborated by the patients' comments, which indicated an effective MVI strategy transfer to daily life. Our results suggest that the MVI programme tackles a common cognitive process of scene construction present in AM and EFT.

  20. Pharmacokinetics and pharmacokinetic/pharmacodynamic associations of ofatumumab, a human monoclonal CD20 antibody, in patients with relapsed or refractory chronic lymphocytic leukaemia: a phase 1-2 study

    DEFF Research Database (Denmark)

    Coiffier, Bertrand; Losic, Nedjad; Rønn, Birgitte Biilmann

    2010-01-01

    The purpose of this phase 1-2 study was to investigate the association between the pharmacokinetic properties of ofatumumab, a human monoclonal CD20 antibody, and outcomes in 33 patients with relapsed/refractory chronic lymphocytic leukaemia receiving 4 weekly infusions of ofatumumab. The ofatumu...

  1. Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Cook, Stuart; Rammohan, Kottil

    2011-01-01

    On the basis of various clinical and MRI measurements, the phase 3 Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) study in patients with relapsing-remitting multiple sclerosis (RRMS) showed that short-course oral treatment with cladribine at cumulative doses of 3·5 and 5·25 mg...

  2. Clinical Spectrum, Treatment and Relapse Patterns in 353 Patients with Squamous Cell Carcinoma of the Alveobuccal Complex Treated with a Curative Intent: A Retrospective Study.

    Science.gov (United States)

    Shukla, Nootan Kumar; Deo, S V Suryanarayana; Jakhetiya, Ashish; Nml, Manjunath; Sreenivas, Vishnubhatla; Thulkar, Sanjay; Bhasker, Suman; Sharma, Atul

    2018-03-01

    Oral cancer is one of the most common cancers in Indian subcontinent with alveobuccal complex as most common cancer sub site. Cancers of Alveobuccal complex provides maximum challenge and management guidelines are not clear. The aim of the present study is to provide comprehensive demographic, clinical and treatment outcome data of alveobuccal squamous cell carcinoma (SCC) patients treated at a tertiary care cancer center in North India. An analysis of prospectively maintained database in department of surgical oncology at Dr BRA-IRCH, AIIMS, Delhi, India was performed. All alveobuccal cancer patients who had undergone surgery from 1995 to 2010 were included for analysis. A total of 353 patients were included for analysis. Mean age was 49.75 years (SD ±12.04) with male and female ratio of 4:1. Composite resection without mandible was done in 25 % patients and 75 % underwent mandibular resection. Neck dissection was performed in 347 patients. Nodal deposits were identified in 124 (35.73 %) neck dissection specimens. Margin negative resection was performed in 89.5 % cases. After a median follow up of 30 months, 87 (24.64 %) patients developed disease relapse and 25 (7.08 %) patients developed second primaries. Overall 5-year disease free survival (DFS) was 57.65 % and 5 year overall survival (OS) was 59.86 %. Among Indian oral cancer patients alveobuccal complex is most common sub site. Majority presents in locally advanced stage and reasonably good outcomes can be achieved with quality control surgery and judicious use of radiotherapy.

  3. Long-term effects of cladribine tablets on MRI activity outcomes in patients with relapsing-remitting multiple sclerosis: the CLARITY Extension study.

    Science.gov (United States)

    Comi, Giancarlo; Cook, Stuart; Rammohan, Kottil; Soelberg Sorensen, Per; Vermersch, Patrick; Adeniji, Abidemi K; Dangond, Fernando; Giovannoni, Gavin

    2018-01-01

    The CLARITY and CLARITY Extension studies demonstrated that treatment of relapsing-remitting multiple sclerosis (RRMS) with cladribine tablets (CT) results in significant clinical improvements, compared with placebo. This paper presents the key magnetic resonance imaging (MRI) findings from the CLARITY Extension study. Patients who received a cumulative dose of either CT 3.5 or 5.25 mg/kg in CLARITY were rerandomized to either placebo or CT 3.5 mg/kg in CLARITY Extension. Patients from the arm that received placebo in CLARITY were assigned to CT 3.5 mg/kg. MRI assessments were carried out when patients entered CLARITY Extension and after Weeks 24, 48, 72 and 96, and in a supplemental follow-up period. At CLARITY Extension baseline, patients who received placebo during CLARITY had more T1 gadolinium-enhanced (Gd+) lesions than patients who received CT during CLARITY. These patients, who were then exposed to cladribine 3.5 mg/kg during the extension, experienced a 90.4% relative reduction (median difference -0.33, 97.5% confidence interval -0.33-0.00; p MRI activity, and this was associated with a prolonged treatment gap between CLARITY and CLARITY Extension. A 2-year treatment with CT 3.5 mg/kg has a durable effect on MRI outcomes in the majority of patients, an effect that was sustained in patients who were not retreated in the subsequent 2 years after initial treatment. ClinicalTrials.gov identifier: NCT00641537 .

  4. Development and optimization of an in vitro cultivation protocol allows for isolation of Borrelia miyamotoi from patients with hard tick-borne relapsing fever

    NARCIS (Netherlands)

    Koetsveld, Joris; Kolyasnikova, Nadezhda M.; Wagemakers, Alex; Toporkova, Marina G.; Sarksyan, Denis S.; Oei, Anneke; Platonov, Alexander E.; Hovius, Joppe W.

    2017-01-01

    Objectives: Borrelia miyamotoi has been shown to infect humans in Eurasia and North America causing hard tick-borne relapsing fever (HTBRF). In vitro cultivation of B. miyamotoi was described recently; but clinical isolation of relapsing fever Borrelia is cumbersome. Our aim was to develop a

  5. Impact of tall cell variant histology on predicting relapse and changing the management of papillary thyroid carcinoma patients.

    Science.gov (United States)

    Gunalp, Bengul; Okuyucu, Kursat; Ince, Semra; Ayan, Aslı; Alagoz, Engin

    2017-01-01

    There has been much discussion recently about the risk category of tall cell variant (TVC) histology and its effects on the management of papillary thyroid carcinoma (PTC). We, therefore, undertook a retrospective study to compare stage-matched risk factors and recurrence rates between classical PTC (cPTC) patients and patients with TCV histology. A total of 3128 well-differentiated thyroid carcinoma patients who were treated and followed-up for more than 5 years in our clinic from 1995 to 2016 were included in this study. There were 2783 PTC (89%) patients, 1113 (40%) of them were cPTC and 56 (2%) of them were TCV patients. In all stages, the stage-matched incidence of extrathyroidal extension (ETE), lymphovascular invasion and initial lymph node metastases were significantly higher in TCV patients than in cPTC patients (Papproach and closer follow-up than classical patients.

  6. Why do even satisfied newlyweds eventually go on to divorce?

    Science.gov (United States)

    Lavner, Justin A; Bradbury, Thomas N

    2012-02-01

    Although divorce typically follows an extended period of unhappiness that begins early in marriage, some couples who are very happy throughout the first several years of marriage will also go on to divorce. This study aimed to identify risk factors early in marriage that distinguish initially satisfied couples who eventually divorce from those who remain married. We identified 136 couples reporting stably high levels of relationship satisfaction in the first 4 years of marriage. We compared the couples who went on to divorce by the 10-year follow-up with the couples who remained married on initial measures of commitment, observed communication, stress, and personality. Divorcing couples displayed more negative communication, emotion, and social support as newlyweds compared with couples who did not divorce. No significant differences were found in the other domains, in relationship satisfaction, or in positive behaviors. Overall, results indicate that even couples who are very successful at navigating the early years of marriage can be vulnerable to later dissolution if their interpersonal exchanges are poorly regulated. We speculate that, paradoxically, the many strengths possessed by these couples may mask their potent interpersonal liabilities, posing challenges for educational interventions designed to help these couples.

  7. Electrolysis with diamond anodes: Eventually, there are refractory species!

    Science.gov (United States)

    Mena, Ismael F; Cotillas, Salvador; Díaz, Elena; Sáez, Cristina; Rodríguez, Juan J; Cañizares, P; Mohedano, Ángel F; Rodrigo, Manuel A

    2018-03-01

    In this work, synthetic wastewater polluted with ionic liquid 1-butyl-3-methylimidazolium (Bmim) bis(trifluoromethanesulfonyl)imide (NTf 2 ) undergoes four electrolytic treatments with diamond anodes (bare electrolysis, electrolysis enhanced with peroxosulfate promoters, irradiated with UV light and with US) and results obtained were compared with those obtained with the application of Catalytic Wet Peroxide Oxidation (CWPO). Despite its complex heterocyclic structure, Bmim + cation is successfully depleted with the five technologies tested, being transformed into intermediates that eventually can be mineralized. Photoelectrolysis attained the lowest concentration of intermediates, while CWPO is the technology less efficient in their degradation. However, the most surprising result is that concentration of NTf 2 - anion does not change during the five advanced oxidation processes tested, pointing out its strong refractory character, being the first species that exhibits this character in wastewater undergoing electrolysis with diamond. This means that the hydroxyl and sulfate radicals mediated oxidation and the direct electrolysis are inefficient for breaking the C-S, C-F and S-N bounds of the NTf 2 - anion, which is a very interesting mechanistic information to understand the complex processes undergone in electrolysis with diamond. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Efficacy and safety of the glycine transporter-1 inhibitor org 25935 for the prevention of relapse in alcohol-dependent patients: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    de Bejczy, Andrea; Nations, Kari R; Szegedi, Armin; Schoemaker, Joep; Ruwe, Frank; Söderpalm, Bo

    2014-09-01

    Org 25935 is a glycine transporter inhibitor that increases extracellular glycine levels and attenuates alcohol-induced dopaminergic activity in the nucleus accumbens. In animal models, Org 25935 has dose-dependent effects on ethanol intake, preference, and relapse-like behavior without tolerance. The current study aimed to translate these animal findings to humans by examining whether Org 25935 prevents relapse in detoxified alcohol-dependent patients. This was a multicenter, randomized, double-blind, placebo-controlled clinical trial. Adult patients diagnosed with alcohol dependence were randomly assigned to receive Org 25935 12 mg twice a day or placebo for 84 days. The primary end point was percentage heavy drinking days (defined as ≥ 5 standard drinks per day for men and ≥ 4 for women). Secondary end points included other measures of relapse-related drinking behavior (e.g., drinks per day, time to relapse), as well as measures of global functioning, alcohol-related thoughts and cravings, and motivation. A total of 140 subjects were included in the intent-to-treat analysis. The trial was stopped approximately midway after a futility analysis showing that the likelihood of detecting a signal at study term was Org 25935 and placebo on percentage heavy drinking days or any other measure of relapse-related drinking behavior. Org 25935 showed no safety issues and was fairly well tolerated, with fatigue, dizziness, and transient visual events as the most commonly occurring side effects. Org 25935 demonstrated no benefit over placebo in preventing alcohol relapse. Study limitations and implications are discussed. Copyright © 2014 by the Research Society on Alcoholism.

  9. Nivolumab as salvage treatment in a patient with HIV-related relapsed/refractory Hodgkin lymphoma and liver failure with encephalopathy.

    Science.gov (United States)

    Sandoval-Sus, Jose D; Mogollon-Duffo, Francis; Patel, Ankita; Visweshwar, Nathan; Laber, Damian A; Kim, Richard; Jagal, Michael V

    2017-01-01

    We report the first case to our knowledge of a patient with relapsed/refractory classical hodgkin lymphoma and liver failure with encephalopathy along with human immunodeficiency virus/acquired immunodeficiency syndrome infection, successfully treated with nivolumab without major side effects and encouraging prolonged disease control. In December 2015, at the time of the patient's progression from his Hodgkin lymphoma after fourth line treatment, he developed persistent fevers, abdominal distension, jaundice and worsening of his liver function tests. Magnetic resonance imaging of abdomen/pelvis demonstrated hepatomegaly with innumerable new liver lesions, splenomegaly with multiple splenic nodules and several new mediastinal, intraperitoneal and retroperitoneal lymphadenopathy. In accordance with the patient's wishes before admission, and after agreement with the family, nivolumab (3 mg/kg every 2 weeks) was given. Of note, antiretroviral therapy was on hold due to liver function tests, his viral load was undectable and cluster of differentiation 4 counts were 103/uL at the time of nivolumab administration. One week after the first dose of nivolumab both his hepatic encephalopathy and constitutional symptoms started to improve, and after 2 doses, (January 2016) his LFTs were almost back to normal. After 5 months of nivolumab treatment (10 doses), restaging (computerized tomography scans of neck, chest, abdomen, pelvis) done on May 2016 showed resolution of hepatosplenomegaly with two residual small hepatic lesions, heterogeneous spleen with no splenic lesions, and stable non-enlarged retroperitoneal lymph nodes without intraabdominal lymphadenopathy; consistent with partial response. We report a case of a patient with human immunodeficiency virus/acquired immunodeficiency syndrome -related relapsed/refractory classical Hodgkin lymphoma and acute liver failure with encephalopathy successfully treated with nivolumab after failing all standard therapeutic options

  10. Role of FDG-PET for the diagnosis of differentiated thyroid cancer relapse examination of 39 patients

    International Nuclear Information System (INIS)

    Groheux, D.; Garin, E.; Bernard, A.M.; Devillers, A.; Lescouarc'h, J.; Prigent-Le Jeune, F.; Carsin, A.; Bourguet, P.; Herry, J.Y.; Mesbah, H.

    2005-01-01

    Thirty nine patients with differentiated thyroid carcinoma (32 papillary, 4 follicular and 3 oncocytic) were studied by 18FDG whole-body PET in most cases because of elevated thyroglobulin. All patients were examined with hormone substitution at low TSH levels. Fourteen patients had 18FD G uptake in cervical region, 9 in mediastinum and 5 in lungs. Sensitivity of FDG-PET was 68%, specificity 71%, PPV 8% and NPV 56%. Sensitivity was respectively 53% and 90% if thyroglobulin was inferior or superior to 10 ng/ml. FDG-PET changed cancer staging in 27 patients and changed treatment strategy in 11 patients (10 surgical treatments and 1 radioiodine therapy). (author)

  11. A Phase I Study of Pulse High-Dose Vorinostat (V) plus Rituximab (R), Ifosphamide, Carboplatin, and Etoposide (ICE) in Patients with Relapsed Lymphoma

    Science.gov (United States)

    Budde, Lihua E.; Zhang, Michelle M.; Shustov, Andrei R.; Pagel, John M.; Gooley, Ted A.; Oliveira, George R.; Chen, Tara L.; Knudsen, Nancy L.; Roden, Jennifer E.; Kammerer, Britt E.; Frayo, Shani L.; Warr, Thomas A.; Boyd, Thomas E.; Press, Oliver W.; Gopal, Ajay K.

    2013-01-01

    SUMMARY Given the poor outcomes of relapsed aggressive lymphomas and preclinical data suggesting that ≥2.5 μM concentrations of vorinostat synergize with both etoposide and platinums, we hypothesized that pulse high-dose vorinostat could safely augment the anti-tumour activity of (R)ICE [(rituximab), ifosphamide, carboplatin, etoposide] chemotherapy. We conducted a phase I dose escalation study using a schedule with oral vorinostat ranging from 400 mg/d to 700 mg bid for 5 days in combination with the standard (R)ICE regimen (days 3, 4 and 5). Twenty-nine patients (median age 56 years, median 2 prior therapies, 14 chemoresistant [of 27 evaluable], 2 prior transplants) were enrolled and treated. The maximally tolerated vorinostat dose was defined as 500 mg twice daily × 5 days. Common dose limiting toxicities included infection (n=2), hypokalaemia (n=2), and transaminitis (n=2). Grade 3 related gastrointestinal toxicity was seen in 9 patients. The median vorinostat concentration on day 3 was 4.5 μM (range 4.2–6.0 μM) and in vitro data confirmed the augmented antitumour and histone acetylation activity at these levels. Responses were observed in 19 of 27 evaluable patients (70%) including 8 complete response/unconfirmed complete response. High-dose vorinostat can be delivered safely with (R)ICE, achieves potentially synergistic drug levels, and warrants further study, although adequate gastrointestinal prophylaxis is warranted. PMID:23356514

  12. The Combined Quantification and Interpretation of Multiple Quantitative Magnetic Resonance Imaging Metrics Enlightens Longitudinal Changes Compatible with Brain Repair in Relapsing-Remitting Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Guillaume Bonnier

    2017-09-01

    Full Text Available ObjectiveQuantitative and semi-quantitative MRI (qMRI metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration, and repair. Moreover, advanced magnetic resonance imaging (MRI metrics with overlapping elements amplify the true tissue-related information and limit measurement noise. In this work, we combined multiple advanced MRI parameters to assess focal and diffuse brain changes over 2 years in a group of early-stage relapsing-remitting MS patients.MethodsThirty relapsing-remitting MS patients with less than 5 years disease duration and nine healthy subjects underwent 3T MRI at baseline and after 2 years including T1, T2, T2* relaxometry, and magnetization transfer imaging. To assess longitudinal changes in normal-appearing (NA tissue and lesions, we used analyses of variance and Bonferroni correction for multiple comparisons. Multivariate linear regression was used to assess the correlation between clinical outcome and multiparametric MRI changes in lesions and NA tissue.ResultsIn patients, we measured a significant longitudinal decrease of mean T2 relaxation times in NA white matter (p = 0.005 and a decrease of T1 relaxation times in the pallidum (p < 0.05, which are compatible with edema reabsorption and/or iron deposition. No longitudinal changes in qMRI metrics were observed in controls. In MS lesions, we measured a decrease in T1 relaxation time (p-value < 2.2e−16 and a significant increase in MTR (p-value < 1e−6, suggesting repair mechanisms, such as remyelination, increased axonal density, and/or a gliosis. Last, the evolution of advanced MRI metrics—and not changes in lesions or brain volume—were correlated to motor and cognitive tests scores evolution (Adj-R2 > 0.4, p < 0.05. In summary, the combination of multiple advanced MRI provided evidence of changes compatible with focal and diffuse brain repair at

  13. A Distinct Class of Antibodies May Be an Indicator of Gray Matter Autoimmunity in Early and Established Relapsing Remitting Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Ann J. Ligocki

    2015-10-01

    Full Text Available * These authors contributed equally to the work in this manuscript.We have previously identified a distinct class of antibodies expressed by B cells in the cerebrospinal fluid (CSF of early and established relapsing remitting multiple sclerosis (RRMS patients that is not observed in healthy donors. These antibodies contain a unique pattern of mutations in six codons along VH4 antibody genes that we termed the antibody gene signature (AGS. In fact, patients who have such B cells in their CSF are identified as either having RRMS or developing RRMS in the future. As mutations in antibody genes increase antibody affinity for particular antigens, the goal for this study was to investigate whether AGS+ antibodies bind to brain tissue antigens. Single B cells were isolated from the CSF of 10 patients with early or established RRMS. We chose 32 of these B cells that expressed antibodies enriched for the AGS for further study. We generated monoclonal full-length recombinant human antibodies (rhAbs and used both immunological assays and immunohistochemistry to investigate the capacity of these AGS+ rhAbs to bind brain tissue antigens. AGS+ rhAbs did not recognize myelin tracts in the corpus callosum. Instead, AGS+ rhAbs recognized neuronal nuclei and/or astrocytes, which are prevalent in the cortical gray matter. This pattern was unique to the AGS+ antibodies from early and established RRMS patients, as AGS+ antibodies from an early neuromyelitis optica patient did not display the same reactivity. Prevalence of CSF-derived B cells expressing AGS+ antibodies that bind to these cell types may be an indicator of gray matter-directed autoimmunity in early and established RRMS patients.

