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Sample records for acute relapse patients

  1. Relapsed/Refractory acute myeloid leukemia patients | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available Treatment of relapsed/refractory leukemia with intravenous administration of Dacarbazine Trattamento della leucemia...tment of relapsed/refractory leukemia with intravenous administration of Dacarbazine Trattamento della leucemia...on(s) being investigated Relapsed/Refractory acute myeloid leukemia patients Pazienti affetti da leucemia... language Relapsed/Refractory acute myeloid leukemia patients Pazienti affetti da leucemia acuta mieloide re...arbazina nei pazienti affetti da leucemia acuta mieloide recidivata/refrattaria i cui blasti esprimono bassi

  2. Acute myocardial/cerebral infarction as first/relapse manifestation in one acute promyelocytic leukemia patient.

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    Li, Ying; Suo, Shanshan; Mao, Liping; Wang, Lei; Yang, Chunmei; Xu, Weilai; Lou, Yinjun; Mai, Wenyuan

    2015-01-01

    In the clinical setting, bleeding is a common manifestation of acute promyelocytic leukemia (APL), whereas thrombosis is relatively rare, especially as an initial symptom. Here, we report an unusual case of APL with acute myocardial infarction as the first manifestation and cerebral infarction as the relapse manifestation in a healthy young woman. This unique case emphasizes that a thrombotic event could be the first manifestation of an underlying hematological disorder such as APL and could also be a sign of relapse. Rapid detection of the underlying disorder and the timely use of anticoagulation therapy and ATRA are crucial for preventing further deterioration of the disease and saving the patient's life.

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

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    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…

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

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    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…

  5. 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.

  6. UNUSUAL CLINICAL PRESENTATION OF RELAPSE IN PATIENT WITH ACUTE LYMPHOBLASTIC LEUKEMIA.

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    Vanya Slavcheva

    2015-04-01

    Full Text Available Acute lymphoblastic leukemia is a disease, which is more common in children. We report a clinical case of a patient aged 25. Thirty-two months before his last admission in Hematology clinic, acute pre- B lymphoblastic leukemia had been diagnosed and treated till March 2012. In September 2013 after bone marrow aspiration, flow cytometric analysis, trepan biopsy and biopsy of the kidney had been carried out, the patient was diagnosed with first late relapse, involving bone marrow and kidney. A second remission was achieved using Berlin- Frankfurt– Munster chemotherapy [BFM] and allogenic stem cell transplantation was performed.

  7. 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....

  8. Rhabdomyolysis Following Initiation of Posaconazole Use for Antifungal Prophylaxis in a Patient With Relapsed Acute Myeloid Leukemia

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    Mody, Mayur D.; Ravindranathan, Deepak; Gill, Harpaul S.; Kota, Vamsi K.

    2017-01-01

    Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia. PMID:28203579

  9. Rhabdomyolysis Following Initiation of Posaconazole Use for Antifungal Prophylaxis in a Patient With Relapsed Acute Myeloid Leukemia: A Case Report.

    Science.gov (United States)

    Mody, Mayur D; Ravindranathan, Deepak; Gill, Harpaul S; Kota, Vamsi K

    2017-01-01

    Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia.

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

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    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.

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

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    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.

  12. Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Acute Promyelocytic Leukemia

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    2016-07-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  13. 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.

  14. Effects of antipsychotics on insight in schizophrenia: results from independent samples of first-episode and acutely relapsed patients.

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    Misiak, Błażej; Frydecka, Dorota; Beszłej, Jan A; Moustafa, Ahmed A; Tybura, Piotr; Kucharska-Mazur, Jolanta; Samochowiec, Agnieszka; Bieńkowski, Przemysław; Samochowiec, Jerzy

    2016-07-01

    We aimed to investigate whether antipsychotics differentially impact insight and whether these effects appear because of improvement in psychopathological manifestation in 132 first-episode schizophrenia patients and 201 acutely relapsed schizophrenic patients, who were followed up for 12 weeks. Olanzapine and risperidone were administered to first-episode schizophrenia patients, whereas acutely relapsed schizophrenic patients were treated with olanzapine, perazine and ziprasidone. The Positive And Negative Syndrome Scale (PANSS) was used to assess psychopathology. Insight was assessed using the G12 item of PANSS. Unadjusted mixed-model regression analysis indicated a significant improvement in the PANSS G12 item score in both groups. There were no significant differences between distinct treatment subgroups of patients in terms of improvement in the PANSS G12 item score. After adjustment for the trajectories of changes in symptom dimensions, a decrease in the PANSS G12 item score was because of an improvement in positive, negative and excitement symptoms. A decrease in the PANSS G12 item score was also related to an increase in the severity of depressive symptomatology. Our results indicate that antipsychotics exert similar effects on insight in acute psychosis. These effects are likely because of an improvement in psychopathological manifestation. The improvement in insight might be related to the development of depressive symptoms.

  15. 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...

  16. Outcomes of patients with acute leukaemia who relapsed after reduced-intensity stem cell transplantation from HLA-identical or one antigen-mismatched related donors.

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    Kobayashi, Kazuhiko; Kami, Masahiro; Murashige, Naoko; Kusumi, Eiji; Kishi, Yukiko; Hamaki, Tamae; Hori, Akiko; Matsumura, Tomoko; Yuji, Koichiro; Masuo, Shigeru; Mori, Shinichiro; Miyakoshi, Shigesaburo; Tanosaki, Ryuji; Mitamura, Tadayuki; Takaue, Yoichi; Taniguchi, Shuichi

    2005-06-01

    The characteristics of relapse following reduced-intensity stem-cell transplantation (RIST) remain to be clarified. We reviewed the medical records of 19 patients with acute leukaemia [acute myeloid leukaemia (AML), 16; acute lymphoblastic leukaemia (ALL), 3] who relapsed after RIST from related donors using purine-analogue-based regimens. Their median age was 55 years (range, 29-65 years). Median interval between RIST and relapse was 4.9 months (range, 1.8-24.9 months). Three chose not to receive interventions. The remaining 16 patients received withdrawal of immunosuppression (n = 3), chemotherapy (n = 2), donor lymphocyte infusion (n = 10) and second transplantation (n = 7), alone (n = 9) or in combination (n = 7). Four are alive with a median follow-up of 27.6 months (range, 16.0-28.9 months); three in remission and one in relapse. The 2-year overall survival after relapse was 28.9%. Causes of death in 15 patients included progressive disease (n = 7), graft-versus-host disease (n = 5) and infections (n = 3). Cumulative incidences of relapse-related and non-relapse-related deaths at 2 years after relapse were 37% and 32% respectively. Two prognostic factors were identified on univariate analysis: age [P = 0.017; hazard ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.32], and ALL as underlying disease (P = 0.011; HR, 10.4; 95% CI, 1.73-62.4). Some AML patients who relapse after RIST achieve durable remission with allogeneic immunotherapy-based interventions; however they carry a significant risk of non-relapse mortality.

  17. Comparison of newly diagnosed and relapsed patients with acute promyelocytic leukemia treated with arsenic trioxide: insight into mechanisms of resistance.

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    Ezhilarasi Chendamarai

    Full Text Available There is limited data on the clinical, cellular and molecular changes in relapsed acute promyeloytic leukemia (RAPL in comparison with newly diagnosed cases (NAPL. We undertook a prospective study to compare NAPL and RAPL patients treated with arsenic trioxide (ATO based regimens. 98 NAPL and 28 RAPL were enrolled in this study. RAPL patients had a significantly lower WBC count and higher platelet count at diagnosis. IC bleeds was significantly lower in RAPL cases (P=0.022. The ability of malignant promyelocytes to concentrate ATO intracellularly and their in-vitro IC50 to ATO was not significantly different between the two groups. Targeted NGS revealed PML B2 domain mutations in 4 (15.38% of the RAPL subset and none were associated with secondary resistance to ATO. A microarray GEP revealed 1744 genes were 2 fold and above differentially expressed between the two groups. The most prominent differentially regulated pathways were cell adhesion (n=92, cell survival (n=50, immune regulation (n=74 and stem cell regulation (n=51. Consistent with the GEP data, immunophenotyping revealed significantly increased CD34 expression (P=0.001 in RAPL cases and there was in-vitro evidence of significant microenvironment mediated innate resistance (EM-DR to ATO. Resistance and relapse following treatment with ATO is probably multi-factorial, mutations in PML B2 domain while seen only in RAPL may not be the major clinically relevant cause of subsequent relapses. In RAPL additional factors such as expansion of the leukemia initiating compartment along with EM-DR may contribute significantly to relapse following treatment with ATO based regimens.

  18. Nivolumab and Dasatinib in Treating Patients With Relapsed or Refractory Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

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    2016-08-25

    B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  19. Heterogeneity in the therapeutic approach to relapsed elderly patients with acute myeloid leukaemia: a survey from the Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) Acute Leukaemia Working Party.

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    Ferrara, Felicetto; Fazi, Paola; Venditti, Adriano; Pagano, Livio; Amadori, Sergio; Mandelli, Franco

    2008-06-01

    The percentage of long-term survivors in acute myeloid leukaemia (AML) in the elderly does not exceed 10-15% of patients enrolled into clinical trials because of lower complete remission (CR) rates and higher incidence of relapse. However, few data are available as the treatment of elderly patients with relapsed disease is concerned. The aim of this study was of collecting data on criteria adopted for the treatment of these patients. A questionnaire was e-mailed to 32 haematologic institutions involved in the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) group. Questions to be addressed regarded: (1) per cent of relapsed elderly patients treated with aggressive salvage chemotherapy; (2) the selection criteria adopted for inclusion into intensive reinduction; (3) the specific treatment adopted; (4) the treatment given to patients not eligible for intensive salvage. Per cent of patients enrolled into aggressive salvage regimens varied from 10 to 80% (median 50%). The most frequent factor influencing the therapeutic choice was performance status (97%). Additional factors were age >70 years (44%) and duration of first CR (53%). Fludarabine including regimens were most frequently used as aggressive salvage therapy (59%), while gemtuzumab ozogamicin was adopted in various combinations at 11 out of 32 institutions (34%). For patients not eligible to aggressive therapy, the most frequent approach included hydroxyurea (59%). Low dose ARA-C (LDARA-C) was adopted at five centres: as single agent (n = 1), with 6-thioguanine (n = 1), with vitamin D3 and all-trans retinoic acid (ATRA) (n = 2), or with ATRA alone (n = 1). The FLT3 inhibitor CEP-701 was used at one centre. We conclude that the treatment of AML in elderly relapsed patients is extremely heterogeneous. A marked selection is operated as to inclusion into aggressive salvage regimens and only a small minority of patients are offered experimental approaches.

  20. Ipilimumab and Decitabine in Treating Patients With Relapsed or Refractory Myelodysplastic Syndrome or Acute Myeloid Leukemia

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    2016-09-12

    Chimerism; Hematopoietic Cell Transplantation Recipient; Previously Treated Myelodysplastic Syndrome; RAEB-1; RAEB-2; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. Clofarabine, Cytarabine, and G-CSF in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

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    2015-05-05

    Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  2. Romidepsin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

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    2015-12-03

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  3. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-10-04

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  4. Decitabine, Vorinostat, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

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    2014-12-19

    Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  5. PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome

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    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

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

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    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.

  7. A Unique Case of Relapsing Polychondritis Presenting with Acute Pericarditis

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    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.

  8. Population pharmacokinetics and pharmacokinetics/pharmacodynamics of bendamustine in pediatric patients with relapsed/refractory acute leukemia.

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    Darwish, Mona; Megason, Gail; Bond, Mary; Hellriegel, Edward; Robertson, Philmore; Grasela, Thaddeus; Phillips, Luann

    2014-11-01

    The pharmacokinetic (PK) profile of bendamustine has been characterized in adults with indolent non-Hodgkin lymphoma (NHL), but remains to be elucidated in pediatric patients with hematologic malignancies. This analysis used data from a nonrandomized pediatric study in patients with relapsed/refractory acute lymphocytic leukemia or acute myeloid leukemia. Bendamustine 90 or 120 mg/m(2) (60-minute infusion) was administered on days 1 and 2 of 21 day cycles. The population PK base model was adjusted for body surface area (BSA), and the appropriateness of the final model was evaluated by visual predictive check. A covariate analysis explored PK variability. Bayesian PK parameter estimates and concentration-time profiles for each patient were generated. Bendamustine PK in pediatric patients was compared with that of adults with indolent NHL. PK/pharmacodynamic analyses were conducted for fatigue, nausea, vomiting, and infection. Thirty-eight patients (median age: 7 years; range: 1-19 years) receiving bendamustine 120 mg/m(2) and an additional five patients receiving bendamustine 90 mg/m(2) (median age: 12 years; range: 8-14 years) were included in the population PK analysis. Peak plasma concentrations of bendamustine (Cmax) occurred at the end of infusion (about 1 h). Decline from peak showed a rapid distribution phase (t½α = 0.308 h) and a slower elimination phase (t½β = 1.47 h). Model-predicted mean Cmax and area under the curve values from time 0-24 h were 6806 ng/mL and 8240 ng*h/mL, respectively. When dosed based upon BSA, it appeared that age, body weight, race, mild renal (n = 3) or hepatic (n = 2) dysfunction, cancer type, and cytochrome P450 1A2 inhibitors (n = 17) or inducers (n = 3) did not affect systemic exposure, which was comparable between pediatric and adult patients. Infection was the only adverse event associated with bendamustine Cmax. However, due to the small sample size for some subgroups, the

  9. Evaluating frequency of PML-RARA mutations and conferring resistance to arsenic trioxide-based therapy in relapsed acute promyelocytic leukemia patients.

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    Lou, Yinjun; Ma, Yafang; Sun, Jianai; Ye, Xiujin; Pan, Hanzhang; Wang, Yungui; Qian, Wenbin; Meng, Haitao; Mai, Wenyuan; He, JingSong; Tong, Hongyan; Jin, Jie

    2015-11-01

    The aim of the study is to better understand the mechanism of relapse and acquired clinical resistance to arsenic trioxide (ATO) and/or all-trans retinoic acid (ATRA). Thirty relapsed acute promyelocytic leukemia (APL) patients were followed. Fifteen patients experienced two or more relapses; nine patients had clinical resistance to ATO-based therapy. The frequency and clinical significance of promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARA) mutational status using Sanger sequencing were evaluated. Overall, eight different types of mutations in the RARA region (V218D, R272Q, T278A, T291I, N299D, R294W, A300G, and L220_F228delinsP) were identified in 11 patients. Eight missense mutations (L211P, C213R, S214L, A216V, L217F, D219H, S221G, and D241G) were found in the PML portion of PML-RARA in 14 patients, with A216V as the predominant mutation. Eight patients were found to harbor both PML and RARA mutations over the course of the disease. The PML-region mutations were associated with response to ATO-based therapy (P < 0.0001), number of relapses (P = 0.001), and early relapse (P = 0.013). Notably, one case sampled at nine different time points showed alternating clonal dominance over the course of treatment. This study demonstrated frequent mutations of PML-RARA and supported a clonal selection model in relation to APL relapse and ATO resistance.

  10. Genomic profiling of thousands of candidate polymorphisms predicts risk of relapse in 778 Danish and German childhood acute lymphoblastic leukemia patients.

    Science.gov (United States)

    Wesołowska-Andersen, A; Borst, L; Dalgaard, M D; Yadav, R; Rasmussen, K K; Wehner, P S; Rasmussen, M; Ørntoft, T F; Nordentoft, I; Koehler, R; Bartram, C R; Schrappe, M; Sicheritz-Ponten, T; Gautier, L; Marquart, H; Madsen, H O; Brunak, S; Stanulla, M; Gupta, R; Schmiegelow, K

    2015-02-01

    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 single-nucleotide polymorphisms (SNPs) to identify host genome profiles associated with relapse risk in 352 patients from the Nordic ALL92/2000 protocols and 426 patients from the German Berlin-Frankfurt-Munster (BFM) ALL2000 protocol. Patients were enrolled between 1992 and 2008 (median follow-up: 7.6 years). Eleven cross-validated SNPs were significantly 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 ranged from 4% (95% confidence interval (CI): 1.6-6.3%) for the best group (72% of patients) to 76% (95% CI: 41-90%) for the worst group (5% of patients, Prisk-based treatments adaptation.

  11. T-cell receptor excision circle levels after allogeneic stem cell transplantation are predictive of relapse in patients with acute myeloid leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Uzunel, Mehmet; Sairafi, Darius; Remberger, Mats; Mattsson, Jonas; Uhlin, Michael

    2014-07-15

    In this retrospective study, 209 patients with malignant disease were analyzed for levels of T-cell receptor excision circles (TRECs) for the first 24 months after allogeneic stem cell transplantation. CD3(+) cells were separated by direct antibody-coupled magnetic beads, followed by DNA extraction according to a standard protocol. The δRec-ψJα signal joint TREC was measured with real-time quantitative PCR. Patients were grouped based on malignant disease: chronic myeloid leukemia, chronic lymphatic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and myelodysplastic syndrome (MDS). Patients were further subdivided based on TREC levels below (low-TREC) or above (high-TREC) median at each time point. TREC levels were then correlated to relapse incidence and relapse-free survival (RFS). For patients with AML, low TREC levels 2 months post-transplantation were correlated to high relapse incidence at 5 years (Pleukemia, high TREC levels were correlated with improved RFS (Pafter allogeneic hematopoietic stem cell transplantation.

  12. 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.

  13. Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse

    Science.gov (United States)

    Riccheri, María C.; Nuñez, Myriam; Alfonso, Graciela; Gueron, Geraldine; De Siervi, Adriana; Vazquez, Elba; Cotignola, Javier

    2017-01-01

    The inclusion of genotype at Acute Lymphoblastic Leukemia (ALL) diagnosis as a genetic predictor of disease outcome is under constant study. However, results are inconclusive and seem to be population specific. We analyzed the predictive value of germline polymorphisms for childhood ALL relapse and survival. We retrospectively recruited 140 Argentine patients with de novo ALL. Genotypes were analyzed using PCR-RFLP (GSTP1 c.313A > G, MDR1 c.3435T > C, and MTHFR c.665C > T) and multiplex PCR (GSTT1 null, GSTM1 null). Patients with the GSTP1 c.313GG genotype had an increased risk for relapse in univariate (OR = 2.65, 95% CI = 1.03–6.82, p = 0.04) and multivariate (OR = 3.22, 95% CI = 1.17–8.83, p = 0.02) models. The combined genotype slightly increased risk for relapse in the univariate (OR = 2.82, 95% CI = 1.09–7.32, p = 0.03) and multivariate (OR = 2.98, 95% CI = 1.14–7.79, p = 0.03) models for patients with 2/3-risk-genotypes (GSTT1 null, GSTM1 null, GSTP1 c.313GG). The Recurrence-Free Survival (RFS) was shorter for GSTP1 c.313GG (p = 0.025) and 2/3-risk-genotypes (p = 0.021). GST polymorphisms increased the risk of relapse and RFS of patients with childhood ALL. The inclusion of these genetic markers in ALL treatment protocols might improve risk stratification and reduce the number of relapses and deaths. PMID:27058755

  14. High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

    Science.gov (United States)

    2016-11-14

    Acute Leukemia of Ambiguous Lineage; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  15. Therapy-induced secondary acute myeloid leukemia with t(11;19)(q23;p13.1) in a pediatric patient with relapsed acute promyelocytic leukemia.

    Science.gov (United States)

    Dang, Daniel N; Morris, Heather D; Feusner, James H; Koduru, Prasad; Wilson, Kathleen; Timmons, Charles F; Cavalier, MaryEllen; Luu, Hung S

    2014-11-01

    Acute myeloid leukemia is classified based upon recurrent cytogenetic abnormalities. The t(15;17)(q24.1;q21.1) abnormality is found in 5% to 8% of de novo acute myeloid leukemia and is diagnostic of acute promyelocytic leukemia (APL). The translocation results in fusion of the retinoic acid receptor-α (RARA) gene at 17q21.1 and the promyelocytic leukemia (PML) gene at 15q24.1. Standard APL therapy is a combination of all-trans retinoic acid and anthracycline-based chemotherapy. Anthracycline treatment is associated with secondary clonal chromosomal aberrations that can lead to therapy-related secondary myeloid neoplasms. We present a pediatric case of relapsed APL coexistent with treatment-associated secondary myeloid neoplasm with t(11;19)(q23;p13.1).

  16. Phase 1 and Extension Study of Clofarabine plus Cyclophosphamide in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

    Science.gov (United States)

    Faderl, S; Balakrishnan, K; Thomas, DA; Ravandi, F; Borthakur, G; Burger, J; Ferrajoli, A; Cortes, J; O’Brien, S; Kadia, T; Feliu, J; Plunkett, W; Gandhi, V; Kantarjian, HM

    2014-01-01

    Background Clofarabine is a nucleoside analog with activity in children with ALL. Based on the hypothesis that clofarabine inhibits DNA repair following exposure to DNA damaging agents, we designed a phase 1 and extension study to evaluate the combination of clofarabine with cyclophosphamide in adult patients with relapsed/refractory ALL. Methods The continual reassessment method (CRM) was used to define the maximum tolerated dose (MTD). Results Fifty patients with a median age of 30 years (range 21–72 years) were enrolled of whom 30 patients were part of the phase 1 group. Clofarabine 40 mg/m2 iv daily x 3 days and cyclophosphamide 200 mg/m2 iv q 12 hours x 3 days were established as the MTD. Dose limiting toxicities were diarrhea, transaminase elevations, and skin rashes. The response rate of the whole study group was 14% including 10% of patients who achieved complete remission (CR) or CR without platelet recovery. Three responses occurred in patients with primary refractory disease. Early mortality (< 30 days) was 6%. The median response duration was 69 days (range 5–315 days). Median overall survival was about 3 months. Compared to day 1 (cyclophosphamide alone), H2AX phosphorylation was increased on day 2 when clofarabine and cyclophosphamide were administered as a couplet (n = 8). Conclusions The combination of clofarabine plus cyclophosphamide at the doses used in this study and in a group of heavily pretreated patients with ALL is only moderately effective. Other doses, alternative schedules, or a more favorable patient population may achieve better results. (Word count: 248) PMID:24440659

  17. Decitabine, Donor Natural Killer Cells, and Aldesleukin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-01-07

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  18. 7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

    Science.gov (United States)

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasms; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  19. [A relapse of multiple sclerosis manifesting as acute delirium].

    Science.gov (United States)

    Castellanos-Pinedo, F; Galindo, R; Adeva-Bartolomé, M T; Zurdo, M

    2004-01-01

    Psychotic symptoms are infrequent in multiple sclerosis (MS) and their relationship to cerebral lesions has not been clearly documented. The case of a 58 year old woman with secondary progressive MS is presented. She had acute delirium with persecutory delusions associated to paresis of her left leg. Magnetic resonance imaging of the brain disclosed an active lesion in the left hippocampus. The patient was treated with risperidone and megadoses of methylprednisolone, with dramatic improvement. Clinical and radiological data in this patient suggest that psychotic disorders can be symptomatic of a relapse in MS and, therefore, susceptible to be treated with steroids.

  20. Decitabine Followed by Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes

    Science.gov (United States)

    2013-10-09

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts

  1. 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.

    2016-01-01

    Summary Background Safe and effective treatments are urgently needed for patients with relapsed/refractory acute myeloid leukaemia (AML). We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed/refractory AML. Methods VALOR was a phase 3, double-blind, placebo-controlled trial conducted at 101 international sites. Patients were randomised 1:1 to vosaroxin (90 mg/m2 IV days 1,4) plus cytarabine (1 g/m2 IV days 1–5) (vos/cyt) or placebo plus cytarabine (pla/cyt) using a permuted block procedure stratified by disease status, age, and geographic location. All participants were blind to treatment assignment. Primary endpoints were overall survival (OS) and 30- and 60-day mortality. Efficacy analyses were by intention-to-treat; safety analyses included all treated patients. This study is registered at clinicaltrials.gov (NCT01191801). Findings Between December 2010 and September 2013, 711 patients were randomised to vos/cyt (n=356) or pla/cyt (n=355). Median OS was 7·5 months with vos/cyt and 6·1 months with pla/cyt (hazard ratio 0·87; unstratified log-rank p=0·061; stratified p=0·0241) and was supported by a sensitivity analysis censoring for subsequent transplant (6·7 and 5·3 months; p=0·0243). Complete remission (CR) rate was higher with vos/cyt vs pla/cyt (30·1% vs 16·3%, p<0·0001). Early mortality rates were equivalent (vos/cyt vs pla/cyt: 30-day, 7·9% vs 6·6%; 60-day, 19·7% vs 19·4%). Treatment-related deaths occurred at any time in 18 patients (5·1%) with vos/cyt and 8 (2·3%) with pla/cyt. Grade ≥3 adverse events more frequent with vos/cyt included febrile neutropenia (167/355 [47%] vs 117/350 [33%]), stomatitis (54 [15%] vs 10 [3%]), hypokalaemia (52 [15%] vs 21 [6%]), sepsis (42 [12%] vs 18 [5%]), and pneumonia (39 [11%] vs 26 [7%]). Interpretation Addition of vosaroxin to cytarabine prolonged survival in patients with relapsed/refractory AML

  2. Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase Chronic Myelogenous Leukemia

    Science.gov (United States)

    2015-04-27

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  3. Vorinostat, Cytarabine, and Etoposide in Treating Patients With Relapsed and/or Refractory Acute Leukemia or Myelodysplastic Syndromes or Myeloproliferative Disorders

    Science.gov (United States)

    2013-05-01

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  4. 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

    genome profiles associated with relapse risk in 352 patients from the Nordic ALL92/2000 protocols and 426 patients from the German Berlin–Frankfurt–Munster (BFM) ALL2000 protocol. Patients were enrolled between 1992 and 2008 (median follow-up: 7.6 years). Eleven cross-validated SNPs were significantly...... 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...

  5. Azacitidine in Combination With Mitoxantrone, Etoposide Phosphate, and Cytarabine in Treating Patients With Relapsed and Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-12-19

    Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Promyelocytic Leukemia With PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia

  6. Testicular relapse in childhood acute lymphoblastic leukemia: The challenges and lessons

    Directory of Open Access Journals (Sweden)

    K P Kulkarni

    2010-01-01

    Full Text Available Background : Relapse of disease is documented in 15-20% of children with acute lymphoblastic leukemia (ALL. Although testicular relapse is rare with modern risk-adapted treatment protocols, earlier, the testes were a frequently encountered site of relapse and were designated as "drug sanctuaries". Purpose : This descriptive study was designed to assess the pattern of testicular relapse and to identify high-risk factors. Materials and Methods : Data obtained from case records of 407 boys with ALL were analyzed. Fine needle aspiration cytology was carried out in children presenting with painless enlargement of testi(es. Bone marrow aspiration and cerebrospinal fluid examination were performed concomitantly to confirm or exclude disease at these sites. Results : Testicular relapse was documented in 30 boys. It was isolated in 17 patients and associated with bone marrow and/or central nervous system relapse in 13. At relapse, nine boys were over the age of 10 years. The majority were very early and early relapsers. Hyperleucocytosis was documented in five of 30 and seven of 137 relapsers and nonrelapsers, respectively (P = 0.04. Twelve of the 30 boys with testicular relapse were treated with testicular irradiation, reinduction and maintenance therapy. The estimated median overall survival was 33 months. Conclusion : Testicular relapse, which depends on the therapy administered, may manifest several months/years after completion of treatment. The high incidence of testicular relapse in our series implicates the need of revaluation of our protocol and incorporation of high/intermediate dose methotrexate therapy upfront.

  7. Phase II Study of Bortezomib as a Single Agent in Patients with Previously Untreated or Relapsed/Refractory Acute Myeloid Leukemia Ineligible for Intensive Therapy

    Directory of Open Access Journals (Sweden)

    Chiara Sarlo

    2013-01-01

    Full Text Available We explored the safety and efficacy of bortezomib given as single agent in patients with untreated or relapsed/refractory acute myeloid leukemia (AML, unfit for conventional chemotherapy. Fourteen patients were treated with bortezomib 1.5 mg/m2 administered twice weekly for two weeks, every 3 weeks. Median age was 70 years (range 60–81 and the median number of cycles delivered was 2 (range 1–4. Of 13 evaluable patients, in 8 (61%, the administration of bortezomib resulted in an antileukemic effect as demonstrated by peripheral blood and/or bone marrow blast reduction. In 4 (50% of these 8, a decrease by 37% of transfusion requirement was also observed . Overall median survival was 4 months (range 0.25–10. Neurotoxicity was the most frequent adverse event with 7 of 13 (54% patients experiencing grades 3-4 peripheral neuropathy. Neurotoxicity led to treatment discontinuation in 4 (57% of 7. In conclusion, the observed anti-leukemic activity of bortezomib indicates that there is room for designing additional studies in which combination with other chemotherapeutic agents should be considered. Clinical registration no.: EUDRACT 2006-006923-38.

  8. Molecular monitoring of minimal residual disease in two patients with MLL-rearranged acute myeloid leukemia and haploidentical transplantation after relapse

    Directory of Open Access Journals (Sweden)

    Burmeister Thomas

    2012-04-01

    Full Text Available Abstract This report describes the clinical courses of two acute myeloid leukemia patients. Both had MLL translocations, the first a t(10;11(p11.2;q23 with MLL-AF10 and the second a t(11;19(q23;p13.1 with MLL-ELL fusion. They achieved a clinical remission under conventional chemotherapy but relapsed shortly after end of therapy. Both had a history of invasive mycoses (one had possible pulmonary mycosis, one systemic candidiasis. Because no HLA-identical donor was available, a haploidentical transplantation was performed in both cases. Using a specially designed PCR method for the assessment of minimal residual disease (MRD, based on the quantitative detection of the individual chromosomal breakpoint in the MLL gene, both patients achieved complete and persistent molecular remission after transplantation. The immune reconstitution after transplantation is described in terms of total CD3+/CD4+, CD3+/CD8+, CD19+, and CD16+/CD56+ cell numbers over time. The KIR and HLA genotypes of donors and recipients are reported and the possibility of a KIR-mediated alloreactivity is discussed. This report illustrates that haploidentical transplantation may offer a chance of cure without chronic graft-versus-host disease in situations where no suitable HLA-identical donor is available even in a high-risk setting and shows the value of MRD monitoring in the pre- and posttransplant setting.

  9. Relapsing steroid-responsive idiopathic acute interstitial nephritis.

    Science.gov (United States)

    Enriquez, R; Gonzalez, C; Cabezuelo, J B; Lacueva, J; Ruiz, J A; Tovar, J V; Niembro, E

    1993-01-01

    A 49-year-old woman developed acute renal failure secondary to interstitial nephritis. Her clinical history, complementary studies and two renal biopsies could not establish the etiology. She showed signs of incomplete Fanconi syndrome. Treatment with corticosteroids was very effective, though she tended to relapse. We comment briefly on some aspects of idiopathic acute interstitial nephritis.

  10. Extramedullary Relapse of Acute Myeloid and Lymphoid Leukemia in Children: A Retrospective Analysis

    Directory of Open Access Journals (Sweden)

    Jee Young Kim

    2016-05-01

    Full Text Available Background Extramedullary relapse (EMR is a recurrence of leukemia in sites other than the bone marrow, and it exhibits a relatively rare presentation of relapse of acute leukemia. However, EMR is an important cause of treatment failure among patients with acute leukemia. Therefore, early detection of these relapses may improve the prognosis. Objectives To describe the disease-related demographic and clinical features and radiologic findings for children diagnosed with EMR in acute leukemia. Patients and Methods The study was based on 22 children (M: F = 14: 8; mean age 7.30 (2.1 - 15.7 years with 8 acute myeloid leukemia (AML and 14 acute lymphoid leukemia (ALL who had experienced an EMR. Age, gender, clinical symptoms, initial extramedullary disease (EMD, French-American-British (FAB morphology, cytogenetics, time to and site of EMR, concurrent bone marrow relapse (BMR, radiologic findings, and outcomes were evaluated. Results No definite relationship was found between initial EMD and EMR. A predilection for AML to relapse in the central nervous system (CNS, except for the CSF and bone, and for ALL to relapse in the CSF and kidney seemed to occur. Patients with EMR had a significantly higher incidence of t(8: 21 cytogenetics and FAB M2 and L1 morphologies. EMR accompanied with concurrent BMR occurred in 31.8% of the patients, who exhibited a relatively grave clinical course. Radiologic findings were nonspecific and had a great variety of structure involved, including bulging enhancing mass in the CT scan, hypoechoic mass in the US, and enhanced mass-like lesion in the MRI. Conclusions Knowledge of the potential sites of EMR, their risk factors, and their clinical and radiologic features may be helpful in the early diagnosis of relapse and planning for therapy.

  11. Complete Hematologic and Molecular Response in Adult Patients With Relapsed/Refractory Philadelphia Chromosome-Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multicenter Study.

    Science.gov (United States)

    Martinelli, Giovanni; Boissel, Nicolas; Chevallier, Patrice; Ottmann, Oliver; Gökbuget, Nicola; Topp, Max S; Fielding, Adele K; Rambaldi, Alessandro; Ritchie, Ellen K; Papayannidis, Cristina; Sterling, Lulu Ren; Benjamin, Jonathan; Stein, Anthony

    2017-06-01

    Purpose Few therapeutic options are available for patients with Philadelphia chromosome-positive (Ph(+)) B-precursor acute lymphoblastic leukemia (ALL) who progress after failure of tyrosine kinase inhibitor (TKI) -based therapy. Here, we evaluated the efficacy and tolerability of blinatumomab in patients with relapsed or refractory Ph(+) ALL. Patients and Methods This open-label phase II study enrolled adults with Ph(+) ALL who had relapsed after or were refractory to at least one second-generation or later TKI or were intolerant to second-generation or later TKIs and intolerant or refractory to imatinib. Blinatumomab was administered in 28-day cycles by continuous intravenous infusion. The primary end point was complete remission (CR) or CR with partial hematologic recovery (CRh) during the first two cycles. Major secondary end points included minimal residual disease response, rate of allogeneic hematopoietic stem-cell transplantation, relapse-free survival, overall survival, and adverse events (AEs). Results Of 45 patients, 16 (36%; 95% CI, 22% to 51%) achieved CR/CRh during the first two cycles, including four of 10 patients with the T315I mutation; 88% of CR/CRh responders achieved a complete minimal residual disease response. Seven responders (44%) proceeded to allogeneic hematopoietic stem-cell transplantation, including 55% (six of 11) of transplantation-naïve responders. Median relapse-free survival and overall survival were 6.7 and 7.1 months, respectively. The most frequent AEs were pyrexia (58%), febrile neutropenia (40%), and headache (31%). Three patients had cytokine release syndrome (all grade 1 or 2), and three patients had grade 3 neurologic events, one of which (aphasia) required temporary treatment interruption. There were no grade 4 or 5 neurologic events. Conclusion Single-agent blinatumomab showed antileukemia activity in high-risk patients with Ph(+) ALL who had relapsed or were refractory to TKIs. AEs were consistent with previous

  12. High WT1 expression is an early predictor for relapse in patients with acute promyelocytic leukemia in first remission with negative PML-RARa after anthracycline-based chemotherapy: a single-center cohort study

    Directory of Open Access Journals (Sweden)

    Jae-Ho Yoon

    2017-01-01

    Full Text Available Abstract Wilms’ tumor gene 1 (WT1 expression is a well-known predictor for relapse in acute myeloid leukemia. We monitored WT1 decrement along the treatment course to identify its significant role as a marker for residual disease in acute promyelocytic leukemia (APL and tried to suggest its significance for relapse prediction. In this single center retrospective study, we serially measured PML-RARa and WT1 expression from 117 APL patients at diagnosis, at post-induction and post-consolidation chemotherapies, and at every 3 months after starting maintenance therapy. All 117 patients were in molecular remission after treatment of at least 2 consolidation chemotherapies. We used WT1 ProfileQuant™ kit (Ipsogen for WT1 monitoring. High WT1 expression (>120 copies/104 ABL1 after consolidation and at early period (3 months after maintenance therapy significantly predicted subsequent relapse. All paired PML-RARa RQ-PCR were not detected except for one sample with early relapse. Patients with high WT1 expression at 3 months after maintenance therapy (n = 40 showed a significantly higher relapse rate (30.5 vs. 6.9%, P < 0.001 and inferior disease free survival (62.8 vs. 91.4%, P < 0.001. Multivariate analysis revealed that high peak leukocyte counts at diagnosis (HR = 6.4, P < 0.001 and high WT1 expression at 3 months after maintenance therapy (HR = 7.1, P < 0.001 were significant factors for prediction of relapse. Our data showed high post-remission WT1 expression was a reliable marker for prediction of subsequent molecular relapse in APL. In this high-risk group, early intervention with ATRA ± ATO, anti-CD33 antibody therapy, and WT1-specific therapy may be used for relapse prevention. Trial registration Clinical Research Information Service (CRIS, KCT0002079

  13. Cardiac Relapse of Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Sánchez-Quintana, Ana; Quijada-Fumero, Alejandro; Laynez-Carnicero, Ana; Breña-Atienza, Joaquín; Poncela-Mireles, Francisco J.; Llanos-Gómez, Juan M.; Cabello-Rodríguez, Ana I.; Ramos-López, María

    2016-01-01

    Secondary or metastatic cardiac tumors are much more common than primary benign or malignant cardiac tumors. Any tumor can cause myocardial or pericardial metastasis, although isolated or combined tumor invasion of the pericardium is more common. Types of neoplasia with the highest rates of cardiac or pericardial involvement are melanoma, lung cancer, and breast and mediastinal carcinomas. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Initial treatment involves chemotherapy followed by consolidation treatment to reduce the risk of relapse. In high-risk patients, the treatment of choice for consolidation is hematopoietic stem cell transplantation (HSCT). Relapse of AML is the most common cause of HSCT failure. Extramedullary relapse is rare. The organs most frequently affected, called “sanctuaries,” are the testes, ovaries, and central nervous system. We present a case with extramedullary relapse in the form of a solid cardiac mass. PMID:27642531

  14. Adult patients with relapsed and/or refractory B-precursor Acute lymphoblastic leukaemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available alutare l’efficacia dell’anticorpo BiTE® blinatumomab rispetto alla chemioterapia standard in soggetti adulti affetti da leucemia...rispetto alla chemioterapia standard, in soggetti adulti con leucemia linfoblastica acuta che non hanno risp... with relapsed and/or refractory B-precursor Acute lymphoblastic leukaemia Soggetti adulti affetti da leucemia...esponding to therapy Pazienti adulti con leucemia linfoblastica acuta - un tumore del sangue e midollo - che...alattia- Neoplasia prostatica intraepiteliale senza evidenza di tumore alla prostata .2 . diagnosi di leucemia

  15. Kinase domain mutations of BCR-ABL frequently precede imatinib-based therapy and give rise to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL).

    Science.gov (United States)

    Pfeifer, Heike; Wassmann, Barbara; Pavlova, Anna; Wunderle, Lydia; Oldenburg, Johannes; Binckebanck, Anja; Lange, Thoralf; Hochhaus, Andreas; Wystub, Silvia; Brück, Patrick; Hoelzer, Dieter; Ottmann, Oliver G

    2007-07-15

    Acquired imatinib resistance in advanced Philadelphia-positive acute lymphoblastic leukemia (Ph(+) ALL) has been associated with mutations in the kinase domain (KD) of BCR-ABL. We examined the prevalence of KD mutations in newly diagnosed and imatinib-naive Ph(+) ALL patients and assessed their clinical relevance in the setting of uniform frontline therapy with imatinib in combination with chemotherapy. Patients enrolled in the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia (GMALL) trial ADE10 for newly diagnosed elderly Ph(+) ALL were retrospectively examined for the presence of BCR-ABL KD mutations by denaturing high-performance liquid chromatography (D-HPLC), cDNA sequencing, and allele-specific polymerase chain reaction (PCR). A KD mutation was detected in a minor subpopulation of leukemic cells in 40% of newly diagnosed and imatinib-naive patients. At relapse, the dominant cell clone harbored an identical mutation in 90% of cases, the overall prevalence of mutations at relapse was 80%. P-loop mutations predominated and were not associated with an inferior hematologic or molecular remission rate or shorter remission duration compared with unmutated BCR-ABL. BCR-ABL mutations conferring high-level imatinib resistance are present in a substantial proportion of patients with de novo Ph(+) ALL and eventually give rise to relapse. This provides a rationale for the frontline use of kinase inhibitors active against these BCR-ABL mutants.

  16. Treatment of refractory/relapsed adult acute lymphoblastic leukemia with bortezomib- based chemotherapy

    Directory of Open Access Journals (Sweden)

    Zhao J

    2015-06-01

    Full Text Available Junmei Zhao,* Chao Wang,* Yongping Song, Yuzhang Liu, Baijun FangHenan Key Lab of Experimental Haematology, Henan Institute of Haematology, Henan Tumor Hospital, Zhengzhou University, Zhengzhou, People’s Republic of China  *These authors contributed equally to this work Abstract: Nine pretreated patients aged >19 years with relapsed/refractory acute lymphoblastic leukemia (ALL were treated with a combination of bortezomib plus chemotherapy before allogeneic hematopoietic stem cell transplantation (allo-HSCT. Eight (88.9% patients, including two Philadelphia chromosome-positive ALL patients, achieved a complete remission. Furthermore, the evaluable patients have benefited from allo-HSCT after response to this reinduction treatment. We conclude that bortezomib-based chemotherapy was highly effective for adults with refractory/relapsed ALL before allo-HSCT. Therefore, this regimen deserves a larger series within prospective trials to confirm these results. Keywords: acute lymphoblastic leukemia, refractory, relapsed, bortezomib

  17. Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

    Science.gov (United States)

    2014-08-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Secondary Acute Myeloid Leukemia; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma

  18. 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

  19. Relapse of acute lymphoblastic leukemia in the pancreas after bone marrow transplant

    Institute of Scientific and Technical Information of China (English)

    Guang-Xian Wang; Jun-Lin Liao; Dong Zhang; Li Wen

    2015-01-01

    Background: Relapse of acute lymphoblastic leukemia (ALL) in the pancreas is rare. We report a case of a 12-year-old boy who experienced a relapse of ALL in the pancreas after a bone marrow transplant. Methods: Clinical data, including course of illness, laboratory results, and imaging studies are included. The patient presented with acute pancreatitis, suspected to be secondary to gallstones, with ampullary obstruction. Ultrasound and magnetic resonance imaging demonstrated a distended gallbladder and intra- and extra-hepatic biliary dilatation with a cutoff at the pancreatic head, but with no evidence of gallstones. Results: Ultrasound-guided biopsy of the pancreas revealed ALL in the pancreas. Systematic chemotherapy was recommended, but was declined by the parents. The patient died one week later. Conclusion: Relapse of ALL in the pancreas is rare, but when a history of ALL is present, it should be considered in patients with pancreatic enlargement, obstructive jaundice, and pancreatitis.

  20. Relapse of acute lymphoblastic leukemia in the pancreas after bone marrow transplant.

    Science.gov (United States)

    Wang, Guang-Xian; Liao, Jun-Lin; Zhang, Dong; Wen, Li

    2015-11-01

    Relapse of acute lymphoblastic leukemia (ALL) in the pancreas is rare. We report a case of a 12-year-old boy who experienced a relapse of ALL in the pancreas after a bone marrow transplant. Clinical data, including course of illness, laboratory results, and imaging studies are included. The patient presented with acute pancreatitis, suspected to be secondary to gallstones, with ampullary obstruction. Ultrasound and magnetic resonance imaging demonstrated a distended gallbladder and intra- and extra-hepatic biliary dilatation with a cutoff at the pancreatic head, but with no evidence of gallstones. Ultrasound-guided biopsy of the pancreas revealed ALL in the pancreas. Systematic chemotherapy was recommended, but was declined by the parents. The patient died one week later. Relapse of ALL in the pancreas is rare, but when a history of ALL is present, it should be considered in patients with pancreatic enlargement, obstructive jaundice, and pancreatitis.

  1. RALLE pilot: response-guided therapy for marrow relapse in acute lymphoblastic leukemia in children.

    Science.gov (United States)

    Saarinen-Pihkala, Ulla M; Parto, Katriina; Riikonen, Pekka; Lähteenmäki, Päivi M; Békàssy, Albert N; Glomstein, Anders; Möttönen, Merja

    2012-05-01

    Despite improved treatment results of childhood acute lymphoblastic leukemia (ALL), 20% to 30% have a relapse, and then the outcome is very poor. We studied 40 children with ALL marrow relapse piloting an ALL relapse protocol with well-known drugs and drug combinations by using a concept of response-guided design. We also measured response in logarithmic fashion. Our primary end points were achievement of M1 marrow status, minimal residual disease status below 10, and second remission. The remission induction rate was 90% with 10% induction mortality. After the A blocks (dexamethasone, vincristine, idarubicin and pegylated L-asparaginase), 85% had M1 status, 39% had minimal residual disease ≤1×10, and 66% had 2 to 3 log response. After B1 block (cyclo, VP-16) the figures were 92%, 58%, and 83%, respectively. Twenty-five of 40 patients received allogeneic stem cell transplantation. Three-year event-free survival of the whole cohort was 37%, and the relapse rate was 38%. Three-year event-free survival by risk group was 53% for late, 34% for early, and 21% for very early relapses. An ALL marrow relapse nonresponsive to steroids, vincristine, asparaginase, anthracyclines, and alkylating agents is uncommon, and these classic drugs can still be advocated for induction of ALL relapse. The problems lie in creating a consolidation capable of preventing particularly posttransplant relapses.

  2. Cytoreductive treatment with clofarabine/ara-C combined with reduced-intensity conditioning and allogeneic stem cell transplantation in patients with high-risk, relapsed, or refractory acute myeloid leukemia and advanced myelodysplastic syndrome.