  14. Dose study of the multikinase inhibitor, LY2457546, in patients with relapsed acute myeloid leukemia to assess safety, pharmacokinetics, and pharmacodynamics

    International Nuclear Information System (INIS)

    Wacheck, Volker; Lahn, Michael; Dickinson, Gemma; Füreder, Wolfgang; Meyer, Renata; Herndlhofer, Susanne; Füreder, Thorsten; Dorfner, Georg; Pillay, Sada; André, Valérie; Burkholder, Timothy P; Akunda, Jacqueline K; Flye-Blakemore, Leann; Van Bockstaele, Dirk; Schlenk, Richard F; Sperr, Wolfgang R; Valent, Peter

    2011-01-01

    Acute myeloid leukemia (AML) is a life-threatening malignancy with limited treatment options in chemotherapy-refractory patients. A first-in-human dose study was designed to investigate a safe and biologically effective dose range for LY2457546, a novel multikinase inhibitor, in patients with relapsed AML. In this nonrandomized, open-label, dose escalation Phase I study, LY2457546 was administered orally once a day. Safety, pharmacokinetics, changes in phosphorylation of target kinases in AML blasts, and risk of drug–drug interactions (DDI) were assessed. Five patients were treated at the starting and predicted minimal biologically effective dose of 50 mg/day. The most commonly observed adverse events were febrile neutropenia, epistaxis, petechiae, and headache. The majority of adverse events (81%) were Grade 1 or 2. One patient had generalized muscle weakness (Grade 3), which was deemed to be a dose-limiting toxicity. Notably, the pharmacokinetic profile of LY2457546 showed virtually no elimination of LY2457546 within 24 hours, and thus prevented further dose escalation. No significant DDI were observed. Ex vivo flow cytometry studies showed downregulation of the phosphoproteins, pcKIT, pFLT3, and pS6, in AML blasts after LY2457546 administration. No medically relevant responses were observed in the five treated patients. No biologically effective dose could be established for LY2457546 in chemotherapy-resistant AML patients. Lack of drug clearance prevented safe dose escalation, and the study was terminated early. Future efforts should be made to develop derivatives with a more favorable pharmacokinetic profile

  15. A phase I trial of vorinostat and alvocidib in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2.

    Science.gov (United States)

    Holkova, Beata; Supko, Jeffrey G; Ames, Matthew M; Reid, Joel M; Shapiro, Geoffrey I; Perkins, Edward Brent; Ramakrishnan, Viswanathan; Tombes, Mary Beth; Honeycutt, Connie; McGovern, Renee M; Kmieciak, Maciej; Shrader, Ellen; Wellons, Martha D; Sankala, Heidi; Doyle, Austin; Wright, John; Roberts, John D; Grant, Steven

    2013-04-01

    This phase I study was conducted to identify the maximum-tolerated dose (MTD) of alvocidib when combined with vorinostat in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Secondary objectives included investigating the pharmacokinetic and pharmacodynamic effects of the combination. Patients received vorinostat (200 mg orally, three times a day, for 14 days) on a 21-day cycle, combined with 2 different alvocidib administration schedules: a 1-hour intravenous infusion, daily × 5; or a 30-minute loading infusion followed by a 4-hour maintenance infusion, weekly × 2. The alvocidib dose was escalated using a standard 3+3 design. Twenty-eight patients were enrolled and treated. The alvocidib MTD was 20 mg/m(2) (30-minute loading infusion) followed by 20 mg/m(2) (4-hour maintenance infusion) on days one and eight, in combination with vorinostat. The most frequently encountered toxicities were cytopenias, fatigue, hyperglycemia, hypokalemia, hypophosphatemia, and QT prolongation. Dose-limiting toxicities (DLT) were cardiac arrhythmia-atrial fibrillation and QT prolongation. No objective responses were achieved although 13 of 26 evaluable patients exhibited stable disease. Alvocidib seemed to alter vorinostat pharmacokinetics, whereas alvocidib pharmacokinetics were unaffected by vorinostat. Ex vivo exposure of leukemia cells to plasma obtained from patients after alvocidib treatment blocked vorinostat-mediated p21(CIP1) induction and downregulated Mcl-1 and p-RNA Pol II for some specimens, although parallel in vivo bone marrow responses were infrequent. Alvocidib combined with vorinostat is well tolerated. Although disease stabilization occurred in some heavily pretreated patients, objective responses were not obtained with these schedules. ©2013 AACR.

  16. Phase I Study of Vorinostat as a Radiation Sensitizer with 131I-Metaiodobenzylguanidine (131I-MIBG) for Patients with Relapsed or Refractory Neuroblastoma.

    Science.gov (United States)

    DuBois, Steven G; Groshen, Susan; Park, Julie R; Haas-Kogan, Daphne A; Yang, Xiaodong; Geier, Ethan; Chen, Eugene; Giacomini, Kathy; Weiss, Brian; Cohn, Susan L; Granger, M Meaghan; Yanik, Gregory A; Hawkins, Randall; Courtier, Jesse; Jackson, Hollie; Goodarzian, Fariba; Shimada, Hiroyuki; Czarnecki, Scarlett; Tsao-Wei, Denice; Villablanca, Judith G; Marachelian, Araz; Matthay, Katherine K

    2015-06-15

    (131)I-metaiodobenzylguanidine (MIBG) is a radiopharmaceutical with activity in neuroblastoma. Vorinostat is a histone deacetylase inhibitor that has radiosensitizing properties. The goal of this phase I study was to determine the MTDs of vorinostat and MIBG in combination. Patients ≤ 30 years with relapsed/refractory MIBG-avid neuroblastoma were eligible. Patients received oral vorinostat (dose levels 180 and 230 mg/m(2)) daily days 1 to 14. MIBG (dose levels 8, 12, 15, and 18 mCi/kg) was given on day 3 and peripheral blood stem cells on day 17. Alternating dose escalation of vorinostat and MIBG was performed using a 3+3 design. Twenty-seven patients enrolled to six dose levels, with 23 evaluable for dose escalation. No dose-limiting toxicities (DLT) were seen in the first three dose levels. At dose level 4 (15 mCi/kg MIBG/230 mg/m(2) vorinostat), 1 of 6 patients had DLT with grade 4 hypokalemia. At dose level 5 (18 mCi/kg MIBG/230 mg/m(2) vorinostat), 2 patients had dose-limiting bleeding (one grade 3 and one grade 5). At dose level 5a (18 mCi/kg MIBG/180 mg/m(2) vorinostat), 0 of 6 patients had DLT. The most common toxicities were neutropenia and thrombocytopenia. The response rate was 12% across all dose levels and 17% at dose level 5a. Histone acetylation increased from baseline in peripheral blood mononuclear cells collected on days 3 and 12 to 14. Vorinostat at 180 mg/m(2)/dose is tolerable with 18 mCi/kg MIBG. A phase II trial comparing this regimen to single-agent MIBG is ongoing. ©2015 American Association for Cancer Research.

  17. Dedicated mobile application for drug adverse reaction reporting by patients with relapsing remitting multiple sclerosis (Vigip-SEP study): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Defer, Gilles; Le Caignec, Florian; Fedrizzi, Sophie; Montastruc, François; Chevanne, Damien; Parienti, Jean-Jacques; Peyro-Saint-Paul, Laure

    2018-03-09

    The reporting of adverse drug reactions (ADR) by patients represents an interesting challenge in the field of pharmacovigilance, but the reporting system is not adequately implemented in France. In 2015, only 20 MS patients in France reported ADR due to first-line disease-modifying drugs (DMD), while more than 3000 patients were initiated on DMD. The aim of this study is to validate a proof-of-concept as to whether the use of a mobile application (App) increases ADR reporting among patients with relapsing-remitting multiple sclerosis (RR-MS) receiving DMD. We designed a multi-centric, open cluster-randomized controlled trial, called the Vigip-SEP study (NCT03029897), using the App My eReport France® to report ADR to the appropriate authorities in E2B language, in accordance with European regulations. RR-MS patients who were initiated on, or switched, first-line DMD will be included. In the experimental arm, a neurologist will introduce the patient to the App to report ADR to the appropriate French authorities. In the control arm, the patient will be informed of the existence of the App but will not be introduced to its use and will then report ADR according to the usual reporting procedures. Primary assessment criteria are defined as the average number of ADR per patient and per center. We assume that the App will increase patient reporting by 10-fold. Therefore, we will require 24 centers (12 per arm: 6 MS academic expert centers, 3 general hospitals, 3 private practice neurologists), allowing for an expected enrollment of 180 patients (alpha risk 5%, power 90% and standard deviation 4%). Increasing patient reporting of ADR in a real-life setting is extremely important for therapeutic management of RR-MS, particularly for monitoring newly approved DMD to gain better knowledge of their safety profiles. To increase patient involvement, teaching patients to use tools, such as mobile applications, should be encouraged, and these tools should be tested rigorously

  18. Investigation of autoantibody profiles for cerebrospinal fluid biomarker discovery in patients with relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Beyer, Natascha Helena; Lueking, Angelika; Kowald, Axel

    2012-01-01

    Using the UNIarray® marker technology platform, cerebrospinal fluid immunoglobulin G reactivities of 15 controls and 17 RRMS patients against human recombinant proteins were investigated. Patient cerebrospinal fluids were oligoclonal band positive and reactivities were compared to that of sex...

  19. [Malnutrition and weight loss - nurse assessment of nutritional status and counselling: experiences of patients with newly diagnosed or relapsed cancer].

    Science.gov (United States)

    Kröner, A; Stoll, H; Spichiger, E

    2012-04-01

    Due to the anorexia-cachexia syndrome, cancer patients are already suffering from nutritional problems and weight loss by the time they receive their diagnosis and start chemotherapy. In the oncology outpatient clinic of a Swiss university hospital, patients currently undergo a nutritional assessment and receive individual counselling at the beginning of cancer treatment. This qualitative study explored cancer patients' experiences with weight loss and nutritional problems as well as how they experienced the assessment and the consecutive counselling by nurses. Interviews were conducted with 12 patients and qualitative content analysis was used for data analysis. Results showed that patients barely registered the weight loss and did not interpret it as an early warning signal. Nevertheless, they attempted to improve their nutritional habits soon after diagnosis, prior to receiving any counselling. The patients did not experience the assessment as troublesome. They appreciated the nurses' advice and implemented the suggestions they found appropriate. This study highlights the importance of patient education regarding weight loss and nutritional problems early in the course of an illness. Patients may not be aware of nutritional problems at this early stage and may lack the necessary specialised knowledge. Assessment and counselling provided by nurses offer targeted measures for prevention of malnutrition and weight loss.

  20. Expression of Five Neuroblastoma Genes in Bone Marrow or Blood of Patients with Relapsed/Refractory Neuroblastoma Provides a New Biomarker for Disease and Prognosis.

    Science.gov (United States)

    Marachelian, Araz; Villablanca, Judith G; Liu, Cathy W; Liu, Betty; Goodarzian, Fariba; Lai, Hollie A; Shimada, Hiroyuki; Tran, Hung C; Parra, Jaime A; Gallego, Richard; Bedrossian, Nora; Young, Sabrina; Czarnecki, Scarlett; Kennedy, Rebekah; Weiss, Brian D; Goldsmith, Kelly; Granger, Meaghan; Matthay, Katherine K; Groshen, Susan; Asgharzadeh, Shahab; Sposto, Richard; Seeger, Robert C

    2017-09-15

    Purpose: We determined whether quantifying neuroblastoma-associated mRNAs (NB-mRNAs) in bone marrow and blood improves assessment of disease and prediction of disease progression in patients with relapsed/refractory neuroblastoma. Experimental Design: mRNA for CHGA, DCX, DDC, PHOX2B, and TH was quantified in bone marrow and blood from 101 patients concurrently with clinical disease evaluations. Correlation between NB-mRNA (delta cycle threshold, Δ C t , for the geometric mean of genes from the TaqMan Low Density Array NB5 assay) and morphologically defined tumor cell percentage in bone marrow, 123 I-meta-iodobenzylguanidine (MIBG) Curie score, and CT/MRI-defined tumor longest diameter was determined. Time-dependent covariate Cox regression was used to analyze the relationship between Δ C t and progression-free survival (PFS). Results: NB-mRNA was detectable in 83% of bone marrow (185/223) and 63% (89/142) of blood specimens, and their Δ C t values were correlated (Spearman r = 0.67, P neuroblastoma. Clin Cancer Res; 23(18); 5374-83. ©2017 AACR . ©2017 American Association for Cancer Research.

  1. Are Fusion Transcripts in Relapsed/Metastatic Head and Neck Cancer Patients Predictive of Response to Anti-EGFR Therapies?

    Directory of Open Access Journals (Sweden)

    Paolo Bossi

    2017-01-01

    Full Text Available Prediction of benefit from combined chemotherapy and the antiepidermal growth factor receptor cetuximab is a not yet solved question in head and neck squamous cell carcinoma (HNSCC. In a selected series of 14 long progression-free survival (PFS and 26 short PFS patients by whole gene and microRNA expression analysis, we developed a model potentially predictive of cetuximab sensitivity. To better decipher the “omics” profile of our patients, we detected transcript fusions by RNA-seq through a Pan-Cancer panel targeting 1385 cancer genes. Twenty-seven different fusion transcripts, involving mRNA and long noncoding RNA (lncRNA, were identified. The majority of fusions (81% were intrachromosomal, and 24 patients (60% harbor at least one of them. The presence/absence of fusions and the presence of more than one fusion were not related to outcome, while the lncRNA-containing fusions resulted enriched in long PFS patients (P=0.0027. The CD274-PDCD1LG2 fusion was present in 7/14 short PFS patients harboring fusions and was absent in long PFS patients (P=0.0188. Among the short PFS patients, those harboring this fusion had the worst outcome (P=0.0172 and increased K-RAS activation (P=0.00147. The associations between HNSCC patient’s outcome following cetuximab treatment and lncRNA-containing fusions or the CD274-PDCD1LG2 fusion deserve validation in prospective clinical trials.

  2. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

    NARCIS (Netherlands)

    P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth)

    2005-01-01

    textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

  3. Relapsing polychondritis: commentary

    Directory of Open Access Journals (Sweden)

    R.D. Altman

    2011-09-01

    Full Text Available Relapsing Polychondritis (RP is a multisystem disease of unknown etiology characterized by episodic inflammation of cartilage and potentially progressive degeneration of cartilaginous tissue, such as auricular, nasal and laryngotracheobronchial cartilage. However, many other proteoglycan- rich structures may be involved, such as inner ear, eyes, blood vessels, heart and kidneys (1- 4. RP was first described by Jacksh-Wartenhorst in 1923, who named it “polychondropathia” (5. Pearson et al. (6 introduced the term “relapsing polychondritis” in 1960...

  4. Radioimmunotherapy for first-line and relapse treatment of aggressive B-cell non-Hodgkin lymphoma: an analysis of 215 patients registered in the international RIT-Network

    Energy Technology Data Exchange (ETDEWEB)

    Hohloch, Karin; Lankeit, H.K.; Truemper, L. [Georg August University, Hematology and Oncology, Goettingen (Germany); Zinzani, P.L. [University of Bologna, Institute of Hematology and Medical Oncology ' ' L. e A. Seragnoli' ' , Bologna (Italy); Scholz, C.W. [Charite, University Berlin, Hematology, Oncology and Tumor Immunology, Berlin (Germany); Lorsbach, M.; Windemuth-Kieselbach, C. [Alcedis GmbH, Giessen (Germany)

    2014-08-15

    Very few reliable clinical data about the use of radioimmunotherapy in aggressive B-cell lymphoma exist. Patients with aggressive B-cell lymphoma registered in the international RIT-Network were analysed with regard to prior treatment, response and side effects. The RIT-Network is a web-based registry that collects observational data from radioimmunotherapy-treated patients with malignant lymphoma across 13 countries. This analysis included 215 with aggressive B-cell lymphoma out of 232 patients registered in the RIT-Network. Histological subtypes were as follows: 190 diffuse large B-cell, 15 primary mediastinal, 9 anaplastic large cell, and 1 intravascular lymphoma. The median age of the patients was 62 years (range 17 - 88), with 27 % above the age of 70 years. Radioimmunotherapy was mainly used as consolidation after first-line or second-line chemotherapy (56.1 %), as part of third-line to eighth-line therapy for relapse (16.4 %), and in refractory disease (12.2 %). Grade IV neutropenia and thrombopenia and grade III anaemia were observed. The median time to recovery of blood count was 81 days (range 0 - 600 days). The overall response rate was 63.3 %. The complete response rate was 76.4 % in patients treated as part of first-line therapy, and 44.3 % in patients with relapse. Mean overall survival in first-line therapy patients was 32.7 months and 14.0 months in patients with relapse or refractory disease, respectively. Most patients with aggressive B-cell lymphoma in the RIT-Network received radioimmunotherapy as consolidation after first-line therapy with excellent complete remission and overall survival rates compared to published data. In relapsed aggressive B-cell lymphoma, radioimmunotherapy is a safe and feasible treatment leading to satisfactory response rates with acceptable toxicity. (orig.)