    Science.gov (United States)

    Buchholz, Stefanie; Dammann, Elke; Stadler, Michael; Krauter, Juergen; Beutel, Gernot; Trummer, Arne; Eder, Matthias; Ganser, Arnold

    2012-01-01

    The combination of cytoreductive chemotherapy with reduced-intensity conditioning (RIC) is a highly effective antileukemic therapy. Purpose of this retrospective analysis was to evaluate the antileukemic efficacy and toxicity of clofarabine-based chemotherapy followed by RIC and allogeneic stem cell transplantation (SCT) for high-risk, relapsed, or refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). From May 2007 until October 2009, a total of 27 patients underwent allogeneic SCT after treatment with clofarabine and ara-C for 5d and RIC (4Gy TBI/cyclophosphamide/ATG). Prophylaxis of graft-versus-host disease (GvHD) consisted of cyclosporine and mycophenolate mofetil. Unmanipulated G-CSF mobilized PBSC (n=26) or bone marrow cells (n=1) were transplanted from unrelated (n=21) or matched related (n=6) donors. Non-hematological toxicities of this regimen mainly affected liver and skin and were all reversible. Seven patients relapsed within a median time of 5.7 months. The overall survival (OS) and relapse-free survival rates were 56% and 52% at 2 yr, respectively. In this cohort of patients, cytoreduction with clofarabine/ara-C (ClAraC) followed by RIC allogeneic SCT was well tolerated and showed good antileukemic efficacy even in patients with high-risk AML or MDS, with engraftment and GvHD-incidence comparable to other RIC regimens.

  3. Patient with antibody-negative relapse of Goodpasture syndrome.

    Science.gov (United States)

    Benz, K; Amann, K; Dittrich, K; Hugo, C; Schnur, K; Dötsch, J

    2007-04-01

    Smoking in young men may trigger anti-GBM disease manifesting with hemoptysis. We present a male adolescent in whom hemoptysis was mistaken to be a sign of airway infection for several months and who later on underwent an unusual antibody-negative relapse. The 16-year-old patient had a history of smoking and therapy-refractant hemoptysis and, later, acute macrohematuria with renal insufficiency necessitating hemodialysis (initial creatinine 4.2 mg/ dl). Chest X-ray showed diffuse lung infiltration. Renal biopsy revealed linear IgG deposits along the glomerular basement membrane (GBM) and cellular crescents in 13/16 glomeruli, simultaneously increased anti-GBM antibodies were detected. Thus, anti-GBM glomerulonephritis was diagnosed. After treatment with prednisone, oral cyclophosphamide and plasmapheresis, chest X-ray and hemoptysis improved, but renal failure persisted. Anti-GBM antibodies were negative. 4 weeks later, the patient presented again with a clinical relapse of severe hemoptysis and respiratory insufficiency after smoke exposition. Despite negative anti-GBM antibodies, he was treated similarly to a relapse and after the second course of plasmapheresis the patients' general condition improved and hemoptysis subsided. During the next 10 months the patient was stable with negative antibodies. He was under intermittent hemodialysis until laboratory measurements showed improved renal function. Now, 30 months after the acute episode, the patient is off dialysis for 17 months with stable creatinine values of 1.9 - 2.4 mg/dl, and is currently being treated with antihypertensive medicaments, calcitriol, calciumacetate, natriumhydrogencarbonate and allopurinol. The prognosis of anti-GBM glomerulonephritis depends on serum creatinine and the need of dialysis at initial presentation. In these patients, one-year survival rate is 67% and 5% for kidney function. Of note, despite the unfavorable prognosis in our patient, renal function recovered after 1 year of

  4. CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia.

    Science.gov (United States)

    Green, Margaret L; Leisenring, Wendy M; Xie, Hu; Walter, Roland B; Mielcarek, Marco; Sandmaier, Brenda M; Riddell, Stanley R; Boeckh, Michael

    2013-08-15

    The association between cytomegalovirus (CMV) reactivation and relapse was evaluated in a large cohort of patients with acute myeloid leukemia (AML) (n = 761), acute lymphoblastic leukemia (ALL) (n = 322), chronic myeloid leukemia (CML) (n = 646), lymphoma (n = 254), and myelodysplastic syndrome (MDS) (n = 371) who underwent allogeneic hematopoietic cell transplantation (HCT) between 1995 and 2005. In multivariable models, CMV pp65 antigenemia was associated with a decreased risk of relapse by day 100 among patients with AML (hazard ratio [HR] = 0.56; 95% confidence interval [CI], 0.3-0.9) but not in patients with ALL, lymphoma, CML, or MDS. The effect appeared to be independent of CMV viral load, acute graft-versus-host disease, or ganciclovir-associated neutropenia. At 1 year after HCT, early CMV reactivation was associated with reduced risk of relapse in all patients, but this did not reach significance for any disease subgroup. Furthermore, CMV reactivation was associated with increased nonrelapse mortality (HR = 1.31; 95% CI, 1.1-1.6) and no difference in overall mortality (HR = 1.05; 95% CI, 0.9-1.3). This report demonstrates a modest reduction in early relapse risk after HCT associated with CMV reactivation in a large cohort of patients without a benefit in overall survival.

  5. Isolated testicular relapse in acute lymphoblastic leukemia - Effective treatment with the modified CCG-112 protocol

    Directory of Open Access Journals (Sweden)

    Shama Goyal

    2005-01-01

    Full Text Available BACKGROUND: The testes have been considered a sanctuary site for leukemic cells and testicular relapses used to account for a major proportion of the poor outcome of boys with acute lymphoblastic leukemia. With use of aggressive chemotherapy which includes intermediate or high dose methotrexate, the incidence of testicular relapses has declined. However once these patients have received cranial irradiation as a part of the front line protocol, high dose methotrexate needs to be avoided because of risk of developing leucoencephalopathy. AIM: To study the use of non cross resistant chemotherapeutic agents along with a regimen containing lower doses of methotrexate in patients of isolated testicular relapse (ITR. MATERIALS AND METHODS: This is a retrospective analysis of 12 consecutive patients with ITR treated with modified version of the CCG-112 protocol which consists of intensive systemic chemotherapy, cranial chemoprophylaxis along with testicular irradiation. RESULTS: One patient died of regimen related toxicity. Two patients relapsed in the bone marrow during maintenance. Of the nine patients who completed treatment, eight are alive and in remission. One patient had a bone marrow relapse two months after completing treatment. The Kaplan Meier estimates give us an Event Free Survival (EFS of 66.7% at 10 yrs. CONCLUSIONS: Thus, though the incidence is very low, patients with ITR should be treated aggressively since they have an excellent chance of achieving a long term EFS.

  6. Acute Lymphoblastic Leukemia in a Man Treated With Fingolimod for Relapsing Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Stanley Cohan MD, PhD

    2015-03-01

    Full Text Available A man with relapsing multiple sclerosis, treated with fingolimod 0.5 mg/d for 15 months, developed acute lymphoblastic leukemia and died 4 months after immune ablation and bone marrow allograft, from graft versus host disease. To our knowledge, this is the first case of acute lymphoblastic leukemia reported in a patient treated with fingolimod. Although no causal relationship can be established between fingolimod use and acute lymphoblastic leukemia risk in this single case, future surveillance for lymphatic cell malignancies in patients treated with fingolimod appears justified.

  7. 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

    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...

  8. Unilateral Exudative Retinal Detachment as the Sole Presentation of Relapsing Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Fatih Mehmet Azık

    2012-06-01

    Full Text Available Ocular findings are rarely the initial symptom of leukemia, although up to 90% of all leukemia patients have fundus changes during the course of the disease. Herein we report a relapsing acute lymphoblastic leukemia patient with the sole presentation of sudden visual loss and exudative retinal detachment. An 8-year-old boy with acute lymphoblastic leukemia developed sudden visual loss during his first remission period. Bullous retinal detachment with total afferent pupillary defect was observed. Orbital magnetic resonance imaging revealed an intraocular mass lesion; simultaneously obtained bone marrow and cerebrospinal fluid samples showed no evidence of leukemic cells. Following local irradiation, and systemic and intrathecal chemotherapy the mass disappeared. Local irradiation, and systemic and intrathecal chemotherapy effectively controlled the isolated ocular relapse of acute lymphoblastic leukemia and eliminated the need for enucleation.

  9. Treatment of acute relapses in neuromyelitis optica: Steroids alone versus steroids plus plasma exchange.

    Science.gov (United States)

    Abboud, Hesham; Petrak, Alex; Mealy, Maureen; Sasidharan, Sarana; Siddique, Laila; Levy, Michael

    2016-02-01

    Although adding plasma exchange (PLEX) to steroids in severe neuromyelitis optica (NMO) attacks is common practice in steroid-resistant cases, the benefit of this strategy has not been previously quantified. The objective of this paper is to compare the efficacy of high-dose intravenous methylprednisolone (IVMP) versus IVMP+PLEX in treatment of acute NMO relapses. We conducted a retrospective review of the last 83 NMO admissions to the Johns Hopkins Hospital treated with IVMP alone versus IVMP+PLEX (for steroid-resistant cases). Extended Disability Status Scale (EDSS) score was calculated at baseline, at presentation, at discharge, and on follow-up. Eighteen NMO relapses (16 patients, 87% female, mean age at relapse: 33.9±23.8, median baseline EDSS 2.5) were treated with IVMP alone and 65 relapses (43 patients, 95% female, mean age at relapse: 43.8±15.7, median baseline EDSS 5.75) were treated with IVMP + PLEX. Sixty-five percent of IVMP + PLEX patients achieved an EDSS equal or below their baseline at follow-up while only 35% of the IVMP-only patients achieved their baseline EDSS on follow-up (odds ratio=3.36, 95% CI 1.0657 to 10.6004, p = 0.0386). PLEX was more effective in improving EDSS in patients on preventive immunosuppressive medications at time of relapse. PLEX+IVMP are more likely to improve EDSS after NMO relapses compared to IVMP alone, especially in patients taking preventive medications. © The Author(s), 2015.

  10. Pseudo-Guillain–Barré syndrome masking acute myeloid leukemia relapse: Brief report and review

    Directory of Open Access Journals (Sweden)

    Fadi El Karak

    2015-01-01

    Full Text Available Central nervous system (CNS relapse is not a rare presentation in acute myeloid leukemia (AML as its incidence ranges between 2% and 9%. It manifests with meningeal leukemia, cranial nerve palsies or cerebral mesenchymal myeloid sarcoma. We herein report the case of a 69 year-old female that presented a pseudo-Guillain–Barré syndrome masking an AML CNS relapse. Her symptoms completely resolved upon administration of a tailored treatment. This case suggests that puzzling neurological manifestations in patients with a history of AML should be considered as a CNS recurrence and investigated accordingly even in the context of normal imaging findings.

  11. Study Links Pot Use to Relapse in Psychosis Patients

    Science.gov (United States)

    ... html Study Links Pot Use to Relapse in Psychosis Patients But experts note effect is small, and ... boost the risk that people who struggle with psychosis will relapse. But critics said the effect seems ...

  12. Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Nestor R. Ramos

    2015-04-01

    Full Text Available The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for “complete” remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or refractory AML is generally poor. In this review, we outline the commonly utilized salvage cytotoxic therapy interventions and then highlight novel investigational efforts currently in clinical trials using both pathway-targeted agents and immunotherapy based approaches. We conclude that there is no current standard of care for adult relapsed or refractory AML other than offering referral to an appropriate clinical trial.

  13. Secondary Philadelphia chromosome and erythrophagocytosis in a relapsed acute myeloid leukemia after hematopoietic cell transplantation.

    Science.gov (United States)

    Kelemen, Katalin; Galani, Komal; Conley, Christopher R; Greipp, Patricia T

    2014-06-01

    The acquisition of the Philadelphia chromosome (Ph) as a secondary change during the course of hematopoietic malignancies is rare and is associated with poor prognosis. Few cases of secondary Ph have been reported after hematopoietic cell transplantation (HCT). A secondary Ph at relapse is of clinical importance because it provides a therapeutic target for tyrosine kinase inhibitors along with or in replacement of chemotherapy. We describe a case of relapsed acute myeloid leukemia (AML) after HCT that developed a BCR-ABL1 translocation along with erythrophagocytosis by blasts as a secondary change at the time of relapse. The progression of this patient's myeloid neoplasm from myelodysplastic syndrome to AML to relapsed AML after HCT was accompanied by a stepwise cytogenetic evolution: A deletion 20q abnormality subsequently acquired a deletion 7q and, finally, at relapse after HCT, a secondary Ph was gained. The relationship between the secondary Ph and the erythrophagocytosis by blasts is not clear. We review the possible pathogenesis and cytogenetic associations of erythrophagocytosis by blasts, a rare feature in acute leukemias.

  14. The dynamics of RUNX1-RUNX1T1 transcript levels after allogeneic hematopoietic stem cell transplantation predict relapse in patients with t(8;21) acute myeloid leukemia.

    Science.gov (United States)

    Qin, Ya-Zhen; Wang, Yu; Xu, Lan-Ping; Zhang, Xiao-Hui; Chen, Huan; Han, Wei; Chen, Yu-Hong; Wang, Feng-Rong; Wang, Jing-Zhi; Chen, Yao; Mo, Xiao-Dong; Zhao, Xiao-Su; Chang, Ying-Jun; Liu, Kai-Yan; Huang, Xiao-Jun

    2017-02-06

    The optimal monitoring schedules and cutoff minimal residual disease (MRD) levels for the accurate prediction of relapse at all time points after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unclear in patients with t(8;21) acute myeloid leukemia (AML). RUNX1-RUNX1T1 transcript levels were measured in bone marrow samples collected from 208 patients at scheduled time points after transplantation (1530 samples in total). A total of 92.3% of the requested samples were collected, and 74.0% of patients had complete sample collection. The 1-, 3-, and 6-month RUNX1-RUNX1T1 transcript levels could significantly discriminate between continuous complete remission and a hematologic relapse at 1.5-3, 4-6, and 7-12 months but not at >3, >6, and >12 months, respectively. Over 90% of the 175 patients who were in continuous complete remission had a ≥3-log reduction in RUNX1-RUNX1T1 transcript levels from the time of diagnosis at each time point after transplantation and a ≥4-log reduction at ≥12 months. A 1-log (0 vs. 55.0%, P = 0.015). RUNX1-RUNX1T1 transcripts with a <3-log reduction from diagnosis within 12 months and/or a <4-log reduction at ≥12 months after allo-HSCT could accurately predict relapse and may prompt a timely intervention in patients with t(8;21) AML.

  15. Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

    Science.gov (United States)

    Cancela, Camila Silva Peres; Murao, Mitiko; Viana, Marcos Borato; de Oliveira, Benigna Maria

    2012-01-01

    Background Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. Methods This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. Results The estimated probabilities of overall survival and event free survival at 5 years were 69.5% (± 3.6%) and 58.8% (± 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis ≥ 50 x 109/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count 50 x 109/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia. PMID:23323068

  16. Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Camila Silva Peres Cancela

    2012-01-01

    Full Text Available BACKGROUND: Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. METHODS: This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99 treatment protocol. RESULTS: The estimated probabilities of overall survival and event free survival at 5 years were 69.5% ( 3.6% and 58.8% ( 4.0%, respectively. The cumulative incidence of central nervous system (isolated or combined relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis > 50 x 10(9/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count 50 x 10(9/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia.

  17. Isolated extra-medullary relapse of acute leukemia following allogeneic bone marrow transplantation.

    Science.gov (United States)

    Firas, Al Sabty; Demeckova, E; Bojtarova, E; Czako, B; Hrubisko, M; Mistrik, M

    2008-01-01

    Isolated extramedullary relapse (IEMR) of acute leukemia (AL) after allogeneic bone marrow transplantation (BMT) is a rare occurrence. It is seen more commonly after BMT than after conventional chemotherapy (CHT) alone. We describe the natural history and response to treatment in four patients with IEMR following allogeneic BMT. The results indicate a stronger graft-versus-leukemia (GVL) effect in the marrow than in the peripheral tissues (Fig. 4, Ref. 13). Full Text (Free, PDF) www.bmj.sk.

  18. Clinical relevance of molecular aberrations in paediatric acute myeloid leukaemia at first relapse

    NARCIS (Netherlands)

    Bachas, Costa; Schuurhuis, Gerrit Jan; Reinhardt, Dirk; Creutzig, Ursula; Kwidama, Zinia J.; Zwaan, C. Michel; van den Heuvel-Eibrink, Marry M.; De Bont, Evelina S. J. M.; Elitzur, Sarah; Rizzari, Carmelo; de Haas, Valerie; Zimmermann, Martin; Cloos, Jacqueline; Kaspers, Gertjan J. L.

    2014-01-01

    Outcome for relapsed paediatric acute myeloid leukaemia (AML) remains poor. Strong prognostic factors at first relapse are lacking, which hampers optimization of therapy. We assessed the frequency of molecular aberrations (FLT3, NRAS, KRAS, KIT, WT1 and NPM1 genes) at first relapse in a large set (n

  19. Clinical relevance of molecular aberrations in paediatric acute myeloid leukaemia at first relapse

    NARCIS (Netherlands)

    Bachas, Costa; Schuurhuis, Gerrit Jan; Reinhardt, Dirk; Creutzig, Ursula; Kwidama, Zinia J.; Zwaan, C. Michel; van den Heuvel-Eibrink, Marry M.; De Bont, Evelina S. J. M.; Elitzur, Sarah; Rizzari, Carmelo; de Haas, Valerie; Zimmermann, Martin; Cloos, Jacqueline; Kaspers, Gertjan J. L.

    2014-01-01

    Outcome for relapsed paediatric acute myeloid leukaemia (AML) remains poor. Strong prognostic factors at first relapse are lacking, which hampers optimization of therapy. We assessed the frequency of molecular aberrations (FLT3, NRAS, KRAS, KIT, WT1 and NPM1 genes) at first relapse in a large set (n

  20. Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2017-01-09

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  1. Prediction of acute multiple sclerosis relapses by transcription levels of peripheral blood cells

    Directory of Open Access Journals (Sweden)

    Or-Bach Rotem

    2009-07-01

    Full Text Available Abstract Background The ability to predict the spatial frequency of relapses in multiple sclerosis (MS would enable physicians to decide when to intervene more aggressively and to plan clinical trials more accurately. Methods In the current study our objective was to determine if subsets of genes can predict the time to the next acute relapse in patients with MS. Data-mining and predictive modeling tools were utilized to analyze a gene-expression dataset of 94 non-treated patients; 62 patients with definite MS and 32 patients with clinically isolated syndrome (CIS. The dataset included the expression levels of 10,594 genes and annotated sequences corresponding to 22,215 gene-transcripts that appear in the microarray. Results We designed a two stage predictor. The first stage predictor was based on the expression level of 10 genes, and predicted the time to next relapse with a resolution of 500 days (error rate 0.079, p Conclusion We conclude that gene expression analysis is a valuable tool that can be used in clinical practice to predict future MS disease activity. Similar approach can be also useful for dealing with other autoimmune diseases that characterized by relapsing-remitting nature.

  2. Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse.

    Science.gov (United States)

    Garg, Manoj; Nagata, Yasunobu; Kanojia, Deepika; Mayakonda, Anand; Yoshida, Kenichi; Haridas Keloth, Sreya; Zang, Zhi Jiang; Okuno, Yusuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Ding, Ling-Wen; Alpermann, Tamara; Sun, Qiao-Yang; Lin, De-Chen; Chien, Wenwen; Madan, Vikas; Liu, Li-Zhen; Tan, Kar-Tong; Sampath, Abhishek; Venkatesan, Subhashree; Inokuchi, Koiti; Wakita, Satoshi; Yamaguchi, Hiroki; Chng, Wee Joo; Kham, Shirley-Kow Yin; Yeoh, Allen Eng-Juh; Sanada, Masashi; Schiller, Joanna; Kreuzer, Karl-Anton; Kornblau, Steven M; Kantarjian, Hagop M; Haferlach, Torsten; Lill, Michael; Kuo, Ming-Chung; Shih, Lee-Yung; Blau, Igor-Wolfgang; Blau, Olga; Yang, Henry; Ogawa, Seishi; Koeffler, H Phillip

    2015-11-26

    Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. To identify the mutational spectrum associated with relapse, whole-exome sequencing was performed on 13 matched diagnosis, relapse, and remission trios followed by targeted sequencing of 299 genes in 67 FLT3-ITD patients. The FLT3-ITD genome has an average of 13 mutations per sample, similar to other AML subtypes, which is a low mutation rate compared with that in solid tumors. Recurrent mutations occur in genes related to DNA methylation, chromatin, histone methylation, myeloid transcription factors, signaling, adhesion, cohesin complex, and the spliceosome. Their pattern of mutual exclusivity and cooperation among mutated genes suggests that these genes have a strong biological relationship. In addition, we identified mutations in previously unappreciated genes such as MLL3, NSD1, FAT1, FAT4, and IDH3B. Mutations in 9 genes were observed in the relapse-specific phase. DNMT3A mutations are the most stable mutations, and this DNMT3A-transformed clone can be present even in morphologic complete remissions. Of note, all AML matched trio samples shared at least 1 genomic alteration at diagnosis and relapse, suggesting common ancestral clones. Two types of clonal evolution occur at relapse: either the founder clone recurs or a subclone of the founder clone escapes from induction chemotherapy and expands at relapse by acquiring new mutations. Relapse-specific mutations displayed an increase in transversions. Functional assays demonstrated that both MLL3 and FAT1 exert tumor-suppressor activity in the FLT3-ITD subtype. An inhibitor of XPO1 synergized with standard AML induction chemotherapy to inhibit FLT3-ITD growth. This study clearly shows that FLT3-ITD AML requires additional driver genetic alterations in addition to FLT3-ITD alone.

  3. 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

    BACKGROUND: Comprehensive data on late relapse (LR) and very LR (VLR) in patients with clinical stage I (CS-1) testicular cancer followed on surveillance are missing. These data are essential for planning optimal follow-up. OBJECTIVE: Assess incidence and outcome of LR (>2 yr) and VLR (>5 yr...... patients with LR(VLR) do not differ significantly from patients with ER. PATIENT SUMMARY: We compared stage I testicular cancer surveillance patients with early relapse (ER) versus late relapse (LR; >2 yr). LR patients as a group did no worse than ER patients, although increased time to relapse......) in a large cohort of CS-1 surveillance patients, and examine differences in the clinical characteristics of patients with early relapse (ER), LR, and VLR. DESIGN, SETTING, AND PARTICIPANTS: CS-1 surveillance patients diagnosed between 1984 and 2007 were identified from the retrospective Danish Testicular...

  4. Laboratory-Treated Donor Cord Blood Cell Infusion Following Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-10-31

    Acute Leukemia of Ambiguous Lineage; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Childhood Acute Myeloid Leukemia in Remission; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  5. A phase I trial of the aurora kinase inhibitor, ENMD-2076, in patients with relapsed or refractory acute myeloid leukemia or chronic myelomonocytic leukemia.

    Science.gov (United States)

    Yee, Karen W L; Chen, Hsiao-Wei T; Hedley, David W; Chow, Sue; Brandwein, Joseph; Schuh, Andre C; Schimmer, Aaron D; Gupta, Vikas; Sanfelice, Deborah; Johnson, Tara; Le, Lisa W; Arnott, Jamie; Bray, Mark R; Sidor, Carolyn; Minden, Mark D

    2016-10-01

    ENMD-2076 is a novel, orally-active molecule that inhibits Aurora A kinase, as well as c-Kit, FLT3 and VEGFR2. A phase I study was conducted to determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D) and toxicities of ENMD-2076 in patients with acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML). Patients received escalating doses of ENMD-2076 administered orally daily [225 mg (n = 7), 375 mg (n = 6), 325 mg (n = 9), or 275 mg (n = 5)]. Twenty-seven patients were treated (26 AML; 1 CMML-2). The most common non-hematological toxicities of any grade, regardless of association with drug, were fatigue, diarrhea, dysphonia, dyspnea, hypertension, constipation, and abdominal pain. Dose-limiting toxicities (DLTs) consisted of grade 3 fatigue, grade 3 typhilitis, grade 3 syncope and grade 3 QTc prolongation). Of the 16 evaluable patients, one patient achieved a complete remission with incomplete count recovery (CRi), three experienced a morphologic leukemia-free state (MLFS) with a major hematologic improvement in platelets (HI-P), and 5 other patients had a reduction in marrow blast percentage (i.e. 11-65 %). The RP2D in this patient population is 225 mg orally once daily.

  6. Decitabine and Valproic Acid in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2013-09-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Untreated Adult Acute Myeloid Leukemia

  7. 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

    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...

  8. Combination chemotherapy for marrow relapse in children and adolescents with acute lymphocytic leukaemia.

    Science.gov (United States)

    Amadori, S; Spiriti, M A; Meloni, G; Pacilli, L; Papa, G; Mandelli, F

    1981-04-01

    38 children with acute lymphocytic leukaemia (ALL) in haematologic relapse were retreated with vincristine, daunomycin and prednisone (VPD) together with intrathecal methotrexate and prednisone, followed by asparaginase in those patients not in complete remission after 4 weeks. The overall complete remission (CR) rate was 79%; asparaginase was needed to achieve CR in 7 of the 30 responding patients. The median duration of second remission was only 36 weeks, but 6 out of 15 children receiving the COAP-POMP-CART consolidation regimen remain in continuous second remission after 37-260 weeks; 3 of them are currently off all therapy. It is concluded that a prolonged second remission can be achieved in children with ALL in bone marrow relapse by combining intensive chemotherapy with the prevention of meningeal leukaemia.

  9. Kidney and Pancreatic Extramedullary Relapse in Adult Acute Lymphoblastic Leukemia: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Leslie Skeith

    2013-01-01

    Full Text Available Extramedullary relapse of acute lymphoblastic leukemia (ALL is rare and has been primarily reported in pediatric patients or hematopoietic stem cell transplant recipients. We report a case of a 62-year-old woman who presented with relapsed ALL involving her kidneys, pancreas, and bone marrow 2 years after completing chemotherapy with a standard ALL protocol. Unfortunately, her extramedullary disease progressed despite treatment. To the best of our knowledge, this is the first reported case of extramedullary relapse of B-cell ALL to the kidneys and pancreas occurring in an adult patient who had not previously undergone a hematopoietic stem cell transplant. A literature review of kidney and pancreatic extramedullary relapse in ALL is also included.

  10. Leukaemia relapse after allogeneic transplants for acute myeloid leukaemia: predictive role of WT1 expression.

    Science.gov (United States)

    Pozzi, Sarah; Geroldi, Simona; Tedone, Elisabetta; Luchetti, Silvia; Grasso, Raffaella; Colombo, Nicoletta; Di Grazia, Carmen; Lamparelli, Teresa; Gualandi, Francesca; Ibatici, Adalberto; Bregante, Stefania; Van Lint, Maria Teresa; Raiola, Anna Maria; Dominietto, Alida; Varaldo, Riccardo; Signori, Alessio; Bacigalupo, Andrea

    2013-02-01

    We assessed WT1 expression (expressed as messenger copies/10(4) ABL1) from marrow cells of 122 patients with acute myeloid leukaemia (AML), before and after an unmanipulated allogeneic haemopoietic stem cell transplant (HSCT). The median age was 44 years (15-69), 59% were in first remission, 74% received a myeloablative conditioning regimen and the median follow up was 865 d (34-2833). Relapse was higher in 67 patients with WT1 expression, at any time post-HSCT, exceeding 100 copies (54%), as compared to 16%, for 55 patients with post-HSCT WT1 expression <100 copies (P < 0·0001). Similarly, actuarial 5-year survival (OS) was 40% vs. 63%, respectively (P = 0·03). In multivariate Cox analysis, WT1 expression post-HSCT was the strongest predictor of relapse (Hazard Ratio [HR] 4·5, P = 0·0001), independent of disease phase (HR 2·3, P = 0·002). Donor lymphocyte infusions (DLI) were given to 17 patients because of increasing WT1 levels: their OS was 44%, vs. 14% for 21 patients with increasing WT1 expression who did not receive DLI (P = 0·004). In conclusion, WT1 expression post-HSCT is a strong predictor of leukaemia relapse and survival in AML; WT1 may be used as a marker for early interventional therapy.

  11. Combination of arsenicum trioxide and all trans retinoic acid in the treatment of relapsed acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    A. N. Sokolov

    2015-01-01

    Full Text Available From 2001 to 2013 eleven patients with relapsed acute promyelocytic leukemia (APL (median age – 30 years received arsenicum trioxide (ATO. ATO was administered as a 2nd line relapse therapy in 9 patients, as 1st line relapse therapy in 2 patients. ATO was administered in a dose of 0.1 mg/kg in 7 patients, 0.15 mg/kg – in 4 patients. The induction duration was 14 days in 3 patients, 24–35 days in 2 patients, 60 days in 6 patients. From the 1st day of ATO patients received 45 mg/m2 all trans retinoic acid (ATRA (1 patient – from day 29 of ATO therapy. Maintenance therapy ATO + ATRA (10–14 days courses, every four weeks patients were receiving during 10–15 months. 2 from 3 patients with molecular relapses achieved remission lasting 57 and 89 months after the 14-day ATO courses. 1 from 2 patients with bone marrow relapse achieved remission lasting 27 months after the 24–35-day ATO courses. 60-day courses were effective in 5 of 6 patients: in 4 of which remission are retained during 16, 19, 27, 57 months; 1 patient was relapsed after 12 months; 1 patient did not achieve molecular remission. 3 patients received allogeneic hematopoietic stem cell transplantation (alloHSCT, 2 of which alive in remission. 1 patient received autologous hematopoietic stem cell transplantation in the 2nd molecular remission (alive in remission. 4 patients died: 1 – in the 3rd relapse (duration of 2nd remission – 9 months, 1 – in remission from complications after alloHSCT, 1 – from APL progression, 1 – sudden death in 2nd remission lasting 72 months. ATO + ATRA for 60 days with supportive therapy are more effective than chemotherapy in the treatment of APL relapse. Interferon α + ATRA are inappropriate treatment of APL molecular and cytogenetic relapse. Using autologous HSCT in 2nd molecular remission will improve the results of APL relapse treatment.

  12. Combination of Cladribine plus Topotecan for Relapsed or Refractory Pediatric Acute Myeloid Leukemia

    Science.gov (United States)

    Inaba, Hiroto; Stewart, Clinton F.; Crews, Kristine R.; Yang, Shengping; Pounds, Stanley; Pui, Ching-Hon; Rubnitz, Jeffrey E.; Razzouk, Bassem I.; Ribeiro, Raul C.

    2009-01-01

    BACKGROUND The prognosis after relapse of pediatric acute myeloid leukemia (AML) is poor and effective salvage regimens are urgently needed. METHODS In Phase I and pilot studies, we evaluated the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a 5-day course of cladribine (2-CDA) followed by topotecan in pediatric patients with relapsed/refractory AML. The 2-CDA dose was escalated as follows: 9.1, 13.6, 16.3, and 19.5 mg/m2 per day (8.9 mg/m2 per day in the pilot study). Outcome was analyzed according to the absence (stratum 1) vs. presence (stratum 2) of previous allogeneic hematopoietic stem cell transplantation. Twenty-six patients (20 in stratum 1, 6 in stratum 2) were treated. RESULTS The MTD was not reached in stratum 1, but DLT occurred at the lowest 2-CDA dosage (9.1 mg/m2 per day) in stratum 2. Febrile neutropenia was common in both strata. Nine (34.6%) of 26 patients experienced a complete response and 7 (30.4%) had a partial response; 5 (19.2%) are long-term survivors. Clinical outcome was not associated with 2-CDA or topotecan systemic exposure. CONCLUSION The combination was well tolerated in stratum 1, and the response rate is encouraging. This regimen offers a post-relapse treatment alternative for patients, especially those who have received anthracycline-containing chemotherapy. PMID:19885837

  13. Secondary pure erythroid leukaemia in relapsed acute lymphoblastic leukaemia: lineage switch or chemotherapy effect?

    Science.gov (United States)

    Gupta, Sanjeev Kumar; Kumar, Rajive; Chharchhodawala, Taher; Kumar, Lalit

    2014-05-19

    Pure erythroid leukaemia is a rare subtype of acute myeloid leukaemia (AML) and its occurrence at acute lymphoblastic leukaemia (ALL) relapse has not been reported earlier. A 39-year-old man received chemotherapy for Philadelphia-negative B cell ALL. Subsequently, he developed pure erythroid leukaemia with >80% immature erythroid precursors in bone marrow showing block positivity on periodic acid-Schiff stain, expressing CD71, CD34 but lacking CD235a. The interval between exposure to multidrug chemotherapy including cyclophosphamide and AML diagnosis was 2 years and 9 months. No cytogenetic abnormality was detected at the time of relapse. The patient died 2 weeks after starting AML chemotherapy. The relatively narrow time interval (usually 5-10 years) between chemotherapy and AML development and normal karyotype at relapse raises a possibility of lineage switch besides therapy-related AML as the likely pathogenesis. Further exploration of such cases may unravel the pathways responsible for lineage assignment in pluripotent stem cells. 2014 BMJ Publishing Group Ltd.

  14. Sequential Administration of Methotrexate and Asparaginase in Relapsed or Refractory Pediatric Acute Myeloid Leukemia

    Science.gov (United States)

    Buaboonnam, Jassada; Cao, Xueyuan; Pauley, Jennifer L.; Pui, Ching-Hon; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Inaba, Hiroto

    2014-01-01

    Background The efficacy of combination chemotherapy with methotrexate (MTX) and asparaginase is not well known in relapsed and refractory acute leukemia after contemporary therapy. Procedure A retrospective study of pediatric patients with relapsed or refractory acute myeloid leukemia (AML) who received MTX and asparaginase as a salvage therapy at St. Jude Children Research Hospital was performed. MTX was given intravenously followed by a dose of asparaginase intramuscularly or intravenously 24 hours later. The chemotherapy cycle was repeated every 7-10 days. Response, survival, and toxicities were evaluated. Results Fifteen patients, median age 10.5 years (range, 1.1-18.5 years), were treated. Median number of previous therapeutic regimens was 3 (range, 1-4). Six patients responded to treatment (3 had morphologic complete remission with incomplete blood count recovery, 2 had partial remission, and 1 had stable disease for 16 months), and 4 are still alive. Three of 6 responders had monoblastic leukemia, and also developed tumor lysis syndrome. The 1- and 2-year overall survival rates are 35.6% and 17.8%, respectively. The most common adverse event was transient elevation of transaminases (9 patients). Two patients developed pancreatitis. Episodes of febrile neutropenia were rare (2 patients), and most courses (75 out of 93 total courses) were given in an outpatient setting. Conclusions Combination chemotherapy with MTX and asparaginase appears to be an effective salvage therapy and well tolerated in patients with relapsed or refractory childhood AML, even in those heavily pretreated with contemporary frontline or salvage therapy. PMID:23335430

  15. Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies.

    Science.gov (United States)

    Hogan, Laura E; Meyer, Julia A; Yang, Jun; Wang, Jinhua; Wong, Nicholas; Yang, Wenjian; Condos, Gregory; Hunger, Stephen P; Raetz, Elizabeth; Saffery, Richard; Relling, Mary V; Bhojwani, Deepa; Morrison, Debra J; Carroll, William L

    2011-11-10

    Despite an increase in survival for children with acute lymphoblastic leukemia (ALL), the outcome after relapse is poor. To understand the genetic events that contribute to relapse and chemoresistance and identify novel targets of therapy, 3 high-throughput assays were used to identify genetic and epigenetic changes at relapse. Using matched diagnosis/relapse bone marrow samples from children with relapsed B-precursor ALL, we evaluated gene expression, copy number abnormalities (CNAs), and DNA methylation. Gene expression analysis revealed a signature of differentially expressed genes from diagnosis to relapse that is different for early (diversity of genetic changes are seen at relapse, integration of gene expression, CNA, and methylation data suggest a possible convergence on the WNT and mitogen-activated protein kinase pathways.

  16. Persistent and relapsing babesiosis in immunocompromised patients.

    Science.gov (United States)

    Krause, Peter J; Gewurz, Benjamin E; Hill, David; Marty, Francisco M; Vannier, Edouard; Foppa, Ivo M; Furman, Richard R; Neuhaus, Ellen; Skowron, Gail; Gupta, Shaili; McCalla, Carlo; Pesanti, Edward L; Young, Mary; Heiman, Donald; Hsue, Gunther; Gelfand, Jeffrey A; Wormser, Gary P; Dickason, John; Bia, Frank J; Hartman, Barry; Telford, Sam R; Christianson, Diane; Dardick, Kenneth; Coleman, Morton; Girotto, Jennifer E; Spielman, Andrew

    2008-02-01

    Human babesiosis is a tickborne malaria-like illness that generally resolves without complication after administration of atovaquone and azithromycin or clindamycin and quinine. Although patients experiencing babesiosis that is unresponsive to standard antimicrobial therapy have been described, the pathogenesis, clinical course, and optimal treatment regimen of such cases remain uncertain. We compared the immunologic status, clinical course, and treatment of 14 case patients who experienced morbidity or death after persistence of Babesia microti infection, despite repeated courses of antibabesial treatment, with those of 46 control subjects whose infection resolved after a single course of standard therapy. This retrospective case-control study was performed in southern New England, New York, and Wisconsin. All case patients were immunosuppressed at the time of acute babesiosis, compared with or=6 weeks to achieve cure, including 2 weeks after parasites are no longer detected on blood smear.

  17. Effective re-induction therapy with dasatinib and clofarabine in relapsed Philadelphia chromosome positive acute lymphoblastic leukemia

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    Anne Loes van den Boom

    2012-12-01

    Full Text Available This case discusses a 10 year old female patient with a late relapse of Ph-chromosome positive B-cell precursor acute lymphoblastic leukaemias (ALL who had previously been treated with chemotherapy and allogeneic stem-cell transplantation. Treatment for relapse consisted of single-agent dasatinib, followed by 2 blocks of a combination of dasatinib and clofarabine as consolidation therapy. Using this schedule both morphological and cytogenetic complete remission were obtained. This regimen was well tolerated, and no major toxicity concerns occurred. Subsequently, the patient received a 2nd stem cell transplantation from a matched unrelated donor. Unfortunately, the child died after complete molecular remission at day +104 post-transplantation, due to a disseminated adenoviral infection. We conclude that dasatinib and clofarabine combination therapy was safe and effective in this patient, and should be further explored as a salvage regimen in relapsed/refractory Philadelphia chromosome positive ALL patients.

  18. Phase 1 trial of gemtuzumab ozogamicin in combination with enocitabine and daunorubicin for elderly patients with relapsed or refractory acute myeloid leukemia: Japan Adult Leukemia Study Group (JALSG)-GML208 study.

    Science.gov (United States)

    Ito, Yoshikazu; Wakita, Atsushi; Takada, Satoru; Mihara, Masahiro; Gotoh, Moritaka; Ohyashiki, Kazuma; Ohtake, Shigeki; Miyawaki, Shuichi; Ohnishi, Kazunori; Naoe, Tomoki

    2012-10-01

    We conducted a phase 1 study of a combination of gemtuzumab ozogamicin (GO) plus conventional chemotherapy in elderly patients (≥ 65 years old) with relapsed or refractory CD33-positive acute myeloid leukemia (AML). Patients received a standard dose of enocitabine (200 mg/m² × 8 days) and daunorubicin (30 mg/m² × days 1-3) plus an escalating dose of GO (1.5-5 mg/m² on day 4). The dose escalation of GO was done according to a standard 3 + 3 design following a modified Fibonacci sequence. No dose-limiting toxicities were observed in three patients (median age, 71) at level 1 (1.5 mg/m²) or in three patients (median age, 73) at level 2 (3 mg/m²). Neither veno-occlusive diseases nor sinusoidal obstructive syndromes were noted at either level. However, as GO was withdrawn from the US market in June 2010, based on a randomized study in newly diagnosed AML, we decided not to proceed to the level 3 (5 mg/m²) in order to avoid possibly more severe adverse effects, and also because all six patients experienced grade 4 myelosuppression, with complete remission in three. This study showed that 3 mg/m² of GO in combination with enocitabine and daunorubicin may be a recommendable dose for a phase 2 study in Japanese elderly patients with CD33-positive AML. The study was registered at the University Hospital Medical Information Network (UMIN) Clinical Trials Registry ( http://www.umin.ac.jp/ctr/ ) as UMIN000002603.

  19. A HIGHER INCIDENCE OF RELAPSE FOR ACUTE LYMPHOCYTIC LEUKEMIA TREATED WITH ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION CONDITIONED WITH BU-CY2 REGIMEN

    Institute of Scientific and Technical Information of China (English)

    朱康儿; 钟隽; 张涛; 曾慧兰

    2003-01-01

    Objective: To analyze long-term outcome in sixty leukemia patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) following busulfan and cyclophosphamide (BU-CY2) between 1994 and 2000. Methods: BU-CY2 was used as the conditioning regimen and allo-HSCT was performed for all patients. All the patients were followed-up until August 2001 or death. The leukemia-free survival, relapse and transplant-related mortality were discussed. Results: All 60 patients had sustained engraftment. Acute GVHD occurred in 22 out of 60 patients (36.7%), and the incidence of acute GVHD was 48% in the patients with CML, 30% in AML and 26.7% in ALL. 38 patients are still alive in continuous remission with a median follow-up of 30 months (range 12-84) and 22 patients have died. The main causes of death were acute GVHD in 3 patients, CMV-IP in 7 patients and relapse in 11 patients, the remaining one died of pulmonary infection. Among 11 patients who died of relapse, 8 patients with ALL relapsed in the early stage post transplant (8/15, 53.3%), relapse was observed in the remaining 3 patients with AML, and however, no relapse was observed in CML. The probability of disease-free survival at 3 years for CML. AML and ALL patients was 80%, 70% and 26.7%, respectively. Conclusion: This results suggests that BU-CY2 is an effective conditioning regimen in patients with AML and CML, resulting in a low relapse rate and high long-term survival rate, but not as effective in patients with ALL, with a higher incidence of relapse and therefore, not recommended for ALL patients.

  20. Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2017-07-06

    CD19-Positive Neoplastic Cells Present; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

  1. Health-related quality of life in long-term survivors of relapsed childhood acute lymphoblastic leukemia.

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    Stefan Essig

    Full Text Available BACKGROUND: Relapses occur in about 20% of children with acute lymphoblastic leukemia (ALL. Approximately one-third of these children can be cured. Their risk for late effects is high because of intensified treatment, but their health-related quality of life (HRQOL was largely unmeasured. Our aim was to compare HRQOL of ALL survivors with the general population, and of relapsed with non-relapsed ALL survivors. METHODOLOGY/PRINCIPAL FINDINGS: As part of the Swiss Childhood Cancer Survivor Study (SCCSS we sent a questionnaire to all ALL survivors in Switzerland who had been diagnosed between 1976-2003 at age <16 years, survived ≥5 years, and were currently aged ≥16 years. HRQOL was assessed with the Short Form-36 (SF-36, which measures four aspects of physical health and four aspects of mental health. A score of 50 corresponded to the mean of a healthy reference population. We analyzed data from 457 ALL survivors (response: 79%. Sixty-one survivors had suffered a relapse. Compared to the general population, ALL survivors reported similar or higher HRQOL scores on all scales. Survivors with a relapse scored lower in general health perceptions (51.6 compared to those without (55.8;p=0.005, but after adjusting for self-reported late effects, this difference disappeared. CONCLUSION/SIGNIFICANCE: Compared to population norms, ALL survivors reported good HRQOL, even after a relapse. However, relapsed ALL survivors reported poorer general health than non-relapsed. Therefore, we encourage specialists to screen for poor general health in survivors after a relapse and, when appropriate, specifically seek and treat underlying late effects. This will help to improve patients' HRQOL.

  2. Relapse in childhood acute lymphoblastic leukemia after elective cessation of initial treatment: failure of subsequent treatment with cyclophosphamide, cytosine arabinoside, vincristine and prednisone (COAP).

    Science.gov (United States)

    Sallan, S E; Hitchcock-Bryan, S

    1981-01-01

    Although the majority of children with acute lymphoblastic leukemia (ALL) can electively stop treatment after 2 1/2-5 years of continuous disease-free remission, 20-25% of those patients relapse after discontinuation of therapy. We treated 15 patients whose disease recurred after stopping treatment. Fourteen of them attained complete remission, but the median duration of disease-free survival was only 11 months. In this population, the site of initial relapse, bone marrow or testicle, did not influence subsequent outcome. Patients who relapsed within six months of stopping initial therapy had shorter second remissions than those who relapsed after six months. We conclude that the combination chemotherapy utilized in this study was inadequate for the control of relapsed ALL. Future programs will have to use different drug combinations or bone marrow transplantation.

  3. Cytomegalovirus Reactivation after Allogeneic Hematopoietic Stem Cell Transplantation is Associated with a Reduced Risk of Relapse in Patients with Acute Myeloid Leukemia Who Survived to Day 100 after Transplantation: The Japan Society for Hematopoietic Cell Transplantation Transplantation-related Complication Working Group.

    Science.gov (United States)

    Takenaka, Katsuto; Nishida, Tetsuya; Asano-Mori, Yuki; Oshima, Kumi; Ohashi, Kazuteru; Mori, Takehiko; Kanamori, Heiwa; Miyamura, Koichi; Kato, Chiaki; Kobayashi, Naoki; Uchida, Naoyuki; Nakamae, Hirohisa; Ichinohe, Tatsuo; Morishima, Yasuo; Suzuki, Ritsuro; Yamaguchi, Takuhiro; Fukuda, Takahiro

    2015-11-01

    Cytomegalovirus (CMV) infection is a major infectious complication after allogeneic hematopoietic cell transplantation (allo-HSCT). Recently, it was reported that CMV reactivation is associated with a decreased risk of relapse in patients with acute myeloid leukemia (AML). The aim of this study was to evaluate the impact of early CMV reactivation on the incidence of disease relapse after allo-HSCT in a large cohort of patients. The Japan Society for Hematopoietic Cell Transplantation's Transplantation-Related Complication Working Group retrospectively surveyed the database of the Transplant Registry Unified Management Program at the Japan Society for Hematopoietic Cell Transplantation. Patients with AML (n = 1836), acute lymphoblastic leukemia (ALL, n = 911), chronic myeloid leukemia (CML, n = 223), and myelodysplastic syndrome (MDS, n = 569) who underwent their first allo-HSCT from HLA-matched related or unrelated donors between 2000 and 2009 and who survived without disease relapse until day 100 after transplantation were analyzed. Patients who received umbilical cord blood transplantation were not included. Patients underwent surveillance by pp65 antigenemia from the time of engraftment, and the beginning of preemptive therapy was defined as CMV reactivation. Cox proportional hazards models were used to evaluate the risk factors of relapse, nonrelapse, and overall mortality. CMV reactivation and acute/chronic graft-versus-host disease (GVHD) were evaluated as time-dependent covariates. CMV reactivation was associated with a decreased incidence of relapse in patients with AML (20.3% versus 26.4%, P = .027), but not in patients with ALL, CML, or MDS. Among 1836 patients with AML, CMV reactivation occurred in 795 patients (43.3%) at a median of 42 days, and 436 patients (23.7%) relapsed at a median of 221 days after allo-HSCT. Acute GVHD grades II to IV developed in 630 patients (34.3%). By multivariate analysis considering competing risk factors, 3

  4. Acute Myeloid Leukemia Relapse Presenting as Complete Monocular Vision Loss due to Optic Nerve Involvement

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    Shyam A. Patel

    2016-01-01

    Full Text Available Acute myeloid leukemia (AML involvement of the central nervous system is relatively rare, and detection of leptomeningeal disease typically occurs only after a patient presents with neurological symptoms. The case herein describes a 48-year-old man with relapsed/refractory AML of the mixed lineage leukemia rearrangement subtype, who presents with monocular vision loss due to leukemic eye infiltration. MRI revealed right optic nerve sheath enhancement and restricted diffusion concerning for nerve ischemia and infarct from hypercellularity. Cerebrospinal fluid (CSF analysis showed a total WBC count of 81/mcl with 96% AML blasts. The onset and progression of visual loss were in concordance with rise in peripheral blood blast count. A low threshold for diagnosis of CSF involvement should be maintained in patients with hyperleukocytosis and high-risk cytogenetics so that prompt treatment with whole brain radiation and intrathecal chemotherapy can be delivered. This case suggests that the eye, as an immunoprivileged site, may serve as a sanctuary from which leukemic cells can resurge and contribute to relapsed disease in patients with high-risk cytogenetics.

  5. Encefalopatia necrotizante aguda: paciente com evolução recidivante e letal Acute necrotizing encephalopathy: patient with a relapsing and lethal evolution

    Directory of Open Access Journals (Sweden)

    Erasmo B. Casella

    2007-06-01

    Full Text Available A encefalopatia necrotizante aguda foi descrita inicialmente em crianças japonesas e se caracteriza por rápida evolução e lesões simétricas no tronco encefálico, cerebelo e especialmente nos tálamos. Avaliamos uma menina de 7 meses de idade, que apresentou dois episódios de depressão da consciência de rápida instalação e paresias, sem alterações metabólicas. Houve uma rápida melhora na primeira crise, porém o segundo episódio foi fulminante, tendo evoluído para estado de morte encefálica em dois dias. Os estudos de ressonância magnética mostraram lesões simétricas nos tálamos e acometimento também do tronco encefálico e cerebelo.Acute necrotizing encephalopathy was initially reported in Japanese children. The rapid evolution and symmetrical brain lesions seen in the brainstem, cerebellum and specially in the thalamus characterize the disease. We studied a 7-month-old-girl, who presented with two episodes of rapid loss of consciousness and paresis without metabolic disturbances. At the first time she had a rapid improvement, but at the second episode the course was fulminant and in two days she lapsed into a clinical state of brain death. The magnetic resonance studies showed symmetrical lesions in the thalamus and additional lesions involving the brainstem and the cerebellum.

  6. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis and/or at first relapse: results from the GET-LALA group.

    Science.gov (United States)

    Reman, Oumedaly; Pigneux, Arnaud; Huguet, Françoise; Vey, Norbert; Delannoy, André; Fegueux, Nathalie; de Botton, Stéphane; Stamatoullas, Aspasia; Tournilhac, Olivier; Buzyn, Agnès; Charrin, Christiane; Boucheix, Claude; Gabert, Jean; Lhéritier, Véronique; Vernant, Jean-Paul; Fière, Denis; Dombret, Hervé; Thomas, Xavier

    2008-11-01

    Outcome of adult acute lymphoblastic leukemia (ALL) with central nervous system (CNS) involvement is not clearly defined. We studied 104 patients presenting with CNS involvement at diagnosis among 1493 patients (7%) included into the LALA trials, and 109 patients presenting CNS disease at the time of first relapse among the 709 relapsing patients (15%). Eighty-seven patients (84%) with CNS leukemia at diagnosis achieved complete remission (CR). Fifty-three patients underwent stem cell transplantation (SCT): 25 allogeneic SCT, 28 autologous SCT, while 34 continued with chemotherapy alone. Seven-year overall survival (OS) and disease-free survival (DFS) were 34% and 35%, respectively. There were no significant differences in terms of CR, OS and DFS among patients with CNS involvement at diagnosis and those without CNS disease. There were also no differences among the two groups regarding T lineage ALL, B lineage ALL, and among those who underwent SCT. After a first relapse, 38 patients with CNS recurrence (35%) achieved a second CR. The median OS was 6.3 months. Outcome was similar to that of relapsing patients without CNS disease. CNS leukemia in adult ALL is uncommon at diagnosis as well as at the time of first relapse. With intensification therapy, patients with CNS leukemia at diagnosis have a similar outcome than those who did not present with CNS involvement. CNS leukemia at first relapse remains of similar poor prognosis than all other adult ALL in first relapse.

  7. Relapsing acute myeloid leukemia presenting as hypopyon uveitis

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    Sapna P Hegde

    2011-01-01

    Full Text Available Anterior segment infiltration in acute myeloid leukemia (AML presenting as hypopyon uveitis is very rare. We report this case as an uncommon presentation in a patient on remission after bone marrow transplant for AML. In addition to the hypopyon, the patient presented with "red eye" caused by ocular surface disease due to concurrent graft-versus-host disease and glaucoma. The classical manifestations of masquerade syndrome due to AML were altered by concurrent pathologies. Media opacities further confounded the differential diagnosis. We highlight the investigations used to arrive at a definitive diagnosis. In uveitis, there is a need to maintain a high index of clinical suspicion, as early diagnosis in ocular malignancy can save sight and life.

  8. Outcome of treatment after first relapse in adults with acute lymphoblastic leukemia initially treated by the LALA-94 trial.

    Science.gov (United States)

    Tavernier, E; Boiron, J-M; Huguet, F; Bradstock, K; Vey, N; Kovacsovics, T; Delannoy, A; Fegueux, N; Fenaux, P; Stamatoullas, A; Tournilhac, O; Buzyn, A; Reman, O; Charrin, C; Boucheix, C; Gabert, J; Lhéritier, V; Vernant, J-P; Dombret, H; Thomas, X

    2007-09-01

    Fifty-four percent of adults with acute lymphoblastic leukemia (ALL) who entered the LALA-94 trial experienced a first relapse. We examined the outcome of these 421 adult patients. One hundred and eighty-seven patients (44%) achieved a second complete remission (CR). The median disease-free survival (DFS) was 5.2 months with a 5-year DFS at 12%. Factors predicting a better outcome after relapse were any transplant performed in second CR (P1 year (P=0.04) and platelet level >100 x 10(9)/l at relapse (P=0.04). Risk groups defined at diagnosis and treatment received in first CR did not influence the outcome after relapse. The best results were obtained in a subset of patients who were eligible for allogeneic stem cell transplantation (SCT). Geno-identical allogeneic SCT was performed in 55 patients, and 3 patients received donor lymphocyte infusions. Forty-four transplantations were performed from an unrelated donor (of which four were cord blood). We conclude that most adult patients with recurring ALL could not be rescued using current available therapies, although allogeneic SCT remains the best therapeutic option.

  9. Preferential loss of mismatch repair function in refractory and relapsed acute myeloid leukemia: potential contribution to AML progression

    Institute of Scientific and Technical Information of China (English)

    Guogen Mao; Fenghua Yuan; Kimberly Absher; C Darrell Jennings; Dianna S Howard; Craig T Jordan; Liya Gu

    2008-01-01

    Acute myeloid leukemia (AML) is an aggressive hematological cancer. Despite therapeutic regimens that lead to complete remission, the vast majority of patients undergo relapse. The molecular mechanisms underlying AML development and relapse remain incompletely defined. To explore whether loss of DNA mismatch repair (MMR) function is involved in AML, we screened two key MMR genes, MSH2 and MLH1, for mutations and promoter hypermethylation in leukemia specimens from 53 AML patients and blood from 17 non-cancer controls. We show here that whereas no amino acid alteration or promoter hypermethylation was detected in all control samples, 18 AML patients exhibited either mutations in MMR genes or hypermethylation in the MLH1 promoter. In vitro functional MMR analysis revealed that almost all the mutations analyzed resulted in loss of MMR function. MMR defects were significantly more frequent in patients with refractory or relapsed AML compared with newly diagnosed patients. These observations suggest for the first time that the loss of MMR function is associated with refractory and relapsed AML and may contribute to disease pathogenesis.

  10. Superior GVHD-free, relapse-free survival for G-BM to G-PBSC grafts is associated with higher MDSCs content in allografting for patients with acute leukemia.

    Science.gov (United States)

    Fan, Qian; Liu, Hui; Liang, Xinquan; Yang, Ting; Fan, Zhiping; Huang, Fen; Ling, Yiwen; Liao, Xin; Xuan, Li; Xu, Na; Xu, Xiaojun; Ye, Jieyu; Liu, Qifa

    2017-07-04

    Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (G-PBSC) has largely replaced unstimulated bone marrow (un-BM) for allografting because of accelerated engraftment, but with a higher morbidity and mortality of graft-versus-host-disease (GVHD). Recent studies suggested that G-CSF-primed BM (G-BM) had similar engraftment but lower morbidity and mortality of GVHD comparing to G-PBSC. A prospective, randomized, multicenter study was conducted to compare G-BM with G-PBSC as the grafts in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia in first complete remission (CR1). Totally 101 adult leukemia in CR1 undergoing HLA-identical sibling transplants were randomized into G-BM or G-PBSC group. The primary study endpoint was GVHD-free/relapse-free survival (GRFS). Both the engraftment of neutrophil and platelet were 2 days later in G-BM than in G-PBSC group (P = 0.412, P = 0.39). G-BM group showed significantly lower II-IV acute GVHD (aGVHD) and similar III-IV aGVHD compared with G-PBSC group (12.2% vs 28.8% for II-IV, P = 0.048; 4.1% vs 9.6% for III-IV aGVHD, P = 0.267, respectively). The overall cumulative incidence of chronic GVHD (cGVHD) at 3 years were 22.3% ± 6.3% and 44.8% ± 7.6% (P = 0.026), respectively, and extensive cGHVD were 4.5% ± 3.1% and 15% ± 5.3% (P = 0.08), respectively, in G-BM and G-PBSC groups. Two groups had similar 3-year relapse, transplant-related mortality (TRM), overall survival (OS), and disease-free survival (DFS) (all P > 0.05). G-BM group showed significantly higher probability of GRFS than G-PBSC group (73.5% ± 6.3% vs 55.8% ± 6.9% at 1 year, P = 0.049; 69.0% ± 6.7% vs 49.7% ± 7.0% at 2 and 3 years, P = 0.03, respectively). Graft content analysis revealed statistically higher frequency of myeloid-derived suppressor cells (MDSCs) in the G-BM than in G-PBSC grafts (P G-BM than in G-PBSC group (P

  11. Treatment of newly diagnosed and relapsed acute promyelocytic leukemia with intravenous liposomal all-trans retinoic acid.

    Science.gov (United States)

    Douer, D; Estey, E; Santillana, S; Bennett, J M; Lopez-Bernstein, G; Boehm, K; Williams, T

    2001-01-01

    A novel intravenous liposomal formulation of all-trans retinoic acid (ATRA) was evaluated in 69 patients with acute promyelocytic leukemia (APL): 32 new diagnoses, 35 relapses, and 2 oral ATRA failures. Liposomal ATRA (90 mg/m(2)) was administered every other day until complete remission (CR) or a maximum of 56 days. Treatment following CR was liposomal ATRA with or without chemotherapy. In an intent-to-treat (ITT) analysis of all patients, CR rates were 62%, 70%, and 20% in newly diagnosed, group 1 first relapses (ATRA naive or off oral ATRA more than or equal to 1 year), or group 2 relapses (second or subsequent relapse or first relapses off oral ATRA less than 1 year), respectively. In 56 evaluable patients (receiving 4 or more doses), CR rates for the same groups were 87% (20 of 23), 78% (14 of 18), and 23% (3 of 13). Remission failure in newly diagnosed patients was not from resistant disease. Several patients in CR became polymerase chain reaction (PCR) negative for promyelocytic leukemia/retinoic acid receptor-alpha (PML/RARalpha) after liposomal ATRA alone. Toxicity was generally mild, most commonly headaches (67. 5%). Eighteen patients (26%) had ATRA syndrome develop during induction. One-year survival of ITT patients was 62%, 56%, and 20% for newly diagnosed, group 1, and group 2, respectively. The medium duration of CR has not yet been reached and was 18 and 5.5 months in the same groups. These results demonstrate that liposomal ATRA is effective in inducing CR in newly diagnosed or group 1 APL patients. It provides a reliable dosage of ATRA for patients with APL unable to swallow or absorb medications and can induce molecular remissions without chemotherapy.

  12. RNA sequencing unravels the genetics of refractory/relapsed T-cell acute lymphoblastic leukemia. Prognostic and therapeutic implications

    Science.gov (United States)

    Gianfelici, Valentina; Chiaretti, Sabina; Demeyer, Sofie; Di Giacomo, Filomena; Messina, Monica; La Starza, Roberta; Peragine, Nadia; Paoloni, Francesca; Geerdens, Ellen; Pierini, Valentina; Elia, Loredana; Mancini, Marco; De Propris, Maria Stefania; Apicella, Valerio; Gaidano, Gianluca; Testi, Anna Maria; Vitale, Antonella; Vignetti, Marco; Mecucci, Cristina; Guarini, Anna; Cools, Jan; Foà, Robin

    2016-01-01

    Despite therapeutic improvements, a sizable number of patients with T-cell acute lymphoblastic leukemia still have a poor outcome. To unravel the genomic background associated with refractoriness, we evaluated the transcriptome of 19 cases of refractory/early relapsed T-cell acute lymphoblastic leukemia (discovery cohort) by performing RNA-sequencing on diagnostic material. The incidence and prognostic impact of the most frequently mutated pathways were validated by Sanger sequencing on genomic DNA from diagnostic samples of an independent cohort of 49 cases (validation cohort), including refractory, relapsed and responsive cases. Combined gene expression and fusion transcript analyses in the discovery cohort revealed the presence of known oncogenes and identified novel rearrangements inducing overexpression, as well as inactivation of tumor suppressor genes. Mutation analysis identified JAK/STAT and RAS/PTEN as the most commonly disrupted pathways in patients with chemorefractory disease or early relapse, frequently in association with NOTCH1/FBXW7 mutations. The analysis on the validation cohort documented a significantly higher risk of relapse, inferior overall survival, disease-free survival and event-free survival in patients with JAK/STAT or RAS/PTEN alterations. Conversely, a significantly better survival was observed in patients harboring only NOTCH1/FBXW7 mutations: this favorable prognostic effect was abrogated by the presence of concomitant mutations. Preliminary in vitro assays on primary cells demonstrated sensitivity to specific inhibitors. These data document the negative prognostic impact of JAK/STAT and RAS/PTEN mutations in T-cell acute lymphoblastic leukemia and suggest the potential clinical application of JAK and PI3K/mTOR inhibitors in patients harboring mutations in these pathways. PMID:27151993

  13. Treatment of acute relapses in multiple sclerosis at home with oral dexamethasone : a pilot study

    NARCIS (Netherlands)

    De Keyser, J; Zwanikken, C; Zorgdrager, A; Oenema, D

    1999-01-01

    The objective of this study was to investigate the feasibility of treating relapses of multiple sclerosis (MS) at home with oral dexamethasone. Twenty-five out of 28 consecutive patients with MS who presented with a relapse of less than 2 weeks' duration were treated on an open basis with oral dexam

  14. Long-term Survival and Late Effects among 1-year Survivors of Second Allogeneic Hematopoietic Cell Transplantation for Relapsed Acute Leukemia and Myelodysplastic Syndromes

    Science.gov (United States)

    Duncan, Christine N.; Majhail, Navneet S.; Brazauskas, Ruta; Wang, Zhiwei; Cahn, Jean-Yves; Frangoul, Haydar A.; Hayashi, Robert J.; Hsu, Jack W.; Kamble, Rammurti T.; Kasow, Kimberly A.; Khera, Nandita; Lazarus, Hillard M.; Loren, Alison W.; Marks, David I.; Maziarz, Richard T.; Mehta, Paulette; Myers, Kasiani C.; Norkin, Maxim; Pidala, Joseph A.; Porter, David L.; Reddy, Vijay; Saber, Wael; Savani, Bipin N.; Schouten, Harry C.; Steinberg, Amir; Wall, Donna A.; Warwick, Anne B.; Wood, William A.; Yu, Lolie C.; Jacobsohn, David A.; Sorror, Mohamed L.

    2014-01-01

    We analyzed the outcomes of patients who survived disease-free for 1-year or more following second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant following disease relapse; among these 325 survived relapse-free at 1-year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplant in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least one year were 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status prior to second HCT was significantly associated with higher risk for overall mortality (HR 1.71 for patients with disease not in complete remission prior to second HCT, Ptransplant. Chronic GVHD was the leading cause of non-relapse mortality followed by organ failure and infection. The cumulative incidence of developing at least one of the studied late effects at 10-years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence 22%) and cataracts (20%), and in adults were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease-free for at least 1-year, many can be expected to survive long term. However, they continue to be at risk for relapse and non-relapse morbidity and mortality. Novel approaches are needed to minimize relapse risk and long-term transplant morbidity in this population. PMID:25316109

  15. Clinicopathological features of acute promyelocytic leukemia: an experience in one institute emphasizing the morphological and immunophenotypic changes at the time of relapse.

    Science.gov (United States)

    Yoshii, Miyuki; Ishida, Mitsuaki; Yoshida, Takashi; Okuno, Hiroko; Nakanishi, Ryota; Horinouchi, Akiko; Hodohara, Keiko; Okabe, Hidetoshi

    2013-01-01

    Acute promyelocytic leukemia (APL) has two morphological variants, namely macrogranular (M3) and microgranular (M3v). M3v, characterized by the presence of neoplastic promyelocytes with only sparse fine azurophilic granules, accounts for 10-25% of all APL and has unique biological characteristics. Relapse occurs in approximately 20% of patients with APL. The morphological type of the leukemic cells at relapse is usually identical with the primary disease, and only one case of morphological change at relapse has been reported. Here, we analyzed the clinicopathological features of APL, including 4 relapsed cases emphasizing morphological changes at the time of relapse. The unique finding of the present study is that 2 of 4 relapsed cases changed from M3 to M3v at relapse. The morphological features of these were different in each case (one had blastic features and the other resembled monocytoid leukemic cells). Cytogenetic analyses revealed the continued presence of t(15;17)(q22;q12) at the time of relapse and morphological change. Moreover, the immune phenotype of the leukemic cells changed from CD2(-)/CD34(-) to CD2(+)/CD34(+) at that time. These findings suggest that morphological change at relapse in APL may not be a rare event, and that the leukemic cells can show variable morphological features at the time of relapse, which could result in misdiagnosis as a different type of acute myeloid leukemia. Therefore, a comprehensive approach with emphasis on combined morphological, immunophenotypic, and cytogenetic analyses is important for diagnosis and appropriate treatment of relapsed APL.

  16. An improved anti-leukemic effect achieved with donor progenitor cell infusion for relapse patients after allogeneic bone marrow transplantation

    Institute of Scientific and Technical Information of China (English)

    黄晓军; 郭乃榄; 任汉云; 张耀臣; 高志勇; 陆道培

    2003-01-01

    Objective To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.Methods Twenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n=11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n=9).Results Five patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.Conclusion Donor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.

  17. A Predictive Model for Corticosteroid Response in Individual Patients with MS Relapses

    Science.gov (United States)

    Rakusa, Martin; Cano, Stefan J.; Porter, Bernadette; Riazi, Afsane; Thompson, Alan J.; Chataway, Jeremy; Hardy, Todd A.

    2015-01-01

    Objectives To derive a simple predictive model to guide the use of corticosteroids in patients with relapsing remitting MS suffering an acute relapse. Materials and Methods We analysed individual patient randomised controlled trial data (n=98) using a binary logistic regression model based on age, gender, baseline disability scores [physician-observed: expanded disability status scale (EDSS) and patient reported: multiple sclerosis impact scale 29 (MSIS-29)], and the time intervals between symptom onset or referral and treatment. Results Based on two a priori selected cut-off points (improvement in EDSS ≥ 0.5 and ≥ 1.0), we found that variables which predicted better response to corticosteroids after 6 weeks were younger age and lower MSIS-29 physical score at the time of relapse (model fit 71.2% - 73.1%). Conclusions This pilot study suggests two clinical variables which may predict the majority of the response to corticosteroid treatment in patients undergoing an MS relapse. The study is limited in being able to clearly distinguish factors associated with treatment response or spontaneous recovery and needs to be replicated in a larger prospective study. PMID:25785460

  18. Lineage switch in relapse of acute leukemia with rearrangement of MLL gene (KMT2A. literature review and case reports

    Directory of Open Access Journals (Sweden)

    E. A. Zerkalenkova

    2016-01-01

    Full Text Available Lineage switch is a rare phenomenon in which a transition from lymphoid to myeloid was observed in relapse of acute leukemia, or vice versa. This paper presents the four clinical case reports of acute lymphoblastic leukemia with MLL gene rearrangement (KMT2A with myeloid phenotype in relapse.

  19. Gemcitabine Induced Radiation Recall Myositis in a Patient with Relapsed Nasopharyngeal Carcinoma

    Science.gov (United States)

    Patel, Sagar C.; Paulino, Arnold C.; Johnston, Danielle; Wiederhold, Lee; Castillo, Richard; Venkatramani, Rajkumar

    2016-01-01

    Radiation recall reaction is an acute inflammatory response evident in previously irradiated fields, induced by chemotherapy administration. Sixteen-year-old female with relapsed nasopharyngeal carcinoma was treated with gemcitabine and oxaliplatin. Disease remission was observed after four cycles. After the seventh cycle, patient developed acute pain and swelling involving the neck muscles. The affected muscles were within the previous irradiation field. Her symptoms improved with corticosteroid treatment. In contrast to other chemotherapy agents, gemcitabine can induce recall reaction involving deeper tissues. Gemcitabine therapy should be discontinued in the event of a radiation recall, as subsequent exposure will likely exacerbate symptoms. PMID:27637134

  20. Relapses in bipolar patients: changes in social rhythm?

    Science.gov (United States)

    Kadri, Nadia; Mouchtaq, Nadia; Hakkou, Farid; Moussaoui, Driss

    2000-03-01

    The Ramadan month represents a valuable opportunity to test the hypothesis that the course of the illness of bipolar patients can be disrupted by the change in social rhythm which usually occurs during this month. The objectives of this study were to follow up the mood state and blood lithium level of fasting Muslim bipolar patients who had been on lithium therapy for at least 3 months, and were clinically stable before being included in the study. Twenty bipolar patients were enrolled during the month of Ramadan in 1997. Diagnosis of bipolar disorder was according to ICD-10 criteria. Patients were assessed during the week before Ramadan, the second and the fourth weeks of the fasting month and the first week after its end, with the Hamilton Depression and Bech-Rafaelsen scales. The plasma concentration of lithium was also assessed. The main finding of the study was that 45% of the patients relapsed, 70% during the second week and the remaining patients at the end of Ramadan. These relapses were not related to plasma concentration of lithium. Most of the relapses were manic (71.4 %). Patients who did not relapse had insomnia and anxiety during the second and third weeks of the study. Side-effects of lithium increased and were observed in 48% of the sample, mostly dryness of the mouth with thirst and tremor. The result of this pilot study indicates that the Ramadan month may disrupt the mood state of bipolar patients. More studies are needed to confirm this observation and to evaluate the validity of the Ramadan model to study the impact of social rhythms on bipolar patients.

  1. Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-01-22

    Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  2. Prediction of immunophenotype, treatment response, and relapse in childhood acute lymphoblastic leukemia using DNA microarrays

    DEFF Research Database (Denmark)

    Willenbrock, Hanni; Juncker, Agnieszka; Schmiegelow, K.

    2004-01-01

    Gene expression profiling is a promising tool for classification of pediatric acute lymphoblastic leukemia ( ALL). We analyzed the gene expression at the time of diagnosis for 45 Danish children with ALL. The prediction of 5-year event-free survival or relapse after treatment by NOPHO-ALL92 or 2000...

  3. ASSOCIATION OF POLYMORPHISM IN BIOTRANSFORMATION SYSTEM GENES CYP1A1 AND GST WITH RISK OF RELAPSE IN CHILDHOOD ACUTE LEUKEMIA

    Directory of Open Access Journals (Sweden)

    O.A. Gra

    2007-01-01

    Full Text Available Presence of polymorphism in genes coding biotransformation system may play an important role in formation of primary childhood acute leukemia, and affects the incidence and features of relapse. We developed a biological microchip which allows to analyze 14 mutations in eight genes of biotransfor mation system: cyp1a1, cyp2d6, gstt1, gstm1, nat2, mthfr, cyp2c9 and cyp2c19. This biochip has been used to study DNA samples from 332 children with diagnosis of acute lymphoblastic leukemia (all and 71 children with diagnosis of acute myeloblastic leukemia (AML. it was obtained that variant genotype cyp1a1 *1/*2а more often occur in children with relapse of disease than in children with primary diagnosed leukemia (or = 2,11, p = 0,0291. Also it has been shown, that «null» gstt1 genotype is less frequent in children with relapse of disease than in children with primary diagnosed leukemia (or = 0,55, p = 0,0265. Upon sex stratification, boys with relapse of all demonstrated an increased occurrence of the cyp1a1 genotype *1/*2а in combination with the gstt1 «nonnull» genotype relative to patients with primarily diagnosed all (or = 3,09, p = 0,0254. In addition, girls with relapse of acute leukemia displayed a 2,4_fold lower frequency of the «null» gstm1 genotype as compared with the girls group with primary leukemia (or = 0,41, p = 0,0175. Thus, it was shown that studied genotypes cyp1a1 and GST might be prognostic risk factors of relapse in childhood acute leukemia.Key words: acute leukemia, drug resistance, cytochrome p 450, glutathione-s-transferases, polymorphism, oligonucleotide biochips.

  4. A therapeutic trial of decitabine and vorinostat in combination with chemotherapy for relapsed/refractory acute lymphoblastic leukemia.

    Science.gov (United States)

    Burke, Michael J; Lamba, Jatinder K; Pounds, Stanley; Cao, Xueyuan; Ghodke-Puranik, Yogita; Lindgren, Bruce R; Weigel, Brenda J; Verneris, Michael R; Miller, Jeffrey S

    2014-09-01

    DNA hypermethylation and histone deacetylation are pathways of leukemia resistance. We investigated the tolerability and efficacy of decitabine and vorinostat plus chemotherapy in relapse/refractory acute lymphoblastic leukemia (ALL). Decitabine (15 mg/m(2) iv) and vorinostat (230 mg/m(2) PO div BID) were given days 1-4 followed by vincristine, prednisone, PEG-asparaginase, and doxorubicin. Genome wide methylation profiles were performed in 8 matched patient bone marrow (BM) samples taken at day 0 and day 5 (postdecitabine). The median age was 16 (range, 3-54) years. All patients had a prior BM relapse, with five relapsing after allogeneic transplant. The most common nonhematological toxicities possibly related to decitabine or vorinostat were infection with neutropenia (grade 3; n = 4) and fever/neutropenia (grade 3, n = 4; grade 4, n = 1). Of the 13 eligible patients, four achieved complete remission without platelet recovery (CRp), two partial response (PR), one stable disease (SD), one progressive disease (PD), two deaths on study and three patients who did not have end of therapy disease evaluations for an overall response rate of 46.2% (CRp + PR). Following decitabine, significant genome-wide hypo-methylation was observed. Comparison of clinical responders with nonresponders identified methylation profiles of clinical and biological relevance. Decitabine and vorinostat followed by re-Induction chemotherapy was tolerable and demonstrated clinical benefit in relapsed patients with ALL. Methylation differences were identified between responders and nonresponders indicating interpatient variation, which could impact clinical outcome. This study was registered at www.clinicaltrials.gov as NCT00882206.

  5. Spontaneous Remission in an Older Patient with Relapsed FLT3 ITD Mutant AML

    Directory of Open Access Journals (Sweden)

    Pankit Vachhani

    2016-01-01

    Full Text Available Spontaneous remission (SR of acute myeloid leukemia (AML is a very rare phenomenon. AML characterized by FLT3 internal tandem duplication (FLT3 ITD is typically associated with an aggressive clinical course with rapid progression, relapse, and short overall survival in the absence of transplantation. We report here the first case of SR of FLT3 ITD mutant AML in the literature. Our patient was an elderly woman with relapsed NPM1 and FLT3 ITD mutant AML whose disease underwent SR for a brief duration without precipitating cause. We review the potential immune mechanisms underlying SR in AML and discuss the implications for novel immunotherapeutic approaches for FLT3 mutant AML.

  6. Testicular relapse of acute lymphocytic leukemia: Usefulness of color and power Doppler sonography

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kwang Hun; Yoon, Choon Sik; Lee, Sung Il; Kim, Myung Joon [Yonsei University College of Medicine, Seoul (Korea, Republic of); Yang, Chang Hyun [Yang Dong Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1999-09-15

    To evaluate the usefulness of color and power Doppler sonography in detecting testicular relapse of leukemia. Both gray- scale and color (power) Doppler ultrasound (US) were performed in seven patients. Two additional patients examined by gray-scale US only were included. The patients were 4-14 years old (mean age, 9 years). Ten tests were confirmed to have leukemic relapse, eight by pathology and two by clinical evidence. Gray-scale US showed variable findings: heterogeneous hypoechogenicity (5) and homogeneous isoechogenicity (5). In all seven patients (8 tests) who underwent both color and power Doppler US, diffuse and marked hypervascularity was demonstrated. One case showed enlarged epididymis with heterogeneous echogenicity, which was the same character as the involved testis. Color and power Doppler US are useful methods in the identification of the testicular relapse of leukemia by demonstrating diffuse, marked hypervascularity in the proper clinical settings.

  7. Relapse Prevention in Major Depressive Disorder After Successful Acute Electroconvulsive Treatment

    DEFF Research Database (Denmark)

    Martiny, K; Larsen, E R; Licht, R W

    2015-01-01

    ) score≤9) received randomly escitalopram 10 mg, 20 mg, 30 mg or nortriptyline 100 mg as monotherapies and were followed for 6 months in a multicentre double-blind set-up. Primary endpoint was relapse (HAM-D17≥16). RESULTS: As inclusion rate was low the study was prematurely stopped with only 47 patients...... randomised (20% of the planned sample size). No statistically significant between-group differences could be detected. When all patients receiving escitalopram were compared with those receiving nortriptyline, a marginal superiority of nortriptyline was found (p=0.08). One third of patients relapsed during...

  8. Core-binding factor acute myeloid leukemia in first relapse: a retrospective study from the French AML Intergroup.

    Science.gov (United States)

    Hospital, Marie-Anne; Prebet, Thomas; Bertoli, Sarah; Thomas, Xavier; Tavernier, Emmanuelle; Braun, Thorsten; Pautas, Cécile; Perrot, Aurore; Lioure, Bruno; Rousselot, Philippe; Tamburini, Jérôme; Cluzeau, Thomas; Konopacki, Johanna; Randriamalala, Edouard; Berthon, Céline; Gourin, Marie-Pierre; Recher, Christian; Cahn, Jean-Yves; Ifrah, Norbert; Dombret, Hervé; Boissel, Nicolas

    2014-08-21

    Although core-binding factor-acute myeloid leukemia (CBF-AML) (t[8;21] or inv[16]/t[16;16]) represents a favorable cytogenetic AML subgroup, 30% to 40% of these patients relapse after standard intensive chemotherapy. The encouraging results of gemtuzumab ozogamicin (GO) in newly diagnosed AML, and particularly in CBF-AML, incited us to retrospectively investigate the impact of GO-based salvage in these patients. We retrospectively analyzed the outcome of 145 patients with CBF-AML (59 t[8;21], 86 inv[16]/t[16;16]) in first relapse. As salvage, 48 patients received GO-based chemotherapy and 97 patients received conventional chemotherapy. Median age was 43 years (range, 16-76). Median first complete remission duration was 12.1 months (range, 2.1-93.6). Overall, second complete remission (CR2) rate was 88%. With a median follow-up from relapse of 3.5 years, the estimated 5-year disease-free survival (DFS) was 50% and 5-year overall survival (OS) was 51%. Older age and shorter first complete remission duration was associated with a shorter OS. Patients treated with GO had similar CR2 rate but significantly higher 5-year DFS (68% vs 42%; P = .05) and OS (65% vs 44%; P = .02). In multivariate analysis, GO salvage was still associated with a significant benefit in DFS and OS. In the 78 patients who received allogeneic hematopoietic stem cell transplantation in CR2, GO before transplant significantly improved posttransplant DFS and OS without excess of treatment-related mortality.

  9. Defining the Survival Benchmark for Breast Cancer Patients with Systemic Relapse

    OpenAIRE

    Zeichner, Simon B.; Tadeu Ambros; John Zaravinos; Montero, Alberto J.; Mahtani, Reshma L; Ahn, Eugene R; Aruna Mani; Markward, Nathan J; Vogel, Charles L.

    2015-01-01

    BACKGROUND Our original paper, published in 1992, reported a median overall survival after first relapse in breast cancer of 26 months. The current retrospective review concentrates more specifically on patients with first systemic relapse, recognizing that subsets of patients with local recurrence are potentially curable. METHODS Records of 5,168 patients from a largely breast-cancer-specific oncology practice were reviewed to identify breast cancer patients with their first relapse between ...

  10. Expression profile and specific network features of the apoptotic machinery explain relapse of acute myeloid leukemia after chemotherapy

    Directory of Open Access Journals (Sweden)

    Di Pietro Cinzia

    2010-07-01

    Full Text Available Abstract Background According to the different sensitivity of their bone marrow CD34+ cells to in vitro treatment with Etoposide or Mafosfamide, Acute Myeloid Leukaemia (AML patients in apparent complete remission (CR after chemotherapy induction may be classified into three groups: (i normally responsive; (ii chemoresistant; (iii highly chemosensitive. This inversely correlates with in vivo CD34+ mobilization and, interestingly, also with the prognosis of the disease: patients showing a good mobilizing activity are resistant to chemotherapy and subject to significantly higher rates of Minimal Residual Disease (MRD and relapse than the others. Based on its known role in patients' response to chemotherapy, we hypothesized an involvement of the Apoptotic Machinery (AM in these phenotypic features. Methods To investigate the molecular bases of the differential chemosensitivity of bone marrow hematopoietic stem cells (HSC in CR AML patients, and the relationship between chemosensitivity, mobilizing activity and relapse rates, we analyzed their AM expression profile by performing Real Time RT-PCR of 84 AM genes in CD34+ pools from the two extreme classes of patients (i.e., chemoresistant and highly chemosensitive, and compared them with normal controls. Results The AM expression profiles of patients highlighted features that could satisfactorily explain their in vitro chemoresponsive phenotype: specifically, in chemoresistant patients we detected up regulation of antiapoptotic BIRC genes and down regulation of proapoptotic APAF1, FAS, FASL, TNFRSF25. Interestingly, our analysis of the AM network showed that the dysregulated genes in these patients are characterized by high network centrality (i.e., high values of betweenness, closeness, radiality, stress and high involvement in drug response. Conclusions AM genes represent critical nodes for the proper execution of cell death following pharmacological induction in patients. We propose that their

  11. 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.

  12. Hypertension and Life-Threatening Bleeding in Children with Relapsed Acute Myeloblastic Leukemia Treated with FLT3 Inhibitors

    Directory of Open Access Journals (Sweden)

    Deniz Yılmaz Karapınar

    2015-09-01

    Full Text Available Experiences with new multikinase inhibitors are limited, especially in children. In this report we summarize our experience with 2 patients with relapsed acute myeloblastic leukemia (AML, one with FMS-like tyrosine kinase-3-internal tandem duplication mutation and the other with a single base mutation (D835Y. Both patients received sorafenib, one for 19 days and the other for 42 days, with clofarabine-including chemotherapy. One additionally received sunitinib for a total of 20 days. Both patients developed severe pancytopenia, hypertension, life-threatening bleedings from the gastrointestinal system, and, finally, intrapulmonary hemorrhage. Although both reached severe aplasia of the bone marrow without blastic infiltration, death occurred with neutropenic sepsis.

  13. Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial

    Science.gov (United States)

    Platzbecker, U; Wermke, M; Radke, J; Oelschlaegel, U; Seltmann, F; Kiani, A; Klut, I-M; Knoth, H; Röllig, C; Schetelig, J; Mohr, B; Graehlert, X; Ehninger, G; Bornhäuser, M; Thiede, C

    2012-01-01

    This study evaluated azacitidine as treatment of minimal residual disease (MRD) determined by a sensitive donor chimerism analysis of CD34+ blood cells to pre-empt relapse in patients with CD34+ myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT). At a median of 169 days after HSCT, 20/59 prospectively screened patients experienced a decrease of CD34+ donor chimerism to <80% and received four azacitidine cycles (75 mg/m2/day for 7 days) while in complete hematologic remission. A total of 16 patients (80%) responded with either increasing CD34+ donor chimerism to ⩾80% (n=10; 50%) or stabilization (n=6; 30%) in the absence of relapse. Stabilized patients and those with a later drop of CD34+ donor chimerism to <80% after initial response were eligible for subsequent azacitidine cycles. A total of 11 patients (55%) received a median of 4 (range, 1–11) additional cycles. Eventually, hematologic relapse occurred in 13 patients (65%), but was delayed until a median of 231 days (range, 56–558) after initial decrease of CD34+ donor chimerism to <80%. In conclusion, pre-emptive azacitidine treatment has an acceptable safety profile and can substantially prevent or delay hematologic relapse in patients with MDS or AML and MRD after allogeneic HSCT. PMID:21886171

  14. Targeting interleukin-2 to the bone marrow stroma for therapy of acute myeloid leukemia relapsing after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Schliemann, Christoph; Gutbrodt, Katrin L; Kerkhoff, Andrea; Pohlen, Michele; Wiebe, Stefanie; Silling, Gerda; Angenendt, Linus; Kessler, Torsten; Mesters, Rolf M; Giovannoni, Leonardo; Schäfers, Michael; Altvater, Bianca; Rossig, Claudia; Grünewald, Inga; Wardelmann, Eva; Köhler, Gabriele; Neri, Dario; Stelljes, Matthias; Berdel, Wolfgang E

    2015-05-01

    The antibody-based delivery of IL2 to extracellular targets expressed in the easily accessible tumor-associated vasculature has shown potent antileukemic activity in xenograft and immunocompetent murine models of acute myelogenous leukemia (AML), especially in combination with cytarabine. Here, we report our experience with 4 patients with relapsed AML after allogeneic hematopoietic stem cell transplantation (allo-HSCT), who were treated with the immunocytokine F16-IL2, in combination with low-dose cytarabine. One patient with disseminated extramedullary AML lesions achieved a complete metabolic response identified by PET/CT, which lasted 3 months. Two of 3 patients with bone marrow relapse achieved a blast reduction with transient molecular negativity. One of the 2 patients enjoyed a short complete remission before AML relapse occurred 2 months after the first infusion of F16-IL2. In line with a site-directed delivery of the cytokine, F16-IL2 led to an extensive infiltration of immune effector cells in the bone marrow. Grade 2 fevers were the only nonhematologic side effects in 2 patients. Grade 3 cytokine-release syndrome developed in the other 2 patients but was manageable in both cases with glucocorticoids. The concept of specifically targeting IL2 to the leukemia-associated stroma deserves further evaluation in clinical trials, especially in patients who relapse after allo-HSCT. ©2015 American Association for Cancer Research.

  15. Mutations of the epigenetics-modifying gene (DNMT3a, TET2, IDH1/2) at diagnosis may induce FLT3-ITD at relapse in de novo acute myeloid leukemia.

    Science.gov (United States)

    Wakita, S; Yamaguchi, H; Omori, I; Terada, K; Ueda, T; Manabe, E; Kurosawa, S; Iida, S; Ibaraki, T; Sato, Y; Todoroki, T; Hirakawa, T; Ryotokuji, T; Arai, K; Kitano, T; Mitamura, Y; Kosaka, F; Dan, K; Inokuchi, K

    2013-04-01

    Gene mutations were found in acute myeloid leukemia (AML) and their importance has been noted. To clarify the importance and stability of mutations, we examined gene mutations in paired samples at diagnosis and relapse of 34 adult AML patients. Five acquired gene mutations were detected at relapse. Of the 45 gene mutations at diagnosis, 11 of them were lost at relapse. The acquired mutations at relapse were all class I mutations as Fms-like tyrosine kinase 3 (FLT3) and rat sarcoma viral oncogene homolog (RAS) mutations. The disappeared mutations at relapse were 3 of 11 internal tandem duplications of FLT3 (FLT3-ITD) (27.3%), 3 of 3 FLT3 tyrosine kinase domain (FLT3-TKD) (100%), 3 of 13 Nucleophosmin 1 (23.1%) and 2 of 5 CCAAT/enhancer-binding protein-α (40%) mutations. However, epigenetics-modifying gene (DNMT3a, TET2 and IDH1/2) mutations had no change between diagnosis and relapse samples, and may become minimal residual disease marker. The frequency of FLT3-ITD at relapse in patients with DNMT3a mutation at diagnosis is significantly higher than those in patients without them (P=0.001). Moreover, the high frequency of FLT3-ITD at relapse is also seen in AML cases that initially present with any epigenetics-modifying gene mutations (Pgene mutations may cause genetic instability and induce FLT3-ITD, leading to resistance to therapy and relapse.

  16. Unilateral optic disk edema with central retinal artery and vein occlusions as the presenting signs of relapse in acute lymphoblastic leukemia.

    Science.gov (United States)

    Salazar Méndez, R; Fonollá Gil, M

    2014-11-01

    A 39-year-old man with Philadelphia chromosome-positive acute lymphoblastic leukemia (LAL Ph+) developed progressive vision loss to no light perception in his right eye. He had optic disk edema and later developed central artery and vein occlusions. Pan-photocoagulation, as well as radiotherapy of the whole brain were performed in several fractions. Unfortunately the patient died of hematological relapse 4 months later. Optic nerve infiltration may appear as an isolated sign of a leukemia relapse, even before a hematological relapse occurs. Leukemic optic neuropathy is a critical sign, not only for vision, but also for life, and radiotherapy should be immediately performed before irreversible optic nerve damage occurs. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  17. Survival of pediatric patients after relapsed osteosarcoma: the St. Jude Children’s Research Hospital experience

    Science.gov (United States)

    Leary, Sarah E. S.; Wozniak, Amy W.; Billups, Catherine A.; Wu, Jianrong; McPherson, Valerie; Neel, Michael D.; Rao, Bhaskar N.; Daw, Najat C.

    2013-01-01

    Background Chemotherapy has improved the outcome of patients with newly diagnosed osteosarcoma, but its role in relapsed disease is unclear. Methods We reviewed the records of all patients who were treated for relapsed high-grade osteosarcoma at our institution between 1970 and 2004. Post-relapse event-free survival (PREFS) and post-relapse survival (PRS) were estimated, and outcome comparisons were made using the exact log-rank test. Results The 10-year PREFS and PRS of the 110 patients were 11.8% ± 3.5% and 17.0% ± 4.3%, respectively. Metastasis at initial diagnosis (14%), and relapse in lung only (75%) were not significantly associated with PREFS or PRS. Time from initial diagnosis to first relapse (RL1) ≥18 months (43%), surgery at RL1 (76%), and ability to achieve second complete remission (CR2, 56%) were favorably associated with PREFS and PRS (p≤0.0002). In patients without CR2, chemotherapy at RL1 was favorably associated with PREFS (p=0.01) but not with PRS. In patients with lung relapse only, unilateral relapse and number of nodules (≤3) were associated with better PREFS and PRS (p≤0.0005); no patients with bilateral relapse survived 10 years. The median PREFS after treatment with cisplatin, doxorubicin, methotrexate, and ifosfamide was 3.5 months (95% CI, 2.1-5.2) and median PRS 8.2 months (95% CI, 5.2-15.1). Conclusions Late relapse, surgical resection, and unilateral involvement (in lung relapse only) favorably impact outcome after relapse. Surgery is essential for survival; chemotherapy may slow disease progression in patients without CR2. These data are useful for designing clinical trials that evaluate novel agents. PMID:23625626

  18. Administration of alemtuzumab and G-CSF to adults with relapsed or refractory acute lymphoblastic leukemia: results of a phase II study.