  5. High-dose chemotherapy and auto-SCT for relapsed and refractory Hodgkin's lymphoma patients refractory to first-line salvage chemotherapy but responsive to second-line salvage chemotherapy.

    Science.gov (United States)

    Rauf, Muhammad Shahzad; Maghfoor, Irfan; Elhassan, Tusneem Ahmed M; Akhtar, Saad

    2015-01-01

    Relapsed or primary refractory Hodgkin's lymphoma (HL) patients refractory to first-line salvage chemotherapy (first salvage) and unable to undergo high-dose chemotherapy (HDC) and autologous stem cell transplant (auto-SCT) have very poor outcome. Some patients are offered second-line salvage chemotherapy (second salvage), if they are responsive and may receive HDC auto-SCT. We identified 31 patients (18 males, 13 females) from 1996-2012 who received second salvage prior to auto-SCT. Median age at auto-SCT is 22 years. Patients were grouped as (1) relapsed-refractory (Rel:Ref): patients with prior complete response (CR) and on relapse found refractory to first salvage and received second salvage and (2) refractory-refractory (Ref:Ref): patients refractory to both primary treatment and first salvage and received second salvage. Median follow-up is 63 months (18-170). Disease status after second salvage prior to HDC was CR 16 %, partial response (PR) 71 % and stable disease 13 %. After HDC auto-SCT, CR:PR: progressive disease was observed in 18 (58 %): four (12 %): nine (29 %) patients, respectively. Five-year overall survival (OS) for whole group is 57 % (Rel:Ref vs. Ref:Ref, 73 % vs. 48 %, p = 0.48). Progression-free survival (PFS) for whole group is 52 % (Rel:Ref vs. Ref:Ref, 73 % vs. 40 % respectively, p = 0.11). Second-line salvage is a valid approach with no long-term side effects for those HL patients who do not respond to first-line salvage chemotherapy and they can be candidate of HDC and stem cell transplant with a high ORR, the PFS and OS in relapse-refractory and refractory-refractory group of patients.

  6. Dexamethasone, rituximab and cyclophosphamide for relapsed and/or refractory and treatment-naïve patients with Waldenstrom macroglobulinemia.

    Science.gov (United States)

    Paludo, Jonas; Abeykoon, Jithma P; Kumar, Shaji; Shreders, Amanda; Ailawadhi, Sikander; Gertz, Morie A; Kourelis, Taxiarchis; King, Rebecca L; Reeder, Craig B; Leung, Nelson; Kyle, Robert A; Buadi, Francis K; Habermann, Thomas M; Dingli, David; Witzig, Thomas E; Dispenzieri, Angela; Lacy, Martha Q; Go, Ronald S; Lin, Yi; Gonsalves, Wilson I; Warsame, Rahma; Lust, John A; Rajkumar, S Vincent; Ansell, Stephen M; Kapoor, Prashant

    2017-10-01

    The management of Waldenström macroglobulinaemia (WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide (DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88 WT genotype. Herein, we additionally report on the activity of DRC based on the MYD88 L265P mutation status. Of 100 WM patients evaluated between January 2007 and December 2014 who received DRC, 50 had R/R WM. The overall response rate (ORR) was 87%. The median progression-free survival (PFS) and time-to-next-therapy (TTNT) were 32 (95% confidence interval [CI]: 15-51) and 50 (95% CI: 35-60) months, respectively. In the previously untreated cohort (n = 50), the ORR was 96%, and the median PFS and TTNT were 34 months (95% CI: 23-not reached [NR]) and NR (95% CI: 37-NR), respectively. Twenty-five (86%) of 29 genotyped patients harbored MYD88 L265P . The response rates and outcomes were independent of MYD88 mutation status. Grade ≥3 adverse effects included neutropenia (20%), thrombocytopenia (7%) and infections (3%). Similar to the frontline setting, DRC is an effective and well-tolerated salvage regimen for WM. In contrast to ibrutinib, DRC offers a less expensive, fixed-duration option, with preliminary data suggesting efficacy independent of the patients' MYD88 status. © 2017 John Wiley & Sons Ltd.

  7. Focal cortical thinning in patients with stable relapsing-remitting multiple sclerosis. Cross-sectional-based novel estimation of gray matter kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Orbach, Lior; Menascu, Shay; Hoffmann, Chen; Achiron, Anat [Sheba Medical Center, Multiple Sclerosis Center, Tel-Hashomer (Israel); Tel-Aviv University, Sackler School of Medicine, Tel-Aviv (Israel); Miron, Shmuel [Sheba Medical Center, Multiple Sclerosis Center, Tel-Hashomer (Israel)

    2018-02-15

    The aim of our study is to identify radiological patterns of cortical gray matter atrophy (CGMA) that correlate with disease duration in patients with relapsing-remitting multiple sclerosis (RRMS). RRMS patients were randomly selected from the Sheba Multiple Sclerosis (MS) center computerized data registry based on stratification of disease duration up to 10 years. Patients were scanned by 3.0 T (Signa, GE) MRI, using a T1 weighted 3D high resolution, FSPGR, MS protocol. Neurological disability was assessed by the Expanded Disability Status Scale (EDSS). FreeSurfer was used to obtain brain volumetric segmentation and to perform cortical thickness surface-based analysis. Clusters of change in cortical thickness with correlation to disease duration were produced. Two hundred seventy-one RRMS patients, mean ± SD age 33.0 ± 7.0 years, EDSS 1.6 ± 1.2, disease duration 5.0 ± 3.4 years. Cortical thickness analysis demonstrated focal areas of cerebral thinning that correlated with disease duration. Seven clusters accounting for 11.7% of the left hemisphere surface and eight clusters accounting for 10.6% of the right hemisphere surface were identified, with cluster-wise probability of p < 0.002 and p < 0.02, respectively.The clusters included bilateral involvement of areas within the cingulate, precentral, postcentral, paracentral, superior-parietal, superior-frontal gyri and insular cortex. Mean and cluster-wise cortical thickness negatively correlated with EDSS score, p < 0.001, with stronger Spearman rho for cluster-wise measurements. We identified CGMA patterns in sensitive brain regions which give insight and better understanding of the progression of cortical gray matter loss in relation to dissemination in space and time. These patterns may serve as markers to modulate therapeutic interventions to improve the management of MS patients. (orig.)

  8. Novel multi-peptide vaccination in Hla-A2+ hormone sensitive patients with biochemical relapse of prostate cancer.

    Science.gov (United States)

    Feyerabend, Susan; Stevanovic, Stefan; Gouttefangeas, Cécile; Wernet, Dorothee; Hennenlotter, Jörg; Bedke, Jens; Dietz, Klaus; Pascolo, Steve; Kuczyk, Markus; Rammensee, Hans-Georg; Stenzl, Arnulf

    2009-06-15

    A phase I/II trial was conducted to assess feasibility and tolerability of tumor associated antigen peptide vaccination in hormone sensitive prostate carcinoma (PC) patients with biochemical recurrence after primary surgical treatment. Nineteen HLA-A2 positive patients with rising PSA without detectable metastatic disease or local recurrence received 11 HLA-A*0201-restricted and two HLA class II synthetic peptides derived from PC tumor antigens subcutaneously for 18 months or until PSA progression. The vaccine was emulgated in montanide ISA51 and combined with imiquimod, GM-CSF, mucin-1-mRNA/protamine complex, local hyperthermia or no adjuvant. PSA was assessed, geometric mean doubling times (DT) calculated and clinical performance monitored. PSA DT of 4 out of 19 patients (21%) increased from 4.9 to 25.8 months during vaccination. Out of these, two patients (11%) exhibited PSA stability for 28 and 31 months which were still continuing at data cut-off. One patient showed no change of PSA DT during vaccination but decline after the therapy. Three patients had an interim PSA decline or DT increase followed by DT decrease compared to baseline PSA DT. Three of the responding patients received imiquimod and one the mucin-1-mRNA/protamine complex as adjuvant; both are Toll-like receptor-7 agonists. Eleven (58%) patients had progressive PSA values. The vaccine was well tolerated, and no grade III or IV toxicity occurred. Multi-peptide vaccination stabilized or slowed down PSA progress in four of 19 cases. The vaccination approach is promising with moderate adverse events. Long-term stability delayed androgen deprivation up to 31 months. TLR-7 co-activation seems to be beneficial.

  9. Computer-aided cognitive rehabilitation improves cognitive performances and induces brain functional connectivity changes in relapsing remitting multiple sclerosis patients: an exploratory study.

    Science.gov (United States)

    Bonavita, S; Sacco, R; Della Corte, M; Esposito, S; Sparaco, M; d'Ambrosio, A; Docimo, R; Bisecco, A; Lavorgna, L; Corbo, D; Cirillo, S; Gallo, A; Esposito, F; Tedeschi, G

    2015-01-01

    To better understand the effects of short-term computer-based cognitive rehabilitation (cCR) on cognitive performances and default mode network (DMN) intrinsic functional connectivity (FC) in cognitively impaired relapsing remitting (RR) multiple sclerosis (MS) patients. Eighteen cognitively impaired RRMS patients underwent neuropsychological evaluation by the Rao's brief repeatable battery and resting-state functional magnetic resonance imaging to evaluate FC of the DMN before and after a short-term (8 weeks, twice a week) cCR. A control group of 14 cognitively impaired RRMS patients was assigned to an aspecific cognitive training (aCT), and underwent the same study protocol. Correlations between DMN and cognitive performances were also tested. After cCR, there was a significant improvement of the following tests: SDMT (p Color-Word Interference Test and FC in the PCC emerged. After aCT, the control group did not show any significant effect either on FC or neuropsychological tests. No significant differences were found in brain volumes and lesion load in both groups when comparing data acquired at baseline and after cCR or aCT. In cognitively impaired RRMS patients, cCR improves cognitive performances (i.e., processing speed and visual and verbal sustained memory), and increases FC in the PCC and IPC of the DMN. This exploratory study suggests that cCR may induce adaptive cortical reorganization favoring better cognitive performances, thus strengthening the value of cognitive exercise in the general perspective of building either cognitive or brain reserve.

  10. Efficacy of Mindfulness-Based Cognitive Therapy in Prevention of Depressive Relapse: An Individual Patient Data Meta-analysis From Randomized Trials

    NARCIS (Netherlands)

    Kuyken, W.; Warren, F.C.; Taylor, R.S.; Whalley, B.; Crane, C.; Bondolfi, G.; Hayes, R.; Huijbers, M.J.; Ma, H.; Schweizer, S.; Segal, Z.; Speckens, A.E.M.; Teasdale, J.D.; Heeringen, K. Van; Williams, M.; Byford, S.; Byng, R.; Dalgleish, T.

    2016-01-01

    IMPORTANCE: Relapse prevention in recurrent depression is a significant public health problem, and antidepressants are the current first-line treatment approach. Identifying an equally efficacious nonpharmacological intervention would be an important development. OBJECTIVE: To conduct a

  11. Multiple Sclerosis Relapses: Epidemiology, Outcomes and Management. A Systematic Review.

    Science.gov (United States)

    Kalincik, Tomas

    2015-01-01

    Relapses (episodic exacerbations of neurological signs or symptoms) are a defining feature of relapsing-remitting multiple sclerosis (MS), the most prevalent MS phenotype. While their diagnostic value relates predominantly to the definition of clinically definite MS, their prognostic value is determined by their relatively high associated risk of incomplete remission resulting in residual disability. The mechanisms governing a relapse incidence are unknown, but numerous modifiers of relapse risk have been described, including demographic and clinical characteristics, many of which represent opportunities for improved disease management. Also relapse phenotypes have been associated with patient and disease characteristics and an individual predisposition to certain phenotypic presentations may imply individual neuroanatomical disease patterns. While immunomodulatory therapies and corticosteroids represent the mainstay of relapse prevention and acute management, respectively, their effect has only been partial and further search for more efficient relapse therapies is warranted. Other areas of research include pathophysiology and determinants of relapse incidence, recurrence and phenotypes, including the characteristics of the relapsing and non-relapsing multiple sclerosis variants and their responsiveness to therapies. © 2015 S. Karger AG, Basel.

  12. Second allogeneic hematopoietic SCT for relapsed ALL in children.

    Science.gov (United States)

    Kato, M; Horikoshi, Y; Okamoto, Y; Takahashi, Y; Hasegawa, D; Koh, K; Takita, J; Inoue, M; Kigasawa, H; Ogawa, A; Sasahara, Y; Kawa, K; Yabe, H; Sakamaki, H; Suzuki, R; Kato, K

    2012-10-01

    A second SCT is generally accepted as the only potentially curative approach for ALL patients that relapse after SCT, but the role of second SCT for pediatric ALL is not fully understood. We performed a retrospective analysis of 171 pediatric patients who received a second allo-SCT for relapsed ALL after allo-SCT. OS at 2 years was 29.4 ± 3.7%, the cumulative incidence of relapse was 44.1 ± 4.0% and non-relapse mortality was 18.8 ± 3.5%. Relapse occurred faster after the second SCT than after the first SCT (117 days vs 164 days, P=0.04). Younger age (9 years or less), late relapse (180 days or more after first SCT), CR at the second SCT, and myeloablative conditioning were found to be related to longer survival. Neither acute GVHD nor the type of donor influenced the outcome of second SCT. Multivariate analysis showed that younger age and late relapse were associated with better outcomes. Our analysis suggests that second SCT for relapsed pediatric ALL is an appropriate treatment option for patients that have achieved CR, which is associated with late relapse after the first SCT.

  13. Feasibility of implementing molecular-guided therapy for the treatment of patients with relapsed or refractory neuroblastoma

    International Nuclear Information System (INIS)

    Saulnier Sholler, Giselle L; Bond, Jeffrey P; Bergendahl, Genevieve; Dutta, Akshita; Dragon, Julie

    2015-01-01

    The primary objective of the study was to evaluate the feasibility and safety of a process which would utilize genome-wide expression data from tumor biopsies to support individualized treatment decisions. Current treatment options for recurrent neuroblastoma are limited and ineffective, with a survival rate of <10%. Molecular profiling may provide data which will enable the practitioner to select the most appropriate therapeutic option for individual patients, thus improving outcomes. Sixteen patients with neuroblastoma were enrolled of which fourteen were eligible for this study. Feasibility was defined as completion of tumor biopsy, pathological evaluation, RNA quality control, gene expression profiling, bioinformatics analysis, generation of a drug prediction report, molecular tumor board yielding a treatment plan, independent medical monitor review, and treatment initiation within a 21 day period. All eligible biopsies passed histopathology and RNA quality control. Expression profiling by microarray and RNA sequencing were mutually validated. The average time from biopsy to report generation was 5.9 days and from biopsy to initiation of treatment was 12.4 days. No serious adverse events were observed and all adverse events were expected. Clinical benefit was seen in 64% of patients as stabilization of disease for at least one cycle of therapy or partial response. The overall response rate was 7% and the progression free survival was 59 days. This study demonstrates the feasibility and safety of performing real-time genomic profiling to guide treatment decision making for pediatric neuroblastoma patients

  14. Recurrence and Relapse in Bipolar Mood Disorder

    Directory of Open Access Journals (Sweden)

    S Gh Mousavi

    2004-06-01

    Full Text Available Background: Despite the effectiveness of pharmacotherapy in acute phase of bipolar mood disorder, patients often experience relapses or recurrent episodes. Hospitalization of patients need a great deal of financial and humanistic resources which can be saved through understanding more about the rate of relapse and factors affecting this rate. Methods: In a descriptive analytical study, 380 patients with bipolar disorder who were hospitalized in psychiatric emergency ward of Noor hospital, Isfahan, Iran, were followed. Each patient was considered for; the frequency of relapse and recurrence, kind of pharmachotherapy, presence of psychotherapeutic treatments, frequency of visits by psychiatrist and the rank of present episode. Results: The overall prevalence of recurrence was 42.2%. Recurrence was lower in patients using lithium carbonate or sodium valproate or combined therapy (about 40%, compared to those using carbamazepine (80%. Recurrence was higher in patients treated with only pharmacotherapy (44.5% compared to those treated with both pharmacotherapy and psychotherapy (22.2%. Patients who were visited monthy by psychiatrist had lower rate of recurrence compared to those who had irregular visits. Conclusion: The higher rate of recurrence observed in carbamazepine therapy may be due to its adverse reactions and consequently poor compliance to this drug. Lower rates of recurrence with psychotherapy and regular visits may be related to the preventive effects of these procedures and especially to the effective management of stress. Keywords: Bipolar Mood Disorder, Recurrence, Relapse.