    Science.gov (United States)

    Gorin, Norbert-Claude; Isnard, Françoise; Garderet, Laurent; Ikhlef, Souhila; Corm, Selim; Quesnel, Bruno; Legrand, Ollivier; Cachanado, Marine; Rousseau, Alexandra; Laporte, Jean-Philippe

    2013-10-01

    The outlook for adults with refractory and relapsed acute lymphocytic leukemia (ALL) is poor. CD52 is expressed in most patients with ALL. Alemtuzumab is an anti-CD52 humanized monoclonal antibody. This phase II study assessed the efficacy of alemtuzumab combined with granulocyte-colony stimulating factor (G-CSF) to boost antibody-dependent cell cytotoxicity mediated by neutrophils. Twelve patients with relapsed (n = 11) or refractory (n = 1) ALL, including four relapses postallogeneic stem cell transplantation, were treated and monitored between October 2006 and January 2011. Patients received 1 wk of alemtuzumab every other day at increasing doses of 3, 10, and 30 mg to test tolerance and 30 mg three times a week for 12-18 infusions. If in complete remission (CR), patients received maintenance therapy for 1 wk, every 2 months. G-CSF was administered at 5 μg/kg per day during alemtuzumab administration. The primary endpoint was disappearance of blast cells on a marrow aspirate. CD52 was expressed in all patients. Four patients reached CR. In one additional patient, clearance of blast cells was observed in peripheral blood but not in the marrow. The most frequent adverse events during course 1 of treatment were fever and chills (n = 3), skin rash (n = 3), and bronchospasm (n = 2). Tumor lysis syndrome was observed at treatment initiation in one patient who reached CR. All patients progressed within a few months and all but one died. The surviving patient is still alive after relapse and a second allogeneic stem cell transplantation. This study shows that in relapse/refractory ALL, alemtuzumab with G-CSF can produce good responses of short duration.

  19. Outcome of patients developing GVHD after DLI given to treat CML relapse: a study by the Chronic Leukemia Working Party of the EBMT

    DEFF Research Database (Denmark)

    Chalandon, Y; Passweg, J R; Schmid, C

    2010-01-01

    We studied GVHD after donor lymphocyte infusion (DLI) in 328 patients with relapsed CML between 1991 and 2004 . A total of 122 patients (38%) developed some form of GVHD. We analyzed GVHD by clinical presentation (acute or chronic GVHD) and onset time after the first DLI (early (

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

    DEFF Research Database (Denmark)

    Espersen, Maiken Lise Marcker; Linnemann, Dorte; Alamili, Mahdi;

    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...... high levels of SOX9 of primary stage II colon tumors predict low riskof relapse whereas low levels of SOX9 predict high risk of relapse. SOX9 may have an important value as a biomarker when evaluating risk of relapse for personalized treatment....

  1. Efficacy and safety analysis of the combination of cladribine, cytarabine, granulocyte colony-stimulating factor (CLAG) regime in patients with refractory or relapsed acute myeloid leukemia%CLAG方案治疗33例难治复发急性髓系白血病的疗效及安全性

    Institute of Scientific and Technical Information of China (English)

    段明辉; 张岩; 张梅; 韩潇; 张炎; 杨辰; 冯俊; 张路; 张薇

    2016-01-01

    Objective To analyze efficacy and safety of CLAG regimen in patients with refractory or relapsed acute myeloid leukemia (AML).Methods Efficacy and adverse events of patients with refractory or relapsed AML who were treated with one course of CLAG from April 1st,2014 through December 9th,2015 in our hospital were retrospectively reviewed.Results Thirty-three patients (16 males and 17 females) with refractory or relapsed AML were treated with one course of CLAG with a median age of 49 (14-68) years.According to FAB subtype,there were 22 patients with M2,and 11 with other types.According to NCCN criteria,there were 6,18 and 9 patients with favorable,intermediate and unfavorable risk respectively,including 5 with FLT3-ITD mutation.Of 16 refractory and 17 relapsed patients;the median previous chemotherapy courses were 2 (1-36).After one course of CLAG,78.8% (26/ 33) patients achieved hematological complete response (CR),with 93.8 %(15/16) in relapsed and 64.7 % (11/17) in refractory groups respectively.All five patients with FLT3-ITD mutation achieved CR.All patients had grade 4 neutropenia and thrombocytopenia and infection in different sites;three patients died early from infections.Five patients received allogeneic hematopoietic stem cell transplantation (alloHSCT).Ten patients relapsed and thirteen patients died after the median follow-up 142 (9-525) days.The median EFS and OS were 230 (9-525) and 419 (9-525) days respectively,which in CR group (n=26) were significantly longer than those in NR one (n=7) [447(165-525)d vs 52 (9-162)d,P< 0.001].Conclusions CLAG regimen was effective and well tolerable in patients with refractory or relapsed AML,with the CR rate in relapsed patients higher than in refractory counterparts.Control of infections was imperative for treatment.%目的 分析CLAG方案(克拉屈滨+阿糖胞苷+G-CSF)对难治复发急性髓系白血病(AML)的疗效及安全性.方法 回顾性分析2014年4月1日至2015年12月9日采用1

  2. 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

    and robust efficacy as a single agent in patients with relapsed and refractory (RR) multiple myeloma (MM) (Lokhorst HM. J Clin Oncol 2014;32 Suppl:abstr 8513. Lonial S. J Clin Oncol 2015;33 Suppl:abstr LBA8512) and in combination with LEN/Dexamethasone (DEX) in patients with relapsed or RR MM (Plesner T....... Blood 2014;124(21):84). This study assessed the updated safety and efficacy of DARA in combination with LEN/DEX following more than 12 months of exposure in patients with relapsed or RR MM. Methods: The study design of this ongoing, open-label phase 1/2 study of DARA in combination with LEN/DEX has been...... was administered orally on Days 1 through 21 of each cycle, and DEX 40 mg was given weekly. The primary objective was safety. Efficacy was evaluated per the International Myeloma Working Group criteria. The last patient was enrolled in August 2014. Results: Updated safety and efficacy results (data cut January 9...

  3. 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....

  4. Effect of acute and chronic graft-versus-host disease on relapse and survival after reduced-intensity conditioning allogeneic transplantation for myeloma

    Science.gov (United States)

    Ringdén, Olle; Shrestha, Smriti; da Silva, Gisela Tunes; Zhang, Mei-Jie; Dispenzieri, Angela; Remberger, Mats; Kamble, Rammurti; Freytes, Cesar O.; Gale, Robert Peter; Gibson, John; Gupta, Vikas; Holmberg, Leona; Lazarus, Hillard; McCarthy, Philip; Meehan, Kenneth; Schouten, Harry; Milone, Gustavo A.; Lonial, Sagar; Hari, Parameswaran N

    2011-01-01

    We evaluated the effect of acute and chronic graft-versus-host disease (GVHD) on relapse and survival after allogeneic haematopoietic stem cell transplantation (HSCT) for multiple myeloma (MM) using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC). The outcomes of 177 HLA-identical sibling HSCT recipients between 1997 and 2005 following NMA (n=98) or RIC (n=79) were analyzed. In 105 patients, autografting was followed by planned NMA/RIC allogeneic transplantation. The impact of GVHD was assessed as a time-dependent covariate using Cox models. The incidence of acute GVHD (grades I–IV) was 42% (95% confidence interval (CI) 35 – 49%) and of chronic GVHD at five years was 59% (95% CI 49 – 69%), with 70% developing extensive chronic GVHD. In multivariate analysis, acute GVHD (≥ grade I) was associated with an increased risk of TRM (relative risk (RR)=2.42; p=0.016), whereas limited chronic GVHD significantly decreased the risk of myeloma relapse (RR=0.35, p=0.035) and was associated with superior event-free survival (RR=0.40, p=0.027). Acute GVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR=3.52; p=0.001). The reduction in relapse risk associated with chronic GVHD is consistent with a beneficial graft-versus-myeloma effect, but this did not translate into a survival advantage. PMID:21946381

  5. 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.

  6. Safety and pharmacokinetics of the antisense oligonucleotide (ASO) LY2181308 as a single-agent or in combination with idarubicin and cytarabine in patients with refractory or relapsed acute myeloid leukemia (AML).

    Science.gov (United States)

    Erba, Harry P; Sayar, Hamid; Juckett, Mark; Lahn, Michael; Andre, Valerie; Callies, Sophie; Schmidt, Shelly; Kadam, Sunil; Brandt, John T; Van Bockstaele, Dirk; Andreeff, Michael

    2013-08-01

    Survivin is expressed in tumor cells, including acute myeloid leukemia (AML), regulates mitosis, and prevents tumor cell death. The antisense oligonucleotide sodium LY2181308 (LY2181308) inhibits survivin expression and may cause cell cycle arrest and restore apoptosis in AML. In this study, the safety, pharmacokinetics, and pharmacodynamics/efficacy of LY2181308 was examined in AML patients, first in a cohort with monotherapy (n = 8) and then post-amendment in a cohort with the combination of cytarabine and idarubicin treatment (n = 16). LY2181308 was administered with a loading dosage of three consecutive daily infusions of 750 mg followed by weekly intravenous (IV) maintenance doses of 750 mg. Cytarabine 1.5 g/m(2) was administered as a 4-hour IV infusion on Days 3, 4, and 5 of Cycle 1, and idarubicin 12 mg/m(2) was administered as a 30-minute IV infusion on Days 3, 4, and 5 of Cycle 1. Cytarabine and idarubicin were administered on Days 1, 2, and 3 of each subsequent 28-day cycle. Reduction of survivin was evaluated in peripheral blasts and bone marrow. Single-agent LY2181308 was well tolerated and survivin was reduced only in patients with a high survivin expression. In combination with chemotherapy, 4/16 patients had complete responses, 1/16 patients had incomplete responses, and 4/16 patients had cytoreduction. Nine patients died on study: 6 (monotherapy), 3 (combination). LY2181308 alone is well tolerated in patients with AML. In combination with cytarabine and idarubicin, LY2181308 does not appear to cause additional toxicity, and has shown some clinical benefit needing confirmation in future clinical trials.

  7. Long-term survival and late effects among one-year survivors of second allogeneic hematopoietic cell transplantation for relapsed acute leukemia and myelodysplastic syndromes.

    Science.gov (United States)

    Duncan, Christine N; Majhail, Navneet S; Brazauskas, Ruta; Wang, Zhiwei; Cahn, Jean-Yves; Frangoul, Haydar A; Hayashi, Robert J; Hsu, Jack W; Kamble, Rammurti T; Kasow, Kimberly A; Khera, Nandita; Lazarus, Hillard M; Loren, Alison W; Marks, David I; Maziarz, Richard T; Mehta, Paulette; Myers, Kasiani C; Norkin, Maxim; Pidala, Joseph A; Porter, David L; Reddy, Vijay; Saber, Wael; Savani, Bipin N; Schouten, Harry C; Steinberg, Amir; Wall, Donna A; Warwick, Anne B; Wood, William A; Yu, Lolie C; Jacobsohn, David A; Sorror, Mohamed L

    2015-01-01

    We analyzed the outcomes of patients who survived disease-free for 1 year or more after a second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant after disease relapse; among these, 325 were relapse free at 1 year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplantation in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least 1 year was 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status before second HCT was significantly associated with higher risk for overall mortality (hazard ratio, 1.71 for patients with disease not in complete remission before second HCT, P < .01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults after second transplantation. Chronic GVHD was the leading cause of nonrelapse mortality, followed by organ failure and infection. The cumulative incidence of developing at least 1 of the studied late effects within 10 years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence, 22%) and cataracts (20%); in adults they were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease free for at least 1 year, many can be expected to survive long term. However, they continue to be at risk for relapse and nonrelapse morbidity and mortality. Novel

  8. Survival of pediatric patients after relapsed osteosarcoma: the St. Jude Children's Research Hospital experience.

    Science.gov (United States)

    Leary, Sarah E S; Wozniak, Amy W; Billups, Catherine A; Wu, Jianrong; McPherson, Valerie; Neel, Michael D; Rao, Bhaskar N; Daw, Najat C

    2013-07-15

    Chemotherapy has improved the outcome of patients with newly diagnosed osteosarcoma, but its role in relapsed disease is unclear. We reviewed the records of all patients who were treated for relapsed high-grade osteosarcoma at our institution between 1970 and 2004. Postrelapse event-free survival (PREFS) and postrelapse survival (PRS) were estimated, and outcome comparisons were made using an exact log-rank test. The 10-year PREFS and PRS of the 110 patients were 11.8% ± 3.5% and 17.0% ± 4.3%, respectively. Metastasis at initial diagnosis (14%), and relapse in lung only (75%) were not significantly associated with PREFS or PRS. Time from initial diagnosis to first relapse (RL1) ≥18 months (43%), surgery at RL1 (76%), and ability to achieve second complete remission (CR2, 56%) were favorably associated with PREFS and PRS (P  ≤  0.0002). In patients without CR2, chemotherapy at RL1 was favorably associated with PREFS (P = 0.01) but not with PRS. In patients with lung relapse only, unilateral relapse and number of nodules ( ≤ 3) were associated with better PREFS and PRS (P  ≤  0.0005); no patients with bilateral relapse survived 10 years. The median PREFS after treatment with cisplatin, doxorubicin, methotrexate, and ifosfamide was 3.5 months (95% confidence interval, 2.1-5.2), and the median PRS was 8.2 months (95% confidence interval, 5.2-15.1). Late relapse, surgical resection, and unilateral involvement (in lung relapse only) favorably impact outcome after relapse. Surgery is essential for survival; chemotherapy may slow disease progression in patients without CR2. These data are useful for designing clinical trials that evaluate novel agents. © 2013 American Cancer Society.

  9. Pathogenesis of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia and mechanisms underlying its relapse.

    Science.gov (United States)

    Sun, Congcong; Chang, Lixian; Zhu, Xiaofan

    2017-05-23

    ETV6/RUNX1 (E/R) is the most common fusion gene in childhood acute lymphoblastic leukemia (ALL). Multiple lines of evidence imply a "two-hit" model for the molecular pathogenesis of E/R-positive ALL, whereby E/R rearrangement is followed by a series of secondary mutations that trigger overt leukemia. The cellular framework in which E/R arises and the maintenance of a pre-leukemic condition by E/R are fundamental to the mechanism that underlies leukemogenesis. Accordingly, a variety of studies have focused on the relationship between the clones giving rise to the primary and recurrent E/R-positive ALL. We review here the most recent insights into the pathogenic mechanisms underlying E/R-positive ALL, as well as the molecular abnormalities prevailing at relapse.

  10. 难治复发性急性髓系白血病患者缓解状态对异基因造血干细胞移植预后影响的分析%Impact of Disease Status on Outcomes of Allogeneic Hematopietic Stem Cell Transplantation in Patients with Refractory and Relapsed Acute Myeloid Leukemia

    Institute of Scientific and Technical Information of China (English)

    周倩兰; 陈广华; 吴德沛; 唐晓文; 孙爱宁; 仇惠英; 金正明; 苗瞄; 付铮铮; 赵丙瑞; 施晓兰

    2012-01-01

    The study was aimed to evaluate the impact of disease status on the outcomes of allogeneic hematopietic stem cell transplantation (allo-HSCT) in patients with refractory and relapsed acute myeloid leukemia ( AML). 32 patients with refractory and relapsed AML received allo-HSCT after myeloablative conditioning regimen, including 17 patients in no-remission ( NR) and 15 patients in complete remission ( CR) at the time of transplant. Treatment related adverse events, relapse rate and leukemia free survival(LFS) were analyzed. The results showed that the parameters of sex, age, cytogenetic risk and transplant procedures were comparable between the two groups. 30 patients had successful engraftment, except one had graft failure and one died from severe veno-occlusive disease in the NR group. The incidences of aGVHD in NR group and CR group were 47. 1% (8 patients) and 33.5% (5 patients) respectively. Out of comparable patients, 5 from 9 patients in NR group developed with cGVHD, and 4 from 11 patients in CR group were subjected to cGVHD. There were no statistic difference in incidences of aGVHD and cGVHD between two group. Compa- red with CR group, NR group had a higher treatment-related mortality (29.4% vs 14.3% , P =0.392) and relapse rate (42.9% vs 26.7% p =0. 300), but there was no significant difference. With a median follow-up of 13 (1 - 124) months, 6 patients remained alive in both of the two groups ,and the 2 year LFS of them were parallel (35. 3% vs 40.0% , P =0.267). Among these 32 patients, overall survival (OS) was better in patients with age <35 years(P = 0.044) and with the appearance of cGVHD(P =0. 046). It is concluded that allo-HSCT is an effective salvage therapy for patients with refractory and relapsed AML, and the overall outcome seems unrelated to the disease status ( NR or CR) before transplantation. As such, for refractory and relapsed AML patients in non-remnission, performance of allo-HSCT to achieve long-term survival is feasible.%本研究

  11. Identification of a homozygous JAK3 V674A mutation caused by acquired uniparental disomy in a relapsed early T-cell precursor ALL patient.

    Science.gov (United States)

    Kawashima-Goto, Sachiko; Imamura, Toshihiko; Seki, Masafumi; Kato, Motohiro; Yoshida, Kenichi; Sugimoto, Atsuya; Kaneda, Daisuke; Fujiki, Atsushi; Miyachi, Mitsuru; Nakatani, Takuya; Osone, Shinya; Ishida, Hiroyuki; Taki, Tomohiko; Takita, Junko; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Ogawa, Seishi; Hosoi, Hajime

    2015-04-01

    Investigation of genetic alterations associated with relapse in acute lymphoblastic leukemia (ALL) may help to identify druggable targets for specific therapies. Early T-cell precursor ALL (ETP-ALL) is a subtype of T-ALL with poor prognosis. Although the genetic landscape of ETP-ALL has been determined, genetic alterations related to the relapse of ETP-ALL have not been fully investigated. Here, we report the first patient with relapsed pediatric ETP-ALL to exhibit a homozygous JAK3 activating mutation, V674A, caused by acquired uniparental disomy (UPD). Single nucleotide polymorphism array analysis revealed acquired UPD (aUPD) at the 19p13.3-p12 locus only in leukemic cells at relapse. Sanger sequence of the JAK3 gene, which was located at 19p13.1 and frequently mutated in ETP-ALL, was performed in paired leukemic samples to determine homozygous JAK3 V674A mutation only in relapsed leukemic cells. In contrast, leukemic cells at initial diagnosis harbored hemizygous JAK3 V674A mutation. Further, whole-exome sequencing revealed mutations in 18 genes only in relapsed samples, although none of these was recurrent in T-ALL. These findings suggest that aUPD at 19p13.1 is partly associated with relapse in this patient. Pharmacological inhibition of JAK3 may be therapeutic in such cases.

  12. Treatment of isolated testicular relapse in childhood acute lymphoblastic leukemia: an Italian multicenter study. Associazione Italiana Ematologia ed Oncologia Pediatrica.

    Science.gov (United States)

    Uderzo, C; Grazia Zurlo, M; Adamoli, L; Zanesco, L; Aricò, M; Calculli, G; Comelli, A; Cordero di Montezemolo, L; Di Tullio, M T; Guazzelli, C

    1990-04-01

    Between May 1980 and April 1987, 49 children with acute lymphoblastic leukemia (ALL) in isolated testicular and first leukemia relapse (ITR) were enrolled in the Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP) multicenter study REC80-ITR. According to the Rome Workshop criteria, 77% were at standard and 23% at high initial prognostic risk. In 33% of the cases, ITR occurred during first treatment. The REC80-ITR protocol consisted of an induction phase regimen of vincristine (VCR), cytarabine (ARA-C), methotrexate (MTX), and asparaginase (L-asp), and bilateral testicular irradiation, and CNS prophylaxis with intrathecal MTX and a maintenance phase with a multidrug rotating regimen. Total treatment duration was 30 months. The median time of observation after ITR was 51 months. The Kaplan-Meier estimates of survival and disease-free survival (DFS) at 4 years were 67.7% and 41%, respectively. Patients who had an ITR on therapy or within the first off-therapy year showed the poorest outcome. The DFS at 3 years was 20%, 47.6%, and 100%, respectively, for children who had an ITR on treatment (n = 16), within the first year of treatment withdrawal (n = 22), or later (n = 10) (P = .001). Patients with an asymptomatic occult testicular infiltrate at treatment discontinuation had a very unfavorable prognosis. Eighty-one percent of second relapses involved the bone marrow. In our experience, children presenting an early ITR (ie, within 6 months of treatment withdrawal) need a very aggressive treatment because of the high probability of an underlying systemic disease. On the other hand, patients with a late ITR seem to have a truly local recurrence and can apparently be cured by standard protocols, as shown in protocol REC80-ITR.

  13. Extending supplementary feeding for children younger than 5 years with moderate acute malnutrition leads to lower relapse rates

    Science.gov (United States)

    Children with moderate acute malnutrition (MAM) have a high rate of relapse and death in the year following recovery. In this pilot study, we evaluate the long-term benefits of an extended course of nutritional therapy for children with MAM. Rural Malawian children 6 to 59 months old with MAM, defin...

  14. 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

    to receive treatment, with the exception of the patient with grade 3 laryngeal edema, who recovered but was discontinued from treatment per protocol. The overall response rate (Rajkumar SV. Blood. 2011;117:4691-5) was 88%, with 11 (34%) partial responses and 17 (53%) >very good partial responses (VGPRs....... Blood 2014;124(21):84). This study assessed the updated safety and efficacy of DARA in combination with LEN/DEX following more than 12 months of exposure in patients with relapsed or RR MM. Methods: The study design of this ongoing, open-label phase 1/2 study of DARA in combination with LEN/DEX has been...... 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...

  15. [Clinical efficacy of decitabine combined with modified CAG regimen for relapsed-refractory acute myeloid leukemia with AML1-ETO⁺].

    Science.gov (United States)

    Jing, Yu; Zhu, Cheng-Ying; Zhang, Qi; Niu, Jian-Hua; Yang, Hua; Liu, Shi-Yan; Zhu, Hai-Yan; Yu, Li

    2014-10-01

    This study was aimed to investigate the clinical characteristics of relapsed-refractory acute myeloid leukemia (AML) with AML1-ETO⁺, and its therapeutic efficacy and side effects when decitabine combined with modified CAG regimen was used. Clinical data of 5 cases of AML with AML1-ETO⁺ from January 2013 to Agust 2013 were analyzed retrospectively. The analyzed data included age, sex, initial symptoms, peripheral blood and bone marrow characteristics. Meanwhile, the therapeutic effecacy and side effects of decitabine combined with modified CAG regimen were evaluated. The 5 patients were with median age of 35 (17-43) years. Among these 5 patients, 2 patients were relapsed and other 3 patients were relapsed-refractory patients, their median white blood cell count was 12.55 (7.8-66.55) × 10⁹/L, median platelets count was 44 (20-72) × 10⁹/L, median hemoglobin level was 110 (77-128) g/L, median lactate dehydrogenase level was 312.9 U/L (123.6-877.8) at the initial diagnosis. The results showed that after decitabine combined with modified CAG regimen was administered, 4 patients achieved complete remission, 1 patient did not achieve remission, the overall remission rate was 80% (4/5). The main side effects of this regimen was myelosuppression, these were no new lung infection and other serious complications, one case without complete remission treated with FLAG once again died of heart failure when being mobilized for transplantation. It is concluded that according to preliminary results of decitabine combined with modified CAG regimen for relapsed and refractory AML patients with AML1-ETO⁺ displays higher remission rate and lower side effects, which worthy to further explore for clinal application.

  16. Clinical characteristics and prognostic factors for relapse in patients with polymyalgia rheumatica (PMR).

    Science.gov (United States)

    Lee, Jung Hwa; Choi, Sang Tae; Kim, Jin Su; Yoon, Bo Young; Kwok, Seung-Ki; Kim, Hyun-Sook; Kim, Yun Sung; Song, Jung-Soo; Lee, Sang-Heon; Kim, Hae-Rim

    2013-06-01

    Polymyalgia rheumatica (PMR) is a common inflammatory disease of the elderly in western countries, but the prevalence is apparently different between races and countries. Until now, an epidemiologic study of PMR is limited in Korea. We retrospectively evaluated the clinical data of 78 patients with PMR who were treated in 5 tertiary hospitals, and analyzed initial laboratory data, symptoms, therapeutic responses, and prognostic factors for relapse 1 year after treatments. Sixty percent of patients had pain in both shoulder and hip girdles with 10.6 weeks of duration, 75.9 ± 32.7 mm/h of erythrocyte sedimentation rate (ESR), and 6.2 ± 6.4 mg/dl of C-reactive protein. The rate of relapse and remission at 1 year was 38.4 and 2.5 %, respectively. The rate of overall relapse was 46.1 %, and the relapse occurred mostly in a year, especially between 6 and 12 months after diagnosis. There were more female in relapse group (88.9 %, p = 0.037), and cumulative steroid dose of 1 year was significantly higher in relapse group (5.5 ± 2.7 vs. 4.4 ± 2.5 g, p = 0.018). Independent risk factors for relapse were initial CRP ≥ 2.5 mg/dl (OR 6.296, p = 0.047) and the use of hydroxychloroquine (OR 6.798, p = 0.035). Initial dosage or tapering speed of steroid did not influence on prognosis. In Korean patients with PMR, baseline clinical characteristics and relapse rate were similar to previous studies, but our patients accompanied no giant cell arteritis and showed lower remission rate as well as delayed therapeutic response and later occurrence of relapse. More aggressive management would be needed according to the clinical status of patients.

  17. [Experience in irradiating with helium-neon lasers to treat patients with relapsing aphthous stomatitis].

    Science.gov (United States)

    Prikuls, V F

    2000-01-01

    Seventy-five patients with relapsing aphthous stomatitis (41 with the fibrinous form, 25 with glandular form, and 9 with necrotic form) were treated using He-Ne laser and a photosensitizer. A good therapeutic effect was attained.

  18. Pancreatitis aguda recidivante con enteropatía por gluten asociada: Características clínico-analíticas y evolutivas en 34 pacientes Relapsing acute pancreatitis associated with gluten enteropathy: Clinical, laboratory, and evolutive characteristics in thirty-four patients

    Directory of Open Access Journals (Sweden)

    L. Rodrigo

    2008-12-01

    Full Text Available Objetivos: describir la frecuencia y características clínico-analíticas de la pancreatitis aguda (PA recidivante con enteropatía por gluten (EG asociada. Pacientes y métodos: estudiamos de forma prospectiva los casos de pancreatitis agudas ingresados en nuestro Servicio durante el año 2006. Registramos un total de 185 pacientes. A las formas recurrentes que fueron 40 en total (22%, les aplicamos un protocolo clínico-analítico consistente en la determinación de marcadores serológicos, genéticos y biopsias duodenales, para descartar una EG asociada. Resultados: un total de 34 pacientes (18% cumplían criterios clínico-biológicos de EG asociada (grupo 1 y se compararon con el resto de las PA no-EG (n = 161 (grupo 2. La edad media en la EG fue de 54 ± 25 años, ligeramente inferior al grupo 2, (61 ± 14 (NS. Existía un ligero predominio de mujeres (50% en el grupo 1, respecto al grupo 2 (38,5% (NS. Siete pacientes del grupo 1 (20% presentaron una PA grave, frente a 27 (17% en el grupo 2 (NS. La presencia de colelitiasis en el grupo 1, fue de 6 casos (18%, significativamente inferior a la del grupo 2, de 72 casos (45% (p Objectives: to describe the frequency and the clinical and laboratory characteristics of relapsing acute pancreatitis (AP associated with gluten enteropathy (GE. Patients and methods: we prospectively examined all acute pancreatitis cases admitted to our Department in 2006. We recorded a total of 185 patients. With recurring forms, 40 (22% in all, we used a clinical-lab protocol including serologic and genetic markers, and duodenal biopsy to rule out GE. Results: a total of 34 patients (18% met clinical-biological criteria for GE (group 1, and were compared to the remaining non-GE AP cases (n = 161 (group 2. Mean age in the GE group was 54 ± 25 years, slightly younger than group 2 (61 ± 14 (NS. There was a mild predominance of women (50% in group 1 versus group 2 (38.5% (NS. Seven patients in group 1 (20% had severe

  19. Peripheral Blood WT1 Expression Predicts Relapse in AML Patients Undergoing Allogeneic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Michele Malagola

    2014-01-01

    Full Text Available To evaluate if WT1 expression may predict relapse after allo-SCT, we analyzed WT1 levels on peripheral blood (PB and bone marrow (BM before and after allo-SCT in 24 AML patients with WT1 overexpression at diagnosis. Five copies of WT1/ABL × 104 from PB were identified as the threshold value that correlated with relapse after allo-SCT. The same correlation was not identified when WT1 expression was assessed from bone marrow (BM. Eight out of 11 (73% patients with a pre-allo-SCT PB-WT1 ≥ 5 and 4/13 (31% patients with a pre-allo-SCT PB-WT1 < 5 relapsed, respectively (P = 0.04. The incidence of relapse was higher in patients with PB-WT1 ≥ 5 measured after allo-SCT, at the 3rd (56% versus 38%; P = 0.43 and at the 6th month (71% versus 20%; P = 0.03. Patients with pretransplant PB-WT1 < 5 had significantly better 2-year OS and LFS than patients with a PB-WT1 ≥ 5 (81% versus 0% and 63% versus 20% (P = 0.02. Our data suggest the usefulness of WT1 monitoring from PB to predict the relapse in allotransplanted AML patients and to modulate the intensity of conditioning and/or the posttransplant immunosuppression in an attempt to reduce the posttransplant relapse risk.

  20. Expression of Ik6 and Ik8 Isoforms and Their Association with Relapse and Death in Mexican Children with Acute Lymphoblastic Leukemia.

    Directory of Open Access Journals (Sweden)

    Adriana Reyes-León

    Full Text Available Expression of the 6 and 8 dominant-negative Ikaros isoforms in pediatric patients with acute lymphoblastic leukemia has been associated with a high risk of relapse and death; due to these isoforms disrupting the differentiation and proliferation of lymphoid cells. The aim of this study was to know the frequency of Ik6 and Ik8 in 113 Mexican ALL-children treated within the National Popular Medical Insurance Program to determine whether there was an association with relapse-free survival, event-free survival and overall survival, and to assess its usefulness in the initial stratification of patients. The expression of these isoforms was analyzed using specific primer sets and nested RT-PCR. The detected transcripts were classified according to the isoforms's sizes reported. A non-expected band of 300 bp from one patient was analyzed by sequencing. Twenty-six patients expressed Ik6 and/or Ik8 and one of them expressed a variant of Ik8 denominated Ik8-deleted. Although the presence of them was not statistically associated with lower relapse free survival (p = 0.432, event free survival (p = 0.667 or overall survival (p = 0.531, inferior overall survival was observed in patients that expressed these isoforms and showed high or standard risk by age and white blood-cell count at diagnosis. Of the 26 patients Ik6+ and/or Ik8+, 14 did not present adverse events; from them 6 were exclusively Ik6+ and/or Ik8+, and 8 were positive for the other Ikaros isoforms (Ik1, Ik2, Ik5, Ik3A, Ik4, Ik4A, Ik7. In the patients studied, the expression of Ik6 and Ik8 did not constitute an independent prognostic factor for relapse or death related to disease; therefore, they could not be used in the initial risk stratification.

  1. Expression of Ik6 and Ik8 Isoforms and Their Association with Relapse and Death in Mexican Children with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Reyes-León, Adriana; Juárez-Velázquez, Rocío; Medrano-Hernández, Alma; Cuenca-Roldán, Teresa; Salas-Labadía, Consuelo; del Pilar Navarrete-Meneses, María; Rivera-Luna, Roberto; López-Hernández, Gerardo; Paredes-Aguilera, Rogelio; Pérez-Vera, Patricia

    2015-01-01

    Expression of the 6 and 8 dominant-negative Ikaros isoforms in pediatric patients with acute lymphoblastic leukemia has been associated with a high risk of relapse and death; due to these isoforms disrupting the differentiation and proliferation of lymphoid cells. The aim of this study was to know the frequency of Ik6 and Ik8 in 113 Mexican ALL-children treated within the National Popular Medical Insurance Program to determine whether there was an association with relapse-free survival, event-free survival and overall survival, and to assess its usefulness in the initial stratification of patients. The expression of these isoforms was analyzed using specific primer sets and nested RT-PCR. The detected transcripts were classified according to the isoforms’s sizes reported. A non-expected band of 300 bp from one patient was analyzed by sequencing. Twenty-six patients expressed Ik6 and/or Ik8 and one of them expressed a variant of Ik8 denominated Ik8-deleted. Although the presence of them was not statistically associated with lower relapse free survival (p = 0.432), event free survival (p = 0.667) or overall survival (p = 0.531), inferior overall survival was observed in patients that expressed these isoforms and showed high or standard risk by age and white blood-cell count at diagnosis. Of the 26 patients Ik6+ and/or Ik8+, 14 did not present adverse events; from them 6 were exclusively Ik6+ and/or Ik8+, and 8 were positive for the other Ikaros isoforms (Ik1, Ik2, Ik5, Ik3A, Ik4, Ik4A, Ik7). In the patients studied, the expression of Ik6 and Ik8 did not constitute an independent prognostic factor for relapse or death related to disease; therefore, they could not be used in the initial risk stratification. PMID:26131904

  2. [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.

  3. Defining the Survival Benchmark for Breast Cancer Patients with Systemic Relapse

    Science.gov (United States)

    Zeichner, Simon B; Ambros, Tadeu; Zaravinos, John; Montero, Alberto J; Mahtani, Reshma L; Ahn, Eugene R; Mani, Aruna; Markward, Nathan J; Vogel, Charles L

    2015-01-01

    BACKGROUND Our original paper, published in 1992, reported a median overall survival after first relapse in breast cancer of 26 months. The current retrospective review concentrates more specifically on patients with first systemic relapse, recognizing that subsets of patients with local recurrence are potentially curable. METHODS Records of 5,168 patients from a largely breast-cancer-specific oncology practice were reviewed to identify breast cancer patients with their first relapse between 1996 and 2006 after primary treatment. There were 189 patients diagnosed with metastatic disease within 2 months of being seen by our therapeutic team and 101 patients diagnosed with metastatic disease greater than 2 months. The patients were divided in order to account for lead-time bias than could potentially confound the analysis of the latter 101 patients. RESULTS Median survival for our primary study population of 189 patients was 33 months. As expected, the median survival from first systemic relapse (MSFSR) for the 101 patients excluded because of the potential for lead-time bias was better at 46 months. Factors influencing prognosis included estrogen receptor (ER) status, disease-free interval (DFI), and dominant site of metastasis. Compared with our original series, even with elimination of local-regional recurrences in our present series, the median survival from first relapse has improved by 7 months over the past two decades. CONCLUSION The new benchmark for MSFSR approaches 3 years. PMID:25922577

  4. Quantitative chimerism kinetics in relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    QIN Xiao-ying; WANG Jing-zhi; ZHANG Xiao-hui; LI Jin-lan; LI Ling-di; LIU Kai-yan; HUANG Xiao-jun; LI Guo-xuan; QIN Ya-zhen; WANG Yu; WANG Feng-rong; LIU Dai-hong; XU Lan-ping; CHEN Huan; HAN Wei

    2012-01-01

    Background Chimerism analysis is an important tool for the surveillance of post-transplant engraftment.It offers the possibility of identifying impending graft rejection and recurrence of underlying malignant or non-malignant disease.Here we investigated the quantitative chimerism kinetics of 21 relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation (HSCT).Methods A panel of 29 selected sequence polymorphism (SP) markers was screened by real-time polymerase chain reaction (RT-PCR) to obtain the informative marker for every leukemia patient.Quantitative chimerism analysis of bone marrow (BM) samples of 21 relapsed patients and 20 patients in stable remission was performed longitudinally.The chimerisms of BM and peripheral blood (PB) samples of 14 patients at relapse were compared.Results Twenty-one patients experienced leukemia relapse at a median of 135 days (range,30-720 days) after transplantation.High recipient chimerism in BM was found in all patients at relapse,and increased recipient chimerism in BM samples was observed in 90% (19/21) of patients before relapse.With 0.5% recipient DNA as the cut-off,median time between the detection of increased recipient chimerism and relapse was 45 days (range,0-120 days),with 76% of patients showing increased recipient chimerism at least 1 month prior to relapse.Median percentage of recipient DNA in 20 stable remission patients was 0.28%,0.04%,0.05%,0.05%,0.08%,and 0.05% at 1,2,3,6,9,and 12 months,respectively,after transplantation.This was concordant with other specific fusion transcripts and fluorescent in situ hybridization examination.The recipient chimerisms in BM were significantly higher than those in PB at relapse (P=0.001).Conclusions This SP-based RT-PCR essay is a reliable method for chimerism analysis.Chimerism kinetics in BM can be used as a marker of impending leukemia relapse,especially when no other specific marker is available.Based on our findings

  5. Peripheral blood minimal residual disease may replace bone marrow minimal residual disease as an immunophenotypic biomarker for impending relapse in acute myeloid leukemia.

    Science.gov (United States)

    Zeijlemaker, W; Kelder, A; Oussoren-Brockhoff, Y J M; Scholten, W J; Snel, A N; Veldhuizen, D; Cloos, J; Ossenkoppele, G J; Schuurhuis, G J

    2016-03-01

    As relapses are common in acute myeloid leukemia (AML), early relapse prediction is of high importance. Although conventional minimal residual disease (MRD) measurement is carried out in bone marrow (BM), peripheral blood (PB) would be an advantageous alternative source. This study aims to investigate the specificity of leukemia-associated immunophenotypes used for MRD detection in blood samples. Consistency of PB MRD as compared with BM MRD was determined in flow cytometric data of 205 paired BM and PB samples of 114 AML patients. A significant correlation was found between PB and BM MRD (r=0.67, P<0.001), while median PB MRD percentage was factor 4-5 lower compared with BM MRD. Primitive blast (CD34+/CD117+/CD133+) frequency was significantly lower in PB (median factor 23.7), indicating that PB MRD detection is more specific than BM. Cumulative incidence of relapse 1 year after induction therapy was 29% for PB MRD-negative and 89% for PB MRD-positive patients (P<0.001). Three-year OS was 52% for MRD-negative and 15% for MRD-positive patients (P=0.034). Similar differences were found after consolidation therapy. As PB MRD appeared to be an independent predictor for response duration, the highly specific PB MRD assay may have a prominent role in future MRD assessment in AML.

  6. 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.

  7. Risk factors associated with relapse or infectious complications in Japanese patients with microscopic polyangiitis.

    Science.gov (United States)

    Kitagawa, Kiyoki; Furuichi, Kengo; Sagara, Akihiro; Shinozaki, Yasuyuki; Kitajima, Shinji; Toyama, Tadashi; Hara, Akinori; Iwata, Yasunori; Sakai, Norihiko; Shimizu, Miho; Kaneko, Shuichi; Wada, Takashi

    2016-10-01

    The prevention of relapse and infection complications during remission maintenance therapy is required to improve the prognosis of patients with microscopic polyangiitis (MPA) showing rapidly progressive glomerulonephritis (RPGN). The clinicopathological characteristics of patients with ANCA-positive MPA were examined to determine the risk factors for relapse or infectious complications after remission induction therapy. The study population consisted of 52 patients diagnosed as ANCA-positive MPA showing RPGN from 2002 to 2012, after publication of the Japanese guideline for RPGN. The clinicopathological findings were examined between the presence and absence of relapse or infectious complications. The value of vasculitis damage index (VDI) was high for the relapse group and VDI value was identified as the leading factor associated with relapse [hazard ratio (HR) 3.36, 95 % confidence interval (CI) 1.58-7.12, P < 0.01]. On the other hand, the values of Birmingham Vasculitis Activity Score, clinical grade category of RPGN at diagnosis, and VDI at remission were high in the infectious group. Furthermore, clinical grade category of RPGN was the leading factor associated with infectious complications (HR 5.30, 95 % CI 1.41-19.9, P = 0.01). The disease activity at diagnosis and severity of organ damage at remission were associated with relapse and infectious complications during remission maintenance therapy and infectious complication affected kidney survival and all-cause mortality in patients with ANCA-positive MPA exhibiting RPGN.

  8. Testis Scintigraphy in a Patient with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Mine Şencan Eren

    2014-02-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a pediatric malignancy associated with remissions and relapses. Common relapsing sitesare meninges, testis and ovary. Testicular scintigraphy is a highly specific modality used mainly in the differential diagnosis of testicular torsion and epidydimitis/epidydimo-orchitis. There is only one interesting image on leukemic infiltration with scrotal scintigraphy in the literature. The aim of this case presentation is to report that although the scintigraphic appearance of testicular torsion was observed in a patient with the diagnosis of ALL, testicular ALL infiltration was revealed in pathologic examination.

  9. Fulminant type I diabetes mellitus associated with nivolumab in a patient with relapsed classical Hodgkin lymphoma.

    Science.gov (United States)

    Munakata, Wataru; Ohashi, Ken; Yamauchi, Nobuhiko; Tobinai, Kensei

    2017-03-01

    We report the case of a patient with relapsed classical Hodgkin lymphoma who developed fulminant type I diabetes mellitus as a severe adverse event of treatment with the anti-programmed cell death-1 (PD-1) antibody, nivolumab. On the first day of the sixth cycle, the blood glucose level was markedly elevated (375 mg/dL). Although neither ketoacidosis nor ketonuria was detected, the markedly acute onset of the hyperglycemia was consistent with the typical clinical course of fulminant type I diabetes mellitus, and this diagnosis was supported by clinical data. All autoantibodies associated with type I diabetes mellitus were negative. The endogenous insulin secretion ceased completely within 2 weeks. After the blood glucose level was brought under control, nivolumab was resumed and continued without other major adverse events. Human leukocyte antigen (HLA) analysis revealed that the patient carried the HLA-B*4002 haplotype, a susceptibility allele for this type of diabetes mellitus. This case suggests that fulminant type I diabetes mellitus may be triggered by nivolumab in patients with a genetic background associated with the condition, warranting careful future consideration of this particular adverse event.

  10. 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)...

  11. [Clinical, microbiological and evolutionary profile of patients experiencing failures and relapses of tuberculosis in Ivory Coast].

    Science.gov (United States)

    Kouamé-N'Takpé, N; Horo, K; Koné, A; N'guessan, K R; Touré, K; Kouadio, C; Assi, D; Coulibaly, I; Kouakou, A

    2015-02-01

    Multidrug-resistant tuberculosis (MDR-TB) is a major obsession for TB control. The main risk factor for MDR-TB remains a history of TB treatment especially bad conduct. The objective of this study is to describe the profile of patients in situations of failure and relapse of tuberculosis. We performed a retrospective survey of the analysis of records of patients starting TB retreatment for failure or relapse of tuberculosis. We used 193 cases with results of culture-sensitivity. The proportion of failure is 59/193 (30.6 %) and cases of relapse are 134/193 (69.4 %). The proportion of married life is 23.4 % (11/47) in chess against 41.5 % (51/123) in relapse of TB [P=0.021, OR=0.431 (0.201 to 0.927)]. Patients failing therapy have more chest pain [5.8 % (3/52) versus 0 % (0/126) with P=0.024]. The proportion of MDR-TB was 61.4 (38/59) in case of failure against 41 % (55/134) in case of relapse [P=0.002, OR=2.599 (1.378 to 4.902)]. The evolution is the same whatever the indication of reprocessing. The proportion of MDR-TB is very important in case of reprocessing failure and relapse of tuberculosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. 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.

  13. Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning.

    Science.gov (United States)

    Kahl, Christoph; Storer, Barry E; Sandmaier, Brenda M; Mielcarek, Marco; Maris, Michael B; Blume, Karl G; Niederwieser, Dietger; Chauncey, Thomas R; Forman, Stephen J; Agura, Edward; Leis, Jose F; Bruno, Benedetto; Langston, Amelia; Pulsipher, Michael A; McSweeney, Peter A; Wade, James C; Epner, Elliot; Bo Petersen, Finn; Bethge, Wolfgang A; Maloney, David G; Storb, Rainer

    2007-10-01

    Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies depends on graft-versus-tumor effects for eradication of cancer. Here, we estimated relapse risks according to disease characteristics. Between 1997 and 2006, 834 consecutive patients (median age, 55 years; range, 5-74 years) received related (n = 498) or unrelated (n = 336) HCT after 2 Gy total body irradiation alone (n = 171) or combined with fludarabine (90 mg/m(2); n = 663). Relapse rates per patient year (PY) at risk, corrected for follow-up and competing nonrelapse mortality, were calculated for 29 different diseases and stages. The overall relapse rate per PY was 0.36. Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) in remission (CR), low-grade or mantle cell non-Hodgkin lymphoma (NHL) (CR + partial remission [PR]), and high-grade NHL-CR had the lowest rates (0.00-0.24; low risk). In contrast, patients with advanced myeloid and lymphoid malignancies had rates of more than 0.52 (high risk). Patients with lymphoproliferative diseases not in CR (except Hodgkin lymphoma and high-grade NHL) and myeloid malignancies in CR had rates of 0.26-0.37 (standard risk). In conclusion, patients with low-grade lymphoproliferative disorders experienced the lowest relapse rates, whereas patients with advanced myeloid and lymphoid malignancies had high relapse rates after nonmyeloablative HCT. The latter might benefit from cytoreductive treatment before HCT.

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

    Science.gov (United States)

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

    2016-04-26

    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 the dialysis bag was the suspected source of infection with B. cereus. 2016 BMJ Publishing Group Ltd.

  15. Ocular complications in incident relapsed borderline lepromatous and lepromatous leprosy patients in south India.

    Directory of Open Access Journals (Sweden)

    Daniel Ebenezer

    2003-01-01

    Full Text Available Purpose: To determine the magnitude of ocular complications that present in incident cases of relapsed borderline lepromatous (BL and lepromatous leprosy (LL patients. Method: From 1991 to 1997, all new BL and LL patients who had relapsed from an earlier disease, detected by active case finding in the geographically defined area of Gudiyattam taluk, were invited for ocular examination after their leprosy status was confirmed clinically and histopathologically. Results: Sixty relapsed lepromatous patients, 45 male and 15 females, were examined. Fifty-two patients had relapsed after receiving only dapsone mono-therapy, 4 after receiving paucibacillary multi-drug therapy (PB-MDT preceded by dapsone mono-therapy and 4 after only PB-MDT. Three (5% patients had lagophthalmos, 1 (1.6% patients each had ectropion and trichiasis, 32 (53% patients had impaired corneal sensation in both eyes, 2 (3.3% patients each had corneal opacity (associated with reduced vision, corneal nerve beading, punctate keratitis, keratic precipitates, and iris atrophy, 4 (6.6 % patients had cataract associated with decreased vision, 1 (1.6% patient had blocked naso-lacrimal duct and 13 (21.7% patients had pterygium. Seven (12% patients had a visual acuity of 6/18 or less, 4 (6.7% patients had 6/60 or less and one patients had vision below 3/60. General ocular complications rather than leprosy-related ocular complications were responsible for reduced vision. Lagophthalmos was associated with increased duration of the disease (P=0.009, Grade II deformity (P=0.001, punctate keratitis (P Conclusion: This first report on ocular complications in relapsed lepromatous patients demonstrates that general and leprosy-related ocular complications occur in these patients. However, they are not in excess of those reported in other leprosy groups. Borderline and lepromatous leprosy patients tend to have had more ocular complications than patients with tuberculoid leprosy.

  16. Relapsed APL patient with variant NPM-RARalpha fusion responded to arsenic trioxide-based therapy and achieved long-term survival.

    Science.gov (United States)

    Chen, Yan; Gu, Ling; Zhou, Chenyan; Wu, Xueqiang; Gao, Ju; Li, Qiang; Zhu, Yiping; Jia, Cangsong; Ma, Zhigui

    2010-05-01

    The t(5;17)/NPM-RARalpha is the second variant chromosomal translocation in acute promyelocytic leukemia (APL) to be characterized and also the second most plentiful variant translocation. So far, there is a lack of information on the effectiveness of arsenic trioxide (ATO) in relapsed APL with variant RARalpha chimera including t(5;17)/NPM-RARalpha. We report here a long-term survived APL patient with variant NPM-RARalpha fusion who relapsed four times and each time responded well to ATO or ATO-based re-induction therapy. The patient had received a total of more than 3,500 mg of ATO, but showed no obvious arsenic-related toxicities. This case illustrates the long-term efficiency and safety of ATO-based therapy not only in newly diagnosed APL, but also in relapsed APL including those with variant translocations.

  17. Chemotherapy versus Hypomethylating Agents for the Treatment of Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome after Allogeneic Stem Cell Transplant.

    Science.gov (United States)

    Motabi, Ibraheem H; Ghobadi, Armin; Liu, Jingxia; Schroeder, Mark; Abboud, Camille N; Cashen, Amanda F; Stockler-Goldstein, Keith E; Uy, Geoffrey L; Vij, Ravi; Westervelt, Peter; DiPersio, John F

    2016-07-01

    Allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). For patients with relapsed disease after transplantation, intensive chemotherapy followed by donor lymphocyte infusion (DLI) or a second allo-SCT may result in a durable response in some patients. High-intensity chemotherapy and less aggressive therapy with hypomethylating agents (HAs) with and without DLI are often used for relapse after allo-SCT. Here we compared the treatment outcomes of intensive chemotherapy with that of HAs in relapsed AML and MDS after allo-SCT. Patients who had received a second SCT within 90 days of the relapse date were excluded. The primary endpoints were overall response rate (ORR) and overall survival (OS). Secondary endpoints were complete remission (CR) rate and progression-free survival (PFS). One hundred patients were included: 73 patients received chemotherapy and 27 patients received an HA. Fifty-six percent of patients in the chemotherapy group and 33% of patients in the HA group received at least 1 DLI after treatment. Treatment with chemotherapy resulted in a higher ORR (51% versus 19%, P = .004) and a higher CR rate (40% versus 7%, P = .002). The median OS (6 versus 3.9 months, P = .01) and PFS (4.9 versus 3.8 months, P = .02) were longer in the chemotherapy group. Similar benefit of chemotherapy over HAs was maintained in all treatment outcomes after controlling for the use of DLI. The use of chemotherapy followed by DLI offered the greatest benefit (ORR, 68%; CR, 59%, 1-year OS, 44%; and median OS, 9.8 months). In conclusion, in our hands, with limited numbers, the use of more conventional salvage chemotherapy, with DLI when possible, for the treatment of relapsed AML and MDS after allo-SCT is associated with better outcomes than nonchemotherapy (HA) options.

  18. Site and Timing of First Relapse in Stage III Melanoma Patients: Implications for Follow-Up Guidelines

    Science.gov (United States)

    Romano, Emanuela; Scordo, Michael; Dusza, Stephen W.; Coit, Daniel G.; Chapman, Paul B.

    2010-01-01

    Purpose Stage III melanoma is associated with a high risk of relapse and mortality. Nevertheless, follow-up guidelines have largely been empirical rather than evidence-based. Patients and Methods Clinical records of stage III patients with no evidence of disease seen at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1992 and 2004, who ultimately relapsed, were reviewed retrospectively to evaluate date of first relapse, time to first relapse, method of first relapse detection, and survival. We also determined overall 5-year relapse-free survival (RFS) of all stage III patients seen at MSKCC during this period. Results The overall 5-year RFS for stage IIIA, IIIB, and IIIIC patients was 63%, 32%, and 11%, respectively. Among relapsing patients, 340 had adequate follow-up to be evaluable for all parameters. Site of first relapse was local/in-transit (28%), regional nodal (21%), or systemic (51%). First relapses were detected by the patient or family, physician, or by screening radiologic tests in 47%, 21%, and 32% of patients, respectively. Multivariate analysis revealed that better overall survival was associated with younger age and first relapse being local/in-transit or nodal, asymptomatic, or resectable. For each substage, we estimated site-specific risk of first relapse. Conclusion Patients detected almost half of first relapses. Our data suggest that routine physical examinations beyond 3 years for stage IIIA, 2 years for stage IIIB, and 1 year for stage IIIC patients and radiologic imaging beyond 3 years for stages IIIA and IIIB and 2 years for stage IIIC patients would be expected to detect few first systemic relapses. PMID:20479405

  19. 地西他滨联合减量MA/DA方案治疗复发难治性急性髓系白血病临床观察%Clinical observation of decitabine combined with low-dose MA/DA regimen in the treatment of patients with refractory or relapsed acute myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    梁艳; 唐元艳; 熊涛; 邓鸣凤; 张利铭; 黄知平

    2016-01-01

    目的:观察地西他滨联合减量MA/DA方案治疗复发难治性急性髓系白血病患者的疗效及安全性。方法选取2012年8月至2015年6月本院收治的18例复发难治性急性髓系白血病患者,予以地西他滨联合减量MA [地西他滨20 mg/(m2· d),d1~5;米托蒽醌8~12 mg/m2,d6~8;阿糖胞苷100 mg/m2,d6~8]/DA方案[地西他滨20 mg/(m2· d),d1~5;柔红霉素40~45 mg/m2,d6~8;阿糖胞苷100 mg/m2,d6~8],观察患者临床疗效及不良反应。结果18例患者中完全缓解(CR)6例(33.3%),部分缓解(PR)5例(27.8%),总有效率(ORR)为61.1%;8例染色体异常患者治疗后1例获完全细胞遗传学缓解,3例部分细胞遗传学缓解,总有效率为50.0%。不良反应主要为骨髓抑制及继发感染,经过输血和抗感染等支持治疗均可以耐受。随访至2015年6月,患者中位生存为8个月。结论地西他滨联合减量MA/DA方案治疗复发难治性急性髓系白血病在血液学及细胞遗传学上可以获得较好疗效,且毒副作用较轻,耐受性良好。%Objective To investigate the clinical efficacy and safety of decitabine combined with the reduced quantity of cytarabine (Ara-C) and mitoxantrone (MIT) regimen in the treatment of patients with refractory or re-lapsed acute myeloid leukemia. Methods Eighteen cases with refractory or relapsed acute myeloid leukemia in our hospital from August 2012 to June 2015 were treated with decitabine combined with reduced quantity of MA regimen (decitabine 20 mg/(m2· d), d1~5; MIT 8~12 mg/m2, d6~8;Ara-c100 mg/m2, d6~8)/DA regimen (decitabine 20 mg/(m2· d), d1~5; DNR 40~45 mg/m2, d6~8;Ara-c100 mg/m2, d6~8), and the clinical outcome and adverse events were recorded. Results Among 18 patients, 6 (33.3%) patients achieved complete remission (CR), and 5 (27.8%) were partial remission (PR), with overall remission rate (ORR) of 61.1%;After treatment, of 8 patients with chromosomal ab-normalities, 1 patient

  20. Vorinostat and Decitabine in Treating Patients With Relapsed, Refractory, or Poor-Prognosis Hematologic Cancer or Other Diseases

    Science.gov (United States)

    2013-01-04

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia

  1. Alkaline phosphatase predicts relapse in chronic hepatitis C patients with end-of-treatment response

    Institute of Scientific and Technical Information of China (English)

    Gerd; Bodlaj; Rainer; Hubmann; Karim; Saleh; Tatjana; Stojakovic; Georg; Biesenbach; Jrg; Berg

    2010-01-01

    AIM: To investigate relapse predictors in chronic hepatitis C (CHC) patients with end-of-treatment response (ETR), after pegylated interferon-α (PegIFN-α) and ribavirin treatment. METHODS: In a retrospective study we evaluated a spectrum of predictors of relapse after PegIFN-α and ribavirin treatment in 86 CHC patients with ETR. Viral loads were determined with real-time reverse transcrip-tion polymerase chain reaction. Hepatitis C virus geno-typing was performed by sequencing analysis. Patients with genoty...

  2. Dilated cardiomyopathy in a patient with antibody-negative Goodpasture′s syndrome and pulmonary relapse

    Directory of Open Access Journals (Sweden)

    Solak Yalcin

    2010-01-01

    Full Text Available The Goodpasture′s syndrome, also konwn as anti-GBM disease, is an uncommon disease, responsible for 20% of all cases of rapidly progressive glomerulonephritis. Anti-GBM antibodies are directed against non-collagenous domain (NC-1 of the alpha-3 chain of type IV collagen. When conventional ELISA assays are used, these antibodies can be detected in almost all the patients. Nevertheless, some reports have described antibody-negative relapsing disease. Some aggravating factors, namely, smoking, pulmonary infection and hypervolemia, may expose embedded antigenic target and may be responsible for the relapse. In addition, these antibody-negative relapses also respond to standard treatment, which comprises of plasma exchange, pulse steroids and cyclophosphamide. Herein, we report a patient who presented at the Selcuk Univer-sity Meram School of Medicine, Meram, Konya, Turkey, with the pulmonary-renal syndrome. He was also found to have idiopathic dilated cardiomyopathy (DCM. To our knowledge, this is the first report describing co-existence of DCM and anti-GBM disease. There is growing evidence showing strong relation of both DCM and anti-GBM disease with HLA. Although not proven, this might have occurred in our patient. In our opinion, volume overload was facilitated by anuria and DCM and led to an antibody-negative pulmonary relapse. The relapse was treated just as the first episode and the patient improved satisfactorily.

  3. Recurrence or rebound of clinical relapses after discontinuation of natalizumab therapy in highly active MS patients

    DEFF Research Database (Denmark)

    Sorensen, Per Soelberg; Koch-Henriksen, Nils; Petersen, Thor;

    2014-01-01

    A number of studies have reported flare-up of multiple sclerosis (MS) disease activity after cessation of natalizumab, increasing to a level beyond the pre-natalizumab treatment level. Our aim was to describe the development in clinical disease activity following cessation of natalizumab therapy...... in a large unselected cohort of highly active patients. We studied 375 highly active patients who had suffered at least two significant relapses within 1 year or three relapses within 2 years, or had been treated with mitoxantrone for highly active disease. All patients had discontinued therapy...... with natalizumab after at least 24 weeks on therapy, and had been followed 3-12 months (mean 8.9 months) after cessation of natalizumab therapy. The annualised relapse rate before start of natalizumab therapy was 0.94 (95 % confidence interval [CI] 0.88-1.00), 0.47 (95 % CI 0.43-0.52) during natalizumab therapy, 0...

  4. 地西他滨联合CAG方案治疗复发难治性急性髓系白血病的临床观察%Clinical outcome of decitabine combined with CAG regimen in the treatment of patients with relapsed refractory acute myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    于洪霞; 何娟

    2014-01-01

    目的 观察地西他滨联合CAG方案治疗复发难治性急性髓系白血病(AML)患者的临床疗效和不良反应.方法 收集复发难治性AML患者17例,给予地西他滨(25 mg/d,第1天至第5天静脉滴注)联合CAG方案(阿柔比星20mg/d,第3天至第6天静脉滴注,阿糖胞苷10 mg/m2,第3天至第9天1次/12h皮下注射,粒细胞集落刺激因子400 μg/d,第0天至第9天皮下注射).结果 17例患者经过1个疗程地西他滨联合CAG方案治疗后,完全缓解(CR)10例(58.8%),部分缓解(PR)1例(5.9%),未缓解(NR)6例(35.3%),总有效率(ORR)为64.7%(11/17).染色体核型良好组的1例达CR;染色体核型中等组12例中,CR 8例(66.7%),PR 1例(8.3%);染色体核型不良组4例中,CR1例(25.0%),无PR病例,三组ORR比较差异具有统计学意义(P<0.05).随访至2013年1月31日,17例患者中15例生存,2例早期死亡.中位总生存期为67d (14~307d),中位无复发生存期47 d(14 ~ 152 d).结论 地西他滨联合CAG方案治疗复发难治性AML缓解率较高,非血液学不良反应小,耐受性良好.%Objective To discuss the efficacy and safety of decitabine plus aclacinomycin/cytarabine/ G-CSF (CAG) regimen in the treatment of patients with relapsed refractory acute myeloid leukemia (AML).Methods 17 cases with relapsed refractory AML were collected.They were given decitabine (25 mg/d,d1-5) plus CAG regimen (aclacinomycin 20 mg/d,d3-6; cytarabine 10 mg/m2,d3-9; G-CSF 400 μg/d,d0-9).Results After one course treatment by decitabine plus CAG regimen,10 patients (58.8 %) achieved complete response (CR),1 patient (5.9 %) achieved partial response (PR) and 6 patients (35.3 %) displayed no response (NR),the overall response rate was 64.7 % (11/17).For karyotyping of chromosomal abnormalities,only 1 case (100 %) in CR showed normal karyotype.8 cases (66.7 %) in CR,1 case (8.3 %) in PR showed medium karyotype.1 case (25.0 %) in CR showed bad karyotype.Statistical analysis revealed

  5. Chemokines and relapses in childhood acute lymphoblastic leukemia: A role in migration and in resistance to antileukemic drugs.

    Science.gov (United States)

    Gómez, Ana M; Martínez, Carolina; González, Miguel; Luque, Alfonso; Melen, Gustavo J; Martínez, Jesús; Hortelano, Sonsoles; Lassaletta, Álvaro; Madero, Luís; Ramírez, Manuel

    2015-10-01

    We studied whether chemokines may have a role in relapses in childhood acute lymphoblastic leukemia (ALL). We compared the levels of chemokine receptors in marrow samples from 82 children with ALL at diagnosis versus 15 at relapses, and quantified the levels of chemokines in central system fluid (CSF) samples. The functional role of specific chemokines was studied in vitro and in vivo. The expression of some chemokine receptors was upregulated upon leukemic relapse, both in B- and in T-ALL, and in cases of medullary and extramedullary involvement. CXCL10 induced chemotaxis in leukemic cell lines and in primary leukemic cells, depending upon the levels of CXCR3 expression. CXCL10 specifically diminished chemotherapy-induced apoptosis on ALL cells expressing CXCR3, partially inhibiting caspase activation and maintaining the levels of the antiapoptotic protein Bcl-2. Finally, immunodeficient mice engrafted with CXCR3-expressing human leukemic cells showed decreased infiltration of marrow, spleen, and CNS after receiving a CXCR3-antagonist molecule. CXCR3 signaling in ALL may have a dual function: chemotactic for the localisation of leukemic blasts in specific niches, and it may also confer resistance to chemotherapy, enhancing the chances for relapses.

  6. 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

  7. [Outpatient reinduction therapy with gemcitabine, dexamethasone, Cisplatin (GDP) for patients with relapsed and refractory lymphoma].

    Science.gov (United States)

    Aota, Yasuo; Tanaka, Masaru; Watanabe, Naoki; Tomomatu, Jyunichi; Gotoh, Akihiko; Komatu, Norio

    2015-01-01

    For younger patients with relapsed or refractory lymphomas who respond to salvage therapy, autologous stem cell trans- plantation(ASCT)is the standard of care. Recently, it was demonstrated that the gemcitabine/dexamethasone/cisplatin (GDP) regimen for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) prior to ASCT was not inferior to the standard dexamethasone/cytarabine/cisplatin (DHAP) regimen for patients with relapsed and refractory aggressive lymphoma. In Japan, most patients who receive CDDP-containing regimens are hospitalized because of the substantial transfusions required for preventing renal dysfunction. We initiated GDP therapy combined with a short period of hydration and the administration of a magnesium agent and mannitol for 5 patients with relapsed and refractory aggressive lymphoma. In 4 cases, GDP was safely administered on an outpatient basis. Furthermore, peripheral blood stem cells were successfully collected in 2 patients. After stem cell harvest, ASCT was performed in a patient with diffuse large B-cell lymphoma, with the patient remaining in complete remission (CR) after ASCT.

  8. Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL

    Science.gov (United States)

    Badoux, Xavier C.; Keating, Michael J.; Wang, Xuemei; O'Brien, Susan M.; Ferrajoli, Alessandra; Faderl, Stefan; Burger, Jan; Koller, Charles; Lerner, Susan; Kantarjian, Hagop

    2011-01-01

    Optimal management of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) is dictated by patient characteristics, prior therapy, and response to prior therapy. We report the final analysis of combined fludarabine, cyclophosphamide, and rituximab (FCR) for previously treated patients with CLL and identify patients who benefit most from this therapy. We explore efficacy of FCR in patients beyond first relapse, patients with prior exposure to fludarabine and alkylating agent combinations, and patients with prior exposure to rituximab. The FCR regimen was administered to 284 previously treated patients with CLL. Patients were assessed for response and progression by 1996 National Cancer Institute–Working Group (NCI-WG) criteria for CLL and followed for survival. The overall response rate was 74%, with 30% complete remission. The estimated median overall survival was 47 months and median progression-free survival for all patients was 21 months. Subgroup analyses indicated that the following patients were most suitable for FCR treatment: patients with up to 3 prior treatments, fludarabine-sensitive patients irrespective of prior rituximab exposure, and patients without chromosome 17 abnormalities. FCR is an active and well-tolerated therapy for patients with relapsed CLL. The addition of rituximab to FC improved quality and durability of response in this patient population. PMID:21245487

  9. A 25-Year-Old Man with Exudative Retinal Detachments and Infiltrates without Hematological or Neurological Findings Found to Have Relapsed Precursor T-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Jordan S. Johnson

    2015-09-01

    Full Text Available Background: Precursor T-cell acute lymphoblastic leukemia (pre-T-ALL may cause ocular pathologies such as cotton-wool spots, retinal hemorrhage, and less commonly, retinal detachment or leukemic infiltration of the retina itself. However, these findings are typically accompanied by the pathognomonic hematological signs of acute leukemia. CasePresentation: In this case report and review of the literature, we describe a particularly unusual case of a 25-year-old man who presented to our hospital with bilateral exudative retinal detachments associated with posterior pole thickening without any hematological or neurological findings. The patient, who had a history of previously treated pre-T-ALL in complete remission, was found to have leukemia cell infiltration on retinal biopsy. Conclusion: Our case underscores the fact that the ophthalmologist may be the first provider to detect the relapse of previously treated leukemia, and that ophthalmic evaluation is critical for detecting malignant ocular infiltrates.

  10. Remitting–relapsing multiple sclerosis patient refractory to conventional treatments and bone marrow transplantation who responded to natalizumab

    Directory of Open Access Journals (Sweden)

    Athanasia Mouzaki

    2010-09-01

    Full Text Available Athanasia Mouzaki1, Maria Koutsokera2, Zoe Dervilli1, Maria Rodi1, Dimitra Kalavrizioti1,3, Nikolaos Dimisianos2, Ioannis Matsoukas3, Panagiotis Papathanasopoulos21Division of Hematology, Department of Internal Medicine, 2Neurology Clinic, Medical School and University Hospital, 3Department of Chemistry, University of Patras, Patras, GreeceAbstract: Bone marrow transplantation (BMT was introduced as a treatment option 15 years ago for severe, drug-resistant multiple sclerosis (MS. Up until now, BMT has been undertaken in relatively few patients worldwide, with moderate success, and recent studies suggest that patients with early, highly aggressive MS benefit most from this treatment. In this work, we determined peripheral blood lymphocyte populations in a patient (patient A with remitting–relapsing multiple sclerosis (RR-MS, refractory to conventional treatments, and who underwent BMT, relapsed, and has been treated with natalizumab for the last 22 months. Eleven other RR-MS patients in the acute phase of the disease, untreated or treated with interferon-beta, and 20 healthy subjects served as controls. Natalizumab treatment in patient A resulted in lymphocytosis and increased levels of CD20+/CD20+CD5+ B cells and T regulatory cells (Tregs. The patient maintained relatively low levels of T cells, T helper cells, memory T helper cells, and naive cytotoxic T cells, and very low levels of naive T helper cells and natural killer cells throughout. The Tregs of patient A post-treatment with natalizumab responded well in culture to a peptide mapping to a myelin basic protein antigenic epitope (mean 42% increase compared with Tregs of healthy controls (mean 15% increase whereas Tregs of the RR-MS controls or patient A prenatalizumab treatment either did not respond or responded adversely to the peptide (mean 3% and 21% decreases, respectively. Since the beginning of natalizumab treatment, patient A has had no relapses, and his Expanded Disability

  11. Allogeneic hematopoietic stem cell transplantation in patients with diffuse large B cell lymphoma relapsed after autologous stem cell transplantation: a GITMO study.

    Science.gov (United States)

    Rigacci, Luigi; Puccini, Bendetta; Dodero, Anna; Iacopino, Pasquale; Castagna, Luca; Bramanti, Stefania; Ciceri, Fabio; Fanin, Renato; Rambaldi, Alessandro; Falda, Michele; Milone, Giuseppe; Guidi, Stefano; Martelli, Massimo Fabrizio; Mazza, Patrizio; Oneto, Rosi; Bosi, Alberto

    2012-06-01

    Patients who relapse after an autologous hematopoietic stem cell transplantation (SCT) have a very poor prognosis. We have retrospectively analyzed diffuse large B cell lymphoma patients who underwent an allo-SCT after an auto-SCT relapse reported in the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) database. From 1995 to 2008, 3449 autologous transplants were reported in the GITMO database. Eight hundred eighty-four patients relapsed or progressed after transplant; 165 patients, 19% of the relapsed patients, were treated with allo-transplant. The stem cell donor was related to the patient in 108 cases. A reduced intensity conditioning regimen was used in 116. After allo-SCT, 72 patients (43%) obtained a complete response and 9 obtained a partial response with an overall response rate of 49%; 84 patients (51%) experienced rapid progression of disease. Ninety-one patients died, 45 due to disease and 46 due to treatment-related mortality. Acute graft-versus-host disease was recorded in 57 patients and a chronic GvHD in 38 patients. With a median follow-up of 24 months (2-144) after allo, overall survival (OS) was 39%, and after a median of 21 months (2-138) after allo, progression-free survival (PFS) was 32%. Multivariate analysis indicated that the only factors affecting OS were status at allo-SCT, and those affecting PFS were status at allo-SCT and stem cell donor. This retrospective analysis shows that about one-fifth of patients with diffuse large B cell lymphoma who experience relapse after autologous transplantation may be treated with allogeneic transplantation. Moreover, the only parameter affecting either OS or PFS was the response status at the time of allo-SCT.

  12. Cerebral venous thrombosis in patient of relapse of ulcerative colitis:report of a case

    Institute of Scientific and Technical Information of China (English)

    Rajat Agarwal; Anuradha Batra; Ish Anand; Davinder Singh Rana; Samir Patel

    2016-01-01

    Amongst the various systemic complications of ulcerative colitis, cerebral venous thrombosis (CVT) is an uncommon and serious neurological complication mainly associated during episodes of relapse of ulcerative colitis. CVT is suspected to be a consequence of hypercoagulable state occurring during the disease in genetic predisposed persons. Most patients present with rapid neurological deterioration. This devastating intracranial complication requires immediate medical intervention to avoid potentially life threatening consequences. The outcome is good, provided the disease is diagnosed on time and the treatment is started early. The authors present a patient of CVT, a rare complication seen during relapse of ulcerative colitis.

  13. 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.

  14. 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.

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

    Science.gov (United States)

    Ortiz, Genaro Gabriel; Macías-Islas, Miguel Ángel; Pacheco-Moisés, Fermín P.; Cruz-Ramos, José A.; Sustersik, Silvia; Barba, Elías Alejandro; Aguayo, Adriana

    2009-01-01

    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. PMID:19242067

  16. Donor haplotype B of NK KIR receptor reduces the relapse risk in HLA-identical sibling hematopoietic stem cell transplantation of AML patients.

    Directory of Open Access Journals (Sweden)

    Ulla eImpola

    2014-08-01

    Full Text Available Successful allogeneic hematological stem cell transplantation (HSCT depends not only on good HLA match but also on T-cell mediated graft-versus-leukemia (GvL effect. Natural killer (NK cells are able to kill malignant cells by receiving activation signal from the killer-cell immunoglobulin-like receptors (KIR recognizing HLA molecules on a cancer cell. It has been recently reported that the risk of relapse in allogeneic hematopoietic stem cell transplantation (HSCT is reduced in acute myeloid leukemia (AML patients whose donors have several activating KIR genes or KIR B-motifs in unrelated donor (URD setting, obviously due to enhanced graft-versus-leukemia effect by NK cells. We studied the effect on relapse rate of donor KIR haplotypes in the HLA identical adult sibling HSCT, done in a single center, in Helsinki University Central Hospital, Helsinki, Finland. Altogether 134 patients with 6 different diagnoses were identified. Their donors were KIR genotyped using the Luminex and the SSP techniques. The clinical endpoint, that is, occurrence of relapse, was compared with the presence or absence of single KIR genes. Also, time from transplantation to relapse was analyzed. The patients with AML whose donors have KIR2DL2 or KIR2DS2 had statistically significantly longer relapse-free survival (P=0.015. Our data support previous reports that donors with KIR B-haplotype defining genes have a lower occurrence of relapse in HSCT of AML patients. Determination of donor KIR haplotypes could be a useful addition for a risk assessment of HSCT especially in AML patients.

  17. Donor Haplotype B of NK KIR Receptor Reduces the Relapse Risk in HLA-Identical Sibling Hematopoietic Stem Cell Transplantation of AML Patients.

    Science.gov (United States)

    Impola, Ulla; Turpeinen, Hannu; Alakulppi, Noora; Linjama, Tiina; Volin, Liisa; Niittyvuopio, Riitta; Partanen, Jukka; Koskela, Satu

    2014-01-01

    Successful allogeneic hematopoietic stem cell transplantation (HSCT) depends not only on good HLA match but also on T-cell mediated graft-versus-leukemia (GvL) effect. Natural killer (NK) cells are able to kill malignant cells by receiving activation signal from the killer-cell immunoglobulin-like receptors (KIR) recognizing HLA molecules on a cancer cell. It has been recently reported that the risk of relapse in allogeneic hematopoietic stem cell transplantation (HSCT) is reduced in acute myeloid leukemia (AML) patients whose donors have several activating KIR genes or KIR B-motifs in unrelated donor setting, obviously due to enhanced GvL effect by NK cells. We studied the effect on relapse rate of donor KIR haplotypes in the HLA-identical adult sibling HSCT, done in a single center, in Helsinki University Central Hospital, Helsinki, Finland. Altogether, 134 patients with 6 different diagnoses were identified. Their donors were KIR genotyped using the Luminex and the SSP techniques. The clinical endpoint, that is, occurrence of relapse, was compared with the presence or absence of single KIR genes. Also, time from transplantation to relapse was analyzed. The patients with AML whose donors have KIR2DL2 or KIR2DS2 had statistically significantly longer relapse-free survival (P = 0.015). Our data support previous reports that donors with KIR B-haplotype defining genes have a lower occurrence of relapse in HSCT of AML patients. Determination of donor KIR haplotypes could be a useful addition for a risk assessment of HSCT especially in AML patients.

  18. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study.

    Science.gov (United States)

    Perl, Alexander E; Altman, Jessica K; Cortes, Jorge; Smith, Catherine; Litzow, Mark; Baer, Maria R; Claxton, David; Erba, Harry P; Gill, Stan; Goldberg, Stuart; Jurcic, Joseph G; Larson, Richard A; Liu, Chaofeng; Ritchie, Ellen; Schiller, Gary; Spira, Alexander I; Strickland, Stephen A; Tibes, Raoul; Ustun, Celalettin; Wang, Eunice S; Stuart, Robert; Röllig, Christoph; Neubauer, Andreas; Martinelli, Giovanni; Bahceci, Erkut; Levis, Mark

    2017-08-01

    Internal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia. In this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment. Patients were enrolled into one of seven dose-escalation or dose-expansion cohorts assigned to receive once-daily doses of oral gilteritinib (20 mg, 40 mg, 80 mg, 120 mg, 200 mg, 300 mg, or 450 mg). Cohort expansion was based on safety and tolerability, FLT3 inhibition in correlative assays, and antileukaemic activity. Although the presence of an FLT3 mutation was not an inclusion criterion, we required ten or more patients with locally confirmed FLT3 mutations (FLT3(mut+)) to be enrolled in expansion cohorts at each dose level. On the basis of emerging findings, we further expanded the 120 mg and 200 mg dose cohorts to include FLT3(mut+) patients only. The primary endpoints were the safety, tolerability, and pharmacokinetics of gilteritinib. Safety and tolerability were assessed in the safety analysis set (all patients who received at least one dose of gilteritinib). Responses were assessed in the full analysis set (all patients who received at least one dose of study drug and who had at least one datapoint post-treatment). Pharmacokinetics were assessed in a subset of the safety analysis set for which sufficient data for concentrations of gilteritinib in plasma were available to enable derivation of one or more pharmacokinetic variables. This study is registered with ClinicalTrials.gov, number

  19. Omeprazole and Ranitidine in the Prevention of Relapse in Patients with Duodenal Ulcer Disease

    Directory of Open Access Journals (Sweden)

    K Lauritsen

    1999-01-01

    Full Text Available BACKGROUND: Although the eradication of Helicobacter pylori is of primary importance when initiating treatment, it is also important to have a strategy for patients who are H pylori-negative, fail to demonstrate eradication or have a tendency to become re-infected or relapse.

  20. Combination chemotherapy with cyclophosphamide, thalidomide and dexamethasone for patients with refractory, newly diagnosed or relapsed myeloma.

    Science.gov (United States)

    Sidra, Gamal; Williams, Cathy D; Russell, Nigel H; Zaman, Sonya; Myers, Bethan; Byrne, Jennifer L

    2006-06-01

    We evaluated the combination of thalidomide, pulsed dexamethasone and weekly cyclophosphamide (CTD) for the treatment of patients with newly diagnosed, relapsed or VAD-refractory multiple myeloma. We found that this combination was highly effective in inducing responses in all treatment groups with an overall response rate of 83.8%. CTD was well tolerated and did not impair stem cell mobilization.

  1. 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

    . 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...

  2. 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.

  3. Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma

    DEFF Research Database (Denmark)

    Pettengell, Ruth; Schmitz, Norbert; Gisselbrecht, Christian

    2013-01-01

    The objective of this randomized trial was to assess the efficacy and safety of rituximab as in vivo purging before transplantation and as maintenance treatment immediately after high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT) in patients with relapsed follicular lympho...

  4. Phase I Study of Valspodar (PSC-833) with Mitoxantrone and Etoposide in Refractory and Relapsed Pediatric Acute Leukemia: A Report from the Children’s Oncology Group

    Science.gov (United States)

    O’Brien, Maureen M.; Lacayo, Norman J.; Lum, Bert L.; Kshirsagar, Smita; Buck, Steven; Ravindranath, Yaddanapudi; Bernstein, Mark; Weinstein, Howard; Chang, Myron N.; Arceci, Robert J.; Sikic, Branimir I.; Dahl, Gary V.

    2009-01-01

    Background Valspodar, a non-immunosuppressive analog of cylosporine, is a potent P-glycoprotein (MDR1) inhibitor. As MDR1-mediated efflux of chemotherapeutic agents from leukemic blasts may contribute to drug resistance, a phase 1 study of valspodar combined with mitoxantrone and etoposide in pediatric patients with relapsed or refractory leukemias was performed. Procedure Patients received a valspodar loading dose (2 mg/kg) followed by a five-day continuous valspodar infusion (8, 10, 12.5 or 15 mg/kg/day) combined with lower than standard doses of mitoxantrone and etoposide. The valspodar dose was escalated using a standard 3 + 3 phase I design. Results 21 patients were evaluable for toxicity and 20 for response. The maximum tolerated dose (MTD) of valspodar was 12.5 mg/kg/day, combined with 50% dose-reduced mitoxantrone and etoposide. The clearance of mitoxantrone and etoposide was decreased by 64% and 60%, respectively, when combined with valspodar. Dose-limiting toxicities included stomatitis, ataxia, and bone marrow aplasia. Three of 11 patients with acute lymphoblastic leukemia (ALL) had complete responses while no patient with acute myeloid leukemia (AML) had an objective response. In vitro studies demonstrated P-glycoprotein expression on the blasts of five of 14 patients, although only one had inhibition of rhodamine efflux by valspodar. Conclusions While this regimen was tolerable, responses in this heavily pretreated population were limited to a subset of patients with ALL. PMID:20209646

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

    Directory of Open Access Journals (Sweden)

    Osama Hasan Gaber

    2016-11-01

    Full Text Available 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. Also the result showed that there are no statistically significant relationship between Paranoid personality disorder(PDD, Schizoid personality disorder(SPD, Schizotypal personality disorder (STPD, Histrionic personality disorder(HPD, Narsistic personality disorder(NPD and Obsessive-Compulsive personality disorder (OCPD, The Regression and Prediction Coefficient (stepwise was also used and showed that the Dependent personality disorder, Borderline personality disorder and Antisocial personality disorder predicts substance abuse relapses.

  6. Relationship of expressed emotion with relapse of schizophrenia patients in Kelantan.

    Science.gov (United States)

    Azhar, M Z; Varma, S L

    1996-02-01

    The families of 83 schizophrenic patients were studied to find out the level of expressed emotion in them leading to the relapse of these patients. The patients were having more than two episodes of schizophrenia (DSM-III-R). The most salient finding was the virtual absence of high level of expressed emotion as the cause of relapse. It was found that the majority of the families (72.3%) had low expressed emotion while only 25.3% had high expressed emotion and only 2.4% families were equivocal in this respect. This finding is in contrast with various other findings in this area. The most likely explanation for this disagreement is the cultural differences between Malaysian patients and Western patients.

  7. Prospective noninterventional study on peripheral blood stem cell mobilization in patients with relapsed lymphomas.

    Science.gov (United States)

    van Gorkom, Gwendolyn; Finel, Herve; Giebel, Sebastian; Pohlreich, David; Shimoni, Avichai; Ringhoffer, Mark; Sucak, Gülsan; Schaap, Nicolaas; Dreger, Peter; Sureda, Anna; Schouten, Harry C

    2016-09-10

    High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) to rescue hematopoiesis is considered standard care for patients with a relapsed chemosensitive lymphoma, but diagnosis of lymphoma has been a risk factor for poor mobilization in several studies. The aim of this prospective noninterventional clinical audit was to review the mobilization strategies used by EBMT centers in relapsed lymphoma and to evaluate their efficacy. Between 2010 and 2014, 275 patients with relapsed lymphoma from 30 EBMT centers were prospectively registered. Almost all patients were mobilized with chemotherapy plus G-CSF (96%), but there was a large variation in chemotherapy schedules. Thirty (11%) of them were poor mobilizers (mobilization. Poor mobilization was not associated with gender, age, bone marrow involvement at diagnosis, primary diagnosis, number of previous chemotherapy lines, previous radiotherapy or mobilization with G-CSF alone. The use of high dose cyclophosphamide alone was associated with mobilization failure (P = 0.0006), whereas the use of a platinum-containing regimen was associated with a good mobilization outcome (P = 0.013). Because failure rate is low, we can conclude from this study that PBSC mobilization failure in relapsed lymphomas is not an important problem in the EBMT centers.

  8. 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

  9. FCR and Bevacizumab (FCR-B) Treatment in Patients with Relapsed Chronic Lymphocytic Leukemia (CLL)

    Science.gov (United States)

    Jain, Preetesh; Lee, Hun Ju; Qiao, Wei; Wierda, William; Benjamini, Ohad; Burger, Jan; Ferrajoli, Alessandra; Estrov, Zeev; Kantarjian, Hagop; Keating, Michael; O’Brien, Susan

    2014-01-01

    Patients with relapsed chronic lymphocytic leukemia (CLL) often achieve response with chemoimmunotherapy but have short remission durations. Studies have shown that patients with CLL have increased angiogenesis in the microenvironment; levels of pro-angiogenic growth factors such as VEGF and/or angiopoietin-2 (Ang-2) are also elevated. Increased angiogenesis correlates with poor outcome in CLL. Bevacizumab (B) is a humanized monoclonal antibody targeting VEGF-A. In this study, we analysed whether a combination of bevacizumab (B) with FCR chemoimmunotherapy (FCR-B) could improve outcomes in patients with relapsed CLL. Sixty-two patients were enrolled. The median age of the patients was 60 years (range, 31–84 years) and 40% had received >1 prior therapy for CLL. Sixty-one patients were evaluable for toxicity and 57 were evaluable for response. Six cycles were planned; 36 (59%) patients completed ≥ 4–6 cycles of the regimen. The overall response rate (ORR) was 79% with 13 (23%) complete remissions (CR), 8 (14%) nodular partial remissions (nPR) and 24 (43%) partial remissions (PR). The median progression free survival (PFS) and overall survival (OS) rates were 13.5 and 45 months, respectively. Grade 3 or 4 toxicities included febrile neutropenia (n=40), infections (n=21), thrombocytopenia (n=18) and anemia (n=9). Results with FCR-B were similar to those observed with an historical cohort of relapsed patients treated with FCR. PMID:25043749

  10. MR features of isolated uterine relapse in an adolescent with acute lymphoblastic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Novellas, Sebastien; Fournol, Maude; Geoffray, Anne; Chevallier, Patrick [Regional Hospital Centre and University of Nice, Medical Imaging Service, Archet 2 Hospital, 151 route de Saint Antoine de Ginestiere, B.P. 3079, Nice Cedex 3 (France); Deville, Anne [Regional Hospital Centre and University of Nice, Paediatric Service, Archet 2 Hospital, Nice (France); Kurzenne, Jean-Yves [Regional Hospital Centre and University of Nice, Paediatric Surgery Service, Archet 2 Hospital, Nice (France)

    2008-03-15

    Relapses of lymphoblastic leukaemia traditionally involve the central nervous system and testes in boys. Involvement of the female pelvic organs is frequently found at autopsy; however, involvement of the cervical uterus is rare and even less commonly symptomatic. A 13-cm uterine mass was discovered in a 15-year-old adolescent with a history of lymphoblastic leukaemia during childhood. Pelvic MRI was the best tool to assess the size, characteristics and invasive nature of this lesion of the uterine cervix. To our knowledge, this is a unique case in that we describe the MRI appearance of a relapsing lymphoblastic leukaemic mass both before and after treatment. (orig.)

  11. Regulatory Cell Populations in Relapsing-Remitting Multiple Sclerosis (RRMS) Patients: Effect of Disease Activity and Treatment Regimens

    Science.gov (United States)

    Rodi, Maria; Dimisianos, Nikolaos; de Lastic, Anne-Lise; Sakellaraki, Panagiota; Deraos, George; Matsoukas, John; Papathanasopoulos, Panagiotis; Mouzaki, Athanasia

    2016-01-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) of autoimmune etiology that results from an imbalance between CNS-specific T effector cells and peripheral suppressive mechanisms mediated by regulatory cells (RC). In this research, we collected blood samples from 83 relapsing remitting MS (RRMS) patients and 45 healthy persons (HC), to assess the sizes of their RC populations, including CD4+CD25highFoxp3+ (nTregs), CD3+CD4+HLA−G+, CD3+CD8+CD28−, CD3+CD56+, and CD56bright cells, and how RC are affected by disease activity (acute phase or remission) and types of treatment (methylprednisolone, interferon, or natalizumab). In addition, we isolated peripheral blood mononuclear cells (PBMC) and cultured them with peptides mapping to myelin antigens, to determine RC responsiveness to autoantigens. The results showed decreased levels of nTregs in patients in the acute phase ± methylprednisolone and in remission + natalizumab, but HC levels in patients in remission or receiving interferon. Patients + interferon had the highest levels of CD3+CD4+HLA−G+ and CD3+CD8+CD28− RC, and patients in the acute phase + methylprednisolone the lowest. Patients in remission had the highest levels of CD3+CD56+, and patients in remission + natalizumab the highest levels of CD56bright cells. Only nTregs responded to autoantigens in culture, regardless of disease activity or treatment. The highest suppressive activity was exhibited by nTregs from patients in remission. In conclusion, in RRMS disease activity and type of treatment affect different RC populations. nTregs respond to myelin antigens, indicating that it is possible to restore immunological tolerance through nTreg induction. PMID:27571060

  12. Infusions of recipient-derived cytokine-induced killer cells of donor origin eradicated residual disease in a relapsed leukemia patient after allo-hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHONG Zhao-dong; LUO Yi; ZOU Ping; ZHENG Jin-e; YAO Jun-xia; HUANG Shi-ang; ZHOU Dong-feng; YOU Yong

    2012-01-01

    A female patient diagnosed with acute myelocytic leukemia M5a (AML-M5a) relapsed 986 days after her allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from an unrelated male donor with matched human leukocyte antigen (HLA).Three re-induction chemotherapies were administered,and partial remission was achieved.The patient was given repetitive infusion of cytokine-induced killer (CIK) cells expanded from recipient peripheral mononuclear cells of full donor chimerism due to loss of contact of quondam donor for donor lymphocyte infusion (DLI) and rejection of second transplantation.The patient achieved complete cytogenetical remission.This strategy might overcome the obstacle of donor unavailability and present an appealing new therapeutic alternative to donor-recruited adoptive immunotherapy for relapsed disease at post-transplantation.

  13. Ecthyma gangrenosum in a patient with acute leukemia.

    Science.gov (United States)

    Kryeziu, Emrush; Kryeziu, K; Bajraktari, Gjani; Abazi, M; Zylfiu, B; Rudhani, I; Sadiku, Sh; Ukimeri, A; Brovina, A; Dreshaj, Sh; Telaku, S

    2010-01-01

    Ecthymagangrenosum (EG)is a rare condition with characteristic clinical appearance of red maculae that progresses to a central area of necrosis surrounded by an erythematous halo. The most frequently it is caused by Pseudomonas bacteriaemia in neutropenic patient. The authors presents a patient with acute myloblastic leukemia M4 type in whom in relapse EG caused by Pseudomonas aeruginosa was found. The patient was treated with antibiotics and surgical debridement. The author wants to point out on clinical significance this condition with high mortality rate.

  14. Phylogenetic Analysis of a Virulent Borrelia Species Isolated from Patients with Relapsing Fever▿

    Science.gov (United States)

    Toledo, A.; Anda, P.; Escudero, R.; Larsson, C.; Bergstrom, S.; Benach, J. L.