  15. ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study

    Directory of Open Access Journals (Sweden)

    Lee Su-Chen

    2008-02-01

    Full Text Available Abstract Background Early relapse in colorectal cancer (CRC patients is attributed mainly to the higher malignant entity (such as an unfavorable genotype, deeper tumor invasion, lymph node metastasis and advance cancer stage and poor response to chemotherapy. Several investigations have demonstrated that genetic polymorphisms in drug-targeted genes, metabolizing enzymes, and DNA-repairing enzymes are all strongly correlated with inter-individual differences in the efficacy and toxicity of many treatment regimens. This preliminary study attempts to identify the correlation between genetic polymorphisms and clinicopathological features of CRC, and evaluates the relationship between genetic polymorphisms and chemotherapeutic susceptibility of Taiwanese CRC patients. To our knowledge, this study discusses, for the first time, early cancer relapse and its indication by multiple genes. Methods Six gene polymorphisms functional in drug-metabolism – GSTP1 Ile105Val, ABCB1 Ile1145Ile, MTHFR Ala222Val, TYMS double (2R or triple (3R tandem repeat – and DNA-repair genes – ERCC2 Lys751Gln and XRCC1 Arg399Gln – were assessed in 201 CRC patients using a polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP technique and DNA sequencing. Patients were diagnosed as either high-risk stage II (T2 and 3 N0 M0 or III (any T N1 and 2 M0 and were administered adjuvant chemotherapy regimens that included 5-fluorouracil (5FU and leucovorin (LV. The correlations between genetic polymorphisms and patient clinicopathological features and relapses were investigated. Results In this study, the distributions of GSTP1 (P = 0.003, ABCB1 (P = 0.001, TYMS (P ERCC2 (P XRCC1 (P = 0.006 genotypes in the Asian population, with the exception of MTHFR (P = 0.081, differed significantly from their distributions in a Caucasian population. However, the unfavorable genotype ERCC2 2251A>C (P = 0.006, tumor invasion depth (P = 0.025, lymph node metastasis (P = 0

  16. Sifat Strong Perron-Frobenius Pada Solusi Positif Eventual Sistem Persamaan Differensial Linier Orde Satu

    Directory of Open Access Journals (Sweden)

    Yulian Sari

    2014-12-01

    Full Text Available Artikel ini membicarakan tentang sifat strong Perron-Frobenius pada solusi positif eventual sistem persamaan differensial linier orde satu. Syarat perlu agar solusi positif eventual sistem persamaan differensial linier orde satu diajukan. Beberapa kriteria tentang matriks eksponensial positif eventual dan matriks positif eventual juga akan digunakan dalam teorema.

  17. Sifat Strong Perron-Frobenius Pada Solusi Positif Eventual Sistem Persamaan Differensial Linier Orde Satu

    Directory of Open Access Journals (Sweden)

    Yulian Sari

    2015-04-01

    Full Text Available Artikel ini membicarakan tentang sifat strong Perron-Frobenius pada solusi positif eventual sistem persamaan differensial linier orde satu. Syarat perlu agar solusi positif eventual sistem persamaan differensial linier orde satu diajukan. Beberapa kriteria tentang matriks eksponensial positif eventual dan matriks positif eventual juga akan digunakan dalam teorema.

  18. AP-VAS 2012 case report: two patients with rheumatoid arthritis suspected of relapsed microscopic polyangiitis after initiation of dialysis

    OpenAIRE

    Sugahara, Mai; Nishi, Takahiro; Tanaka, Shinji; Kurita, Noriaki; Sai, Keiko; Kano, Tatsuya; Nishio, Kyosuke; Sugimoto, Tokuichiro; Mise, Naobumi

    2013-01-01

    We report two patients with rheumatoid arthritis (RA) who were suspected of microscopic polyangiitis during maintenance dialysis. Case 1 was a 52-year-old woman with RA diagnosed at the age of 38 years and treated successfully with gold compounds. At the age of 43 years, she presented with progressive renal dysfunction and abnormal urine sediments, and a renal biopsy revealed crescentic nephritis with advanced glomerular sclerosis. Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA...

  19. Correlation of FCGRT genomic structure with serum immunoglobulin, albumin and farletuzumab pharmacokinetics in patients with first relapsed ovarian cancer.

    Science.gov (United States)

    O'Shannessy, Daniel J; Bendas, Katie; Schweizer, Charles; Wang, Wenquan; Albone, Earl; Somers, Elizabeth B; Weil, Susan; Meredith, Rhonda K; Wustner, Jason; Grasso, Luigi; Landers, Mark; Nicolaides, Nicholas C

    2017-07-01

    Farletuzumab (FAR) is a humanized monoclonal antibody (mAb) that binds to folate receptor alpha. A Ph3 trial in ovarian cancer patients treated with carboplatin/taxane plus FAR or placebo did not meet the primary statistical endpoint. Subgroup analysis demonstrated that subjects with high FAR exposure levels (Cmin>57.6μg/mL) showed statistically significant improvements in PFS and OS. The neonatal Fc receptor (fcgrt) plays a central role in albumin/IgG stasis and mAb pharmacokinetics (PK). Here we evaluated fcgrt sequence and association of its promoter variable number tandem repeats (VNTR) and coding single nucleotide variants (SNV) with albumin/IgG levels and FAR PK in the Ph3 patients. A statistical correlation existed between high FAR Cmin and AUC in patients with the highest quartile of albumin and lowest quartile of IgG1. Analysis of fcgrt identified 5 different VNTRs in the promoter region and 9 SNVs within the coding region, 4 which are novel. Copyright © 2017. Published by Elsevier Inc.

  20. The effect of disease modifying therapies on brain atrophy in patients with relapsing-remitting multiple sclerosis: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Georgios Tsivgoulis

    Full Text Available The aim of the present meta-analysis was to evaluate the effect of disease-modifying drugs (DMD on brain atrophy in patients with relapsing-remitting multiple sclerosis (RRMS using available randomized-controlled trial (RCT data.We conducted a systematic review and meta-analysis according to PRISMA guidelines of all available RCTs of patients with RRMS that reported data on brain volume measurements during the study period.We identified 4 eligible studies, including a total of 1819 RRMS patients (71% women, mean age 36.5 years, mean baseline EDSS-score: 2.4. The mean percentage change in brain volume was found to be significantly lower in DMD versus placebo subgroup (standardized mean difference: -0.19; 95%CI: -0.27--0.11; p<0.001. We detected no evidence of heterogeneity between estimates (I2 = 30%, p = 0.19 nor publication bias in the Funnel plots. Sensitivity analyses stratifying studies according to brain atrophy neuroimaging protocol disclosed no evidence of heterogeneity (p = 0.16. In meta-regression analyses, the percentage change in brain volume was found to be inversely related with duration of observation period in both DMD (meta-regression slope = -0.03; 95% CI: -0.04--0.02; p<0.001 and placebo subgroups (meta-regression slope = -0.05; 95% CI: -0.06--0.04; p<0.001. However, the rate of percentage brain volume loss over time was greater in placebo than in DMD subgroup (p = 0.017, ANCOVA.DMD appear to be effective in attenuating brain atrophy in comparison to placebo and their benefit in delaying the rate of brain volume loss increases linearly with longer treatment duration.

  1. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... MS Relapsing-remitting MS (RRMS) Share this page Facebook Twitter Email Relapsing-remitting MS (RRMS) Relapsing-remitting ... Here Start Here Colophon Stay Informed Join Us Facebook Twitter LinkedIn YouTube Pinterest MS Connection About the ...

  2. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Relapsing-remitting MS (RRMS) Share this page Facebook Twitter Email Relapsing-remitting MS (RRMS) Relapsing-remitting MS ( ... Start Here Colophon Stay Informed Join Us Facebook Twitter LinkedIn YouTube Pinterest MS Connection About the Society ...

  3. Medical chart validation of an algorithm for identifying multiple sclerosis relapse in healthcare claims.

    Science.gov (United States)

    Chastek, Benjamin J; Oleen-Burkey, Merrikay; Lopez-Bresnahan, Maria V

    2010-01-01

    Relapse is a common measure of disease activity in relapsing-remitting multiple sclerosis (MS). The objective of this study was to test the content validity of an operational algorithm for detecting relapse in claims data. A claims-based relapse detection algorithm was tested by comparing its detection rate over a 1-year period with relapses identified based on medical chart review. According to the algorithm, MS patients in a US healthcare claims database who had either (1) a primary claim for MS during hospitalization or (2) a corticosteroid claim following a MS-related outpatient visit were designated as having a relapse. Patient charts were examined for explicit indication of relapse or care suggestive of relapse. Positive and negative predictive values were calculated. Medical charts were reviewed for 300 MS patients, half of whom had a relapse according to the algorithm. The claims-based criteria correctly classified 67.3% of patients with relapses (positive predictive value) and 70.0% of patients without relapses (negative predictive value; kappa 0.373: p value of the operational algorithm. Limitations of the algorithm include lack of differentiation between relapsing-remitting MS and other types, and that it does not incorporate measures of function and disability. The claims-based algorithm appeared to successfully detect moderate-to-severe MS relapse. This validated definition can be applied to future claims-based MS studies.

  4. Toxic hepatitis induced by infliximab in a patient with rheumatoid arthritis with no relapse after switching to etanercept

    DEFF Research Database (Denmark)

    Carlsen, K M; Riis, L; Madsen, O R

    2009-01-01

    We present a case of toxic hepatitis related to infliximab treatment in a 38-year-old woman with rheumatoid arthritis (RA). The patient had previously been treated with different disease-modifying drugs (DMARDs) alone or in combination but had never revealed signs of liver dysfunction. Due to high...... elevations of the transaminases up to five times the upper normal limit were noted and treatment with infliximab was terminated. Serological tests for viral and autoimmune hepatitis and for ANA and anti-dsDNA were all negative. Specific infliximab antibodies could not be detected. Ultrasound of the liver...... was normal. Liver biopsy showed late signs of acute toxic hepatitis without MTX-related fibrosis. This is one the first cases that convincingly demonstrates that infliximab treatment may cause toxic hepatitis. Moreover, the case suggests a lack of hepatic cross-toxicity between infliximab and etanercept...

  5. AP-VAS 2012 case report: two patients with rheumatoid arthritis suspected of relapsed microscopic polyangiitis after initiation of dialysis.

    Science.gov (United States)

    Sugahara, Mai; Nishi, Takahiro; Tanaka, Shinji; Kurita, Noriaki; Sai, Keiko; Kano, Tatsuya; Nishio, Kyosuke; Sugimoto, Tokuichiro; Mise, Naobumi

    2013-11-01

    We report two patients with rheumatoid arthritis (RA) who were suspected of microscopic polyangiitis during maintenance dialysis. Case 1 was a 52-year-old woman with RA diagnosed at the age of 38 years and treated successfully with gold compounds. At the age of 43 years, she presented with progressive renal dysfunction and abnormal urine sediments, and a renal biopsy revealed crescentic nephritis with advanced glomerular sclerosis. Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) was not measured on that occasion. She reached end-stage renal failure within 4 months and started peritoneal dialysis. Eight years later, soon after she was switched to hemodialysis, she developed fever of unknown origin. MPO-ANCA was elevated to 37 EU, although there were no other signs or symptoms suggestive of vasculitis. After taking prednisolone orally (10 mg/day), her fever withdrew, and MPO-ANCA became undetectable. Case 2 was a 71-year-old woman with RA diagnosed at the age of 60 years and treated with gold compounds. She developed renal failure of unknown cause (no biopsy was performed), and started hemodialysis at the age of 69 years. One year later, she presented with fever and subsequently developed cough with hemoptysis. MPO-ANCA was elevated to 62 EU. Treatment with azathioprine 50 mg and prednisolone 35 mg daily brought remarkable clinical improvement, and MPO-ANCA became undetectable. These cases highlight the importance of measuring ANCA even in RA patients on dialysis who present with fever of unknown origin or with underlying kidney disease of uncertain etiology.

  6. Long-term follow-up of patients receiving allogeneic stem cell transplant for chronic lymphocytic leukaemia: mixed T-cell chimerism is associated with high relapse risk and inferior survival.

    Science.gov (United States)

    Thompson, Philip A; Stingo, Francesco; Keating, Michael J; Wierda, William G; O'Brien, Susan M; Estrov, Zeev; Ledesma, Celina; Rezvani, Katayoun; Qazilbash, Muzaffar; Shah, Nina; Parmar, Simrit; Popat, Uday; Anderlini, Paolo; Yago, Nieto; Ciurea, Stefan O; Kebriaei, Partow; Champlin, Richard; Shpall, Elizabeth J; Hosing, Chitra M

    2017-05-01

    There is limited information regarding the immunological predictors of post-allogeneic stem cell transplant (alloSCT) outcome in chronic lymphocytic leukaemia (CLL), such as mixed T-cell chimerism. We analysed 143 consecutive patients with relapsed/refractory CLL, transplanted between 2000 and 2012, to determine the prognostic relevance of mixed chimerism post-alloSCT and the ability of post-transplant immunomodulation to treat relapse. Mixed T-cell chimerism occurred in 50% of patients at 3 months and 43% at 6 months post-alloSCT; upon 3- and 6-month landmark analysis, this was associated with inferior progression-free survival (PFS) [Hazard ratio (HR) 1·93, P = 0·003 and HR 2·58, P CLL. © 2017 John Wiley & Sons Ltd.

  7. Increased multiple sclerosis relapses related to lower prevalence of pain

    Directory of Open Access Journals (Sweden)

    José Vinícius Martins da Silva

    2015-07-01

    Full Text Available Objective The study aims to investigate the presence of pain amongst multiple sclerosis (MS patients. Method One hundred MS patients responded to questionnaires evaluating neuropathic and nociceptive pain, depression and anxiety. Statistical analysis was performed using the Mann–Whitney U, Chi-Square and two-tailed Fisher’s exact tests and multivariate logistic regression. Results Women had a statistically higher prevalence of pain (p = 0.037, and chances of having pain after the age of 50 reduced. Women with pain had a statistically significant lower number of relapses (p = 0.003, restricting analysis to those patients with more than one relapse. After the second relapse, each relapse reduced the chance of having pain by 46%. Presence of pain was independent of Expanded Disability Status Scale (EDSS anxiety, and depression. Conclusion Our findings suggest a strong inverse association between relapses and pain indicating a possible protective role of focal inflammation in the control of pain.

  8. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

    NARCIS (Netherlands)

    Rudick, R.A.; Stuart, W.H.; Calabresi, P.A.; Confavreux, C.; Galetta, S.L.; Radue, E.W.; Lublin, F.D.; Weinstock-Guttman, B.; Wynn, D.R.; Lynn, F.; Panzara, M.A.; Sandrock, A.W.

    2006-01-01

    BACKGROUND: Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an alpha4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies.

  9. Anca associated vasculitis : occurrence, prediction, prevention, and outcome of relapses

    NARCIS (Netherlands)

    Boomsma, Maarten Michiel

    2001-01-01

    During follow-up, relapses of disease activity occur in the majority of patients with ANCA associated vasculitis. The general objective brought together in this thesis was to further elucidate the characteristics and consequences of these relapses. Investigated items are the occurrence, the

  10. Spasticity improvement in patients with relapsing-remitting multiple sclerosis switching from interferon-β to glatiramer acetate: the Escala Study.

    Science.gov (United States)

    Meca-Lallana, J E; Balseiro, J J; Lacruz, F; Guijarro, C; Sanchez, O; Cano, A; Costa-Frossard, L; Hernández-Clares, R; Sanchez-de la Rosa, R

    2012-04-15

    A recent pilot study suggested spasticity improvement during glatiramer acetate (GA) treatment in multiple sclerosis (MS) patients who previously received interferon-β (IFN-β). To evaluate changes in spasticity in MS patients switching from IFN-β to GA. Observational, multicentre study in patients with relapsing-remitting MS (RRMS) and spasticity switching from IFN-β to GA. The primary endpoint comprised changes on Penn Spasm Frequency Scale (PSFS), Modified Ashworth Scale (MAS), Adductor Tone Rating Scale (ATRS), and Global Pain Score (GPS) at months 3 and 6 after starting GA. Sixty-eight evaluable patients were included (mean age,41.7±9.5 years; female,70.6%; mean time from MS diagnosis to starting GA,7.6±5.7 years). Previous treatments were subcutaneous IFN-β1a in 42.6% patients, intramuscular IFN-β1a in 41.2% and IFN-β1b in 32.4%, whose mean durations were 3.5±3.3, 2.7±2.5 and 4.4±3.6 years, respectively. Statistically significant reductions in mean scores on all spasticity measurements were observed from baseline to month 3 (PSFS, 1.7±0.9 vs 1.4±0.6, p<0.01; MAS, 0.7±0.5 vs 0.6±0.5, p<0.01; highest MAS score, 1.9±0.8 vs 1.7±0.8, p<0.01; ATRS, 1.6±0.6 vs 1.4±0.6, p<0.01; GPS, 29.4±22.1 vs 24.7±19.4, p<0.01) and from baseline to month 6 (PSFS, 1.7±0.9 vs 1.3±0.6, p<0.01; MAS, 0.7±0.5 vs 0.5±0.5, p<0.01; highest MAS score, 1.9±0.8 vs 1.5±0.9, p<0.01; ATRS, 1.6±0.6 vs 1.3±0.6, p<0.01; GPS, 29.4±22.1 vs 19.1±14.8, p<0.01). Spasticity improvement in terms of spasm frequency, muscle tone and pain can be noted after three months and prolonged for six months of GA treatment. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. PARATHYROID CANCER OCCURRING IN RELAPSING SECONDARY HYPERPARATHYROIDISM

    Directory of Open Access Journals (Sweden)

    I. V. Kotova

    2016-01-01

    Full Text Available We present a clinical case of parathyroid cancer in a patient with relapsing secondary hyperparathyroidism at 4 years after subtotal parathyroidectomy. Its unique character is related to the combination of relapsing secondary hyperparathyroidism, parathyromatosis, ectopic of an adenomatous hyperplastic parathyroid gland into the thyroid gland, and parathyroid cancer. Several most complicated aspects of parathyroid surgery are disclosed, such as the choice of strategy for surgical intervention in secondary hyperparathyroidism, complexity of morphological and cytological diagnostics of this disorder.