    2010-01-01

    Multilocus sequence analysis (MLSA) was used to clarify the taxonomic status of a virulent Borrelia organism previously isolated from patients with relapsing fever and from ticks in Spain that is designated the Spanish relapsing fever (SRF) Borrelia. This species has been used extensively in experimental infection models because of its continued virulence. Seven genes were amplified to analyze the phylogenetic relationships among several Spanish isolates of SRF Borrelia and other relapsing fever Borrelia species. The genes targeted in this study included rrs and flaB, which have commonly been used in phylogenetic studies; the rrf-rrl intergenic spacer (IGS), which is highly discriminatory; and four additional genes, p66, groEL, glpQ, and recC, which are located on the chromosome and which have therefore evolved in a clonal way. The species included in this study were Borrelia duttonii, B. recurrentis, B. crocidurae, and B. hispanica as Old World Borrelia species and B. turicatae and B. hermsii as New World Borrelia species. The results obtained by MLSA of the SRF Borrelia on the basis of 1% of the genomic sequence data analyzed confirmed that the SRF Borrelia isolates are B. hispanica. However, the prototype isolates of B. hispanica used in this study have an uncertain history and display unique phenotypic characteristics that are not shared with the SRF Borrelia. Therefore, we propose to use strain SP1, isolated from a relapsing fever patient in 1994 in southern Spain, as the type strain for B. hispanica. PMID:20463158

  15. Profile of blinatumomab and its potential in the treatment of relapsed/refractory acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Ribera JM

    2015-06-01

    Full Text Available Josep-Maria Ribera, Albert Ferrer, Jordi Ribera, Eulàlia GenescàClinical Hematology Department, ICO-Hospital Germans Trias i Pujol, Josep Carreras Research Institute, Universitat Autònoma de Barcelona, Badalona, SpainAbstract: The CD19 marker is expressed on the surface of normal and malignant immature or mature B-cells. On the other hand, immunotherapy involving T-cells is a promising modality of treatment for many neoplastic diseases including leukemias and lymphomas. The CD19/CD3-bispecific T-cell-engaging (BiTE® monoclonal antibody blinatumomab can transiently engage cytotoxic T-cells to CD19+ target B-cells inducing serial perforin-mediated lysis. In the first clinical trial, blinatumomab showed efficacy in non-Hodgkin’s lymphomas, but the most important trials have been conducted in relapsed/refractory (R/R acute lymphoblastic leukemia (ALL and in ALL with minimal residual disease. Encouraging reports on the activity of blinatumomab in R/R Philadelphia chromosome-negative B-cell precursor ALL led to its approval by the US Food and Drug Administration on December 3, 2014 after an accelerated review process. This review focuses on the profile of blinatumomab and its activity in R/R ALL.Keywords: acute lymphoblastic leukemia, relapsed/refractory, BiTE® monoclonal antibodies, blinatumomab

  16. Alemtuzumab: a review of its use in patients with relapsing multiple sclerosis.

    Science.gov (United States)

    Garnock-Jones, Karly P

    2014-03-01

    Alemtuzumab (Lemtrada™) is a humanized therapeutic monoclonal antibody, which has been approved for use in patients with B-cell chronic lymphocytic leukaemia for several years, and has recently become approved in the EU and several other countries for use in adult patients with active relapsing-remitting multiple sclerosis. This article reviews the available pharmacological properties of intravenous infusions of alemtuzumab and its clinical efficacy and tolerability in adult patients with relapsing-remitting multiple sclerosis. Alemtuzumab is an effective treatment for patients with relapsing-remitting multiple sclerosis, and has a generally acceptable tolerability profile. In phase III trials, it was shown to be more effective than a current first-line treatment, subcutaneous interferon beta-1a, in decreasing relapse rate in treatment-naïve and previously treated patients and in decreasing disability progression in previously treated patients. Of note, these results appear to have extended into the long-term follow-up, despite no further treatment. There was an increased risk of autoimmunity and infection associated with alemtuzumab in these trials; while these adverse events were generally mild to moderate, some were severe. Alemtuzumab is a highly convenient treatment, requiring hospital attendance for an intravenous infusion for a handful of days on two consecutive years, with no treatment required in between; however, this convenience is counterbalanced by the need for regular monitoring for the increased risk of autoimmunity. More investigation is required before final conclusions can be drawn on the correct placement of alemtuzumab in multiple sclerosis treatment; however, it is of a certainty a welcome addition to the treatment options for these patients.

  17. Prognostic impact of LDH levels in patients with relapsed/refractory seminoma.

    Science.gov (United States)

    Powles, Tom; Bascoul-Mollevi, Caroline; Kramar, Andrew; Lorch, Anja; Beyer, Jörg

    2013-08-01

    To evaluate the impact of age and LDH levels in patients with relapsed seminoma. Data on the 204 seminoma from the International Prognostic Factor Study Group (IPFSG) were analyzed. All patients experienced unequivocal relapse/progression after at least three cisplatin-based chemotherapy cycles. Age and LDH at relapse were assessed in addition to previously identified prognostic factors for all germ cell tumor patients from the database (J Clin Oncol 28:4906, 2010). The impact of the IPFSG score remained highly significant in multivariate analysis. In addition, LDH ≥1.5 times the upper limit of normal (ULN) was significant in univariate (HR 1.96; CI 1.06-3.61) and multivariate analysis (HR 1.90; CI 1.00-3.62). Age, however, was not significant. Therefore, LDH was incorporated into a modified new IPFSG seminoma score by moving patients to the next unfavorable group for patients with LDH values ≥1.5 × ULN. Three prognostic groups were thus generated, which better subdivided seminoma patients than the original IPFSG score. Progression-free survival at 2 years: "very low risk" (n = 23) 85.7% (95% CI 62-95), "low risk" (n = 44) 62.7 % (95% CI 46-75) and "intermediate risk" (n = 36) 35.1% (95% CI 20-51). Overall survival at 3 years: "very low risk" 88.8% (95% CI 62-97), "low risk" 71.3% (95% CI 55-83) and "intermediate risk" 51.3% (95% CI 33-67). The addition of LDH, but not age, improves the impact of the IPFSG prognostic score in seminoma patients relapsing or progressing after cisplatin-based chemotherapy.

  18. 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

  19. Mixed T Lymphocyte Chimerism after Allogeneic Hematopoietic Transplantation Is Predictive for Relapse of Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    Science.gov (United States)

    Lee, Hans C; Saliba, Rima M; Rondon, Gabriela; Chen, Julianne; Charafeddine, Yasmeen; Medeiros, L Jeffrey; Alatrash, Gheath; Andersson, Borje S; Popat, Uday; Kebriaei, Partow; Ciurea, Stefan; Oran, Betul; Shpall, Elizabeth; Champlin, Richard

    2015-11-01

    Chimerism testing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represents a promising tool for predicting disease relapse, although its precise role in this setting remains unclear. We investigated the predictive value of T lymphocyte chimerism analysis at 90 to 120 days after allo-HSCT in 378 patients with AML/MDS who underwent busulfan/fludarabine-based myeloablative preparative regimens. Of 265 (70%) patients with available T lymphocyte chimerism data, 43% of patients in first or second complete remission (CR1/CR2) at the time of transplantation had complete (100%) donor T lymphocytes at day +90 to +120 compared with 60% of patients in the non-CR1/CR2 cohort (P = .005). In CR1/CR2 patients, donor T lymphocyte chimerism ≤ 85% at day +90 to +120 was associated with a higher frequency of 3-year disease progression (29%; 95% confidence interval [CI], 18% to 46% versus 15%; 95% CI, 9% to 23%; hazard ratio [HR], 2.1; P = .04). However, in the more advanced, non-CR1/CR2 cohort, mixed T lymphocyte chimerism was not associated with relapse (37%; 95% CI, 20% to 66% versus 34%; 95% CI, 25% to 47%; HR, 1.3; P = .60). These findings demonstrate that early T lymphocyte chimerism testing at day +90 to +120 is a useful approach for predicting AML/MDS disease recurrence in patients in CR1/CR2 at the time of transplantation.

  20. 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

    OBJECTIVE: To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy. METHODS: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE......-MS) II, a 2-year randomized, rater-blinded, active-controlled, head-to-head, phase 3 trial, compared efficacy and safety of alemtuzumab 12 mg with subcutaneous interferon-β-1a (SC IFN-β-1a) 44 μg in patients with RRMS. Prespecified and post hoc disability outcomes based on Expanded Disability Status...... Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Sloan low-contrast letter acuity (SLCLA) are reported, focusing on improvement of preexisting disability in addition to slowing of disability accumulation. RESULTS: Alemtuzumab-treated patients were more likely than SC IFN-β-1a...

  1. Efficacy of lenalidomide, bortezomib, and prednisolone in patients with relapsed or refractory multiple myeloma

    Directory of Open Access Journals (Sweden)

    T. A. Мitinа

    2015-01-01

    Full Text Available 49 patients aged 28 to 81 years old (median age of 55 years old with relapsed or refractory multiple myeloma (MM were enrolled in the study. The relapse was diagnosed in 25 (51 % patients, the refractory disease was determined in 24 (49 % patients (including primary refractory disease in 14 (28.6 % patients. The prior therapy for all patients included bortezomib-based treatment in combination with thalidomide and autologus stem cell transplantation (8.1 %. Lenalidomide had not been used in the previous therapeutic regimens. All patients were given the original treatment regimen, which included lenalidomide, bortezomib, and prednisolone (RVP. The therapy was made up of seven induction cycles with each one lasting for 48 days. Length of courses was 14 days. After seven cycles of RVP therapy were over, such results were achieved: complete response (CR in 1 (2 % patient; very good partial response (VGPR in 4 (8 % patients; partial response (PR in 26 (53 % patients; minimal response (MR in 2 (4 % patients; stable disease (SD in 8 (16.3 % patients, and progressive disease (PD in 8 (16.3 % patients. The objective response rate, including CR+VGPR+PR, was obtained in 31 (63.1 % patients. The objective response rate, including MR, was seen in 33 (67.1 % patients. Hematological and non-hematological toxicities were moderate. Taking into account the above, the RVP therapeutic regimen has demonstrated its efficacy as a second-line therapy for MM, and its clinical use can solve the problem of relapsed/refractory to bortezomib-based regimens MM management.

  2. Increasing aclarubicin dose in low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) is efficacious as salvage chemotherapy for relapsed/refractory mixed-phenotype acute leukemia.

    Science.gov (United States)

    Liu, Limin; Qu, Qi; Jiao, Wenjing; Zhang, Yanming; Li, Xiaoli; Ding, Chao; Wu, Depei

    2015-08-01

    We treated 60 relapsed/refractory mixed-phenotype acute leukemia patients (MPAL-1) with increasing the aclarubicin dose in CAG regimen (HD-CAG, cytarabine (10 mg/m(2)/12 h, days 1-14), aclarubicin (5-7 mg/m(2)/day, days 1-14), granulocyte colony-stimulating factor (200 μg/m(2)/day, days 1-14). This was compared to 64 relapsed/refractory MPAL patients (MPAL-2) treated with DOAP regimen (daunorubicin, vincristine/vindesine, cytarabine and prednisone), 113 relapsed/refractory acute myeloid leukemia (AML) patients and 78 acute lymphocytic leukemia (ALL) patients treated with HD-CAG regimen. After one course, complete remission (CR) and overall response [OR, CR+partial remission (PR)] rates for MPAL-1 exceeded MPAL-2 (CR, 61.02% vs. 28.13%, P=0.000; OR, 72.88% vs. 34.38%, P=0.000), but these data were similar to AML and ALL (P>0.05). In MPAL-1 group, CR and OR rates of T-lymphoid+myeloid immunophenotype were higher than B-lymphoid+myeloid immunophenotype (CR, 81.82% vs. 44.12%, P=0.005; OR, 90.91% vs. 58.82%, P=0.009). The overall survival at 3 years in MPAL-1, MPAL-2, AML and ALL groups were 14.2%±6.8%, 14.1%±6.4%, 17.3%±5.0% and 15.0%±5.3% (P>0.05). Side effects were similar between HD-CAG and DOAP (P>0.05). HD-CAG regimen is efficacious for relapsed/refractory MPAL, especially for T+My patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. 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.

  4. Outcome of ETV6/RUNX1-positive childhood acute lymphoblastic leukaemia in the NOPHO-ALL-1992 protocol: frequent late relapses but good overall survival

    DEFF Research Database (Denmark)

    Forestier, E.; Heyman, M.; Andersen, Mette Klarskov

    2008-01-01

    The prognostic impact of t(12;21)(p13;q22) [ETV6/RUNX1 fusion] in paediatric acute lymphoblastic leukaemia (ALL) has been extensively debated, particularly with regard to the frequency of late relapses and appropriate treatment regimens. We have retrospectively collected 679 ALLs with known ETV6....../RUNX1 status, as ascertained by fluorescence in situ hybridization or reverse-transcription polymerase chain reaction, treated according to the Nordic Society of Paediatric Haematology and Oncology -ALL-1992 protocol. The assigned risk groups/treatment modalities for the 171 (25%) patients with t(12......, there is no reliable plateau in the EFS curve, a fact that raises the question as to when the prognostic ramifications of ALLs harbouring ETV6/RUNX1 should be evaluated Udgivelsesdato: 2008/3...

  5. 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

    or in combination with abnormal blood tests or physical examination in 64% of the patients. Routine imaging prompted relapse investigations in 27% of the patients. The estimated number of routine scans per relapse was 91-255 depending on the lymphoma subtype. Patients with imaging-detected relapse had lower disease...

  6. Relapsed hydroxychloroquine induced thrombocytopenia in a systemic lupus erythematosus patient.

    Science.gov (United States)

    Antón Vázquez, Vanesa; Pascual, Luis; Corominas, Héctor; Giménez Torrecilla, Isabel

    Hydroxychloroquine is used in the long-term therapy of systemic lupus erythematosus (SLE). Although considered to be a safe treatment, side effects have been documented. An uncommon side effect is thrombocytopenia. In order to establish the diagnosis of thrombocytopenia secondary to Hydroxychloroquine, non-pharmacological causes must be ruled out and it is necessary to determine a recurrence after re-exposure to the drug. We present one case of severe thrombocytopenia occurring in a patient with SLE undergoing treatment with Hydroxychloroquine. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  7. Hypokalemia in acute medical patients

    DEFF Research Database (Denmark)

    Jensen, Helene Christine Kildegaard; Brabrand, Mikkel; Vinholt, Pernille Just

    2015-01-01

    . METHODS: We conducted a prospective cohort study involving all first time admissions (n=11988) to the Acute Medical Department at Odense University Hospital linking potassium level at admission with registry data on patient characteristics, laboratory data, redeemed prescriptions and time of death...... or betagonist use. CONCLUSIONS: In a mixed population of hospitalized medical patients, hypokalemia is common and plasma [K(+)

  8. Cell proliferation index predicts relapse of brain metastases in non-irradiated patients

    DEFF Research Database (Denmark)

    Peev, N A; Tonchev, A B; Penkowa, M

    2008-01-01

    BACKGROUND: Brain metastasis is a common complication and a major cause of morbidity and mortality in human malignancies. We investigated whether the proliferating cell index of surgically treated single brain metastasis would predict the relapse at a location remote from the initial resection site...... within 2 months of the excision in patients with uncontrolled systemic disease and not subjected to adjuvant whole brain radio-therapy. MATERIALS AND METHODS: Tissue biopsies derived from 25 patients with brain metastases specifically selected to be a single totally resected lesion and not treated...... subsequently by radiotherapy to the whole brain were stained by immunohistochemistry for the marker CDC47 and the proliferation index was calculated. The index was then analysed with respect to clinical parameters, including the incidence of brain relapse within 2 months of the first resection, the timing...

  9. Active acute leukaemia: should transplant be offered to all patients?

    Science.gov (United States)

    Avni, Batia; Shapira, Michael Y; Resnick, Igor B; Stepensky, Polina; Or, Reuven; Grisariu, Sigal

    2016-06-24

    The probability of achieving long term remission for patients with refractory acute leukaemia is very low. Allogeneic stem cell transplantation (SCT) is offered to these patients in order to improve their dismal outcome. We retrospectively analyzed 361 acute leukaemia patients, who underwent allogeneic SCT in the Hadassah's bone marrow transplantation department between the years 2005 and 2012 and identified 84 patients with active leukaemia at transplantation. Median age was 34 years. Sixty four patients were diagnosed with acute myeloid leukaemia (AML), 18 patients with acute lymphoblastic leukaemia and two with biphenotypic leukaemia. The majority of patients were diagnosed with de-novo AML and transplanted at relapse. In the surviving patients, median follow up was 15 months. One year OS was 20%. At time of last follow up, 13 patients were alive (15.5%): ten patients with AML and two patients with acute lymphoblastic leukaemia. In the univariate analysis, factors associated with significantly better overall survival were as follows: matched unrelated donor (p = 0.006), matched donor (p = 0.014) and occurrence of acute graft-versus-host disease (aGVHD) (p = 0.019). Karnofsky performance score at SCT and occurrence of cGVHD were found to be borderline significant. Only matched unrelated donor and aGVHD were found to affect overall survival significantly in the multivariate analysis. Other than performance score at SCT, none of the pretransplant patients' characteristics were found to influence survival. In conclusion, as none of the pretransplant characteristics were found to influence the ability to select the patients that will benefit from HSC transplantation, this work supports offering HSCT to all active leukaemia eligible patients with reasonable performance status. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  10. 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.

  11. 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

  12. Predictors of distant relapse in patients with FIGO stage IIB-IVA cervical cancer treated with definitive radiotherapy.

    Science.gov (United States)

    Okazawa-Sakai, Mika; Mabuchi, Seiji; Isohashi, Fumiaki; Kawashima, Atsushi; Yokoi, Eriko; Ogawa, Kazuhiko; Kimura, Tadashi

    2017-08-17

    To investigate the predictors of distant relapse in International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IVA cervical cancer patients treated with definitive radiotherapy (RT). The clinical data of 219 patients with FIGO stage IIB-IVA cervical cancer treated with definitive RT between January 1997 and December 2011 were retrospectively reviewed. The cumulative distant relapse, progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards regression model was used to investigate the predictors of distant relapse in patients. Following treatment with definitive RT, 61 of the 219 (27.9%) patients developed distant relapse with median PFS and OS rates of 9.9 and 32.8 months, and estimated five-year PFS and OS rates of 4.9% and 21.3%, respectively. Multivariate analysis revealed that pelvic node metastasis, pretreatment leukocytosis and pretreatment neutrophilia were significant predictors of distant relapse. The risk of developing distant relapse was found to be associated with the number of predictors that the patients displayed: the estimated five-year distant relapse rates of the patients with no predictors, one predictor and two predictors were 20.3%, 35.5% and 88.9%, respectively. Roughly 28% of patients with FIGO stage IIB-IVA cervical cancer developed distant relapse after definitive RT. Pelvic lymph node metastasis and pretreatment leukocytosis/neutrophilia are independent predictors of distant relapse. © 2017 Japan Society of Obstetrics and Gynecology.

  13. 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.

  14. 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.

  15. Lack of topoisomerase copy number changes in patients with de novo and relapsed diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Pedersen, Mette Ø; Poulsen, Tim S; Gang, Anne O

    2015-01-01

    Topoisomerase (TOP) gene copy number changes may predict response to treatment with TOP-targeting drugs in cancer treatment. This was first described in patients with breast cancer and is currently being investigated in other malignant diseases. TOP-targeting drugs may induce TOP gene copy number...... changes at relapse, with possible implications for relapse therapy efficacy. TOP gene alterations in lymphoma are poorly investigated. In this study, TOP1 and TOP2A gene alterations were investigated in patients with de novo diffuse large B-cell lymphoma (DLBCL) (n = 33) and relapsed DLBCL treated...... with chemotherapy regimens including TOP2-targeting drugs (n = 16). No TOP1 or TOP2A copy number changes were found. Polysomy of chromosomes 20 and 17 was seen in 3 of 25 patients (12%) and 2 of 32 patients (6%) with de novo DLBCL. Among relapsed patients, chromosome polysomy was more frequently observed in 5 of 13...

  16. 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

    compared with 30% of the controls (P less than 0.0001). Neuroticism was connected with a high frequency of relapse (P less than 0.05) whereas failure of spontaneous ulcer healing had no certain relation to personality disorders. Patients with non-neurotic personality disorders had more frequently suffered...... 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...

  17. Metastatic Pattern, Local Relapse, and Survival of Patients with Myxoid Liposarcoma: A Retrospective Study of 45 Patients

    Directory of Open Access Journals (Sweden)

    Hanna M. Fuglø

    2013-01-01

    Full Text Available Purpose. To assess the metastatic pattern of the histological subtype myxoid liposarcoma (MLS with no or few round cells. Methods. Forty-five patients (F/M = 27/18, mean age 49 (range 17–85 years were diagnosed with MLS at two Danish sarcoma centres in the period 1995–2004. A retrospective review of patients' files combined with an extraction of survival data from the Danish Centralised Civil Register was performed. Results. Seven patients had distant metastases during the observation period. Two patients had metastases at the time of diagnosis, while metastases occurred within 2.5 years in four patients, and in one patient 11.9 years after primary diagnosis. All metastases occurred at extrapulmonary sites. The first local relapse occurred within 3 years after surgery in six patients, in one patient after 4.0 years, and in one patient 7.7 years after surgery. The 5- and 10-year overall survival was 80% and 69%, respectively. Both the 5- and 10-year distant metastases-free survival was, respectively, 86%. The 5- and 10-year local relapse-free survival was, respectively, 83% and 80%. Conclusions. Patients with MLS had only extra-pulmonary metastases, and no lung metastases were found. Most local relapses and distant metastases occurred within the first 2-3 years after surgery.

  18. Metastatic pattern, local relapse, and survival of patients with myxoid liposarcoma: a retrospective study of 45 patients.

    Science.gov (United States)

    Fuglø, Hanna M; Maretty-Nielsen, Katja; Hovgaard, Dorrit; Keller, Johnny Ø; Safwat, Akmal A; Petersen, Michael M

    2013-01-01

    Purpose. To assess the metastatic pattern of the histological subtype myxoid liposarcoma (MLS) with no or few round cells. Methods. Forty-five patients (F/M = 27/18, mean age 49 (range 17-85) years) were diagnosed with MLS at two Danish sarcoma centres in the period 1995-2004. A retrospective review of patients' files combined with an extraction of survival data from the Danish Centralised Civil Register was performed. Results. Seven patients had distant metastases during the observation period. Two patients had metastases at the time of diagnosis, while metastases occurred within 2.5 years in four patients, and in one patient 11.9 years after primary diagnosis. All metastases occurred at extrapulmonary sites. The first local relapse occurred within 3 years after surgery in six patients, in one patient after 4.0 years, and in one patient 7.7 years after surgery. The 5- and 10-year overall survival was 80% and 69%, respectively. Both the 5- and 10-year distant metastases-free survival was, respectively, 86%. The 5- and 10-year local relapse-free survival was, respectively, 83% and 80%. Conclusions. Patients with MLS had only extra-pulmonary metastases, and no lung metastases were found. Most local relapses and distant metastases occurred within the first 2-3 years after surgery.

  19. Metastatic Pattern, Local Relapse, and Survival of Patients with Myxoid Liposarcoma: A Retrospective Study of 45 Patients

    Science.gov (United States)

    Fuglø, Hanna M.; Hovgaard, Dorrit; Keller, Johnny Ø.; Safwat, Akmal A.; Petersen, Michael M.

    2013-01-01

    Purpose. To assess the metastatic pattern of the histological subtype myxoid liposarcoma (MLS) with no or few round cells. Methods. Forty-five patients (F/M = 27/18, mean age 49 (range 17–85) years) were diagnosed with MLS at two Danish sarcoma centres in the period 1995–2004. A retrospective review of patients' files combined with an extraction of survival data from the Danish Centralised Civil Register was performed. Results. Seven patients had distant metastases during the observation period. Two patients had metastases at the time of diagnosis, while metastases occurred within 2.5 years in four patients, and in one patient 11.9 years after primary diagnosis. All metastases occurred at extrapulmonary sites. The first local relapse occurred within 3 years after surgery in six patients, in one patient after 4.0 years, and in one patient 7.7 years after surgery. The 5- and 10-year overall survival was 80% and 69%, respectively. Both the 5- and 10-year distant metastases-free survival was, respectively, 86%. The 5- and 10-year local relapse-free survival was, respectively, 83% and 80%. Conclusions. Patients with MLS had only extra-pulmonary metastases, and no lung metastases were found. Most local relapses and distant metastases occurred within the first 2-3 years after surgery. PMID:23864817

  20. NPM1 mutation is a stable marker for minimal residual disease monitoring in acute myeloid leukaemia patients with increased sensitivity compared to WT1 expression*

    DEFF Research Database (Denmark)

    Kristensen, Thomas; Møller, Michael B; Friis, Lone;

    2011-01-01

    Mutation in the NPM1 gene occurs in 60% of acute myeloid leukaemia (AML) patients with normal karyotype. NPM1 mutation is potentially a superior minimal residual disease (MRD) marker compared to WT1 gene overexpression by being specific to the malignant clone, although experimental evidence...... published so far includes very limited numbers of relapsed cases. Also, the stability of the NPM1 mutation has been questioned by reports of the mutation being lost at relapse. In the present study we compared NPM1 mutation and WT1 overexpression as MRD markers in 20 cases of relapsed AML. The 20 patients...... experienced a total of 28 morphological relapses. Karyotypic evolution was detected in 56% of relapses. All relapses were accompanied by high levels of NPM1 mutation, along with high WT1 mRNA levels, thus demonstrating complete stability of both markers during relapse. Detectable NPM1 mutation following...

  1. Relapsing polychondritis

    Directory of Open Access Journals (Sweden)

    Lincoln Sakiara Miyasaka

    Full Text Available PURPOSE: This article describes a clinically-diagnosed case of relapsing polychondritis (RP, attended at the Hospital São Paulo, and presents a literature review of the subject. SOURCE OF RESEARCH: The literature review was made via Medline (1990-96, Lilacs (1980-96, textbooks of rheumatology, and some articles about the history of the disease. In Medline, 113 articles from 1990 to 1996 were found, and there were 23 articles from 1980 to 1996 in Lilacs. RESEARCH PROCEDURE: We reviewed the articles available at BIREME (Biblioteca Regional de Medicina with the primary focus being on the disease in question. SUMMARY: RP is a rare disease of unknown etiology described initially by Jackson-Wartenhorst in 1923 and characterized by a recurrent and acute inflammatory process that causes the collapse of the cartilaginous structures and their subsequent replacement by fibrous connective tissue. The cartilage most commonly attacked is that of the auricle of the ear and nasal septum, while the cartilage of the trachea, larynx, epiglottis, ribs, and articulations may also be involved. Ocular inflammations and systemic reactions with fever are also described. In 1976, McAdam presented a complete prospective study of 23 patients, reviewed the 136 cases described up until that time, and then proposed diagnostic criteria which were later expanded by Damiani and Levine. Currently, more than 500 cases have been described. CONCLUSION: Although a rare disease, better knowledge of it is needed, as RP may be lethal with tracheal collapse and obstruction of respiratory pathways, making precise diagnosis and adequate therapeutic intervention necessary.

  2. 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....

  3. Epigenetics targeted protein-vorinostat nanomedicine inducing apoptosis in heterogeneous population of primary acute myeloid leukemia cells including refractory and relapsed cases.

    Science.gov (United States)

    Chandran, Parwathy; Kavalakatt, Anu; Malarvizhi, Giridharan Loghanathan; Vasanthakumari, Divya Rani Vikraman Nair; Retnakumari, Archana Payickattu; Sidharthan, Neeraj; Pavithran, Keechilat; Nair, Shantikumar; Koyakutty, Manzoor

    2014-05-01

    Aberrant epigenetics play a key role in the onset and progression of acute myeloid leukemia (AML). Herein we report in silico modelling based development of a novel, protein-vorinostat nanomedicine exhibiting selective and superior anti-leukemic activity against heterogeneous population of AML patient samples (n=9), including refractory and relapsed cases, and three representative cell lines expressing CD34(+)/CD38(-) stem cell phenotype (KG-1a), promyelocytic phenotype (HL-60) and FLT3-ITD mutation (MV4-11). Nano-vorinostat having ~100nm size exhibited enhanced cellular uptake rendering significantly lower IC50 in AML cell lines and patient samples, and induced enhanced HDAC inhibition, oxidative injury, cell cycle arrest and apoptosis compared to free vorinostat. Most importantly, nanomedicine showed exceptional single-agent activity against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. Collectively, this epigenetics targeted nanomedicine appears to be a promising therapeutic strategy against various French-American-British (FAB) classes of AML. Through the use of a protein-vorinostat agent, exceptional single-agent activity was demonstrated against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. The studied epigenetics targeted nanomedicine approach is a promising therapeutic strategy against various French-American-British classes of acute myeloid leukemia. © 2014 Elsevier Inc. All rights reserved.

  4. Obesity as the initial manifestation of central nervous system relapse of acute lymphoblastic leukemia: case report and literature review.

    Science.gov (United States)

    Zhang, Li-Dan; Li, Yan-Hong; Ke, Zhi-Yong; Huang, Li-Bin; Luo, Xue-Qun

    2012-01-01

    A 6-year-old boy with acute lymphoblastic leukemia in remission experienced hyperphagia, obesity, and emotional disorders. Cytomorphologic examination of cerebral spinal fluid (CSF) and cranial MRI did not help in differentiating between central nervous system leukemia (CNSL) and other CNS diseases including tuberculosis in this boy. Flow cytometric CSF analysis on repeated lumber puncture detected lymphoblasts, while microscopic CSF examination did not definitively show relapse disease. The diagnosis of CNSL was thus made and confirmed by the response to leukemia treatment. Obesity can be the first manifestation of CNSL and the diagnosis can be challenging. A combination of CSF cytomorphology, CSF flow cytometry, and cranial MRI can be useful in the diagnosis of the disease. Two mechanisms of CNSL-related obesity are discussed based on the literature review.

  5. Relapse rates in patients with multiple sclerosis switching from interferon to fingolimod or glatiramer acetate: a US claims database study.

    Directory of Open Access Journals (Sweden)

    Niklas Bergvall

    Full Text Available BACKGROUND: Approximately one-third of patients with multiple sclerosis (MS are unresponsive to, or intolerant of, interferon (IFN therapy, prompting a switch to other disease-modifying therapies. Clinical outcomes of switching therapy are unknown. This retrospective study assessed differences in relapse rates among patients with MS switching from IFN to fingolimod or glatiramer acetate (GA in a real-world setting. METHODS: US administrative claims data from the PharMetrics Plus™ database were used to identify patients with MS who switched from IFN to fingolimod or GA between October 1, 2010 and March 31, 2012. Patients were matched 1∶1 using propensity scores within strata (number of pre-index relapses on demographic (e.g. age and gender and disease (e.g. timing of pre-index relapse, comorbidities and symptoms characteristics. A claims-based algorithm was used to identify relapses while patients were persistent with therapy over 360 days post-switch. Differences in both the probability of experiencing a relapse and the annualized relapse rate (ARR while persistent with therapy were assessed. RESULTS: The matched sample population contained 264 patients (n = 132 in each cohort. Before switching, 33.3% of patients in both cohorts had experienced at least one relapse. During the post-index persistence period, the proportion of patients with at least one relapse was lower in the fingolimod cohort (12.9% than in the GA cohort (25.0%, and ARRs were lower with fingolimod (0.19 than with GA (0.51. Patients treated with fingolimod had a 59% lower probability of relapse (odds ratio, 0.41; 95% confidence interval [CI], 0.21-0.80; p = 0.0091 and 62% fewer relapses per year (rate ratio, 0.38; 95% CI, 0.21-0.68; p = 0.0013 compared with those treated with GA. CONCLUSIONS: In a real-world setting, patients with MS who switched from IFNs to fingolimod were significantly less likely to experience relapses than those who switched to GA.

  6. patients with acute Icteric hepatitis

    African Journals Online (AJOL)

    *S. O. Ola, J. A. Otegbayo, G. N. Odaibo, O.-D. Olaleye and O. I. Olubuyide .... in Nigerian adults patients with acute ictcric hepatitis an d healthy adult at the .... lent in the course to chronicity. .... Corwin AL, Dai TC, Due DD, Suu PI, Van NT et al.

  7. Late recurrence of childhood T-cell acute lymphoblastic leukemia frequently represents a second leukemia rather than a relapse: first evidence for genetic predisposition

    NARCIS (Netherlands)

    Szczepanski, T.; Velden, V.H. van der; Waanders, E.; Kuiper, R.P.; Vlierberghe, P. Van; Gruhn, B.; Eckert, C.; Panzer-Grumayer, R.; Basso, G.; Cave, H.; Stadt, U.Z.; Campana, D.; Schrauder, A.; Sutton, R.; Wering, E. van; Meijerink, J.P.P.; Dongen, J.J. van

    2011-01-01

    PURPOSE: Relapse of childhood T-cell acute lymphoblastic leukemia (T-ALL) often occurs during treatment, but in some cases, leukemia re-emerges off therapy. On the basis of previous analyses of T-cell receptor (TCR) gene rearrangement patterns, we hypothesized that some late recurrences of T-ALL mig

  8. 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.

  9. Lymphadenopathy resulting from acute toxoplasmosis mimicking relapse of non-Hodgkin′s lymphoma on fluorodeoxyglucose positron emission tomography/computed tomography

    Directory of Open Access Journals (Sweden)

    Prathamesh Joshi

    2012-01-01

    Full Text Available We report a case documenting fluorodeoxyglucose (FDG accumulation in cervical, supraclavicular and axillary lymph nodes resulting from acute toxoplasmosis. A 50-year-old Indian female with history of non-Hodgkin′s lymphoma (NHL of left breast, postchemotherapy status, was found to have hypermetabolic right cervical, supraclavicular and axillary lymph nodes on a surveillance FDG positron emission tomography/computed tomography (PET/CT scan. Her previous two PET/CT scans were unremarkable with no evidence of metabolically active disease. Therefore, a differential diagnosis of relapse of NHL versus infectious/inflammatory pathology was raised in the report. Biopsy of axillary lymph node demonstrated features characteristic of toxoplasmosis. The serological test results were also compatible with acute toxoplasmosis infection. Infective and inflammatory diseases are known to accumulate FDG, resulting in false positives for malignancy. This case demonstrates lymph nodal toxoplasmosis as a potential cause of false positive FDG PET/CT findings in patients with known malignancy and highlights the importance of histopathological and laboratory correlation for the accurate interpretation of FDG PET/CT scans.

  10. 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

    compared with 30% of the controls (P less than 0.0001). Neuroticism was connected with a high frequency of relapse (P less than 0.05) whereas failure of spontaneous ulcer healing had no certain relation to personality disorders. Patients with non-neurotic personality disorders had more frequently suffered......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...

  11. Developing a novel risk-scoring system for predicting relapse in patients with ulcerative colitis: A prospective cohort study.

    Science.gov (United States)

    Hosseini, Seyed Vahid; Safarpour, Ali Reza; Taghavi, Seyed Alireza

    2015-01-01

    Ulcerative Colitis (UC) follows a natural clinical course of relapses and remissions. The aim of this study was to construct a risk-scoring formula in order to enable predicting relapses in patients with UC. From October 2012 to October 2013, 157 patients from Shiraz, southern Iran who were diagnosed with UC and in remission were enrolled. At 3-month intervals, multiple risk factors of hemoglobin, complete blood counts, serum iron and albumin, erythrocyte sedimentation rate, and faecal calprotectin levels, sex, age, cigarette smoking, positive family history of inflammatory bowel diseases, past history of appendectomy, extra-intestinal accompanying diseases, extent of disease at the beginning of study, number of previous relapses, duration of disease and duration of remission before the study were assessed. Univariate and multivariate logistic regression were applied to fit the final model. The new risk-scoring system accuracy was assessed using receiver-operating-characteristics (ROC) curve analysis. Seventy four patients (48.1%) experienced a relapse. Multivariate analysis revealed that relapses could significantly be predicted by the level of fecal calprotectin (OR=8.1), age (OR=9.2), the Seo activity index (OR=52.7), and the number of previous relapses (OR=4.2). The risk scoring formula was developed using the regression coefficient values of the aforementioned variables. Four predictor variables were significant in the final model and were used in our risk-scoring formula. It is recommended that patients who achieve high scores are diligently observed, treated, and followed up.

  12. 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

  13. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia

    DEFF Research Database (Denmark)

    Burnett, Alan K; Russell, Nigel H; Hills, Robert K

    2012-01-01

    PURPOSE There has been little survival improvement in older patients with acute myeloid leukemia (AML) in the last two decades. Improving induction treatment may improve the rate and quality of remission and consequently survival. In our previous trial, in younger patients, we showed improved...... National Cancer Research Institute trials showed significant improvements in relapse (HR, 0.82; 95% CI, 0.72 to 0.93; P = .002) and OS (HR, 0.88; 95% CI, 0.79 to 0.98; P = .02). CONCLUSION Adding GO (3 mg/m(2)) to induction chemotherapy reduces relapse risk and improves survival with little increase...

  14. Maintenance therapy with all-trans retinoic acid and arsenic trioxide improves relapse-free survival in adults with low- to intermediate-risk acute promyelocytic leukemia who have achieved complete remission after consolidation therapy.

    Science.gov (United States)

    Liang, Bin; Zheng, Zhouyi; Shi, Yifen; Chen, Jingjing; Hu, Xudong; Qian, Honglan; Shen, Zhijian; Jiang, Songfu; Yu, Kang; Feng, Jianhua

    2017-01-01

    Currently, the optimal maintenance therapy for patients with acute promyelocytic leukemia (APL) who have achieved complete remission (CR) after completing consolidation chemotherapy remains controversial. The comparative effectiveness of the all-trans retinoic acid (ATRA) plus arsenic trioxide (As2O3) maintenance strategy with classic ATRA plus chemotherapy has not been evaluated. In this study, we compared the efficacy and toxicity of maintenance therapy with ATRA plus As2O3 and classic ATRA plus chemotherapy in low- to intermediate-risk APL patients reaching the first CR after induction and consolidation therapy. A retrospective review of 58 adult patients diagnosed with APL was conducted. After receiving consolidation therapy and achieving CR, 30 patients were administered maintenance therapy with an ATRA plus As2O3 regimen (ATRA+As2O3 group), whereas 28 patients were administered 3-monthly cycles of an ATRA plus chemotherapy regimen (ATRA+chemotherapy group). Grade 3-4 neutropenia was significantly more frequent in the ATRA+chemotherapy group (N=9, 32.1%) than in the ATRA+As2O3 group (N=0) (P=0.001). At a median follow-up of 49.1 months (range: 9.7-97.4 months) from the completion of consolidation, no relapses were observed in the ATRA+As2O3 group, whereas seven relapses occurred in the ATRA+chemotherapy group. The risk of relapse in the patients administered ATRA+As2O3 maintenance was significantly lower than that in those administered ATRA+chemotherapy maintenance (P=0.004). Based on log-rank analysis, only maintenance therapy with ATRA and As2O3 was associated with a significantly higher relapse-free survival (P=0.0159). Maintenance therapy with ATRA and As2O3 was beneficial in low- to intermediate-risk APL patients who were effectively treated to achieve CR. Further clinical trials with reliable designs are needed to confirm these observations.

  15. Sinonasal Lymphoma Presenting as a Probable Sanctuary Site for Relapsed B Acute Lymphoblastic Leukaemia: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    W. Y. Lim

    2015-01-01

    Full Text Available Sinonasal lymphoma is a non-Hodgkin lymphoma (NHL representing 1.5% of all lymphomas. It presents as an unremitting ulceration with progressive destruction of midline sinonasal and surrounding structures. Poor prognosis warrants early treatment although diagnosis is challenging and frequently delayed. It is usually primary in origin and to our knowledge the sinonasal region has never been reported as a sanctuary site in leukaemia/lymphoma relapse. We present a unique case of B-cell ALL (acute lymphoblastic leukaemia with late relapse to the nasal septum as a sinonasal lymphoblastic lymphoma and with genetic support for this as a sanctuary site.

  16. Relapse of herpes encephalitis induced by temozolomide-based chemoradiation in a patient with malignant glioma.

    Science.gov (United States)

    Okada, Masaki; Miyake, Keisuke; Shinomiya, Aya; Kawai, Nobuyuki; Tamiya, Takashi

    2013-02-01

    The authors report on a case of concurrent herpes simplex encephalitis (HSE) and malignant glioma. The co-occurrence of HSE and malignant glioma is very rare, but it can occur during glioma treatment. Both radiotherapy and chemoradiation with temozolomide can induce viral reactivation, leading to HSE relapse. Careful observation for HSE is necessary when administering chemoradiation to patients with a history of HSE. Antiviral therapy for HSE must be initiated immediately, and the chemoradiation for glioma should be stopped; however, it is not clear what antitumor therapy is optimal when HSE co-occurs during the treatment of glioma.

  17. Cytarabine and clofarabine after high-dose cytarabine in relapsed or refractory AML patients.

    Science.gov (United States)

    Scappini, Barbara; Gianfaldoni, Giacomo; Caracciolo, Francesco; Mannelli, Francesco; Biagiotti, Caterina; Romani, Claudio; Pogliani, Enrico M; Simonetti, Federico; Borin, Lorenza; Fanci, Rosa; Cutini, Ilaria; Longo, Giovanni; Susini, Maria Chiara; Angelucci, Emanuele; Bosi, Alberto

    2012-12-01

    Clofarabine has been shown to be effective in AML patients, either as single agent or, mainly, in association with intermediate dose cytarabine. Based on these reports, we conducted a preliminary study combining clofarabine and intermediate dose cytarabine in AML patients who relapsed or failed to respond to at least two induction therapies. We treated 47 patients affected by relapsed/refractory AML with a regimen including clofarabine at 22.5 mg/m(2) daily on days 1-5, followed after 3 hr by cytarabine at 1 g/m(2) daily on days 1-5. Ten patients received a further consolidation cycle with clofarabine at 22.5 mg/m(2) and cytarabine at 1 g/m(2) day 1-4. Among the 47 patients, 24/47 (51%) achieved a complete remission, 5/47 (10.5%) a partial response, 10/47 (21%) had a resistant disease, and 6/47 (13%) died of complications during the aplastic phase. The most frequent nonhematologic adverse events were vomiting, diarrhea, transient liver toxicity, febrile neutropenia, and infections microbiologically documented. Among the 24 patients who obtained a CR 13 underwent allogeneic bone marrow transplantation. In 14 patients, complete remission duration was shorter than 12 months, whereas 10 patients experienced longer complete remission duration. These very preliminary results suggest that clofarabine-cytarabine regimen is effective in this particularly poor prognosis category of patients, representing a potential "bridge" toward bone marrow transplant procedures. Safety data were consistent with previously reported salvage therapies. Further studies and a longer follow up are warranted.

  18. 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.

  19. Role of routine imaging in detecting recurrent lymphoma: A review of 258 patients with relapsed aggressive non-Hodgkin and Hodgkin lymphoma.

    Science.gov (United States)

    El-Galaly, T C; Mylam, Karen Juul; Bøgsted, Martin; Brown, Peter; Rossing, Maria; Gang, Anne Ortved; Haglund, Anne; Arboe, Bente; Clausen, Michael Roost; Jensen, Paw; Pedersen, Michael; Bukh, Anne; Jensen, Bo Amdi; Poulsen, Christian Bjørn; d'Amore, Francesco; Hutchings, Martin

    2014-06-01

    After first-line therapy, patients with Hodgkin lymphoma (HL) and aggressive non-HL are followed up 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 HL and aggressive non-HL (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 with 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 or in combination with abnormal blood tests or physical examination in 64% of the patients. Routine imaging prompted relapse investigations in 27% of the patients. The estimated number of routine scans per relapse was 91-255 depending on the lymphoma subtype. Patients with imaging-detected relapse had lower disease burden (P = 0.045) and reduced risk of death following relapse (hazard ratio = 0.62, P = 0.02 in multivariate analysis). Patient-reported symptoms are still the most common factor for detecting lymphoma relapse and the high number of scans per relapse calls for improved criteria for use of surveillance imaging. However, imaging-detected relapse was associated with lower disease burden and a possible survival advantage. The future role of routine surveillance imaging should be defined in a randomized trial.

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

    Science.gov (United States)

    Cohen, Jeffrey A.; Coles, Alasdair J.; Hartung, Hans-Peter; Havrdova, Eva; Selmaj, Krzysztof W.; Margolin, David H.; Lake, Stephen L.; Kaup, Susan M.; Panzara, Michael A.; Compston, D. Alastair S.

    2016-01-01

    Objective: To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy. Methods: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II, a 2-year randomized, rater-blinded, active-controlled, head-to-head, phase 3 trial, compared efficacy and safety of alemtuzumab 12 mg with subcutaneous interferon-β-1a (SC IFN-β-1a) 44 μg in patients with RRMS. Prespecified and post hoc disability outcomes based on Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Sloan low-contrast letter acuity (SLCLA) are reported, focusing on improvement of preexisting disability in addition to slowing of disability accumulation. Results: Alemtuzumab-treated patients were more likely than SC IFN-β-1a–treated patients to show improvement in EDSS scores (p < 0.0001) on all 7 functional systems. Significantly more alemtuzumab patients demonstrated 6-month confirmed disability improvement. The likelihood of improved vs stable/worsening MSFC scores was greater with alemtuzumab than SC IFN-β-1a (p = 0.0300); 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–treated patients. Conclusions: In patients with RRMS and inadequate response to prior disease-modifying therapies, alemtuzumab provides greater benefits than SC IFN-β-1a across several disability outcomes, reflecting improvement of preexisting disabilities. Classification of evidence: This study provides Class I evidence (based on rater blinding and a balance in baseline characteristics between arms) that alemtuzumab modifies disability measures favorably compared with SC IFN-β-1a

  1. Crohn's disease genotypes of patients in remission vs relapses after infliximab discontinuation

    Institute of Scientific and Technical Information of China (English)

    Cathy Lu; Alistair Waugh; Robert J Bailey; Raeleen Cherry; Levinus A Dieleman; Leah Gramlich; Kata Matic

    2012-01-01

    AIM:To investigate genetic differences between Crohn's disease (CD) patients with a sustained remission vs relapsers after discontinuing infliximab while in corticosteroid-free remission.METHODS:Forty-eight CD patients received infliximab and were in full corticosteroid-free clinical remission but then discontinued infliximab for reasons other than a loss of response,were identified by review of an electronic database and charts.Infliximab-associated remission was defined as corticosteroid-free plus normalization of clinical disease activity [CD activity index (CDAI)< 150] during follow-up visits based on physician global assessments.A CD relapse (loss of infliximab-induced remission) was clinically defined as a physician visit for symptoms of disease activity (CDAI > 220) and a therapeutic intervention with CD medication(s),or a hospitalization with complications related to active CD.Genetic analyses were performed on samples from 14 patients (n =6 who had a sustained long term remission after stopping infliximab,n =8 who rapidly relapsed after stopping infliximab).Nucleotide-binding oligomerization domain 2 (NOD2)/caspase activation recruitment domain 15 (CARD15) polymorphisms (R702W,G908R and L1007fs) and the inflammatory bowel disease 5 (IBD5)polymorphisms (IGR2060a1 and IGR3081a1) were analyzed in each group.RESULTS:Five single nucleotide polymorphisms of IBD5 and NOD2/CARD15 genes were successfully analyzed for all 14 subjects.There was no significant increase in frequency of the NOD2/CARD15 polymorphisms (R702W,G908R and L1007fs) and the IBD5 polymorphisms (IGR2060a1 and IGR3081a1) in either group of patients; those whose disease relapsed rapidly or those who remained in sustained long term remission following the discontinuation of infliximab.Nearly a third of patients in full clinical remission who stopped infliximab for reasons other than loss of response remained in sustained clinical remission,while two-thirds relapsed rapidly.There was a marked

  2. Patient-reported adverse effects of high-dose intravenous methylprednisolone treatment : a prospective web-based multi-center study in multiple sclerosis patients with a relapse

    NARCIS (Netherlands)

    Jongen, Peter Joseph; Stavrakaki, Ioanna; Voet, Bernard; Hoogervorst, Erwin; van Munster, Erik; Linssen, Wim H.; Sinnige, Ludovicus G.; Verhagen, Wim I.; Visser, Leo H.; van der Kruijk, Ruud; Verheul, Freek; Boringa, Jan; Heerings, Marco; Gladdines, Werner; Lonnqvist, Fredrik; Gaillard, Pieter

    2016-01-01

    In a prospective multi-center observational study, we evaluated the frequency, severity, and impact on activities of daily living (ADL) of adverse effects (AEs) of high-dose intravenous methylprednisolone (IVMP) in relapsing remitting multiple sclerosis (MS) patients with a relapse. Online self-repo

  3. A Brief Clinical Tool to Estimate Individual Patients' Risk of Depressive Relapse Following Remission: Proof of Concept.