  12. The Role of Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4) Gene, Thyroid Stimulating Hormone Receptor (TSHR) Gene and Regulatory T-cells as Risk Factors for Relapse in Patients with Graves Disease.

    Science.gov (United States)

    Eliana, Fatimah; Suwondo, Pradana; Asmarinah, Asmarinah; Harahap, Alida; Djauzi, Samsuridjal; Prihartono, Joedo; Pemayun, Tjokorda Gde Dalem

    2017-07-01

    graves' disease (GD) is the most common condition of thyrotoxicosis. The management of GD is initiated with the administration of antithyroid drugs; however, it requires a long time to achieve remission. In reality more than 50% of patients who had remission may be at risk for relapse after the drug is stopped. This study aimed to evaluate the role of clinical factors such as smoking habit, degree of ophtalmopathy, degree of thyroid enlargement; genetic factors such as CTLA-4 gene on nucleotide 49 at codon 17 of exon 1, CTLA-4 gene of promotor -318, TSHR gene polymorphism rs2268458 of intron 1; and immunological factors such as regulatory T cells (Treg) and thyroid receptor antibody (TRAb); that affecting the relapse of patients with Graves' disease in Indonesia. this was a case-control study, that compared 72 subjects who had relapse and 72 subjects without relapse at 12 months after cessation of antithyroid treatment, who met the inclusion criteria. Genetic polymorphism examination was performed using PCR-RFLP. The number of regulatory T cells was counted using flow cytometry analysis and ELISA was used to measure TRAb. The logistic regression was used since the dependent variables were categorical variables. the analysis of this study demonstrated that there was a correlation between relapse of disease and family factors (p=0.008), age at diagnosis (p=0.021), 2nd degree of Graves' ophthalmopathy (p=0.001), enlarged thyroid gland, which exceeded the lateral edge of the sternocleidomastoid muscles (p=0.040), duration of remission period (p=0.029), GG genotype of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1 (p=0.016), CC genotype of TSHR gene on the rs2268458 of intron 1 (p=0.003), the number of regulatory T cells (p=0.001) and TRAb levels (p=0.002). genetic polymorphisms of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1, TSHR gene SNP rs2268458 of intron 1, number of regulatory T cells and TRAb levels play a role as risk factors for relapse in

  13. The Role of Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4 Gene, Thyroid Stimulating Hormone Receptor (TSHR Gene and Regulatory T-cells as Risk Factors for Relapse in Patients with Graves Disease

    Directory of Open Access Journals (Sweden)

    Fatimah Eliana

    2017-11-01

    Full Text Available Background: graves’ disease (GD is the most common condition of thyrotoxicosis. The management of GD is initiated with the administration of antithyroid drugs; however, it requires a long time to achieve remission. In reality more than 50% of patients who had remission may be at risk for relapse after the drug is stopped. This study aimed to evaluate the role of clinical factors such as smoking habit, degree of ophtalmopathy, degree of thyroid enlargement; genetic factors such as CTLA-4 gene on nucleotide 49 at codon 17 of exon 1, CTLA-4 gene of promotor -318, TSHR gene polymorphism rs2268458 of intron 1; and immunological factors such as regulatory T cells (Treg and thyroid receptor antibody (TRAb; that affecting the relapse of patients with Graves’ disease in Indonesia. Methods: this was a case-control study, that compared 72 subjects who had relapse and 72 subjects without relapse at 12 months after cessation of antithyroid treatment, who met the inclusion criteria. Genetic polymorphism examination was performed using PCR-RFLP. The number of regulatory T cells was counted using flow cytometry analysis and ELISA was used to measure TRAb. The logistic regression was used since the dependent variables were categorical variables. Results: the analysis of this study demonstrated that there was a correlation between relapse of disease and family factors (p=0.008, age at diagnosis (p=0.021, 2nd degree of Graves’ ophthalmopathy (p=0.001, enlarged thyroid gland, which exceeded the lateral edge of the sternocleidomastoid muscles (p=0.040, duration of remission period (p=0.029, GG genotype of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1 (p=0.016, CC genotype of TSHR gene on the rs2268458 of intron 1 (p=0.003, the number of regulatory T cells (p=0.001 and TRAb levels (p=0.002. Conclusion: genetic polymorphisms of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1, TSHR gene SNP rs2268458 of intron 1, number of regulatory T cells and

  14. Health-Related Quality-of-Life Results From the Open-Label, Randomized, Phase III ASPIRE Trial Evaluating Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma.

    Science.gov (United States)

    Stewart, A Keith; Dimopoulos, Meletios A; Masszi, Tamás; Špička, Ivan; Oriol, Albert; Hájek, Roman; Rosiñol, Laura; Siegel, David S; Niesvizky, Ruben; Jakubowiak, Andrzej J; San-Miguel, Jesus F; Ludwig, Heinz; Buchanan, Jacqui; Cocks, Kim; Yang, Xinqun; Xing, Biao; Zojwalla, Naseem; Tonda, Margaret; Moreau, Philippe; Palumbo, Antonio

    2016-11-10

    Purpose To determine the effects of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) on health-related quality of life (HR-QoL) in the Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone for the Treatment of Patients With Relapsed Multiple Myeloma (ASPIRE) trial. Methods Patients with relapsed multiple myeloma were randomly assigned to receive KRd or Rd. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and myeloma-specific module were administered at baseline; day 1 of cycles 3, 6, 12, and 18; and after treatment. The Global Health Status/Quality of Life (GHS/QoL) scale and seven subscales (fatigue, nausea and vomiting, pain, physical functioning, role functioning, disease symptoms, and adverse effects of treatment) were compared between groups using a mixed model for repeated measures. The percentages of responders with ≥ 5- or 15-point GHS/QoL improvement at each cycle were compared between groups. Results Baseline questionnaire compliance was excellent (94.1% of randomly assigned patients). KRd patients had higher GHS/QoL scores versus Rd patients over 18 treatment cycles (two-sided P < .001). The minimal important difference was met at cycle 12 (5.6 points) and approached at cycle 18 (4.8 points). There was no difference between groups for the other prespecified subscales from ASPIRE. A higher proportion of KRd patients met the GHS/QoL responder definition (≥ 5-point improvement) with statistical differences at cycle 12 (KRd v Rd patients, 25.5% v 17.4%, respectively) and 18 (KRd v Rd patients, 24.2% v 12.9%, respectively). Conclusion KRd improves GHS/QoL without negatively affecting patient-reported symptoms when compared with Rd. These data further support the benefit of KRd in patients with relapsed multiple myeloma.

  15. Genomic profiling of thousands of candidate polymorphisms predicts risk of relapse in 778 Danish and German childhood acute lymphoblastic leukemia patients

    DEFF Research Database (Denmark)

    Wesolowska, Agata; Borst, L.; Dalgaard, Marlene Danner

    2015-01-01

    Childhood acute lymphoblastic leukemia survival approaches 90%. New strategies are needed to identify the 10–15% who evade cure. We applied targeted, sequencing-based genotyping of 25 000 to 34 000 preselected potentially clinically relevant singlenucleotide polymorphisms (SNPs) to identify host...... associated with risk of relapse across protocols. SNP and biologic pathway level analyses associated relapse risk with leukemia aggressiveness, glucocorticosteroid pharmacology/response and drug transport/metabolism pathways. Classification and regression tree analysis identified three distinct risk groups...... defined by end of induction residual leukemia, white blood cell count and variants in myeloperoxidase (MPO), estrogen receptor 1 (ESR1), lamin B1 (LMNB1) and matrix metalloproteinase-7 (MMP7) genes, ATP-binding cassette transporters and glucocorticosteroid transcription regulation pathways. Relapse rates...

  16. A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors: dosimetry, biodistribution, pharmacokinetics, and safety.

    Directory of Open Access Journals (Sweden)

    Joseph J Grudzinski

    Full Text Available (131I-CLR1404 is a small molecule that combines a tumor-targeting moiety with a therapeutic radioisotope. The primary aim of this phase 1 study was to determine the administered radioactivity expected to deliver 400 mSv to the bone marrow. The secondary aims were to determine the pharmacokinetic (PK and safety profiles of (131I-CLR1404.Eight subjects with refractory or relapsed advanced solid tumors were treated with a single injection of 370 MBq of (131I-CLR1404. Whole body planar nuclear medicine scans were performed at 15-35 minutes, 4-6, 18-24, 48, 72, 144 hours, and 14 days post injection. Optional single photon emission computed tomography imaging was performed on two patients 6 days post injection. Clinical laboratory parameters were evaluated in blood and urine. Plasma PK was evaluated on (127I-CLR1404 mass measurements. To evaluate renal clearance of (131I-CLR1404, urine was collected for 14 days post injection. Absorbed dose estimates for target organs were determined using the RADAR method with OLINDA/EXM software.Single administrations of 370 MBq of (131I-CLR1404 were well tolerated by all subjects. No severe adverse events were reported and no adverse event was dose-limiting. Plasma (127I-CLR1404 concentrations declined in a bi-exponential manner with a mean t½ value of 822 hours. Mean Cmax and AUC(0-t values were 72.2 ng/mL and 15753 ng • hr/mL, respectively. An administered activity of approximately 740 MBq is predicted to deliver 400 mSv to marrow.Preliminary data suggest that (131I-CLR1404 is well tolerated and may have unique potential as an anti-cancer agent.ClinicalTrials.gov NCT00925275.

  17. Improved outcome after relapse in children with acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Abrahamsson, Jonas; Clausen, Niels; Gustafsson, Göran

    2007-01-01

    investigated. The study included all 146 children in the Nordic countries diagnosed with AML between 1988 and 2003, who relapsed. Data on disease characteristics and relapse treatment were related to outcome. Sixty-six percentage achieved remission with survival after relapse (5 years) 34 +/- 4%. Of 122......In the Nordic Society for Paediatric Haematology and Oncology paediatric study acute myeloid leukaemia (AML) 93, event-free survival was 50% and overall survival was 66%, indicating that many patients were cured following relapse. Factors influencing outcome in children with relapsed AML were...... patients who received re-induction therapy, 77% entered remission with 40 +/- 5% survival. Remission rates were similar for different re-induction regimens but fludarabine, cytarabine, granulocyte colony-stimulating factor-based therapy had low treatment-related mortality. Prognostic factors for survival...

  18. Pro-Inflammatory Cytokines Predict Relapse-Free Survival after One Month of Interferon-α but Not Observation in Intermediate Risk Melanoma Patients.

    Directory of Open Access Journals (Sweden)

    Ahmad A Tarhini

    Full Text Available E1697 was a phase III trial of adjuvant interferon (IFN-α2b for one month (Arm B versus observation (Arm A in patients with resected melanoma at intermediate risk. We evaluated the levels of candidate serum cytokines, the HLA genotype, polymorphisms of CTLA4 and FOXP3 genes and the development of autoantibodies for their association with relapse free survival (RFS in Arm A and Arm B among 268 patients with banked biospecimens.ELISA was used to test 5 autoantibodies. Luminex/One Lambda LABTypeRSSO was used for HLA Genotyping. Selected CTLA4 and FOXP3 Single nucleotide polymorphisms (SNPs and microsatellites were tested for by polymerase chain reaction (PCR. Sixteen serum cytokines were tested at baseline and one month by Luminex xMAP multiplex technology. Cox Proportional Hazards model was applied and the Wald test was used to test the marginal association of each individual marker and RFS. We used the Lasso approach to select the markers to be included in a multi-marker Cox Proportional Hazards model. The ability of the resulting models to predict one year RFS was evaluated by the time-dependent ROC curve. The leave-one-out method of cross validation (LOOCV was used to avoid over-fitting of the data.In the multi-marker modeling analysis conducted in Arm B, one month serum IL2Rα, IL-12p40 and IFNα levels predicted one year RFS with LOOCV AUC = 82%. Among the three markers selected, IL2Rα and IFNα were the most stable (selected in all the cross validation cycles. The risk score (linear combination of the 3 markers separated the RFS curves of low and high risk groups well (p = 0.05. This model did not hold for Arm A, indicating a differential marker profile in Arm B linked to the intervention (adjuvant therapy.Early on-treatment proinflammatory serum markers (IL2Rα, IL-12p40, IFNα significantly predict RFS in our cohort of patients treated with adjuvant IFN-α2b and warrant further study.

  19. Lapse and relapse following inpatient treatment of opiate dependence.

    LENUS (Irish Health Repository)

    Smyth, B P

    2010-06-01

    We conducted a prospective follow-up study of consecutive opiate dependent patients admitted to a residential addiction treatment service for detoxification. We measured the rate of relapse following discharge, and sought to identify factors that were associated with early relapse (i.e., a return to daily opiate use). Follow-up interviews were conducted with 109 patients, of whom, 99 (91%) reported a relapse. The initial relapse occurred within one week in 64 (59%) cases. Multivariate survival analysis revealed that earlier relapse was significantly predicted by younger age, greater heroin use prior to treatment, history of injecting, and a failure to enter aftercare. Unexpectedly, those who were in a relationship with an opiate user had significantly delayed relapse. Those who completed the entire six-week inpatient treatment programme also had a significantly delayed relapse. In order to reduce relapse and the associated increased risk of fatal overdose, services providing residential opiate detoxification should prepare people for admission, strive to retain them in treatment for the full admission period and actively support their entry into planned aftercare in order to improve outcome.

  20. Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study.

    Science.gov (United States)

    O'Brien, Susan; Jones, Jeffrey A; Coutre, Steven E; Mato, Anthony R; Hillmen, Peter; Tam, Constantine; Österborg, Anders; Siddiqi, Tanya; Thirman, Michael J; Furman, Richard R; Ilhan, Osman; Keating, Michael J; Call, Timothy G; Brown, Jennifer R; Stevens-Brogan, Michelle; Li, Yunfeng; Clow, Fong; James, Danelle F; Chu, Alvina D; Hallek, Michael; Stilgenbauer, Stephan

    2016-10-01

    The TP53 gene, encoding tumour suppressor protein p53, is located on the short arm of chromosome 17 (17p). Patients with 17p deletion (del17p) chronic lymphocytic leukaemia have poor responses and survival after chemoimmunotherapy. We assessed the activity and safety of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase, in relapsed or refractory patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma. We did a multicentre, international, open-label, single-arm study at 40 sites in the USA, Canada, Europe, Australia, and New Zealand. Patients (age ≥18 years) with previously treated del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma received oral ibrutinib 420 mg once daily until progressive disease or unacceptable toxicity. The primary endpoint was overall response in the all-treated population per International Workshop on Chronic Lymphocytic Leukaemia 2008 response criteria modified for treatment-related lymphocytosis. Preplanned exploratory analyses were progression-free survival, overall survival, sustained haematological improvement, and immunological improvement. Patient enrolment is complete, but follow-up is ongoing. Treatment discontinuation owing to adverse events, unacceptable toxicity, or death were collected as a single combined category. This study is registered with ClinicalTrials.gov, number NCT01744691. Between Jan 29, 2013, and June 19, 2013, 145 patients were enrolled. The all-treated population consisted of 144 patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma who received at least one dose of study drug, with a median age of 64 years (IQR 57-72) and a median of two previous treatments (IQR 1-3). At the prespecified primary analysis after a median follow-up of 11·5 months (IQR 11·1-13·8), 92 (64%, 95% CI 56-71) of 144 patients had an overall response according to independent review committee assessment; 119 patients (83%, 95% CI 76-88) had an overall

  1. Social settings and addiction relapse.

    Science.gov (United States)

    Walton, M A; Reischl, T M; Ramanthan, C S

    1995-01-01

    Despite addiction theorists' acknowledgment of the impact of environmental factors on relapse, researchers have not adequately investigated these influences. Ninety-six substance users provided data regarding their perceived risk for relapse, exposure to substances, and involvement in reinforcing activities. These three setting attributes were assessed in their home, work, and community settings. Reuse was assessed 3 months later. When controlling for confounding variables, aspects of the home settings significantly distinguished abstainers from reusers; perceived risk for relapse was the strongest predictor of reuse. Exposure to substances and involvement in reinforcing activities were not robust reuse indicators. The work and community settings were not significant determinants of reuse. These findings offer some initial support for the utility of examining social settings to better understand addiction relapse and recovery. Identification of setting-based relapse determinants provides concrete targets for relapse prevention interventions.

  2. Assessing the potential impact of non-proprietary drug copies on quality of medicine and treatment in patients with relapsing multiple sclerosis: the experience with fingolimod

    Directory of Open Access Journals (Sweden)

    Correale J

    2014-06-01

    Full Text Available Jorge Correale,1 Erwin Chiquete,2 Snezana Milojevic,3 Nadina Frider,3 Imre Bajusz31Raúl Carrea Institute for Neurological Research, Foundation for the Fight against Infant Neurological Illnesses, Buenos Aires, Argentina; 2Department of Neurology and Psychiatry, Salvador Zubirán National Institute of Medical Science and Nutrition, Mexico City, Mexico; 3Novartis Pharma AG, Basel, SwitzerlandBackground: Fingolimod is a once-daily oral treatment for relapsing multiple sclerosis, the proprietary production processes of which are tightly controlled, owing to its susceptibility to contamination by impurities, including genotoxic impurities. Many markets produce nonproprietary medicines; assessing their efficacy and safety is difficult as regulators may approve nonproprietary drugs without bioequivalence data, genotoxic evaluation, or risk management plans (RMPs. This assessment is especially important for fingolimod given its solubility/bioavailability profile, genotoxicity risk, and low-dose final product (0.5 mg. This paper presents an evaluation of the quality of proprietary and nonproprietary fingolimod variants.Methods: Proprietary fingolimod was used as a reference substance against which eleven nonproprietary fingolimod copies were assessed. The microparticle size distribution of each compound was assessed by laser light diffraction, and inorganic impurity content by sulfated ash testing. Heavy metals content was quantified using inductively coupled plasma optical emission spectrometry, and levels of unspecified impurities by high-performance liquid chromatography. Solubility was assessed in a range of solvents at different pH values. Key information from the fingolimod RMP is also presented.Results: Nonproprietary fingolimod variants exhibited properties out of proprietary or internationally accepted specifications, including differences in particle size distribution and levels of impurities such as heavy metals. For microparticle size and

  3. Efficacy and toxicity of the combination chemotherapy of thalidomide, alkylating agent, and steroid for relapsed/refractory myeloma patients: a report from the Korean Multiple Myeloma Working Party (KMMWP) retrospective study.