    Science.gov (United States)

    Judd, Lewis L; Schettler, Pamela J; Rush, A John

    2016-11-01

    The authors sought to determine whether symptoms experienced by formerly depressed patients after at least 8 weeks of remission can be used to identify their risk for relapse during the next 6 months. The study included 188 patients with major depressive disorder from the National Institute of Mental Health Collaborative Depression Study who had at least one Symptom Checklist-90 (SCL-90) assessment after at least 8 weeks of full remission from a depressive episode (defined as a value of 1 on the weekly psychiatric rating scale for all depressive conditions, recorded on Longitudinal Follow-Up Evaluation interviews). Mixed logistic regression was used to identify a set of SCL-90 items that were most predictive of relapse compared with nonrelapse within the next 6 months. Of 514 SCL-90 assessments completed after remission, 73 (14.2%) were followed by depressive relapse within 6 months. Seventeen SCL-90 items (including symptoms of depression, anxiety, and psychological vulnerability) significantly distinguished relapse from nonrelapse. Of these, a set of 12 symptoms maximally separated relapse from nonrelapse. Experiencing one or more of these symptoms had a sensitivity of 80.8% and a specificity of 51.2% for identifying a period in which a relapse occurred, with a positive predictive value of 21.5% and a negative predictive value of 94.2%. The relapse rate was 5.8% when none of the 12 symptoms were present, 16.4% when one to five symptoms were present, 34.1% when six to nine symptoms were present, and 72.7% when 10 or more symptoms were present. A brief symptom scale can be used to identify patients who, despite full remission from a depressive episode, are at substantial risk of relapse within the next 6 months, and this can be used to provide a basis for personalizing the intensity of follow-up visits.

  4. 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

  5. Relapse and deformity among 2177 leprosy patients released from treatment with MDT between 2005 and 2010 in South India: A retrospective cohort study.

    Science.gov (United States)

    Prabu, Rajkumar; Manickam, Ponnaiah; Mahalingam, Vannapatty Nallamuthu; Jayasree, Padma; Selvaraj, Vadivoo; Mehendale, Sanjay Madhav

    2015-12-01

    To estimate the incidence of relapse among leprosy patients released after completing multi-drug therapy (MDT) during 2005-2010 under India's National Leprosy Eradication Programme in South India. We conducted a retrospective cohort study of leprosy patients who were released from treatment (RFT) with MDT during April 2005 and March 2010 in four purposely selected districts from South India. We clinically examined them for signs of relapse, persistence and deformity. We collected slit skin smears from those reporting signs of relapse or persistence. We computed relapse rate per 1000 person years by dividing the number of relapses by person years of follow-up and 95% confidence intervals (CI) for rates. We tracked 3791 RFT patients and examined 58% of them. The examined and those who were not examined were similar in terms of leprosy type, year of completing MDT and gender. We identified 58 relapses (relapse rate 6.1 per 1000 person years) among the examined. Majority of these relapses occurred within 3 years post-MDT. Eighteen (31%) of the relapsed patients had deformity. While low level of relapse indicates effectiveness of MDT, the burden of deformity is of concern. For maximizing treatment effectiveness and minimizing transmission, we recommend educating leprosy patients at treatment completion for self-monitoring of signs of relapse and advising them to visit nearby public health facilities or Community health workers for immediate evaluation and intervention.

  6. Efficacy of a second course of immunosuppressive therapy in patients with membranous nephropathy and persistent or relapsing disease activity.

    NARCIS (Netherlands)

    Buf-Vereijken, P.W.G. du; Wetzels, J.F.M.

    2004-01-01

    BACKGROUND: A single course of immunosuppressive treatment improves renal survival in patients with idiopathic membranous nephropathy (iMN) and renal insufficiency. However, not all patients respond and relapses occur within 5 years in 30% of patients. It is unknown if a second course of

  7. LONG-TERM PROGNOSIS IN PATIENTS WITH A LOCAL BREAST CANCER RELAPSE AFTER ORGAN-SAVING TREATMENT

    Directory of Open Access Journals (Sweden)

    V. A. Uimanov

    2009-01-01

    Full Text Available The paper presents the results of a follow-up of 861 patients who have undergone organ-saving treatment (OST for early breast can- cer. The relapse rate was 7.3% (63/861. The main task was to study an association of survival rates with the predictors characteriz- ing a local relapse. Five-year overall survival after the start of treatment for a local relapse was 65.7% (standard error 8.3. A Cox multivariance regression analysis led to the conclusion that the local relapse is a statistically significant factor of worsening survival without distant metastases when it develops within 3 years after primary OST.

  8. T cell vaccination benefits relapsing progressive multiple sclerosis patients: a randomized, double-blind clinical trial.

    Directory of Open Access Journals (Sweden)

    Dimitrios Karussis

    Full Text Available BACKGROUND: T-cell vaccination (TCV for multiple sclerosis (MS refers to treatment with autologous anti-myelin T-cells, attenuated by irradiation. Previously published clinical trials have been all open-labeled. AIM: To evaluate the safety and efficacy of TCV in progressive MS, in a double-blind, controlled clinical trial. METHODOLOGY: Twenty-six patients with relapsing-progressive MS were enrolled in the study (mean age: 39±9.8 years; mean EDSS: 4.4±1.7. T-cell lines reactive to 9 different peptides of the myelin antigens, MBP, MOG and PLP were raised from the patients' peripheral blood. The patients were randomized into two groups: 19 were treated with TCV (four subcutaneous injections of 10-30×10(6 T-cells, attenuated by irradiation, on days 1, 30, 90 and 180 and 7 patients were treated with sham injections. Twenty-four patients (17 in the TCV group and 7 in the placebo were eligible for per-protocol analysis. RESULTS: At one year following the inclusion, an increase in the EDSS (+0.50 and an increase in 10-meter walking time (+0.18 sec, were observed in the placebo group; in the TCV group there was a decrease in the EDSS (-0.44; p<0.01 and in the 10-meter walking time (0.84 sec; p<0.005. Sixteen of the 17 patients (94.1% in the TCV group remained relapse-free during the year of the study, as compared to 42.9% in the placebo group (p = 0.01 and p = 0.03 with adjustment. The proportion of patients with any relapse during the year of the study in the TCV-group, was reduced by 89.6%., as compared to the placebo-treated group. MRI parameters did not change significantly. CONCLUSIONS: This is the first controlled, double-blind trial with TCV in progressive MS. The results demonstrate the feasibility and safety of the procedure, and provide significant indications of clinical efficacy. Further studies with larger groups of subjects are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT01448252.

  9. Fever of unknown origin in a patient with red ears: relapsing polychondritis.

    Science.gov (United States)

    Avila, Juliana Nunes; Carvalho, Susana Bonacho; Tavares, Graça; Garcia, Ruben

    2014-02-07

    Relapsing polychondritis (RP) is a rare autoimmune disease that affects cartilage and multiple organ system. We describe a case of RP presenting with fever, conjunctivitis and inflammatory signs of the right knee. Infectious and neoplastic diseases were excluded by imaging and laboratory examinations. After 17 days of admission the patient reported coughing and odynophagia, and, a physical examination showed red ears. Otorhinolaryngological examination demonstrated arytenoid chondritis. RP was diagnosed based on four McAdam's criteria. The patient was medicated with oral prednisone, and a positive clinical response was noted. Severe disease may require high doses of corticosteroids or immunosuppressive agents and the biological treatment may be beneficial. Beginning manifestations, such as fever, are often unspecific, leading to RP misdiagnosis. In this case, close attention to the patient's clinical history and a detailed physical examination were fundamental in concluding the correct diagnosis, and consequently beginning the appropriate medication.

  10. Decreasing relapse in colorectal cancer patients treated with cetuximab by using the activating KRAS detection chip.

    Science.gov (United States)

    Huang, Ming-Yii; Liu, Hsueh-Chiao; Yen, Li-Chen; Chang, Jia-Yuan; Huang, Jian-Jhang; Wang, Jaw-Yuan; Lin, Shiu-Ru

    2014-10-01

    The KRAS oncogene was among the first genetic alterations in colorectal cancer (CRC) to be discovered. Moreover, KRAS somatic mutations might be used for predicting the efficiency of anti-epidermal growth factor receptor therapeutic drugs. Because the KRAS mutations are similar in the primary CRC and/or the CRC metastasis, KRAS mutation testing can be performed on both specimen types. The purpose of this study was to investigate the clinical advantage of using a KRAS pathway-associated molecule analysis chip to analyze CRC patients treated with cetuximab. Our laboratory developed a KRAS pathway-associated molecule analysis chip and a weighted enzymatic chip array (WEnCA) technique, activating KRAS detection chip, which can detect KRAS mutation status by screening circulating cancer cells in the bloodstream. We prospectively enrolled 210 stage II-III CRC patients who received adjuvant oxaliplatin plus infusional 5-fluorouracil/leucovorin (FOLFOX)-4 chemotherapy with or without cetuximab. We compared the chip results of preoperative blood specimens with disease control status in these patients. Among the 168 CRC patients with negative chip results, 119 were treated with FOLFOX-4 plus cetuximab chemotherapy, and their relapse rate was 35.3 % (42/119). In contrast, the relapse rate was 71.4 % among the patients with negative chip results who received FOLFOX-4 treatment alone (35/49). Negative chip results were significantly correlated with better treatment outcomes in the FOLFOX-4 plus cetuximab group (P chip is a potential tool for predicting clinical outcomes in CRC patients following FOLFOX-4 treatment with or without cetuximab therapy.

  11. Treatment of acute myeloid leukemia or myelodysplastic syndrome relapse after allogeneic stem cell transplantation with azacitidine and donor lymphocyte infusions--a retrospective multicenter analysis from the German Cooperative Transplant Study Group.

    Science.gov (United States)

    Schroeder, Thomas; Rachlis, Elena; Bug, Gesine; Stelljes, Matthias; Klein, Stefan; Steckel, Nina Kristin; Wolf, Dominik; Ringhoffer, Mark; Czibere, Akos; Nachtkamp, Kathrin; Dienst, Ariane; Kondakci, Mustafa; Stadler, Michael; Platzbecker, Uwe; Uharek, Lutz; Luft, Thomas; Fenk, Roland; Germing, Ulrich; Bornhäuser, Martin; Kröger, Nicolaus; Beelen, Dietrich W; Haas, Rainer; Kobbe, Guido

    2015-04-01

    To expand the current knowledge about azacitidine (Aza) and donor lymphocyte infusions (DLI) as salvage therapy for relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to identify predictors for response and survival, we retrospectively analyzed data of 154 patients with acute myeloid leukemia (AML, n = 124), myelodysplastic (MDS, n = 28), or myeloproliferative syndrome (n = 2). All patients received a median number of 4 courses of Aza (range, 4 to 14) and DLI were administered to 105 patients (68%; median number of DLI, 2; range, 1 to 7). Complete and partial remission rates were 27% and 6%, respectively, resulting in an overall response rate of 33%. Multivariate analysis identified molecular-only relapse (hazard ratio [HR], 9.4; 95% confidence interval [CI], 2.0 to 43.5; P = .004) and diagnosis of MDS (HR, 4.1; 95% CI, 1.4 to 12.2; P = .011) as predictors for complete remission. Overall survival (OS) at 2 years was 29% ± 4%. Molecular-only relapse (HR, .14; 95% CI, .03 to .59; P = .007), diagnosis of MDS (HR, .33; 95% CI, .16 to .67; P = .002), and bone marrow blasts after allo-HSCT, in particular those with MDS or AML and low disease burden. The latter finding emphasizes the importance of stringent disease monitoring and early intervention.

  12. Acute Peritoneal Dialysis in Patients with Acute Kidney Injury.

    Science.gov (United States)

    Cho, Seong; Lee, Yu-Ji; Kim, Sung-Rok

    2017-01-01

    The purpose of this study was to evaluate the efficacy, complications, and mortality rate associated with acute peritoneal dialysis (PD) in patients with acute kidney injury (AKI). A total of 75 patients who were treated at Samsung Changwon Hospital between February 2005 and March 2016 were included in the study sample. The outcomes included in-hospital survival, renal recovery, metabolic and fluid control rates, and technical success rates. Refractory heart failure was the most frequent cause of acute PD (49.3%), followed by hepatic failure (20.0%), septic shock (14.7%), acute pancreatitis (9.3%), and unknown causes (6.7%). The hospital survival of patients in the acute PD was 48.0%. Etiologies of acute kidney injury (AKI) (refractory heart failure, acute pancreatitis compared with hepatic failure, septic shock or miscellaneous causes), use of inotropes, use of a ventilator, and simplified acute physiology score (SAPS) II were associated with survival differences. Maintenance dialysis required after survival was high (80.1% [29/36]) due to AKI etiologies (heart or hepatic failures). Metabolic and fluid control rates were 77.3%. The technical success rate for acute PD was 93.3%. Acute PD remains a suitable treatment modality for patients with AKI in the era of continuous renal replacement therapy (CRRT). Nearly all patients who require dialysis can be dialyzed with acute PD without mechanical difficulties. This is particularly true in patients with refractory heart failure and acute pancreatitis who had a weak requirement for inotropes. Copyright © 2017 International Society for Peritoneal Dialysis.

  13. Disseminated histoplasmosis in HIV-infected patients: determinants of relapse and mortality in a north-eastern area of Brazil.

    Science.gov (United States)

    Damasceno, Lisandra Serra; Ramos, Alberto Novaes; Alencar, Carlos Henrique; Gonçalves, Maria Vânia Freitas; de Mesquita, Jacó Ricarte Lima; Soares, Anne Taumaturgo Dias; Coutinho, Anna Gisele Nunes; Dantas, Carolina Cavalcante; Leitão, Terezinha do Menino Jesus Silva

    2014-07-01

    Many relapses and deaths resulting from disseminated histoplasmosis (DH) in acquired immunodeficiency syndrome (AIDS) patients have been observed in an endemic area in north-eastern Brazil. The objective of this study was to evaluate the risk factors associated with the clinical outcomes of DH/AIDS coinfection in patients from the state of Ceará, Brazil. A retrospective cohort of AIDS patients, after their hospital discharge due to first DH episode in the period 2002-2008, was followed until December 31, 2010, to investigate the factors associated with relapse and mortality. A total of 145 patients were evaluated in the study. Thirty patients (23.3%) relapsed and the overall mortality was 30.2%. The following variables were significantly (P histoplasmosis relapse was also significantly associated with mortality. In the multivariate analysis, non-adherence to HAART was the independent risk factor that was associated with both relapse (Adj OR = 6.28) and overall mortality (Adj OR = 8.03); efavirenz usage was discovered to be significant only for the overall mortality rate (Adj OR = 4.50). Adherence to HAART was the most important variable that influenced the outcomes in this specific population.

  14. A phase II study of decitabine and gemtuzumab ozogamicin in newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndrome.

    Science.gov (United States)

    Daver, N; Kantarjian, H; Ravandi, F; Estey, E; Wang, X; Garcia-Manero, G; Jabbour, E; Konopleva, M; O'Brien, S; Verstovsek, S; Kadia, T; Dinardo, C; Pierce, S; Huang, X; Pemmaraju, N; Diaz-Pines-Mateo, M; Cortes, J; Borthakur, G

    2016-02-01

    Decitabine may open the chromatin structure of leukemia cells making them accessible to the calicheamicin epitope of gemtuzumab ozogamicin (GO). A total of 110 patients (median age 70 years; range 27-89 years) were treated with decitabine and GO in a trial designed on model-based futility to accommodate subject heterogeneity: group 1: relapsed/refractory acute myeloid leukemia (AML) with complete remission duration (CRD) decitabine 20 mg/m(2) daily for 5 days and GO 3 mg/m(2) on day 5. Post-induction therapy included five cycles of decitabine+GO followed by decitabine alone. Complete remission (CR)/CR with incomplete count recovery was achieved in 39 (35%) patients; group 1= 5/28 (17%), group 2=3/5 (60%), group 3=24/57 (42%) and group 4=7/20 (35%). The 8-week mortality in groups 3 and 4 was 16% and 10%, respectively. Common drug-related adverse events included nausea, mucositis and hemorrhage. Decitabine and GO improved the response rate but not overall survival compared with historical outcomes in untreated AML ⩾60 years.

  15. Clinical response and relapse in patients with chronic low back pain following osteopathic manual treatment: results from the OSTEOPATHIC Trial.

    Science.gov (United States)

    Licciardone, John C; Aryal, Subhash

    2014-12-01

    Clinical response and relapse following a regimen of osteopathic manual treatment (OMT) were assessed in patients with chronic low back pain (LBP) within the OSTEOPATHIC Trial, a randomized, double-blind, sham-controlled study. Initial clinical response and subsequent stability of response, including final response and relapse status at week 12, were determined in 186 patients with high baseline pain severity (≥50 mm on a 100-mm visual analogue scale). Substantial improvement in LBP, defined as 50% or greater pain reduction relative to baseline, was used to assess clinical response at weeks 1, 2, 4, 6, 8, and 12. Sixty-two (65%) patients in the OMT group attained an initial clinical response vs. 41 (45%) patients in the sham OMT group (risk ratio [RR], 1.45; 95% confidence interval [CI], 1.11-1.90). The median time to initial clinical response to OMT in these patients was 4 weeks. Among patients with an initial clinical response prior to week 12, 13 (24%) patients in the OMT group vs. 18 (51%) patients in the sham OMT group relapsed (RR, 0.47; 95% CI, 0.26-0.83). Overall, 49 (52%) patients in the OMT group attained or maintained a clinical response at week 12 vs. 23 (25%) patients in the sham OMT group (RR, 2.04; 95% CI, 1.36-3.05). The large effect size for short-term efficacy of OMT was driven by stable responders who did not relapse.

  16. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; Lee, Bang-Ning; Schlette, Ellen J; O'Brien, Susan M; Gao, Hui; Wen, Sijin; Wierda, William G; Estrov, Zeev; Faderl, Stefan; Cohen, Evan N; Li, Changping; Reuben, James M; Keating, Michael J

    2008-06-01

    This study investigated the activity of lenalidomide in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Lenalidomide was given at 10 mg daily with dose escalation up to 25 mg daily. Three patients (7%) achieved a complete response (CR), one a nodular partial remission, and 10 patients a partial remission (PR), for an overall response (OR) rate of 32%. Treatment with lenalidomide was associated with an OR rate of 31% in patients with 11q or 17p deletion, of 24% in patients with unmutated V(H), and of 25% in patients with fludarabine-refractory disease. The most common toxicity was myelosuppression, and the median daily dose of lenalidomide tolerated was 10 mg. Plasma levels of angiogenic factors, inflammatory cytokines, and cytokine receptors were measured at baseline, day 7, and day 28. There was a dramatic increase in median interleukin (IL)-6, IL-10, IL-2, and tumor necrosis factor receptor-1 levels on day 7, whereas no changes were observed in median vascular endothelial growth factor levels (20 patients studied). According to our experience, lenalidomide given as a continuous treatment has antitumor activity in heavily pretreated patients with CLL.

  17. Relapsing-remitting multiple sclerosis patients display an altered lipoprotein profile with dysfunctional HDL

    Science.gov (United States)

    Jorissen, Winde; Wouters, Elien; Bogie, Jeroen F.; Vanmierlo, Tim; Noben, Jean-Paul; Sviridov, Denis; Hellings, Niels; Somers, Veerle; Valcke, Roland; Vanwijmeersch, Bart; Stinissen, Piet; Mulder, Monique T.; Remaley, Alan T.; Hendriks, Jerome J. A.

    2017-01-01

    Lipoproteins modulate innate and adaptive immune responses. In the chronic inflammatory disease multiple sclerosis (MS), reports on lipoprotein level alterations are inconsistent and it is unclear whether lipoprotein function is affected. Using nuclear magnetic resonance (NMR) spectroscopy, we analysed the lipoprotein profile of relapsing-remitting (RR) MS patients, progressive MS patients and healthy controls (HC). We observed smaller LDL in RRMS patients compared to healthy controls and to progressive MS patients. Furthermore, low-BMI (BMI ≤ 23 kg/m2) RRMS patients show increased levels of small HDL (sHDL), accompanied by larger, triglyceride (TG)-rich VLDL, and a higher lipoprotein insulin resistance (LP-IR) index. These alterations coincide with a reduced serum capacity to accept cholesterol via ATP-binding cassette (ABC) transporter G1, an impaired ability of HDL3 to suppress inflammatory activity of human monocytes, and modifications of HDL3’s main protein component ApoA-I. In summary, lipoprotein levels and function are altered in RRMS patients, especially in low-BMI patients, which may contribute to disease progression in these patients. PMID:28230201

  18. Relapse of acute lymphoblastic leukemia in the pancreas after allogeneic bone marrow transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xiao-mu; ZHANG Zhong-tao; LI Jian-she; HAN Wei

    2010-01-01

    @@ The occurrence of metastatic lesions in the pancreas of patients with cancer, including hematological cancers,is uncommon (1.6%-37.5%) and of these, the majority of patients will have widespread disease.1-7 Isolated potentially resectable pancreatic metastases are rarely seen.

  19. Unrelated stem cell transplantation after reduced intensity conditioning for patients with multiple myeloma relapsing after autologous transplantation.

    NARCIS (Netherlands)

    Kroger, N.; Shimoni, A.; Schilling, G.; Schwerdtfeger, R.; Bornhauser, M.; Nagler, A.; Zander, A.R.; Heinzelmann, M.; Brand, R.; Gahrton, G.; Morris, C.; Niederwieser, D.; Witte, T.J.M. de

    2010-01-01

    From 2002 to 2007, 49 myeloma patients who relapsed following autologous SCT were included in a prospective multicenter trial to determine the efficacy of a reduced melphalan/fludarabine regimen followed by allogeneic SCT from unrelated donors. All patients showed leucocyte and platelet engraftment

  20. Unrelated stem cell transplantation after reduced intensity conditioning for patients with multiple myeloma relapsing after autologous transplantation.

    NARCIS (Netherlands)

    Kroger, N.; Shimoni, A.; Schilling, G.; Schwerdtfeger, R.; Bornhauser, M.; Nagler, A.; Zander, A.R.; Heinzelmann, M.; Brand, R.; Gahrton, G.; Morris, C.; Niederwieser, D.; Witte, T.J.M. de

    2010-01-01

    From 2002 to 2007, 49 myeloma patients who relapsed following autologous SCT were included in a prospective multicenter trial to determine the efficacy of a reduced melphalan/fludarabine regimen followed by allogeneic SCT from unrelated donors. All patients showed leucocyte and platelet engraftment

  1. Insufficient Evidence Supports the Use of Low-Level Laser Therapy to Accelerate Tooth Movement, Prevent Orthodontic Relapse, and Modulate Acute Pain During Orthodontic Treatment.

    Science.gov (United States)

    Farsaii, Adrian; Al-Jewair, Thikriat

    2017-09-01

    Efficacy of low-level laser therapy in accelerating tooth movement, preventing relapse and managing acute pain during orthodontic treatment in humans: A systematic review. Sonesson M, De Geer E, Subraian J, Petrén S. BMC Oral Health 2017;17:11. No funding was obtained for this study TYPE OF STUDY/DESIGN: Systematic review. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. 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

  3. Perception of affective prosody in patients at an early stage of relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Kraemer, Markus; Herold, Michele; Uekermann, Jennifer; Kis, Bernhard; Daum, Irene; Wiltfang, Jens; Berlit, Peter; Diehl, Rolf R; Abdel-Hamid, Mona

    2013-03-01

    Cognitive dysfunction is well known in patients suffering from multiple sclerosis (MS) and has been described for many years. Cognitive impairment, memory, and attention deficits seem to be features of advanced MS stages, whereas depression and emotional instability already occur in early stages of the disease. However, little is known about processing of affective prosody in patients in early stages of relapsing-remitting MS (RRMS). In this study, tests assessing attention, memory, and processing of affective prosody were administered to 25 adult patients with a diagnosis of RRMS at an early stage and to 25 healthy controls (HC). Early stages of the disease were defined as being diagnosed with RRMS in the last 2 years and having an Expanded Disability Status Scale (EDSS) of 2 or lower. Patients and HC were comparable in intelligence quotient (IQ), educational level, age, handedness, and gender. Patients with early stages of RRMS performed below the control group with respect to the subtests 'discrimination of affective prosody' and 'matching of affective prosody to facial expression' for the emotion 'angry' of the 'Tübingen Affect Battery'. These deficits were not related to executive performance. Our findings suggest that emotional prosody comprehension is deficient in young patients with early stages of RRMS. Deficits in discriminating affective prosody early in the disease may make misunderstandings and poor communication more likely. This might negatively influence interpersonal relationships and quality of life in patients with RRMS.

  4. Outcome of ETV6/RUNX1-positive childhood acute lymphoblastic leukaemia in the NOPHO-ALL-1992 protocol: frequent late relapses but good overall survival

    DEFF Research Database (Denmark)

    Forestier, Erik; Heyman, Mats; Andersen, Mette K

    2008-01-01

    ;21)-positive ALLs were 74 (43%) standard risk, 71 (42%) intermediate risk and 26 (15%) high risk. The 5- and 10-year event-free survival (EFS) of the 171 patients was 80% and 75% respectively, with no significant differences among the three risk groups. Most of the relapses occurred in boys and were late......, with almost 50% of all relapses occurring > or = 5 years after diagnosis. Of all relapses after 6 years, 80% occurred in the t(12;21)-positive group. The overall survival was 94% at 5 years and 88% at 10 years; thus, the treatment of patients in second or later remission is usually successful. As yet....../RUNX1 status, as ascertained by fluorescence in situ hybridization or reverse-transcription polymerase chain reaction, treated according to the Nordic Society of Paediatric Haematology and Oncology -ALL-1992 protocol. The assigned risk groups/treatment modalities for the 171 (25%) patients with t(12...

  5. Efficacy of low-level laser therapy in accelerating tooth movement, preventing relapse and managing acute pain during orthodontic treatment in humans: a systematic review.

    Science.gov (United States)

    Sonesson, Mikael; De Geer, Emelie; Subraian, Jaqueline; Petrén, Sofia

    2016-07-07

    Recently low-level laser therapy (LLLT) has been proposed to improve orthodontic treatment. The aims of this systematic review were to investigate the scientific evidence to support applications of LLLT: (a) to accelerate tooth movement, (b) to prevent orthodontic relapse and (c) to modulate acute pain, during treatment with fixed appliances in children and young adults. To ensure a systematic literature approach, this systematic review was conducted to Goodman's four step model. Three databases were searched (Medline, Cochrane Controlled Clinical Trials Register and Scitation), using predetermined search terms. The quality of evidence was rated according to the GRADE system. The search identified 244 articles, 16 of which fulfilled the inclusion criteria: three on acceleration of tooth movement by LLLT and 13 on LLLT modulation of acute pain. No study on LLLT for prevention of relapse was identified. The selected studies reported promising results for LLLT; elevated acceleration of tooth movement and lower pain scores, than controls. With respect to method, there were wide variations in type of laser techniques. The quality of evidence supporting LLLT to accelerate orthodontic tooth movement is very low and low with respect to modulate acute pain. No studies met the inclusion criteria for evaluating LLLT to limit relapse. The results highlight the need for high quality research, with consistency in study design, to determine whether LLLT can enhance fixed appliance treatment in children and young adults.

  6. Treatment strategies in patients with core-binding factor acute myeloid leukemia.

    Science.gov (United States)

    Solis, Erick Crespo

    2011-10-01

    Core-binding factor acute myeloid leukemias (CBF AML) are characterized by sensitivity to high-dose cytarabine. Due to good prognosis in CBF AML patients, it is important to determine the optimal treatment. Long-term RFS (relapse-free survival) is reported among 40-60%. Experience with FA/FLAG vs. IA/IAG as front-line chemotherapy has been reported by some authors. Other studies, regarding treatment strategies such as high-dose daunorubicin, do not determine survival curves in this precise subgroup of patients. Preliminary data with gemtuzumab ozogamicin plus FLAG has been reported. There are not studies with FLAG using oral fludarabine in acute leukemia patients.

  7. Are neurosurgeons prepared to electively resample glioblastoma in patients without symptomatic relapse? A qualitative study.

    Science.gov (United States)

    Mir, Tasika; Bernstein, Mark

    2016-06-01

    Background This is a qualitative study designed to examine neurosurgeons' and neuro-oncologists' perceptions of resampling surgery for glioblastoma multiforme electively, post-therapy or at asymptomatic relapse. Methods Twenty-six neurosurgeons, three radiation oncologists and one neuro-oncologist were selected using convenience sampling and interviewed. Participants were presented with hypothetical scenarios in which resampling surgery was offered within a clinical trial and another in which the surgery was offered on a routine basis. Results Over half of the participants were interested in doing this within a clinical trial. About a quarter of the participants would be willing to consider routine resampling surgery if: (1) a resection were done rather than a simple biopsy; (2) they could wait until the patient becomes symptomatic and (3) there was a preliminary in vitro study with existing tumour samples to be able to offer patients some trial drugs. The remaining quarter of participants was entirely against the trial. Participants also expressed concerns about resource allocation, financial barriers, possibilities of patient coercion and the fear of patients' inability to offer true informed consent. Conclusion Overall, if surgeons are convinced of the benefits of the trial from their information from scientists, and they feel that patients are providing truly informed consent, then the majority would be willing to consider performing the surgery. Many surgeons would still feel uncomfortable with the procedure unless they are able to offer the patient some benefit from the procedure such that the risk to benefit ratio is balanced.

  8. 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...... 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...... compared with 30% of the controls (P less than 0.0001). Neuroticism was connected with a high frequency of relapse (P less than 0.05) whereas failure of spontaneous ulcer healing had no certain relation to personality disorders. Patients with non-neurotic personality disorders had more frequently suffered...

  9. Acute leukemic appendicitis in a patient with acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Hatim Karachiwala

    2012-01-01

    Full Text Available Leukemic and lymphomatous infiltration of the appendix is a rare complication. We present the case of a 31-year-old male with acute promyelocytic leukemia who developed acute abdomen on day 11 of induction chemotherapy with idarubicin and cytarabine. After appropriate work-up, a clinical diagnosis of acute appendicitis was made. Despite severe pancytopenia, he successfully underwent laparoscopic appendectomy. The final pathology revealed leukemic infiltration of the appendix. It is hypothesized that the leukemic infiltration may play a role in the development of acute appendicitis. Further, this case demonstrates the need to maintain a high index of suspicion and prompt surgical intervention for surgical pathologies in neutropenic patients.

  10. Integrated differentiated therapy of patients with relapses of rosacea taking into account heart rate variability indices and psychological status changes

    Directory of Open Access Journals (Sweden)

    A. V. Vasilenko

    2015-08-01

    Full Text Available Aim. To develop modern methods of complex differential treatment, prognosis and prevention of development of relapses of rosacea. Methods and results. We examined 50 patients with this dermatosis. Complex clinical data, state of the autonomic nervous system (ANS and changes in the psychological status were studied. Autonomic dysfunction was determined by the method of computer electrocardiography. Psychometric evaluation was conducted by the evaluation scales and questionnaires. The effectiveness of the developed method of treatment was evaluated by clinical manifestations and indicators research. It was found that the imbalance of the ANS and emotional disorders are more prominent in patients with relapses of rosacea. Proposed therapy plan leads to the more rapid regression of symptoms and persistent positive result. Conclusions. Еarly diagnosis of changes in the ANS allows to predict the course of disease and to increase the effectiveness of treatment of relapses of rosacea.

  11. Acute Cholecystitis in Patients with Scrub Typhus

    OpenAIRE

    Lee, Hyun; Ji, Misuk; Hwang, Jeong-Hwan; Lee, Ja-Yeon; Lee, Ju-Hyung; Chung, Kyung Min; Lee, Chang-Seop

    2015-01-01

    Acute cholecystitis is a rare complication of scrub typhus. Although a few such cases have been reported in patients with scrub typhus, the clinical course is not well described. Of 12 patients, acute cholecystitis developed in 66.7% (8/12) of patients older than 60 yr. The scrub typhus group with acute cholecystitis had marginal significant longer hospital stay and higher cost than the group without cholecystitis according to propensity score matching. Scrub typhus should be kept in mind as ...

  12. Daunorubicin, Cytarabine, and Cladribine Regimen Plus Radiotherapy and Donor Lymphocyte Infusion for Extramedullary Relapse of Acute Myeloid Leukemia after Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Marco Sanna

    2013-01-01

    Full Text Available Myeloid sarcoma is a rare tumor consisting of myeloid blasts that involve anatomic sites outside the bone marrow. Fatal prognosis is inevitable in patients with extramedullary relapse after hematopoietic stem cell transplantation (HSCT, and no standard treatments are available yet. We report the first case of extramedullary relapse after HSCT treated with a combination of daunorubicin, cytarabine, and cladribine (DAC regimen plus radiotherapy and donor lymphocyte infusion (DLI. This treatment induced a new and durable remission in our patient. The favorable toxicity profile and the reduced cost make this combination worthy of further investigations.

  13. 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.

  14. Lack of topoisomerase copy number changes in patients with de novo and relapsed diffuse large B-cell lymphoma.

    Science.gov (United States)

    Pedersen, Mette Ø; Poulsen, Tim S; Gang, Anne O; Knudsen, Helle; Lauritzen, Anne F; Pedersen, Michael; Nielsen, Signe L; Brown, Peter; Høgdall, Estrid; Nørgaard, Peter

    2015-07-01

    Topoisomerase (TOP) gene copy number changes may predict response to treatment with TOP-targeting drugs in cancer treatment. This was first described in patients with breast cancer and is currently being investigated in other malignant diseases. TOP-targeting drugs may induce TOP gene copy number changes at relapse, with possible implications for relapse therapy efficacy. TOP gene alterations in lymphoma are poorly investigated. In this study, TOP1 and TOP2A gene alterations were investigated in patients with de novo diffuse large B-cell lymphoma (DLBCL) (n = 33) and relapsed DLBCL treated with chemotherapy regimens including TOP2-targeting drugs (n = 16). No TOP1 or TOP2A copy number changes were found. Polysomy of chromosomes 20 and 17 was seen in 3 of 25 patients (12%) and 2 of 32 patients (6%) with de novo DLBCL. Among relapsed patients, chromosome polysomy was more frequently observed in 5 of 13 patients (38%) and 4 of 16 patients (25%) harboring chromosome 20 and 17 polysomy, respectively; however, these differences only tended to be significant (p = 0.09 and p = 0.09, respectively). The results suggest that TOP gene copy number changes are very infrequent in DLBCL and not likely induced by TOP2-targeting drugs. Increased polyploidy of chromosomes 17 and 20 among patients with relapsed DLBCL may reflect genetic compensation in the tumor cells after TOP2 inhibition, but is more likely due to the increased genetic instability often seen in progressed cancers. Therefore, it is unlikely that TOP1 and TOP2A gene alterations can be used as predictive markers for response to treatment with TOP2-targeting drugs in patients with DLBCL.

  15. New constructs and assessments for relapse and continued use potential in the ASAM Patient Placement Criteria.

    Science.gov (United States)

    Gastfriend, David R; Rubin, Amy; Sharon, Estee; Turner, Winston M; Anton, Raymond F; Donovan, Dennis M; Gorski, Terence; Marlatt, G Alan; Maisto, Steven; Schultz, Terry K; Shulman, Gerald D

    2003-01-01

    One area of intensive study in recent years in addiction research is the characterization and prediction of relapse risk. Given the growing list of findings and assessment tools in this area, in preparation for the second edition, revised volume of the Patient Placement Criteria (PPC) of the American Society of Addiction Medicine (ASAM), a workgroup of the Coalition for National Criteria was assigned the task of creating a revised conceptual organization for Dimension 5: Relapse/Continued Use Potential. The workgroup conducted a review of the previous Dimension 5 constructs and criteria, including a decision analysis of the previous Dimension 5 decision rules. Following that analysis, field data from the ASAM Criteria Validity Study at Massachusetts General Hospital and Harvard Medical School were analyzed from a large cohort of public and indigent patients in eastern Massachusetts. After determining the concurrent validity of the Dimension 5 decision rules and their limitations, the decision rules were rewritten to gain improved validity. This exercise revealed techniques that can and should be used to improve the discrimination of levels of care among all Dimensions. Finally, the workgroup expanded and refined the constructs that should comprise a revised Dimension 5. This revised list of constructs is sequential and hierarchical. It offers face validity on several levels of current basic and clinical research knowledge: behavioral pharmacology, behavioral psychology, learning theory and psychopathology. While the Second Edition-Revised volume of the ASAM PPC (PPC-2R) does not go so far as to propose final decision rules for Dimension 5 based on these new constructs, it does recommend pilot adoption of several new assessment tools for this dimension and provides the framework incorporating those constructs and assessments in the next complete PPC edition.

  16. Overjet, overbite, and anterior crowding relapses in extraction and nonextraction patients, and their correlations.

    Science.gov (United States)

    Francisconi, Manoela Fávaro; Janson, Guilherme; Freitas, Karina Maria Salvatore; Oliveira, Renata Cristina Gobbi de; Oliveira, Ricardo César Gobbi de; Freitas, Marcos Roberto de; Henriques, José Fernando Castanha

    2014-07-01

    In this study, we aimed to compare the relapse of maxillary and mandibular anterior crowding, overjet, and overbite 5 years after treatment in subjects with Class I and Class II malocclusions treated with and without extractions, and also to evaluate the correlations among these factors. The sample comprised 84 subjects with Class I and Class II malocclusions, treated with and without extractions. Group 1 comprised 44 subjects with an initial mean age of 12.96 years treated without extractions. Group 2 included 40 subjects with an initial mean age of 13.01 years treated with 4 premolar extractions. Data were obtained from dental casts at the pretreatment, posttreatment, and long-term posttreatment stages. Intergroup comparisons were performed with t tests. To verify the correlations among the relapse of overjet, overbite, and anterior crowding, the Pearson correlation test was used. Maxillary incisor irregularity and its relapse in the nonextraction group were significantly greater at the long-term posttreatment stage and the long-term posttreatment period, respectively. Long-term postreatment overjet changes were similar in the groups. Overbite and its relapse were significantly greater in the extraction group in the long-term posttreatment stage and period, respectively. There was a positive correlation of the relapse of mandibular incisor crowding with the relapse of overjet and overbite, and also a correlation of overjet and overbite relapses. There was greater maxillary crowding relapse in the nonextraction group and greater overbite relapse in the extraction group. There were significant and positive correlations of overjet and overbite relapses with mandibular anterior crowding relapse and consequently between overjet and overbite relapses. Copyright © 2014 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  17. Fatigue predicts disease worsening in relapsing-remitting multiple sclerosis patients.

    Science.gov (United States)

    Cavallari, Michele; Palotai, Miklos; Glanz, Bonnie I; Egorova, Svetlana; Prieto, Juan Carlos; Healy, Brian C; Chitnis, Tanuja; Guttmann, Charles Rg

    2016-12-01

    It is unclear whether fatigue is a consequence or a predictive trait of disease worsening. To investigate the predictive value of fatigue toward conversion to confirmed moderate-severe disability in patients with relapsing-remitting multiple sclerosis (RRMS). We retrospectively selected from the Comprehensive Longitudinal Investigations in MS at the Brigham and Women's Hospital (CLIMB) study cohort RRMS patients who converted to confirmed (⩾2 years) Expanded Disability Status Scale (EDSS) score ⩾3 within a follow-up period ⩾3 years. We contrasted the Modified Fatigue Impact Scale (MFIS) score of 33 converters, obtained at least 1 year before conversion to EDSS ⩾3, with that of 33 non-converter RRMS patients matched for baseline characteristics. Total MFIS score was higher in converter versus non-converter MS patients (median 37 vs 13; p EDSS and Center for Epidemiological Studies Depression scale (CES-D) scores were also higher in the converters (median EDSS 1.5 vs 0, p EDSS: rho = 0.42, p = 0.0005; CES-D: rho = 0.72, p EDSS and CES-D in multivariate analysis, MFIS remained a significant predictor of subsequent conversion to confirmed EDSS ⩾3. Fatigue is a promising indicator of risk for conversion to confirmed moderate-severe disability in RRMS patients. © The Author(s), 2016.

  18. Lenalidomide induced good clinical response in a patient with multiple relapsed and refractory Hodgkin's lymphoma

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    Kolonic Slobodanka

    2010-05-01

    Full Text Available Abstract Background A 24-year-old female patient was diagnosed with classic Hodgkin's lymphoma in clinical stage II, and combination chemotherapy followed by radiotherapy was initiated. During the following 5 years, the disease progressed despite several standard therapeutic approaches, including autologous and allogeneic stem cell transplantation. Methods Lenalidomide (25 mg daily treatment was then initiated in a continuous dosing schedule. Positron emission tomography scans were performed before and during lenalidomide treatment. Hematologic and laboratory values, as well as physical condition were also assessed before and during lenalidomide treatment. Results Four months after continuous lenalidomide treatment, tumor load was significantly reduced, B symptoms had resolved, and the patient's physical condition had improved, allowing her to resume normal daily-living activities. Evaluations after 15 months of lenalidomide treatment indicated limited disease progression. Nevertheless, the patient was feeling well and maintaining a normal active life. Treatment was well tolerated, allowing the patient to remain on continuous dosing, which has now been maintained for 18 months. Conclusion Daily, long-term lenalidomide treatment provided clinical benefit and was well tolerated in a patient with relapsed, advanced classic Hodgkin's lymphoma.

  19. Chimerism Analysis of Cell-Free DNA in Patients Treated with Hematopoietic Stem Cell Transplantation May Predict Early Relapse in Patients with Hematologic Malignancies

    Directory of Open Access Journals (Sweden)

    Mahmoud Aljurf

    2016-01-01

    Full Text Available Background. We studied DNA chimerism in cell-free DNA (cfDNA in patients treated with HSCT. Methods. Chimerism analysis was performed on CD3+ cells, polymorphonuclear (PMN cells, and cfDNA using 16 small tandem repeat loci. The resulting labeled PCR-products were size-fractionated and quantified. Results. Analyzing samples from 191 patients treated with HSCT for nonneoplastic hematologic disorders demonstrated that the cfDNA chimerism is comparable to that seen in PMN cells. Analyzing leukemia patients (N = 126 showed that, of 84 patients with 100% donor DNA in PMN, 16 (19% had evidence of clinical relapse and >10% recipient DNA in the plasma. Additional 16 patients of the 84 (19% showed >10% recipient DNA in plasma, but without evidence of relapse. Eight patients had mixed chimerism in granulocytes, lymphocytes, and plasma, but three of these patients had >10% recipient DNA in plasma compared to PMN cells and these three patients had clinical evidence of relapse. The remaining 34 patients showed 100% donor DNA in both PMN and lymphocytes, but cfDNA showed various levels of chimerism. Of these patients 14 (41% showed laboratory or clinical evidence of relapse and all had >10% recipient DNA in cfDNA. Conclusion. Monitoring patients after HSCT using cfDNA might be more reliable than cellular DNA in predicting early relapse.

  20. Whole-exome sequencing reveals potential molecular predictors of relapse after discontinuation of the targeted therapy in chronic myeloid leukemia patients.

    Science.gov (United States)

    Smirnikhina, Svetlana A; Lavrov, Alexander V; Chelysheva, Ekaterina Yu; Adilgereeva, Elmira P; Shukhov, Oleg A; Turkina, Anna; Kutsev, Sergey I

    2016-07-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disease well treated by tyrosine kinase inhibitors (TKIs). The aim was to identify genes with a predictive value for relapse-free survival after TKI cessation in CML patients. We performed whole-exome sequencing of DNA from six CML patients in long-lasting deep molecular remission. Patients were divided into two groups with relapse (n = 3) and without relapse (n = 3) after TKI discontinuation. We found variants in genes CYP1B1, ALPK2, and IRF1 in group of patients with relapse and one variant in gene PARP9 in group of patients without relapse. We verified prognostic value of the found markers in a small group of patients with TKI discontinuation and demonstrated their high sensitivity (77%), specificity (86%), positive (85%), and negative (79%) predictive values. Thus we revealed genetic variants, which are potential markers of outcome prediction in CML patients after TKI discontinuation.