    Science.gov (United States)

    Kwon, Jihyun; Min, Chang-Ki; Kim, Kihyun; Han, Jae-Joon; Moon, Joon Ho; Kang, Hye Jin; Eom, Hyeon-Seok; Kim, Min Kyoung; Kim, Hyo Jung; Yoon, Dok Hyun; Lee, Jeong-Ok; Lee, Won Sik; Lee, Jae Hoon; Lee, Je-Jung; Choi, Yoon-Seok; Kim, Sung Hyun; Yoon, Sung-Soo

    2017-01-01

    We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone (CTD) or daily thalidomide, melphalan, and prednisolone (MTP) at 17 medical centers in Korea. Three-hundred and seventy-six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent (TAS) was second-line chemotherapy in 142 (37.8%) patients, and third-line chemotherapy in 135 (35.9%) patients. The response rate overall was 69.4%. Patients who were not treated with bortezomib and lenalidomide before TAS showed a higher response rate compared to those who were exposed to these agents. The estimated median progression-free survival and overall survival times were 10.4 months and 28.0 months, respectively. The adverse events during TAS were generally tolerable, but 39 (10.4%) patients experienced severe infectious complications. There were no differences in terms of efficacy between CTD and MTP, but infectious complications were more common in CTD group. TAS is an effective treatment regimen which induces a high response rate in relapsed or refractory multiple myeloma patients. Due to the high incidence of grade 3 or 4 infection, proper management of infection is necessary during the TAS treatment, especially the CTD. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  4. Relapsing polychondritis and airway involvement.

    Science.gov (United States)

    Ernst, Armin; Rafeq, Samaan; Boiselle, Phillip; Sung, Arthur; Reddy, Chakravarthy; Michaud, Gaetane; Majid, Adnan; Herth, Felix J F; Trentham, David

    2009-04-01

    To assess the prevalence and characteristics of airway involvement in relapsing polychondritis (RP). Retrospective chart review and data analysis of RP patients seen in the Rheumatology Clinic and the Complex Airway Center at Beth Israel Deaconess Medical Center from January 2004 through February 2008. RP was diagnosed in 145 patients. Thirty-one patients had airway involvement, a prevalence of 21%. Twenty-two patients were women (70%), and they were between 11 and 61 years of age (median age, 42 years) at the time of first symptoms. Airway symptoms were the first manifestation of disease in 17 patients (54%). Dyspnea was the most common symptom in 20 patients (64%), followed by cough, stridor, and hoarseness. Airway problems included the following: subglottic stenosis (n = 8; 26%); focal and diffuse malacia (n = 15; 48%); and focal stenosis in different areas of the bronchial tree in the rest of the patients. Twelve patients (40%) required and underwent intervention including balloon dilatation, stent placement, tracheotomy, or a combination of the above with good success. The majority of patients experienced improvement in airway symptoms after intervention. One patient died during the follow-up period from the progression of airway disease. The rest of the patients continue to undergo periodic evaluation and intervention. In this largest cohort described in the English language literature, we found symptomatic airway involvement in RP to be common and at times severe. The nature of airway problems is diverse, with tracheomalacia being the most common. Airway intervention is frequently required and in experienced hands results in symptom improvement.

  5. Dose study of the multikinase inhibitor, LY2457546, in patients with relapsed acute myeloid leukemia to assess safety, pharmacokinetics, and pharmacodynamics

    Directory of Open Access Journals (Sweden)

    Wacheck V

    2011-05-01

    Full Text Available Volker Wacheck1, Michael Lahn2, Gemma Dickinson3, Wolfgang Füreder4, Renata Meyer4, Susanne Herndlhofer4, Thorsten Füreder1, Georg Dorfner5, Sada Pillay2, Valérie André6, Timothy P Burkholder7, Jacqueline K Akunda8, Leann Flye-Blakemore9, Dirk Van Bockstaele9, Richard F Schlenk10, Wolfgang R Sperr4, Peter Valent4,111Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria; 2Early Oncology Clinical Investigation, Eli Lilly and Company, Indianapolis, IN, USA; 3Department of Pharmacokinetics, Eli Lilly and Company, Erl Wood Research Centre, Windlesham, Surrey, UK; 4Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria; 5Eli Lilly GesmbH, Medical Department, Vienna, Austria; 6Department of Statistics, Eli Lilly and Company, Erl Wood Research Centre, Surrey, UK; 7Discovery Chemistry Research and Technology, Eli Lilly and Company, Indianapolis, IN, USA; 8Nonclinical Toxicology, Eli Lilly and Company, Indianapolis, IN, USA; 9Flow Cytometry and Cell Analysis, Esoterix Clinical Trials Services, Mechelen, Belgium; 10Universitätsklinikum Ulm, Klinik für Innere Medizin III, Ulm, Germany; 11Ludwig Boltzmann Cluster Oncology, Vienna, AustriaBackground: Acute myeloid leukemia (AML is a life-threatening malignancy with limited treatment options in chemotherapy-refractory patients. A first-in-human dose study was designed to investigate a safe and biologically effective dose range for LY2457546, a novel multikinase inhibitor, in patients with relapsed AML.Methods: In this nonrandomized, open-label, dose escalation Phase I study, LY2457546 was administered orally once a day. Safety, pharmacokinetics, changes in phosphorylation of target kinases in AML blasts, and risk of drug–drug interactions (DDI were assessed.Results: Five patients were treated at the starting and predicted minimal biologically effective dose of 50 mg

  6. Extinction of relapsed fear does not require the basolateral amygdala.

    Science.gov (United States)

    Lingawi, Nura W; Westbrook, R Frederick; Laurent, Vincent

    2017-03-01

    It is well established that extinguished fears are restored with the passage of time or a change in physical context. These fear restoration phenomena are believed to mimic the conditions under which relapse occurs in patients that have been treated for anxiety disorders by means of cue-exposure therapy. Here, we used a rodent model to extinguish relapsed fear and assess whether this new extinction prevents further relapse. We found that activity in the basolateral amygdala (BLA) is required to initially extinguish conditioned fear, but this activity was not necessary to subsequently extinguish relapsed fear. That is, extinction of spontaneously recovered or renewed fear was spared by BLA inactivation. Yet, this BLA-independent learning of extinction did not protect against further relapse: extinction of relapsed fear conducted without BLA activity was still likely to return after the passage of time or a shift in physical context. These findings have important clinical implications. They indicate that pharmacological agents with anxiolytic properties may disrupt initial cue-exposure therapy but may be useful when therapy is again needed due to relapse. However, they also suggest that these agents will not protect against further relapse, implying the need for developing drugs that target other brain regions involved in fear inhibition. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Treating Multiply Relapsed or Refractory Hairy Cell Leukemia

    Science.gov (United States)

    In this trial, patients with hairy cell leukemia who have not responded or relapsed after initial chemotherapy will be randomly assigned to receive rituximab combined with either pentostatin or bendamustine.

  8. Pyrexia-associated Relapse in Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Case Report.

    Science.gov (United States)

    Ueda, Jun; Yoshimura, Hajime; Kohara, Nobuo

    2018-04-27

    Chronic inflammatory demyelinating polyradiculoneuropathy is a relapsing-remitting or chronic progressive demyelinating polyradiculoneuropathy. We report the case of a patient with chronic inflammatory demyelinating polyradiculoneuropathy who experienced relapses on four occasions after experiencing pyrexia and flu-like symptoms. Our patient showed characteristic features, such as relapse after pyrexia and flu-like symptoms, remission after pyretolysis without treatment, and the absence of remarkable improvement in a nerve conduction study in the remission phase. The serum level of tumor necrosis factor-α was elevated in the relapse phase and reduced in the remission phase; thus, the induction of cytokine release by viral infection might have caused the relapses.

  9. Matched-pair analysis to compare the outcomes of a second salvage auto-SCT to systemic chemotherapy alone in patients with multiple myeloma who relapsed after front-line auto-SCT.

    Science.gov (United States)

    Yhim, H-Y; Kim, K; Kim, J S; Kang, H J; Kim, J-A; Min, C-K; Bae, S H; Park, E; Yang, D-H; Suh, C; Kim, M K; Mun, Y-C; Eom, H S; Shin, H J; Yoon, H-J; Kwon, J H; Lee, J H; Kim, Y S; Yoon, S-S; Kwak, J-Y

    2013-03-01

    The aims of this study were to investigate the outcomes of second salvage auto-SCT and to identify the impacts of a second auto-SCT compared with systemic chemotherapy alone on disease outcome. Data from 48 patients who underwent second auto-SCT were matched to 144 patients (1:3) who received systemic chemotherapy alone from the Korean Myeloma Registry. Groups were matched for nine potential prognostic factors and compared for treatment outcomes. The median age of matching-pairs at relapse was 55.5 years. A total of 156 patients (81%) received vincristine, doxorubicin and dexamethasone induction therapy before the first auto-SCT. Thirty-five patients (73%) in the second auto-SCT group received novel agent-based therapies before the second auto-SCT, and similar proportion in both groups received novel therapies after relapse of front-line auto-SCT. With a median follow-up of 55.3 months, patients who underwent a second auto-SCT had significantly better median OS (55.5 vs 25.4 months, P=0.035). In multivariate analysis for OS, SCT, International Staging System III and salvage chemotherapy alone were independent predictors for worse OS. The outcomes of second auto-SCT appear to be superior to those of systemic chemotherapy alone. A randomized trial comparing both treatment strategies is required.

  10. Proteoglycan-based diversification of disease outcome in head and neck cancer patients identifies NG2/CSPG4 and syndecan-2 as unique relapse and overall survival predicting factors.

    Science.gov (United States)

    Farnedi, Anna; Rossi, Silvia; Bertani, Nicoletta; Gulli, Mariolina; Silini, Enrico Maria; Mucignat, Maria Teresa; Poli, Tito; Sesenna, Enrico; Lanfranco, Davide; Montebugnoli, Lucio; Leonardi, Elisa; Marchetti, Claudio; Cocchi, Renato; Ambrosini-Spaltro, Andrea; Foschini, Maria Pia; Perris, Roberto

    2015-05-03

    Tumour relapse is recognized to be the prime fatal burden in patients affected by head and neck squamous cell carcinoma (HNSCC), but no discrete molecular trait has yet been identified to make reliable early predictions of tumour recurrence. Expression of cell surface proteoglycans (PGs) is frequently altered in carcinomas and several of them are gradually emerging as key prognostic factors. A PG expression analysis at both mRNA and protein level, was pursued on primary lesions derived from 173 HNSCC patients from whom full clinical history and 2 years post-surgical follow-up was accessible. Gene and protein expression data were correlated with clinical traits and previously proposed tumour relapse markers to stratify high-risk patient subgroups. HNSCC lesions were indeed found to exhibit a widely aberrant PG expression pattern characterized by a variable expression of all PGs and a characteristic de novo transcription/translation of GPC2, GPC5 and NG2/CSPG4 respectively in 36%, 72% and 71% on 119 cases. Importantly, expression of NG2/CSPG4, on neoplastic cells and in the intralesional stroma (Hazard Ratio [HR], 6.76, p = 0.017) was strongly associated with loco-regional relapse, whereas stromal enrichment of SDC2 (HR, 7.652, p = 0.007) was independently tied to lymphnodal infiltration and disease-related death. Conversely, down-regulated SDC1 transcript (HR, 0.232, p = 0.013) uniquely correlated with formation of distant metastases. Altered expression of PGs significantly correlated with the above disease outcomes when either considered alone or in association with well-established predictors of poor prognosis (i.e. T classification, previous occurrence of precancerous lesions and lymphnodal metastasis). Combined alteration of all three PGs was found to be a reliable predictor of shorter survival. An unprecedented PG-based prognostic portrait is unveiled that incisively diversifies disease course in HNSCC patients beyond the currently known clinical and molecular

  11. TBI parameters and relapse of acute leukemia

    International Nuclear Information System (INIS)

    Sugawara, Tadashi; Inoue, Toshihiko; Mori, Tomoyuki.

    1994-01-01

    The purpose of this study, which involved 240 acute leukemia patients (ALL: 115, ANL: 125) who received an allogeneic bone marrow transplantation (BMT) with preconditioning by total body irradiation (TBI) and chemotherapy, was to examine retrospectively the TBI factors that may have influenced a leukemic relapse. The patients were divided into two groups: 124 patients who had received their BMT within a diagnosis-transplantation period of 9 months or less (DTP9 group), and 116 patients who had received their BMT within a diagnosis-transplantation period of 10 months or more (DTP10 group). It was concluded that: (1) the higher the TBI dose, the fewer the relapse rates in DTP9 group; (2) the longer the TBI period, the greater the increase in the relapse rate in DTP10 group. It was thus speculated that an effective TBI regimen for acute leukemia patients may vary depending on the length of time that has elapsed from the diagnosis of leukemia to the BMT. (author)

  12. Relapsing Polychondritis Following Alopecia Areata

    Directory of Open Access Journals (Sweden)

    John C. Starr

    2010-01-01

    Full Text Available A case of alopecia areata followed by relapsing polychondritis is presented. Similar cases from the literature are reviewed and speculation about the relationship of these diseases is offered. Although the occurrence of these diseases together could be coincidental, an association seems immunologically plausible. Thus, relapsing polychondritis might be an unusual systemic manifestation of alopecia areata.

  13. Efficacy of melflufen, a peptidase targeted therapy, and dexamethasone in an ongoing open-label phase 2a study in patients with relapsed and relapsed-refractory multiple myeloma (RRMM) including an initial report on progression free survival

    DEFF Research Database (Denmark)

    Voorhees, P. M.; Magarotto, V.; Sonneveld, P.

    2015-01-01

    to DNA or is readily metabolized by intracellular peptidases into hydrophilic alkylating metabolites. With targeted delivery of alkylating metabolites to tumor cells in vitro (such as multiple myeloma that are rich in activating peptidase), melflufen exerts a 20-100 fold higher anti-tumor potency...... and produces a 20 fold higher intracellular concentration of alkylating moieties compared with melphalan. Methods: Melflufen is evaluated in combination with dexamethasone (dex) 40 mg weekly in an ongoing Phase 1/2a study. RRMM patients with measurable disease and at least 2 prior lines of therapy are eligible......%) and constipation and epistaxis (13%). Treatment-related Grade 3 or 4 AEs were reported in 27 patients (87%). Those occurring in >5% of patients were thrombocytopenia (68%), neutropenia (55%), anemia (42%), leukopenia (32%) and febrile neutropenia, fatigue, pyrexia, asthenia and hyperglycemia each occurred in 6...

  14. Impact of the use of autologous stem cell transplantation at first relapse both in naïve and previously rituximab exposed follicular lymphoma patients treated in the GELA/GOELAMS FL2000 study

    Science.gov (United States)

    Le Gouill, Steven; De Guibert, Sophie; Planche, Lucie; Brice, Pauline; Dupuis, Jehan; Cartron, Guillaume; Van Hoof, Achiel; Casasnovas, Olivier; Gyan, Emmanuel; Tilly, Hervé; Fruchart, Christophe; Deconinck, Eric; Fitoussi, Olivier; Gastaud, Lauris; Delwail, Vincent; Gabarre, Jean; Gressin, Rémy; Blanc, Michel; Foussard, Charles; Salles, Gilles

    2011-01-01

    Background We analyzed detailed characteristics and salvage treatment in 175 follicular lymphoma patients from the FL2000 study who were in progression after first-line therapy with or without addition of rituximab to chemotherapy and interferon. Design and Methods The impact of using autologous stem cell transplantation and/or rituximab administration at first progression was investigated, taking into account initial therapy. With a median follow up of 31 months, 3-year event free and overall survival rates after progression were 50% (95%CI 42–58%) and 72% (95%CI 64–78%), respectively. Results The 3-year event free rate of rituximab re-treated patients (n=112) was 52% (95%CI 41–62%) versus 40% (95%CI 24–55%) for those not receiving rituximab second line (n=53) (P=0.075). There was a significant difference in 3-year overall survival between patients receiving autologous stem cell transplantation and those not: 92% (95%CI 78–97%) versus 63% (95%CI 51–72%) (P=0.0003), respectively. In multivariate analysis, both autologous stem cell transplantation and period of progression/relapse affected event free and overall survival. Conclusions Regardless of front-line rituximab exposure, this study supports incorporating autologous stem cell transplantation in the therapeutic approach at first relapse for follicular lymphoma patients. PMID:21486862

  15. Autologous stem cell transplantation for patients aged 60 years or older with refractory or relapsed classical Hodgkin's lymphoma: a retrospective analysis from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC).

    Science.gov (United States)

    Stamatoullas, A; Brice, P; Gueye, M S; Mareschal, S; Chevallier, P; Bouabdallah, R; Nguyenquoc, S; Francois, S; Turlure, P; Ceballos, P; Monjanel, H; Bourhis, J-H; Guillerm, G; Mohty, M; Biron, P; Cornillon, J; Belhadj, K; Bonmati, C; Dilhuydy, M-S; Huynh, A; Bernard, M; Chrétien, M-L; Peffault de Latour, R; Tilly, H

    2016-07-01

    This report retrospectively analyzed the outcome of 91 patients aged 60 years or older with refractory/relapsed (R/R) classical Hodgkin's lymphoma (cHL) who underwent autologous stem cell transplantation (ASCT) between 1992 and 2013 and were reported to the French Society of Bone Marrow Transplantation and Cell Therapies registry. The median age at transplant was 63 years. The majority of patients exhibited disease chemosensitivity to salvage treatment (57 complete responses, 30 partial responses, 1 progressive disease and 3 unknown). The most frequent conditioning regimen consisted of BCNU, cytarabine, etoposide, melphalan (BEAM) chemotherapy (93%). With a median follow-up of 54 months, 5-year estimates of overall survival (OS) and progression free survival (PFS) for the entire group were 67 and 54%, respectively. Despite the missing data, in univariate analysis, the number of salvage chemotherapy lines (1-2 versus ⩾3) significantly influenced the OS, unlike the other prognostic factors (stage III-IV at relapse, disease status before ASCT and negative positron emission tomography (PET) scan) encountered in younger patients. In spite of its limitations, this retrospective study with a long-term follow-up suggests that ASCT is a valid treatment option for chemosensitive R/R cHL in selected elderly patients, with an acceptable rate of toxicity.

  16. Five-day bismuth-free triple therapy for the eradication of Helicobacter pylori and reduction of duodenal ulcer relapse

    International Nuclear Information System (INIS)

    Coelho, L.G.; Passos, M.C.; Chausson, Y.; Castro L de, P.

    1991-01-01

    Previous studies have demonstrated that the eradication of Helicobacter pylori (H. pylori) is associated with a significant reduction of the rate of duodenal ulcer (DU) relapse. The aim of this study was to assess the long-term effect of a bismuth-free triple therapy on the eradication of H. pylori and reduction of DU relapse. After informed consent, 61 patients with endoscopically proven DU and H. pylori infection detected on 14C-urea breath test (BT) were included in the study. All patients received a combination of furazolidone, amoxicillin, and metronidazole, three times a day, for 5 days, in addition to eventual classical antiulcer agents prescribed by their attending physicians. BT was repeated after an interval of at least 60 days to evaluate H. pylori eradication. Endoscopy and another BT were performed again at 6.5 months after therapy to detect possible recurrences. Forty-eight patients completed the trial: 26 (54%) patients were negative for H. pylori at 6.5 months after the end of treatment, and 22 (46%) persisted H. pylori positive. Ninety-two percent of the patients in whom the bacteria were eradicated showed endoscopically healed ulcers and were asymptomatic, and two that were symptomatic presented only occasional pain not requiring therapy. Among the 22 patients who persisted H. pylori positive, six (27%) showed endoscopically active ulcers (p = 0.012) and eight (36%) patients continued to be symptomatic (p less than 0.01), and were still using antiulcer drugs (p = 0.002) 6.5 months after treatment. It is concluded that combined treatment with furazolidone, amoxicillin, and metronidazole for 5 days represents a well-tolerated, inexpensive, and effective therapeutic regime for the eradication of H. pylori and abolition of DU relapse in more than 50% of the patients during a follow-up period of 6.5 months

  17. Relapse of nephrotic syndrome during post-rituximab peripheral blood B-lymphocyte depletion.

    Science.gov (United States)

    Sato, Mai; Kamei, Koichi; Ogura, Masao; Ishikura, Kenji; Ito, Shuichi

    2018-02-01

    Rituximab is effective against complicated childhood steroid-dependent nephrotic syndrome (SDNS). Peripheral blood B-lymphocyte (B-cell) depletion is strongly correlated with persistent remission, relapse rarely occurring during B-cell depletion; however, we have encountered several such patients. We retrospectively analyzed the characteristics and clinical course of 82 patients with SDNS treated with rituximab from January 2007 to December 2012 in our institution. Six of 82 patients (7.3%) had relapses during B-cell depletion after receiving rituximab (relapsed group). The remaining 76 patients did not have relapses during B-cell depletion (non-relapsed group). The median time to initial relapse during B-cell depletion was 85 days after receiving rituximab, which is significantly shorter than in the non-relapsed group (410 days, p = 0.0003). The median annual numbers of relapses after receiving rituximab were 2.5 and 0.9 in the relapsed and non-relapsed groups, respectively (p depletion did not differ between the two groups. Relapse during B-cell depletion after receiving rituximab suggests that various pathophysiological mechanisms play a part in childhood nephrotic syndrome.

  18. Incidence of extramedullary relapse after haploidentical SCT for advanced AML/myelodysplastic syndrome.

    Science.gov (United States)

    Yoshihara, S; Ikegame, K; Kaida, K; Taniguchi, K; Kato, R; Inoue, T; Fujioka, T; Tamaki, H; Okada, M; Soma, T; Ogawa, H

    2012-05-01

    Extramedullary (EM) relapse of leukemia after allo-SCT in patients with AML/myelodysplastic syndrome has been increasingly reported. The reduced effectiveness of the GVL effect in EM sites, as compared with BM, has been suggested to underlie this problem. We retrospectively analyzed the pattern of relapse after haploidentical SCT (haplo-SCT), performed as the first or second SCT. Among 38 patients who received haplo-SCT as their first SCT, the cumulative incidences of BM and EM relapse at 3 years were 40.5 and 10.9%, respectively. Among 19 patients who received haplo-SCT as their second SCT, the cumulative incidences of BM and EM relapse were 30.9 and 31.9%, respectively. Moreover, most of the patients who underwent repeat haplo-SCT for the treatment of EM relapse had further EM relapse at other sites. Post-relapse survival did not differ significantly with different patterns of relapse. The frequent occurrence of EM relapse after haplo-SCT, particularly when performed as a second SCT, suggests that the potent GVL effect elicited by an HLA disparity also occurs preferentially in BM. Our findings emphasize the need for a treatment strategy for EM relapse that recognizes the reduced susceptibility of EM relapse to the GVL effect.

  19. MRI diagnosis of bone marrow relapse in children with ALL

    International Nuclear Information System (INIS)

    Kan, J.H.; Hernanz-Schulman, Marta; Frangoul, Haydar A.; Connolly, Susan A.

    2008-01-01

    Diffuse marrow replacement in acute leukemia is well known, but there are few reports describing the MRI features of pediatric leukemic relapse. Our purpose was to describe the MRI appearance of pediatric leukemic relapse. A total of 53 consecutive children with a history of ALL were referred for musculoskeletal MRI from 1 January 1998 to 28 February 2007 at one center, and from 1 January 2000 to 2 May 2007 at a second center. From this group, 14 children seen at initial diagnosis of leukemia and 2 children who underwent MRI after therapy for relapse were excluded. The remaining 37 children, 8 with relapse and 29 in remission, were studied. Images of patients with relapse and in remission were reviewed for type and configuration of marrow infiltration; coexisting marrow alterations including osteonecrosis or stress reaction were also reviewed. All eight children with relapse demonstrated nodular lesions with well-defined margins. Coexisting osteonecrosis was present in three children (38%) and pathologic fracture in one. Among the 29 children in remission, 9 showed stress reaction/fracture, 14 showed osteonecrosis and 9 showed ill-defined nodules, and in 5 the marrow was completely normal. Well-defined nodules in all patients with leukemic relapse suggest that this appearance is characteristic and distinct from the published findings of diffuse marrow replacement in acute leukemia. (orig.)

  20. MRI diagnosis of bone marrow relapse in children with ALL

    Energy Technology Data Exchange (ETDEWEB)

    Kan, J.H.; Hernanz-Schulman, Marta [Vanderbilt University, Department of Radiology and Radiological Sciences, Vanderbilt Children' s Hospital, Nashville, TN (United States); Frangoul, Haydar A. [Vanderbilt University, Department of Pediatric Hematology-Oncology, Vanderbilt Children' s Hospital, Nashville, TN (United States); Connolly, Susan A. [Harvard Medical School, Department of Radiology, Boston Children' s Hospital, Boston, MA (United States)

    2008-01-15

    Diffuse marrow replacement in acute leukemia is well known, but there are few reports describing the MRI features of pediatric leukemic relapse. Our purpose was to describe the MRI appearance of pediatric leukemic relapse. A total of 53 consecutive children with a history of ALL were referred for musculoskeletal MRI from 1 January 1998 to 28 February 2007 at one center, and from 1 January 2000 to 2 May 2007 at a second center. From this group, 14 children seen at initial diagnosis of leukemia and 2 children who underwent MRI after therapy for relapse were excluded. The remaining 37 children, 8 with relapse and 29 in remission, were studied. Images of patients with relapse and in remission were reviewed for type and configuration of marrow infiltration; coexisting marrow alterations including osteonecrosis or stress reaction were also reviewed. All eight children with relapse demonstrated nodular lesions with well-defined margins. Coexisting osteonecrosis was present in three children (38%) and pathologic fracture in one. Among the 29 children in remission, 9 showed stress reaction/fracture, 14 showed osteonecrosis and 9 showed ill-defined nodules, and in 5 the marrow was completely normal. Well-defined nodules in all patients with leukemic relapse suggest that this appearance is characteristic and distinct from the published findings of diffuse marrow replacement in acute leukemia. (orig.)

  1. Outcome following late marrow relapse in childhood acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Chessells, J.; Leiper, A.; Rogers, D.

    1984-01-01

    Thirty-four children with acute lymphoblastic leukemia, who developed bone marrow relapse after treatment was electively stopped, received reinduction, consolidation, continuing therapy, and intrathecal (IT) methotrexate (MTX). Sixteen children who relapsed within six months of stopping treatment had a median second-remission duration of 26 weeks; all next relapses occurred in the bone marrow. In 18 children who relapsed later, the median duration of second remission was in excess of two years, but after a minimum of four years follow-up, 16 patients have so far relapsed again (six in the CNS). CNS relapse occurred as a next event in four of 17 children who received five IT MTX injections only and in two of 14 children who received additional regular IT MTX. Although children with late marrow relapses may achieve long second remissions, their long-term out-look is poor, and regular IT MTX does not afford adequate CNS prophylaxis. It remains to be seen whether more intensive chemotherapy, including high-dose chemoradiotherapy and bone marrow transplantation, will improve the prognosis in this group of patients

  2. Economic costs associated with an MS relapse

    LENUS (Irish Health Repository)

    O'Connell, K.

    2014-09-01

    This was an prospective audit composed of medical chart review and patient questionnaire. Relapses were stratified into 3 groups: low, moderate and high intensity. Age, gender, MS subtype, disease duration, expanded disability status scale (EDSS) score, disease modifying therapy (DMT) use and employment status were recorded. Direct costs included GP visits, investigations, clinic visit, consultations with medical staff, medication and admission costs. Indirect costs assessed loss of earnings, partner\\'s loss of earnings, childcare, meals and travel costs.

  3. A multicenter, non-randomized, phase II study of docetaxel and carboplatin administered every 3 weeks as second line chemotherapy in patients with first relapse of platinum sensitive epithelial ovarian, peritoneal or fallopian tube cancer

    DEFF Research Database (Denmark)

    Wang, Yun; Herrstedt, Jørn; Havsteen, Hanne

    2014-01-01

    of 398 cycles were given. Grade 3/4 neutropenia was seen in 80% (59 of 74) patients with an incidence of febrile neutropenia of 16%. Grade 2/3 sensory peripheral neuropathy occurred in 7% of patients, but no grade 4 sensory peripheral neuropathy was observed. Sixty patients were evaluable for response...... of platinum-sensitive ovarian, peritoneal and Fallopian tube cancer. The major toxicity was neutropenia, while the frequency of peripheral neuropathy was low.......BACKGROUND: In patients with ovarian cancer relapsing at least 6 months after end of primary treatment, the addition of paclitaxel to platinum treatment has been shown to improve survival but at the cost of significant neuropathy. In the first line setting, the carboplatin-docetaxel combination...

  4. The Cancer of the Prostate Risk Assessment (CAPRA) in patients treated with external beam radiation therapy: Evaluation and optimization in patients at higher risk of relapse

    International Nuclear Information System (INIS)

    Halverson, Schuyler; Schipper, Matthew; Blas, Kevin; Lee, Vivien; Sabolch, Aaron; Olson, Karin; Sandler, Howard M.; Feng, Felix Y.; Hamstra, Daniel A.

    2011-01-01

    Background: The Cancer of the Prostate Risk Assessment (CAPRA) was developed to predict freedom from biochemical failure (FFBF) following radical prostatectomy (RP). Its utility following external beam radiation therapy (EBRT) has not been externally evaluated. Methods: A retrospective study of 612 patients treated with dose-escalated EBRT at University of Michigan Medical Center. Results: Compared to the derivation cohort, EBRT treated patients had higher-risk disease (28% with CAPRA of 6–10 vs. 5%, respectively). A total of 114 patients (19%) had BF with 5-year BF ranging from 7% with CAPRA 0–3 to 35% with CAPRA 7–10. For RT patients the risk of BF at 5-year was similar to 4 surgical cohorts for CAPRA scores 0–2 but lower for all CAPRA scores ⩾ 3. The difference favoring RT increased with increasing CAPRA score reaching a 27–50% absolute improved at 5-years for CAPRA scores of 6–10. On multivariate analysis each CAPRA point increased the risk of BF (p < 0.0001) while Gleason pattern 5 in the biopsy also increased BF (p = 0.01) and long-term androgen deprivation therapy (ADT) significantly reduced the risk of BF (p = 0.015). Conclusions: Compared to surgical series the risk of BF was lower with dose-escalated EBRT with the greatest difference at the highest CAPRA scores.

  5. Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib

    DEFF Research Database (Denmark)

    Vangsted, Annette J.; Klausen, Tobias W.; Abildgaard, Niels

    2011-01-01

    the impact on outcome of HDT, INF-α maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (−3737T...... carrying the wild-type C-allele of IL1B C-3737T (HR, 1.6 (1.1–2.4)). Furthermore, among INF-α treated patients, gene–gene interaction studies on IL1B C-3737T and NFКB1-94ins/del ATTG revealed a fourfold increase in TTF for homozygous carriers of wild-type alleles at both loci as compared to variant allele...... carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (−3737T, −1464G...

  6. Machine Learning Algorithms Utilizing Quantitative CT Features May Predict Eventual Onset of Bronchiolitis Obliterans Syndrome After Lung Transplantation.

    Science.gov (United States)

    Barbosa, Eduardo J Mortani; Lanclus, Maarten; Vos, Wim; Van Holsbeke, Cedric; De Backer, William; De Backer, Jan; Lee, James

    2018-02-19

    Long-term survival after lung transplantation (LTx) is limited by bronchiolitis obliterans syndrome (BOS), defined as a sustained decline in forced expiratory volume in the first second (FEV 1 ) not explained by other causes. We assessed whether machine learning (ML) utilizing quantitative computed tomography (qCT) metrics can predict eventual development of BOS. Paired inspiratory-expiratory CT scans of 71 patients who underwent LTx were analyzed retrospectively (BOS [n = 41] versus non-BOS [n = 30]), using at least two different time points. The BOS cohort experienced a reduction in FEV 1 of >10% compared to baseline FEV 1 post LTx. Multifactor analysis correlated declining FEV 1 with qCT features linked to acute inflammation or BOS onset. Student t test and ML were applied on baseline qCT features to identify lung transplant patients at baseline that eventually developed BOS. The FEV 1 decline in the BOS cohort correlated with an increase in the lung volume (P = .027) and in the central airway volume at functional residual capacity (P = .018), not observed in non-BOS patients, whereas the non-BOS cohort experienced a decrease in the central airway volume at total lung capacity with declining FEV 1 (P = .039). Twenty-three baseline qCT parameters could significantly distinguish between non-BOS patients and eventual BOS developers (P machine), we could identify BOS developers at baseline with an accuracy of 85%, using only three qCT parameters. ML utilizing qCT could discern distinct mechanisms driving FEV 1 decline in BOS and non-BOS LTx patients and predict eventual onset of BOS. This approach may become useful to optimize management of LTx patients. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  7. The effect of Group Cognitive-Behaviour Therapy in combination with Pharmacotherapy on Mania and Depression Symptoms and Awareness of warming signs of relapse in patients with Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Bahram Ali Ghanbari Hashemabadi

    2009-04-01

    Full Text Available "n Objective: This research has been done according to the cognitivebehavioral theories and biochemical model in order to evaluate the efficiency of Group Cognitive-Behavior Therapy in combination with Pharmacotherapy on Mania and Depression Symptoms and Awareness of warning signs of relapse in patients with Bipolar Disorder. "n "nMethods:In this study with the experimental pretest- posttest- follow up plan , 30 women suffering from bipolar disorder, randomly assigned to receive either the group cognitive-behavior therapy (experimental group, n=15 or usual treatment (control group, n=15;and were follow-up for a six months. patients in both groups were prescribed standard Pharmacotherapy. First all subjects were put to a pretest in equal conditions with measures of scale 2 and 9 of MMPI Test, and warning signs checklist. Then the experimental group received group cognitive-behavior therapy for 8 sessions in addition to their medication therapy. The control group only received medicine. At the end of the experiment, all subjects were tested under equal conditions. After completion of the treatment process, the subjects of both groups were supervised for 6 months. The findings of the study were analyzed by the statistical method of Multi-variable analysis of variance with repetitive measurements. "nResults:The findings showed that the group cognitive-behavior therapy had been significantly more efficient in reduction of mania symptoms {p=0/03} and increment of awareness of warning signs of relapse {p=0/00} in comparison with control group; but there is no significantly differences in depression symptoms between two groups. "nConclusion: The findings of this study suggest the beneficial effect of Group cognitive-behavior therapy in reducing of mania symptoms and increment of awareness of warning signs of relapse. Therefore, it can be used as a complementary treatment by clinicians

  8. End-of-Treatment Positron Emission Tomography After Uniform First-Line Therapy of B-Cell Posttransplant Lymphoproliferative Disorder Identifies Patients at Low Risk of Relapse in the Prospective German PTLD Registry.

    Science.gov (United States)

    Zimmermann, Heiner; Denecke, Timm; Dreyling, Martin H; Franzius, Christiane; Reinke, Petra; Subklewe, Marion; Amthauer, Holger; Kneba, Michael; Riess, Hanno; Trappe, Ralf U

    2018-05-01

    Fluorine-18 fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET) is a recommended standard in the staging and response assessment of 18F-FDG-avid lymphoma. Posttransplant lymphoproliferative disorder (PTLD) can be detected by 18F-FDG-PET at diagnosis with high sensitivity and specificity. However, the role of response assessment by end-of-treatment (EOT) PET has only been addressed in small case series. We performed a retrospective, multicenter study of 37 patients with CD20-positive PTLD after solid organ transplantation treated with uniform, up-to-date, first-line protocols in the prospective German PTLD registry who had received EOT 18F-FDG-PET between 2006 and 2014. Median follow-up was 5.0 years. Any nonphysiological 18F-FDG uptake (Deauville score greater 2) was interpreted as PET-positive. By computed tomography (CT) final staging, 18 of 37 patients had a complete response, 18 had a partial response and 1 patient had stable disease. EOT PET was negative in 24 of 37 patients and positive in 13 of 37 patients. The positive predictive value of EOT PET for PTLD relapse was 38%, and the negative predictive value was 92%. Time to progression (TTP) and progression-free-survival were significantly longer in the PET negative group (P = 0.019 and P = 0.013). In the 18 patients in a partial response by CT staging, we noted highly significant differences in overall survival (P = 0.001), time to progression (P = 0.007), and progression-free survival (P < 0.001) by EOT PET. Even without baseline imaging, EOT PET in PTLD identifies patients at low risk of relapse and offers clinically relevant information, particularly in patients in a partial remission by CT staging.

  9. Local Cartilage Trauma as a Pathogenic Factor in Autoimmunity (One Hypothesis Based on Patients with Relapsing Polychondritis Triggered by Cartilage Trauma

    Directory of Open Access Journals (Sweden)

    Carlos A. Cañas

    2012-01-01

    Full Text Available In the recent years, it has been of great interest to study the binding mechanism between the innate and adaptive immune responses as interrelated processes for the development of multiple autoimmune diseases. Infection has been a well-known trigger of autoimmunity and trauma has been related as well too. Cryptogenic antigens release, recognition of pathogenic structure, and metabolic changes generated by both stimuli begin an inflammatory process which in turn activates the immune system amplifying T and B cell responses. The development of relapsing polychondritis after trauma may have a direct association with these events and in turn probably trigger autoimmune phenomena.

  10. Evaluation of post-surgical relapse after mandibular setback surgery with minimal orthodontic preparation.

    Science.gov (United States)

    Lee, Nam-Ki; Kim, Young-Kyun; Yun, Pil-Young; Kim, Jong-Wan

    2013-01-01

    The aim of this study was to evaluate of the patterns of post-surgical relapse after mandibular setback surgery with minimal orthodontic preparation (MS-MO). The subjects consisted of 15 patients with minimal pre-surgical orthodontic preparation (1.37 ± 1.69 months). Lateral cephalograms were taken in pre-surgical (T0), post-surgical 1 month (T1) and immediately after debonding (T2) stages. To evaluate the surgical changes (T1-T0) and the relapse (T2-T1), the linear and angular measurements were analyzed using paired t-test. Pearson's correlation coefficients of the horizontal and vertical relapses of Pog and Me to other measurements were calculated. Pog or Me in T1 were displaced rotationally on Ar-Pog or Ar-Me lines in T2 to evaluate the remaining surgical relapse except the rotational relapse from total relapse. The mandible relapsed anteriorly 3.53 mm (Pog) and 4.00 mm (Me) and superiorly 2.72 mm (Pog) and 2.44 mm (Me). FH to Ar-Pog and FH to Ar-Me decreased by about 2°. Pure surgical relapses at Pog and Me, except rotational relapses, were about 0.5 mm anteriorly and inferiorly 0.8 mm. The vertical relapse might induce mandibular rotation with the horizontal relapse. For an accurate prediction after MS-MO, the rotational relapse might be considered. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  11. Novel therapeutic options for relapsed hairy cell leukemia.

    Science.gov (United States)

    Jain, Preetesh; Polliack, Aaron; Ravandi, Farhad

    2015-01-01

    The majority of patients with hairy cell leukemia (HCL) achieve a response to therapy with cladribine or pentostatin with or without rituximab. However, late relapses can occur. Treatment of relapsed HCL can be difficult due to a poor tolerance to chemotherapy, increased risk of infections and decreased responsiveness to chemotherapy. The identification of BRAFV600E mutations and the role of aberrant MEK kinase and Bruton's tyrosine kinase (BTK) pathways in the pathogenesis of HCL have helped to develop novel targeted therapies for these patients. Currently, the most promising therapeutic strategies for relapsed or refractory HCL include recombinant immunoconjugates targeting CD22 (e.g. moxetumomab pasudotox), BRAF inhibitors such as vemurafenib and B cell receptor signaling kinase inhibitors such as ibrutinib. Furthermore, the VH4-34 molecular variant of classic HCL has been identified to be less responsive to chemotherapy. Herein, we review the results of the ongoing clinical trials and potential future therapies for relapsed/refractory HCL.

  12. Fixed Point of Generalized Eventual Cyclic Gross in Fuzzy Norm Spaces for Contractive Mappings

    Directory of Open Access Journals (Sweden)

    S. A. M. Mohsenialhosseini

    2015-01-01

    Full Text Available We define generalized eventual cyclic gross contractive mapping in fuzzy norm spaces, which is a generalization of the eventual cyclic gross contractions. Also we prove the existence of a fixed point for this type of contractive mapping on fuzzy norm spaces.

  13. A Unique Case of Relapsing Polychondritis Presenting with Acute Pericarditis

    Directory of Open Access Journals (Sweden)

    John V. Higgins

    2013-01-01

    Full Text Available Relapsing polychondritis (RP is an inflammatory disease of the cartilaginous tissue primarily affecting the cartilaginous structures of the ear, nose, joints, and the respiratory system. Cardiovascular complications of RP are associated with high morbidity and mortality and occur most commonly as valvular disease. Pericarditis is a less common complication, occurring in 4% of patients with RP and has not previously been described at presentation. We describe a case of relapsing polychondritis with acute pericarditis at presentation.

  14. Clinical observation of relapsing polychondritis: a report of 23 patients%复发性多软骨炎23例临床观察

    Institute of Scientific and Technical Information of China (English)

    高岭; 娄卫华; 程秀莲

    2012-01-01

    Objective To explore the clinical characteristics of relapsing polychondritis (RP) for its early diagnosis and treatment.Methods A retrospective analysis was performed for the clinical data and prognoses for 23 RP patients from April 1996 to October 2011 at Departments of Respiratory Medicine,Rheumatism and Otorhinolaryngology,First Affiliated Hospital,Zhengzhou University. Results Lesion locations included auricle (n =19),joints (n =17),nose (n =14),respiratory tract (n =10 ),eyes ( n =6 ),inner ear ( n =4),costal cartilage ( n =3 ) and kidney ( n =1 ).Laboratory examinations revealed elevated erythrocyte sedimentation rate (ESR) ( n =18 ),elevated C-reactive protein (CRP) ( n =16 ) andpositive rheumatoid factor (n =2).Laryngeal mucosa was edematous and the vocal cords were paralyzed in the cases with airway involvement under laryngofiberscopy. Tracheal mucosa was highly edematous and tracheal lumen narrowed in the cases examined under bronchofibroscope. Laryngeal mucosa was swollen,glottic chink narrowed,laryngeal cartilage partially absorbed and deformed in the cases examined with neck computed tomography (CT). Tracheal mucosa was thickened,tracheal lumen narrowed and tracheal cartilage was deformed and calcified in the cases on chest CT.Pathological examination on tracheal cartilage showed that cartilage tissue was degenerative and fibrotic.And the proliferation of granulation tissue and the infiltration of inflammatory cells were present around cartilage tissue.Twenty-three RP patients received the therapies of antibiotics, glucocorticosteroid, immunosuppressive agent, tracheotomy or tracheal stent implantation.Two cases died of asphyxia.One casc died of myocardial infarct.The symptoms of other 20 cases improved in different degrees.Conclusion The clinical manifestations are diverse in RP patients.The prognoses of patients with airway involvement are worse and may be improved by an early diagnosis and correct treatment.%目的 研究复发性多软骨炎(RP)

  15. Recognition of viral and self-antigens by TH1 and TH1/TH17 central memory cells in patients with multiple sclerosis reveals distinct roles in immune surveillance and relapses.

    Science.gov (United States)

    Paroni, Moira; Maltese, Virginia; De Simone, Marco; Ranzani, Valeria; Larghi, Paola; Fenoglio, Chiara; Pietroboni, Anna M; De Riz, Milena A; Crosti, Maria C; Maglie, Stefano; Moro, Monica; Caprioli, Flavio; Rossi, Riccardo; Rossetti, Grazisa; Galimberti, Daniela; Pagani, Massimiliano; Scarpini, Elio; Abrignani, Sergio; Geginat, Jens

    2017-09-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that is caused by autoreactive T cells and associated with viral infections. However, the phenotype of pathogenic T cells in peripheral blood remains to be defined, and how viruses promote MS is debated. We aimed to identify and characterize potentially pathogenic autoreactive T cells, as well as protective antiviral T cells, in patients with MS. We analyzed CD4 + helper T-cell subsets from peripheral blood or cerebrospinal fluid for cytokine production, gene expression, plasticity, homing potentials, and their reactivity to self-antigens and viral antigens in healthy subjects and patients with MS. Moreover, we monitored their frequencies in untreated and fingolimod- or natalizumab-treated patients with MS. T H 1/T H 17 central memory (T H 1/T H 17 CM ) cells were selectively increased in peripheral blood of patients with relapsing-remitting MS with a high disease score. T H 1/T H 17 CM cells were closely related to conventional T H 17 cells but had more pathogenic features. In particular, they could shuttle between lymph nodes and the CNS and produced encephalitogenic cytokines. The cerebrospinal fluid of patients with active MS was enriched for CXCL10 and contained mainly CXCR3-expressing T H 1 and T H 1/T H 17 subsets. However, while T H 1 cells responded consistently to viruses, T H 1/T H 17 CM cells reacted strongly with John Cunningham virus in healthy subjects but responded instead to myelin-derived self-antigens in patients with MS. Fingolimod and natalizumab therapies efficiently targeted autoreactive T H 1/T H 17 CM cells but also blocked virus-specific T H 1 cells. We propose that autoreactive T H 1/T H 17 CM cells expand in patients with MS and promote relapses after bystander recruitment to the CNS, whereas T H 1 cells perform immune surveillance. Thus the selective targeting of T H 1/T H 17 cells could inhibit relapses without causing John

  16. Evaluation of the Lactate-to-N-Acetyl-aspartate Ratio Defined With Magnetic Resonance Spectroscopic Imaging Before Radiation Therapy as a New Predictive Marker of the Site of Relapse in Patients With Glioblastoma Multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Deviers, Alexandra [Département de Radiothérapie, Institut Claudius Regaud, Toulouse (France); UMR (Unité Mixte de Recherche) 825, Institut National de la Santé et de la Recherche Médicale, Toulouse (France); INP (Institut National Polytechnique), ENVT (Ecole Nationale Vétérinaire de Toulouse), Unité d' Anatomie-Imagerie-Embryologie, Université de Toulouse, Toulouse (France); Ken, Soléakhéna [Département de Radiothérapie, Institut Claudius Regaud, Toulouse (France); UMR (Unité Mixte de Recherche) 825, Institut National de la Santé et de la Recherche Médicale, Toulouse (France); Filleron, Thomas [Bureau des Etudes Cliniques, Institut Claudius Regaud, Toulouse (France); Rowland, Benjamin; Laruelo, Andrea [Département de Radiothérapie, Institut Claudius Regaud, Toulouse (France); Catalaa, Isabelle; Lubrano, Vincent [UMR (Unité Mixte de Recherche) 825, Institut National de la Santé et de la Recherche Médicale, Toulouse (France); Hôpital de Rangueil, CHU (Centre Hospitalier Universitaire) de Toulouse, Toulouse (France); Celsis, Pierre [UMR (Unité Mixte de Recherche) 825, Institut National de la Santé et de la Recherche Médicale, Toulouse (France); and others

    2014-10-01

    Purpose: Because lactate accumulation is considered a surrogate for hypoxia and tumor radiation resistance, we studied the spatial distribution of the lactate-to-N-acetyl-aspartate ratio (LNR) before radiation therapy (RT) with 3D proton magnetic resonance spectroscopic imaging (3D-{sup 1}H-MRSI) and assessed its impact on local tumor control in glioblastoma (GBM). Methods and Materials: Fourteen patients with newly diagnosed GBM included in a phase 2 chemoradiation therapy trial constituted our database. Magnetic resonance imaging (MRI) and MRSI data before RT were evaluated and correlated to MRI data at relapse. The optimal threshold for tumor-associated LNR was determined with receiver-operating-characteristic (ROC) curve analysis of the pre-RT LNR values and MRI characteristics of the tumor. This threshold was used to segment pre-RT normalized LNR maps. Two spatial analyses were performed: (1) a pre-RT volumetric comparison of abnormal LNR areas with regions of MRI-defined lesions and a choline (Cho)-to- N-acetyl-aspartate (NAA) ratio ≥2 (CNR2); and (2) a voxel-by-voxel spatial analysis of 4,186,185 voxels with the intention of evaluating whether pre-RT abnormal LNR areas were predictive of the site of local recurrence. Results: A LNR of ≥0.4 (LNR-0.4) discriminated between tumor-associated and normal LNR values with 88.8% sensitivity and 97.6% specificity. LNR-0.4 voxels were spatially different from those of MRI-defined lesions, representing 44% of contrast enhancement, 64% of central necrosis, and 26% of fluid-attenuated inversion recovery (FLAIR) abnormality volumes before RT. They extended beyond the overlap with CNR2 for most patients (median: 20 cm{sup 3}; range: 6-49 cm{sup 3}). LNR-0.4 voxels were significantly predictive of local recurrence, regarded as contrast enhancement at relapse: 71% of voxels with a LNR-0.4 before RT were contrast enhanced at relapse versus 10% of voxels with a normal LNR (P<.01). Conclusions: Pre-RT LNR-0.4 in GBM

  17. Adding cognitive therapy to dietetic treatment is associated with less relapse in obesity

    NARCIS (Netherlands)

    Werrij, Marieke Q.; Mulkens, Sandra; Elgersma, Hermien J.; Ament, Andre J. H. A.; Hospers, Hann J.; Jansen, Anita T. M.

    2009-01-01

    Objective: The treatment of obesity is universally disappointing; although usually some weight loss is reported directly after treatment, eventual relapse to, or even above, former body weight is common. In this study it is tested whether the addition of cognitive therapy to a standard dietetic

  18. American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group Consensus Conference on Salvage Hematopoietic Cell Transplantation in Patients with Relapsed Multiple Myeloma

    DEFF Research Database (Denmark)

    Giralt, Sergio; Garderet, Laurent; Durie, Brian

    2015-01-01

    convened a meeting of MM experts to: (1) summarize current knowledge regarding the role of autologous or allogeneic HCT in MM patients progressing after primary therapy, (2) propose guidelines for the use of salvage HCT in MM, (3) identify knowledge gaps, (4) propose a research agenda, and (5) develop...... a collaborative initiative to move the research agenda forward. After reviewing the available data, the expert committee came to the following consensus statement for salvage autologous HCT: (1) In transplantation-eligible patients relapsing after primary therapy that did NOT include an autologous HCT, high...... inhibitors; (5) Autologous HCT consolidation should be explored as a strategy to develop novel conditioning regimens or post-HCT strategies in patients with short (less than 18 months remissions) after primary therapy; and (6) Prospective randomized trials need to be performed to define the role of salvage...

  19. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... in RRMS; however, each person's experience with RRMS will be unique. Following a relapse, the new symptoms ... and worsening, you and your MS care provider will likely want to consider a more aggressive treatment ...

  20. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... course – is characterized by clearly defined attacks of new or increasing neurologic symptoms. These attacks – also called ... either active (with relapses and/or evidence of new MRI activity) or not active , as well as ...

  1. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... defined attacks of new or increasing neurologic symptoms. These attacks – also called relapses or exacerbations – are followed ... as well as the nerve fibers themselves. During these inflammatory attacks, activated immune cells cause small, localized ...

  2. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Treating MS Comprehensive Care Find an MS Care Provider Medications Managing Relapses Rehabilitation Complementary & Alternative Medicines For Clinicians Resources & Support Library & Education Programs Find Support Advanced Care ...

  3. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... without symptoms of which the person is aware. What happens in RRMS? Relapsing-remitting MS is defined ... a different mechanism of action in order to control the disease activity more effectively and help prevent ...

  4. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Rule Out For Clinicians Treating MS Comprehensive Care Find an MS Care Provider Medications Managing Relapses Rehabilitation ... Medicines For Clinicians Resources & Support Library & Education Programs Find Support Advanced Care Needs Resources for Specific Populations ...