  1. [Effects of a Relapse Prevention Program on Insight, Empowerment and Treatment Adherence in Patients with Schizophrenia].

    Science.gov (United States)

    Joung, Jaewon; Kim, Sungjae

    2017-04-01

    The purpose of this study was to develop a relapse prevention program (RPP) and examine the effects of the RPP on insight, empowerment, and treatment adherence in patients with schizophrenia. A non-equivalent control group pretest-posttest design was used. Participants were 54 inpatients who had a diagnosis of schizophrenia (experimental group: 26, control group: 28). The study was carried out from February 7, 2012 to February 6, 2013. Over a 10-day period prior to discharge each participant in the experimental group received three one-hour sessions of RPP a one-to-one patient-nurse interaction. Data were collected using Assess Unawareness of Mental Disorder (SUMD), Empowerment Scale, and Insight and Treatment Attitude Questionnaire (ITAQ) and analyzed using PASW 18.0 with chi-square test, independent t-test, Mann-Whitney U test, and ANCOVA. The experimental group had a significant increase in insight and treatment adherence compared to the control group. However, there was no significant difference in empowerment between the two groups. Findings indicate that the RPP for patients with schizophrenia was effective in improving insight and treatment adherence. A longitudinal study is needed to confirm the persistence of these effects of RPP in patients with schizophrenia.

  2. Treatment Outcome in Older Patients with Childhood Acute Myeloid Leukemia

    Science.gov (United States)

    Rubnitz, Jeffrey E.; Pounds, Stanley; Cao, Xueyuan; Jenkins, Laura; Dahl, Gary; Bowman, W. Paul; Taub, Jeffrey W; Pui, Ching-Hon; Ribeiro, Raul C.; Campana, Dario; Inaba, Hiroto

    2013-01-01

    Background Older age has historically been an adverse prognostic factor in pediatric acute myeloid leukemia (AML). The impact of age relative to that of other prognostic factors on the outcome of patients treated in recent trials is unknown. Methods Clinical outcome and causes of treatment failure of 351 patients enrolled on three consecutive protocols for childhood AML between 1991 and 2008 were analyzed according to age and protocol. Results The more recent protocol (AML02) produced improved outcomes for 10- to 21-year-old patients compared to 2 earlier studies (AML91 and 97), with 3-year rates of event-free survival (EFS), overall survival (OS) and cumulative incidence of refractory leukemia or relapse (CIR) for this group similar to those of 0- to 9-year old patients: EFS, 58.3% ± 5.4% vs. 66.6% ± 4.9%, P=.20; OS, 68.9% ± 5.1% vs. 75.1% ± 4.5%, P=.36; cumulative incidence of refractory leukemia or relapse, 21.9% ± 4.4%; vs. 25.3% ± 4.1%, P=.59. EFS and OS estimates for 10–15-year-old patients overlapped those for 16–21-year-old patients. However, the cumulative incidence of toxic death was significantly higher for 10- to 21-year-old patients compared to younger patients (13.2% ± 3.6 vs. 4.5% ± 2.0%, P=.028). Conclusion The survival rate for older children with AML has improved on our recent trial and is now similar to that of younger patients. However, deaths from toxicity remain a significant problem in the older age group. Future trials should focus on improving supportive care while striving to develop more effective antileukemic therapy. PMID:22674050

  3. Autologous bone marrow transplantation for treatment of isolated central nervous system relapse of childhood acute lymphoblastic leukemia. AIEOP/FONOP-TMO group. Associzione Italiana Emato-Oncologia Pediatrica.

    Science.gov (United States)

    Messina, C; Valsecchi, M G; Aricò, M; Locatelli, F; Rossetti, F; Rondelli, R; Cesaro, S; Uderzo, C; Conter, V; Pession, A; Sotti, G; Loiacono, G; Santoro, N; Miniero, R; Dini, G; Favre, C; Meloni, G; Testi, A M; Werner, B; Silvestri, D; Arrighini, A; Varotto, S; Pillon, M; Basso, G; Zanesco, L

    1998-01-01

    The purpose of this study was to assess the role of ABMT in children with ALL who are in 2nd CR after an early isolated CNS relapse. All children experiencing an isolated CNS relapse at 10 AIEOP centers (Associazione Italiana Emato-Oncologia Pediatrica) from 1986 to 1992 were eligible for this study. The series included 69 patients who relapsed within 3 years from diagnosis: 19 underwent ABMT, nine patients underwent ALLO-BMT from an HLA-identical sibling, and 41 received conventional chemotherapy (CHEMO). Statistical analysis was performed using a Cox's regression model, adjusting for the waiting time before transplantation and prognostic factors. The 5 years DFS was 56.3% (s.e. 12.3) for patients in the ABMT group. This compared favorably with the poor result (12.6% (s.e. 5.9)) seen in the CHEMO group. The risk of failures was reduced by one-third in the ABMT group as compared to the CHEMO group in the multivariate analysis (P < 0.01). In the ALLO group four out of nine patients were in CCR 4-5 years post-transplant. This study suggests that ABMT may also represent a valuable therapeutic choice for patients lacking a matched familiar donor in 2nd CR after an early isolated CNS relapse.

  4. Depressed patients' perceptions of facial emotions in depressed and remitted states are associated with relapse - A longitudinal study

    NARCIS (Netherlands)

    Bouhuys, AL; Geerts, E; Gordijn, MCM

    1999-01-01

    Within the framework of interpersonal and cognitive theories of depression, we investigated whether the perception of facial emotions was associated with subsequent relapse into depression. The 23 inpatients with major depression who remitted (65 admitted patients) were studied at admission (TO), at

  5. Importance of baseline PET/CT imaging on radiation field design and relapse rates in patients with Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    Nick Figura, MD

    2017-04-01

    Conclusions: Patients with stage I/II HL who receive ISRT without pretreatment PET/CT scans appear to have an increased risk for relapse in adjacent nodal stations just outside the radiation field. A larger cohort with a longer follow-up is needed to confirm these findings.

  6. 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...

  7. 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

    High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is the most common first-line treatment for patients with multiple myeloma (MM) under 65 years of age. A second ASCT at first relapse is frequently used but is challenged by the use of novel drugs. We retrospectively ...

  8. A simple scoring system to differentiate between relapse and re-infection in patients with recurrent melioidosis.

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    Direk Limmathurotsakul

    Full Text Available BACKGROUND: Melioidosis is an important cause of morbidity and mortality in East Asia. Recurrent melioidosis occurs in around 10% of patients following treatment either because of relapse with the same strain or re-infection with a new strain of Burkholderia pseudomallei. Distinguishing between the two is important but requires bacterial genotyping. The aim of this study was to develop a simple scoring system to distinguish re-infection from relapse. METHODS: In a prospective study of 2,804 consecutive adult patients with melioidosis presenting to Sappasithiprasong Hospital, NE Thailand, between 1986 and 2005, there were 141 patients with recurrent melioidosis with paired strains available for genotyping. Of these, 92 patients had relapse and 49 patients had re-infection. Variables associated with relapse or re-infection were identified by multivariable logistic regression and used to develop a predictive model. Performance of the scoring system was quantified with respect to discrimination (area under receiver operating characteristic curves, AUC and categorization (graphically. Bootstrap resampling was used to internally validate the predictors and adjust for over-optimism. FINDINGS: Duration of oral antimicrobial treatment, interval between the primary episode and recurrence, season, and renal function at recurrence were independent predictors of relapse or re-infection. A score of or = 5 correctly identified re-infection in 36 of 52 patients (69%. The scoring index had good discriminative power, with a bootstrap bias-corrected AUC of 0.80 (95%CI: 0.73-0.87. CONCLUSIONS: A simple scoring index to predict the cause of recurrent melioidosis has been developed to provide important bedside information where rapid bacterial genotyping is unavailable.

  9. 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.

  10. Serum viral load at the virological relapse predicts subsequent clinical flares in chronic hepatitis B patients off entecavir therapy.

    Science.gov (United States)

    Hsu, Yao-Chun; Mo, Lein-Ray; Chang, Chi-Yang; Wu, Ming-Shiang; Yang, Tzeng-Huey; Kao, Jia-Horng; Chen, Chieh-Chang; Tseng, Cheng-Hao; Tai, Chi-Ming; Lin, Chih-Wen; Wu, Chun-Ying; Lin, Jaw-Town

    2017-08-01

    Therapeutic duration of nucleos(t)ide analogues for chronic hepatitis B (CHB) is not indefinite in many parts of the world. Viral reactivation is common off therapy, but the risk of subsequent clinical outcome remains unclear and unpredictable. We aimed to quantify the incidence of and explore the predictors for clinical flare following virological relapse in CHB patients who discontinue entecavir therapy. This multicenter cohort study prospectively monitored 133 CHB patients who were HBeAg-negative and viral DNA-undetectable when discontinuing entecavir after at least 3 years on therapy. Following virological relapse (viral DNA >2,000 IU/mL) that occurred in 92 patients, the incidences of subsequent clinical flare and persistent (unremittent for 3 months) or severe hepatitis (with jaundice or coagulopathy) were determined, and risk factors were explored. Patients did not resume antiviral therapy until occurrence of persistent or severe hepatitis. The cumulative incidence of clinical hepatitis 2 years after virological relapse was 61.0% (95% confidence interval [CI], 49.9-72.3%) and that of persistent or severe hepatitis was 53.0% (95% CI, 40.9-66.2%). Serum viral load at the virological relapse was associated with both clinical hepatitis (adjusted hazard ratio [HR], 1.31 per log IU/mL; 95% CI, 1.07-1.60) and persistent or severe hepatitis (adjusted HR, 1.63 per log IU/mL; 95% CI, 1.27-2.10), after adjustment for serum aminotransferase and alfa-fetoprotein levels in the multivariate analysis. Viral DNA >100 000 IU/mL predicted a nearly inevitable occurrence of clinical flare (P < 0.0001). A high viral load at the virological relapse predicts subsequent clinical hepatitis in CHB patients who discontinue entecavir. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  11. 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.

  12. 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.)

  13. Sarcoma granulocítico multicêntrico como recidiva de leucemia mieloide aguda Multicentric granulocytic sarcoma as relapse of acute myelogenous leukemia

    Directory of Open Access Journals (Sweden)

    Taciana G. S. Aguiar

    2009-01-01

    Full Text Available Sarcoma granulocítico (SG é um tumor sólido extramedular, constituído por células precursoras de granulócitos. É geralmente associado a leucemia mieloide aguda ou raramente a outras desordens mieloproliferativas. O tumor geralmente ocorre precedendo uma leucemia mieloide aguda, durante o seu curso ou após a remissão ter sido alcançada. O prognóstico é pobre e tem como principais modalidades terapêuticas a quimioterapia e a radioterapia. Relata- se um caso de SG multicêntrico, de evolução rápida, com acometimento difuso de pele, mamas, gânglios linfáticos, tecido celular subcutâneo e líquor, em mulher de 45 anos, fora de tratamento para leucemia mieloide aguda e em remissão hematológica há 18 meses. A paciente apresentava dor intensa em membro inferior direito há uma semana e estava em anticoagulação oral há seis meses por trombose venosa profunda neste membro. Diagnosticado o SG, a paciente foi tratada com radioterapia e quimioterapia com boa resposta. Após três meses de seguimento, em vigência do tratamento quimioterápico, evoluiu com recidiva do SG neste membro, associado ao acometimento das mamas e posteriormente do sistema nervoso central, evoluindo para óbito em aplasia e sepses.Granulocytic sarcoma is an extramedullary solid tumor consisting of immature granulocytic cells. It is often associated with acute myelogenous leukemia and more rarely with other myeloproliferative disorders. The tumor generally occurs before acute myeloid leukemia, during its course or after disease remission. It has a poor prognosis with the main therapeutic options being chemotherapy and radiotherapy. A multicentric accelerated case of granulocytic sarcoma of a 45- year- old woman with diffuse skin, breast, lymphatic ganglia and subcutaneous tissue presentations no longer undergoing treatment for acute myeloid leukemia and in hematologic remission for 18 months is reported. The patient presented with severe pain of right lower

  14. Acute tonsillitis at infectious patients

    Directory of Open Access Journals (Sweden)

    Y. P. Finogeev

    2011-01-01

    Full Text Available We examined 1824 patients with diphtheria treated in Clinical Infectious Diseases Hospital Botkin (St. Petersburg in 1993 – 1994, and more than 500 patients referred to the clinic with a diagnosis of «angina». Based on published data and our own research observations investigated the etiology of acute tonsillitis. Bacterial tonsillitis should be treated with antibiotics, and this is important aetiological interpretation of these diseases. Streptococcal tonsillitis should always be a sore throat syndrome as a diagnostic sign of support. For other forms of lymphoma lesion of the tonsils should not be defined as «angina», and called «tonsillitis». Аngina as β-hemolytic streptococcus group A infection is recognized as the leader in the development of rheumatic fever. On the basis of a large clinical material briefly analyzed the clinical manifestations of various forms of diphtheria with membranous tonsillitis. Also presented with a syndrome of infectious diseases as tonsillitis, therapeutic and surgical «mask» of infectious diseases.

  15. Association Between Serum Level of Hepatitis B Surface Antigen at End of Entecavir Therapy and Risk of Relapse in E Antigen-Negative Patients.

    Science.gov (United States)

    Hsu, Yao-Chun; Mo, Lein-Ray; Chang, Chi-Yang; Wu, Ming-Shiang; Kao, Jia-Horng; Wang, Wen-Lun; Yang, Tzeng-Huey; Wang, Chaur-Shine; Chiang, Ming-Feng; Chen, Chieh-Chang; Fang, Yu-Jen; Hung, Hsu-Wei; Wu, Chun-Ying; Lin, Jaw-Town

    2016-10-01

    This study investigated whether serum level of hepatitis B surface antigen (HBsAg) at the end of entecavir treatment was associated with risk of relapse. We performed a prospective multicenter study of 161 consecutive patients with chronic hepatitis B in whom the hepatitis B virus was no longer detected after 3 years or more of entecavir therapy. Treatment ended between July 1, 2011 and July 1, 2015. Patients were monitored for clinical relapse (hepatitis B virus DNA >2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal) and virologic relapse (hepatitis B virus DNA >2000 IU/mL). Outcomes were calculated using the Kaplan-Meier method and risk factors were identified by Cox proportional hazards modeling. Two years after therapy ended, 49.2% of patients in the entire cohort had a clinical relapse (95% confidence interval [CI], 40.9%-58.1%) and 81.7% had a virologic relapse (95% CI, 74.3%-88.0%). Among patients who were hepatitis B e antigen-negative at the end of therapy, 39.2% had a clinical relapse (95% CI, 30.3%-49.6%) and 77.4% had a virologic relapse (95% CI, 68.6%-85.2%). Serum level of HBsAg was associated with relapse in the hepatitis B e antigen-negative patients (Ptrend = .006 for clinical relapse; Ptrend = .0001 for virologic relapse). In multivariate Cox regression analysis, the hazard ratio (per log IU/mL increment) for clinical relapse was 2.47 (95% CI, 1.45-4.23) and for virologic relapse was 1.80 (95% CI, 1.33-2.45). The 11 (9%) patients with levels of HBsAg <10 IU/mL did not relapse. Serum level of HBsAg is associated with risk of relapse in patients who are hepatitis B e antigen-negative after treatment with entecavir. A low titer of HBsAg might be used to identify patients at low risk for relapse after treatment. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. Recurrent acute pancreatitis and its relative factors

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Hong-Chao Shan; Yan Gu

    2005-01-01

    AIM: To evaluate the causes and the relative factors of recurrent acute pancreatitis.METHODS: From 1997 to 2000, acute pancreatitis relapsed in 77 of 245 acute pancreatitis patients. By reviewing the clinical treatment results and the follow-up data, we analyzed the recurrent factors of acute pancreatitis using univariate analysis and multivariate analysis.RESULTS: Of the 245 acute pancreatitis patients, 77 were patients with recurrent acute pancreatitis. Of them, 56 patients relapsed two times, 19 relapsed three times, each patient relapsed three and four times. Forty-seven patients relapsed in hospital and the other 30 patients relapsed after discharge. Eighteen patients relapsed in 1 year, eight relapsed in 1-3 years, and four relapsed after 3 years. There were 48 cases of biliary pancreatitis, 3 of alcohol pancreatitis, 5 of hyperlipidemia pancreatitis, 21 of idiopathic pancreatitis. Univariate analysis showed that the patients with local complications of pancreas, obstructive jaundice and hepatic function injury were easy to recur during the treatment period of acute pancreatitis (P = 0.022<0.05, P = 0.012<0.05 and P = 0.002<0.05, respectively). Multivariate analysis showed that there was no single factor related to recurrence. Of the 47 patients who had recurrence in hospital, 16 had recurrence in a fast period, 31 after refeeding. CONCLUSION: Acute pancreatitis is easy to recur even during treatment. The factors such as changes of pancreas structure and uncontrolled systemic inflammatory reaction are responsible for the recurrence of acute pancreatitis. Early refeeding increases the recurrence of acute pancreatitis. Defining the etiology is essential for reducing the recurrence of acute pancreatitis.

  17. 地西他滨联合化疗治疗难治复发急性髓系白血病及骨髓增生异常综合征转化白血病的效果观察%Clinical effects of decitabine combined with chemotherapy in the treatment of patients with refractory and relapsed acute myeloid leukemia and myelodysplastic syndrome transformed leukemia

    Institute of Scientific and Technical Information of China (English)

    韩波; 王朝晖; 邵纬; 王九河; 洪青; 范传波; 刘俊玲; 田猛; 王海霞

    2014-01-01

    目的 探讨地西他滨联合化疗治疗难治复发急性髓系白血病(AML)及骨髓增生异常综合征(MDS)转化AML的临床效果.方法 选取2013年2月至2014年3月住院治疗的难治复发AML患者19例及MDS转化AML患者4例,所有患者给予地西他滨联合CAG方案进行治疗,评估患者治疗效果及不良反应.结果 经过1个疗程治疗后,14例(60.9%)完全缓解,2例(8.7%)部分缓解,7例(30.4%)无效,总有效率69.6%,不同染色体核型患者临床治疗效果差异具有统计学意义(P<0.05).23例患者出现不同程度的骨髓抑制,其中Ⅰ~Ⅱ级中性粒细胞减少2例,Ⅲ~Ⅳ级21例,中性粒细胞减少中位时间13 d;Ⅲ~Ⅳ级贫血23例;Ⅲ~Ⅳ级血小板减少23例,血小板减少中位时间16d.Ⅰ~Ⅱ级出血20例,Ⅲ~Ⅳ级3例.Ⅰ~Ⅱ级胃肠道反应1例.Ⅰ~Ⅱ级肝功能异常1例.所有患者随访至2014年3月31日,生存20例,死亡3例,中位总生存期3.1个月,1年累积生存率86%.结论 地西他滨联合化疗治疗难治复发AML及MDS转化白血病的临床缓解率高,不良反应少;染色体核型可能是影响治疗效果的重要因素.%Objective To investigate the clinical effects of decitabine combined with chemotherapy in the treatment of patients with refractory and relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) transformed leukemia.Methods 19 patients with refractory and relapsed AML and 4 cases of patients with MDS transformed AML were enrolled from February 2013 to March 2014.All cases were treated with decitabine combined with CAG regimen.The clinical effects and adverse reactions were evaluated.Results After a course of treatment,14 cases (60.9 %) were complete remission,2 cases (8.7 %) were parrtial remission,7 cases (30.4 %) were non-remission,and the total efficiency rate was 69.6 %.The differences of clinical outcomes among different karyotypes were statistically significant (P < 0.05).There were

  18. Efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung squamous cell carcinoma

    Science.gov (United States)

    Pi, Guoliang; He, Hanping; Bi, Jianping; Li, Ying; Li, Yanping; Zhang, Yong; Wang, Mingwei; Han, Guang; Lin, Chi

    2016-01-01

    Abstract Introduction: Currently, the options are limited for the treatment of patients who have failed 2 lines of chemotherapy for advanced lung squamous cell carcinoma (SCC). Recently, nivolumab, a fully human IgG4 programmed death 1 immune checkpoint inhibitor antibody, was approved to treat patients with advanced stage, relapsed/refractory lung SCC. Although nivolumab has demonstrated antitumor activity with survival benefit in Caucasian patients, its efficacy in Asian patients is unknown. Case Report: In this report, we describe a Chinese patient with relapsed advanced stage lung SCC who had an excellent response to nivolumab after only 2 doses without any adverse effects. Immunohistochemical analysis indicated the tumor was stained positive for programmed death-ligand 1. Conclusion: To our knowledge, this is the first report of satisfactory efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung SCC. Further clinical trials in Asian countries are needed to test whether nivolumab immunotherapy is a safe and effective treatment for Asian patients with lung SCC. PMID:27749580

  19. Efficacy and safety of low-dose lenalidomide plus dexamethasone in patients with relapsed or refractory POEMS syndrome.

    Science.gov (United States)

    Cai, Qian-Qian; Wang, Chen; Cao, Xin-Xin; Cai, Hao; Zhou, Dao-Bin; Li, Jian

    2015-10-01

    Although autologous stem cell transplantation or melphalan-based chemotherapy has significantly improved the prognosis of POEMS syndrome, a few patients will relapse or be refractory to primary therapy, and there is a lack of studies regarding these patients. In this study, we used low-dose lenalidomide (10 mg daily) and dexamethasone (40 mg, once weekly) to treat twelve patients with relapsed (n = 8) or refractory (n = 4) POEMS syndrome. After a median follow-up time of 20 months, the overall hematologic response rate was 77% with 44% having a complete response. Eight (67%) patients had neurological response, and the median overall neuropathy limitation scale score was reduced from 3 (range, 1-9) to 2 (range, 0-6). Serum vascular endothelial growth factor response rate was 91% and 46% of patients had normal serum VEGF levels. One patient had progression of the disease 3 months after the end of treatment and subsequently died from the disease. Therefore, the estimated 2 year overall survival and progression-free survival were 92%. The low-dose lenalidomide and dexamethasone regimen was well tolerated, with no treatment-related death or any grade 3 or 4 toxicity. In conclusion, low-dose lenalidomide plus dexamethasone therapy is an effective and safe regimen for patients with relapsed or refractory POEMS syndrome.

  20. Predictive value of molecular remissions postconsolidation chemotherapy in patients with Core Binding Factor Acute Myeloid Leukemia (CBF-AML) - a single center analysis.

    Science.gov (United States)

    Deotare, Uday; Shaheen, Marwan; Brandwein, Joseph M; Pitcher, Bethany; Kamel-Reid, Suzanne; Yee, Karen W L; Schimmer, Aaron; Minden, Mark D; Gupta, Vikas; Schuh, Andre C

    2016-09-06

    We analyzed the outcome of 80 sequential patients with core binding factor acute myeloid leukemia and evaluated the influence of molecular monitoring by quantitative reverse transcriptase polymerase chain reaction. With a median follow-up of 5 years, the estimated 5-year relapse-free survival and overall survival were 58% and 66%, respectively. Patients who were in molecular remission at the completion of consolidation chemotherapy had a 21% risk of relapse, while the relapse risk for those in molecular remission at the end of 2 years was 5.5%. Our data indicate that postconsolidation molecular remission does not necessarily preclude disease relapse and further monitoring is required. In contrast, molecular negativity by quantitative reverse transcriptase polymerase chain reaction at the end of 2 years is associated with a low risk of relapse. Copyright © 2016 John Wiley & Sons, Ltd.

  1. 雷利度胺治疗难治复发急性粒细胞白血病临床观察%Clinical Observation of Lenalidomide Treat Relapsed or Refractory Acute Myeloblastic Leukemia

    Institute of Scientific and Technical Information of China (English)

    孔德胜; 赵红丽; 董敏; 孙国勋; 施婺丹; 洪珞珈

    2012-01-01

    Objective: To observe toxicities and efficacy in patients relapsed or refractory acute myeloblastic leukemia wit] lenalidomide. Methods: Lenalidomide was given orally at doses of 50mg daily on days 1 through 21 of 28-day cycles. Results: Si Patients were given a median of four prior therapies (range, two to six therapies), frVe patients with AML responded. Two of 6 patient achieved complete remission (CR), two of 6 patients achieved partial remission (PR), one of 6 patients achieved Peripheral bloa improvement,One patient had disease progression death. Toxicities of lenalidomide were Fatigue (4/6), febrile neutropenia (3/6] neutropenia (4/6), thrombocytopenia(l/6), anemia(l/6). Conclusions: Lenalidomide has significant activity in relapsed or refractory acut myeloblastic leukemia patients and the toxicities was active with relatively low toxicity in patients with relapsed/refractory AML.%目的:观察雷利度胺治疗难治复发急性粒细胞白血病的疗效及不良反应.方法:给予雷利度胺单药治疗,雷利度胺50mg/d,口服给药,连续给药21天,28天为一个疗程.结果:应用雷利度胺4(2~6)个疗程,5例有效,2例获得完全缓解,2例部分缓解,1例因疾病迅速进展死亡退出试验.不良反应主要为疲乏4例,中性粒细胞减少性发热3例,中粒细胞减少4例,血小板减少1例,贫血1例.结论:应用雷利度胺治疗难治复发白血病有效,不良反应轻微且易于耐受.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ho Kyun [Dept. of Radiology, Catholic University of Daegu School of Medicine, Daegu (Korea, Republic of); Lee, Hui Joong [Dept. of Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2013-03-15

    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.

  3. 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.

  4. 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

  5. Technical relapsed testicular irradiation for acute lymphoblastic leukemia; Tecnica de irradiacion para testiculos en recidiva de leucemia linfoblastica aguda

    Energy Technology Data Exchange (ETDEWEB)

    Velazquez Miranda, S.; Delgado Gil, M. M.; Ortiz Siedel, M.; Munoz Carmona, D. M.; Gomez-Barcelona, J.

    2011-07-01

    Testicular irradiation in children suffering from acute lymphoblastic leukemia presents difficulties in relation to daily positioning, dosimetry for dose homogenization of complex geometry and volume change during irradiation thereof. This can lead to significant deviations from the prescribed doses. In addition, the usual techniques often associated with unnecessary irradiation of pelvic simphysis, anus and perineum. This, in the case of pediatric patients, is of great importance, since doses in the vicinity of 20 Gy are associated with a deviation of bone growth, low testosterone levels around 24 Gy and high rates of generation of second tumors. To overcome these problems we propose a special restraint in prone and non-coplanar irradiation.

  6. 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.......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....

  7. 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.......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....

  8. Trace elements in scalp hair samples from patients with relapsing-remitting multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Elisa Tamburo

    Full Text Available Epidemiological studies have suggested a possible role of trace elements (TE in the etiology of several neurological diseases including Multiple Sclerosis (MS. Hair analysis provides an easy tool to quantify TE in human subjects, including patients with neurodegenerative diseases.To compare TE levels in scalp hair from patients with MS and healthy controls from the same geographic area (Sicily.ICP-MS was used to determine the concentrations of 21 elements (Ag, Al, As, Ba, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Pb, Rb, Sb, Se, Sr, U, V and Zn in scalp hair of 48 patients with relapsing-remitting Multiple Sclerosis compared with 51 healthy controls.MS patients showed a significantly lower hair concentration of aluminum and rubidium (median values: Al = 3.76 μg/g vs. 4.49 μg/g and Rb = 0.007 μg/g vs. 0.01 μg/g; and higher hair concentration of U (median values U: 0.014 μg/g vs. 0.007 μg/g compared to healthy controls. The percentages of MS patients showing hair elemental concentrations greater than the 95th percentile of controls were 20% for Ni, 19% for Ba and U, and 15% for Ag, Mo and Se. Conversely, the percentages of MS patients showing hair elemental concentrations lower than the 5th percentile of healthy controls were 27% for Al, 25% for Rb, 22% for Ag, 19% for Fe, and 16% for Pb. No significant association was found between levels of each TE and age, disease duration or Expanded Disability Status Scale (EDSS score. After stratification by gender, healthy subjects did not show any significant difference in trace element levels, while MS patients showed significant differences (p<0.01 for the concentrations of Ag, Cr, Fe, Ni and Sr. No significant differences were also found, at p<0.01, in relation to the use of cigarettes, consume of water, vegetables and place of living.The different distributions of TE in hair of MS patients compared to controls provides an additional indirect evidence of metabolic imbalance of chemical elements in the

  9. 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

  10. Early lymphocyte recovery as a predictor of outcome, including relapse, after hematopoieticstem cell transplantation

    Directory of Open Access Journals (Sweden)

    Juliane Morando

    2012-01-01

    Full Text Available BACKGROUND: Despite advances in the treatment of acute leukemia, many patients need to undergo hematopoietic stem cell transplantation. Recent studies show that early lymphocyte recovery may be a predictor of relapse and survival in these patients. OBJECTIVE: To analyze the influence of lymphocyte recovery on Days +30 and +100 post-transplant on the occurrence of relapse and survival. METHODS: A descriptive, retrospective study was performed of 137 under 21-year-old patients who were submitted to hematopoietic stem cell transplantation for acute leukemia between 1995 and 2008. A lymphocyte count 0.3 x 10(9/L were considered adequate. Lymphocyte recovery was also analyzed on Day +100 with < 0.75 x 10(9/Land < 0.75 x 10(9/L being considered inadequate and adequate lymphocyte recovery, respectively. RESULTS: There was no significant difference in the occurrence of relapse between patients with inadequate and adequate lymphocyte recovery on Day +30 post-transplant. However, the transplant-related mortality was significantly higher in patients with inadequate recovery on Day +30. Patients with inadequate lymphocyte recovery on Day +30 had worse overall survival and relapse-free survival than patients with adequate recovery. There was no significant difference in the occurrence of infections and acute or chronic graft-versus-host disease. Patients with inadequate lymphocyte recovery on Day +100 had worse overall survival and relapse-free survival and a higher cumulative incidence of relapse. CONCLUSION: The evaluation of lymphocyte recovery on Day +30 is not a good predictor of relapse after transplant however patients with inadequate lymphocyte recovery had worse overall survival and relapse-free survival. Inadequate lymphocyte recovery on Day +100 is correlated with higher cumulative relapse as well as lower overall survival and relapse-free survival.

  11. Predictors of quality of life in patients with relapsing-remitting multiple sclerosis: a 2-year longitudinal study.

    Science.gov (United States)

    Baumstarck, K; Pelletier, J; Boucekine, M; Auquier, P

    2015-02-01

    Knowledge of which factors are determinant of quality of life (QoL) in patients with multiple scleroris (MS) would assist clinicians in choosing the most appropriate interventions. The aim of this study was to determine the contribution of sociodemographic and clinical factors in the predicting QoL in a 2-year cohort of patients with relapsing-remitting MS (RR-MS). The study had a multi-center, multi-regional, and longitudinal design. Main inclusion criteria were: patient with a RR-MS subtype (McDonald criteria) and an Expanded Disability Status Scale (EDSS) score lower than 7.0. Sociodemographic (age, gender, education level, marital and employment status) and clinical (disability, disease duration, relapse) data were recorded. The QoL was assessed using the MusiQoL (disease-specific) and SF-36 (generic) questionnaires. Each patient was investigated at baseline and 24 months post-inclusion (ClinicalTrials.gov identifier: NCT00702065). Five hundred and twenty-six patients were enrolled in the present study. The 24-month MusiQoL index score was significantly inversely correlated with the disease duration. Baseline EDSS score impacted in both 'physical-like' and 'psychological-like' dimensions. At least one relapse during the follow-up period was associated with lower physical scores. Occupational status and marital status were associated with 24-month scores of MusiQoL and SF-36. After adjusting for disability and relapse occurrence, sociodemographics (age, marital status, and occupational status) and baseline QoL scores were also independent QoL predictors in MS patients. Special attention should be given to subgroups to ensure optimal management. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. [Therapeutic results in patients with biphenotypic acute leukemia at Sapporo Medical University Hospital].

    Science.gov (United States)

    Murase, Kazuyuki; Iyama, Satoshi; Sato, Tsutomu; Takimoto, Rishu; Kobune, Masayoshi; Kato, Junji

    2010-10-01

    We reviewed the results of 6 patients with biphenotypic acute leukemia (BAL) which the diagnostic standard of the European Group for the Immunological Characterization of Leukemia (EGIL) at Sapporo Medical University Hospital between 2006 and 2008. There were 5 males and 1 females with an average age of 35 years. Among them, 4 were B lymphoid and myeloid, 2 were T lymphoid and myeloid, and one was T/B lymphoid. Two of 4 patients did not attain complete remission, and two relapsed after first treatment with acute myeloblastic leukemia (AML) protocol. On the other hand, two showed complete remission after the acute lymphoblastic leukemia (ALL) protocol. One of 4 patients survived who had been treated with hematopoietic stem cell transplantation as a post-remission therapy. The ALL protocol was good for the induction therapy. However, overall treatment-related deaths were 4 patients and considerable caution was necessary.

  13. The Circulating Treg/Th17 Cell Ratio Is Correlated with Relapse and Treatment Response in Pulmonary Sarcoidosis Patients after Corticosteroid Withdrawal.

    Directory of Open Access Journals (Sweden)

    Yongzhe Liu

    Full Text Available Pulmonary sarcoidosis is an immune-mediated disease, and some patients can be effectively treated with corticosteroids. However, nearly half of all sarcoidosis patients relapse after corticosteroid withdrawal. Different subsets of CD4+ helper T cells participate in the immunopathogenesis of sarcoidosis. Thus, the aims of our study were to investigate whether the circulating subsets of CD4+ helper T cells were associated with sarcoidosis relapse and with its remission after retreatment. Additionally, we identified a useful biomarker for predicting the relapse and remission of sarcoidosis patients.Forty-two patients were enrolled in the present study who had previously been diagnosed with pulmonary sarcoidosis and treated with corticosteroids. The patients were allocated into either a stable group if they exhibited sustained remission (n = 22 or a relapse group if they experienced clinical or radiological recurrence after treatment withdrawal (n = 20. Peripheral blood cells were collected from these patients and analyzed to determine the frequencies of subsets of circulating CD4+ helper T cells by flow cytometry. The patients in the relapse group were retreated with corticosteroids and immunosuppressive agents and were then reevaluated to determine the frequencies of dynamic subsets of circulating CD4+ helper T cells after remission.The frequencies of circulating Tregs were significantly increased concomitant with a decrease in the circulating Th17 cell frequency in the relapsed patients compared with the stable patients. The Treg/Th17 ratio was negatively correlated with sarcoidosis activity and was sensitive to retreatment. In addition, the percentage of isolated CD45RO+Ki67+ Tregs was higher in the patients who were stable and in those who recovered after retreatment than in those who relapsed.An imbalance between Tregs and Th17 cells is associated with pulmonary sarcoidosis relapse after corticosteroid withdrawal. The circulating Treg/Th17

  14. Rate of relapse in multibacillary patients after cessation of long-course dapsone monotherapy supplemented by a final supervised single dose of 1500 mg of rifampin.

    Science.gov (United States)

    Cartel, J L; Naudin, J C

    1994-06-01

    When multidrug therapy was implemented in Senegal, 406 multibacillary (MB) patients who had been treated for more than 10 years by dapsone alone, and who had become clinically inactive and skin-smear negative, were released from treatment. Of these 406 patients, 298 were given a supervised single dose of 1500 mg of rifampin. Subsequently, 302 of them (229 who had been given rifampin and 73 who had not) were followed up by means of annual clinical and bacteriological examinations. Of the former 229 followed up for a mean period of 4.9 years, 34 patients relapsed (22 males and 12 females), giving a crude relapse rate of 15% and an overall risk of relapse of 3.1 per 100 patient-years. Of the latter 73 followed up for a mean period of 2.4 years, 5 relapsed (4 males and 1 female), giving a crude relapse rate of 6.8% and an overall risk of relapse of 2.9 per 100 patient-years. Such results, which are in agreement with those of a similar study conducted recently in Mali, indicate that the intake of a single dose of 1500 mg of rifampin by MB patients when they are released from long-course dapsone monotherapy does not result in a decrease of the relapse rate. Therefore, MB patients who have been treated with dapsone alone, even for long periods, should be put under multidrug therapy prior to their release from control.

  15. Proteinuria predicts relapse in adolescent and adult minimal change disease

    Directory of Open Access Journals (Sweden)

    Cristiane Bitencourt Dias

    2012-11-01

    Full Text Available OBJECTIVE: This study sought to outline the clinical and laboratory characteristics of minimal change disease in adolescents and adults and establish the clinical and laboratory characteristics of relapsing and non-relapsing patients. METHODS: We retrospectively evaluated patients with confirmed diagnoses of minimal change disease by renal biopsy from 1979 to 2009; the patients were aged >13 years and had minimum 1-year follow-ups. RESULTS: Sixty-three patients with a median age (at diagnosis of 34 (23-49 years were studied, including 23 males and 40 females. At diagnosis, eight (12.7% patients presented with microscopic hematuria, 17 (27% with hypertension and 17 (27% with acute kidney injury. After the initial treatment, 55 (87.3% patients showed complete remission, six (9.5% showed partial remission and two (3.1% were nonresponders. Disease relapse was observed in 34 (54% patients who were initial responders (n = 61. In a comparison between the relapsing patients (n = 34 and the non-relapsing patients (n = 27, only proteinuria at diagnosis showed any significant difference (8.8 (7.1-12.0 vs. 6.0 (3.6-7.3 g/day, respectively, p = 0.001. Proteinuria greater than 7 g/day at the initial screening was associated with relapsing disease. CONCLUSIONS: In conclusion, minimal change disease in adults may sometimes present concurrently with hematuria, hypertension, and acute kidney injury. The relapsing pattern in our patients was associated with basal proteinuria over 7 g/day.

  16. Optic Coherence Tomography Findings in Relapsing-remitting Multiple Sclerosis Patients of the Northwest of Iran

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    Sasan Andalib

    2013-07-01

    Full Text Available Background: Optical coherence tomography (OCT is a simple, high-resolution technique to quantify the thickness of retinal nerve fiber layer (RNFL and macula volume, which provide an indirect measurement of axonal damage in multiple sclerosis (MS. This study aimed to evaluate OCT finding in relapsing-remitting MS patients of the northwest of Iran and compare them with a normal control group.Methods: In a cross-sectional, descriptive, analytic study, 60 patients with MS as case group and 60 patients as controls were studied. Total macular volume (TMV and retinal nerve fiber layer (RNFL in perioptic disk area (3.4 millimeter around the disk and macula was measured using Stratus 3000 in circular form. These findings were compared between the two groups and their relationship with the duration and severity of MS [based on Expanded Disability Status Scale (EDSS] and history of optic neuritis were evaluated.Results: In total, 35 men and 85 women with a mean age of 34.8 years were evaluated. The mean RNFL in MS patients were 231.9 and 233.1 micrometers in right and left eyes; while they were 246.7 and 250.4 micrometers in right and left eyes of healthy subjects, respectively. This difference in thickness of RNFL in total measure and all quadrants around the optic disk and TMV between case and control groups was analytically meaningful (P = 0.001 and P = 0.001 for right and left eyes, respectively. The mean thickness of RNFL in patients with optic neuritis was significantly lower than other patients in right and left eyes (P = 0.042 and P = 0.005. There was a significant correlation between most of OCT findings and the MS disease duration and EDSS.Conclusion: Findings of the present study in the northwest of Iran buttress the idea that RNFL thickness can be greatly affected by MS. Our results also indicate that this effect is associated with ON and MS duration and severity.

  17. {sup 11}C-Choline PET/CT as a guide to radiation treatment planning of lymph-node relapses in prostate cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Picchio, M.; Busnardo, E.; Giovacchini, G.; Incerti, E.; Gianolli, L. [San Raffaele Scientific Institute, Nuclear Medicine Unit, Milan (Italy); Berardi, G.; Fodor, A.; Di Muzio, N. [San Raffaele Scientific Institute, Radiotherapy Unit, Milan (Italy); Crivellaro, C. [San Gerardo Hospital, Nuclear Medicine Unit, Monza (Italy); Fiorino, C. [San Raffaele Scientific Institute, Medical Physics Unit, Milan (Italy); Kirienko, M. [University of Milano-Bicocca, Milan (Italy); Messa, C. [University of Milano-Bicocca, Milan (Italy); National Research Council (IBFM-CNR), Institute for Bioimaging and Molecular Physiology, Milan (Italy)

    2014-07-15

    To evaluate, in prostate cancer (PCa) patients the potential of {sup 11}C-choline PET/CT as a guide to helical tomotherapy (HTT) of lymph-node (LN) relapses with simultaneous integrated boost (SIB). The efficacy and feasibility of HTT in terms of acute toxicity were assessed. We enrolled 83 PCa patients (mean age 68 years, range 51 - 82 years) with biochemical recurrence after radical primary treatment (mean serum PSA 7.61 ng/ml, range 0.37 - 187.00 ng/ml; PSA{sub 0}) who showed pathological findings on {sup 11}C-choline PET/CT only at the LN site. {sup 11}C-Choline PET/CT was performed for restaging and then for radiation treatment planning (PET/CT{sub 0}). Of the 83 patients, 8 experienced further LN relapse, of whom 5 were retreated once and 3 were retreated twice (total 94 radiotherapy treatments). All pelvic and/or abdominal LNs positive on PET/CT{sub 0} were treated with high doses using SIB. Doses were in the range 36 - 74 Gy administered in 28 fractions. After the end of HTT (mean 83 days, range 16 - 365 days), serum PSA was measured in all patients (PSA{sub 1}) and compared with PSA{sub 0} to evaluate early biochemical response. In 47 patients PET/CT was repeated (PET/CT{sub 1}) to assess metabolic responses at the treated areas. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) were used to assess acute toxicity. PET/CT{sub 0} revealed pathological LNs in the pelvis in 49 patients, pathological LNs in the abdomen in 15 patients pathological LNs in both the pelvis and abdomen in 18 patients, and pathological LNs in the pelvis or abdomen and other sites in 12 patients. All these sites were treated with HTT. With respect to PSA{sub 0}, PSA{sub 1} (mean 6.28 ng/ml, range 0.00 - 220.46 ng/ml) showed a complete biochemical response after 66 of the 94 HTT treatments, a partial response after 12 treatments, stable disease after 1 treatment and progression of disease after 15 treatments. Of the 47 patients receiving PET/CT{sub 1}, 20 showed a

  18. Reduced-intensity stem-cell transplantation for adult acute lymphoblastic leukemia: a retrospective study of 33 patients.

    Science.gov (United States)

    Hamaki, T; Kami, M; Kanda, Y; Yuji, K; Inamoto, Y; Kishi, Y; Nakai, K; Nakayama, I; Murashige, N; Abe, Y; Ueda, Y; Hino, M; Inoue, T; Ago, H; Hidaka, M; Hayashi, T; Yamane, T; Uoshima, N; Miyakoshi, S; Taniguchi, S

    2005-03-01

    Efficacy of reduced-intensity stem-cell transplantation (RIST) for acute lymphoblastic leukemia (ALL) was investigated in 33 patients (median age, 55 years). RIST sources comprised 20 HLA-identical related donors, five HLA-mismatched related, and eight unrelated donors. Six patients had undergone previous transplantation. Disease status at RIST was first remission (n=13), second remission (n=6), and induction failure or relapse (n=14). All patients tolerated preparatory regimens and achieved neutrophil engraftment (median, day 12.5). Acute and chronic graft-versus-host disease (GVHD) developed in 45 and 64%, respectively. Six patients received donor lymphocyte infusion (DLI), for prophylaxis (n=1) or treatment of recurrent ALL (n=5). Nine patients died of transplant-related mortality, with six deaths due to GVHD. The median follow-up of surviving patients was 11.6 months (range, 3.5-37.3 months). The 1-year relapse-free and overall survival rates were 29.8 and 39.6%, respectively. Of the 14 patients transplanted in relapse, five remained relapse free for longer than 6 months. Cumulative rates of progression and progression-free mortality at 3 years were 50.9 and 30.4%, respectively. These findings suggest the presence of a graft-versus-leukemia effect for ALL. RIST for ALL is worth considering for further evaluation.

  19. 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.

  20. Atypical Presentation of PKDL due to Leishmania infantum in an HIV-Infected Patient with Relapsing Visceral Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Benedetto Maurizio Celesia

    2014-01-01

    Full Text Available We describe the case of an Italian patient with HIV infection who developed an atypical rash resembling post-kala-azar dermal leishmaniasis (PKDL when receiving liposomal Amphotericin B (L-AMB for secondary prophylaxis of visceral leishmaniasis (VL. At the time of PKDL appearance, the patient was virologically suppressed but had failed to restore an adequate CD4+ T-cell count. Histology of skin lesions revealed the presence of a granulomatous infiltrate, with lymphocytes, plasma cells, and macrophages, most of which contained Leishmania amastigotes. Restriction fragment length polymorphism-polymerase chain reaction was positive for Leishmania infantum. Paradoxically, cutaneous lesions markedly improved when a new relapse of VL occurred. The patient received meglumine antimoniate, with a rapid clinical response and complete disappearance of cutaneous rash. Unfortunately, the patient had several relapses of VL over the following years, though the interval between them has become wider after restarting maintenance therapy with L-AMB 4 mg/kg/day once a month. Even if rare, PKDL due to Leishmania infantum may occur in Western countries and represents a diagnostic and therapeutic challenge for physicians. The therapeutic management of both PKDL and VL in HIV infection is challenging, because relapses are frequent and evidence is often limited to small case series and case reports.

  1. Curative radio therapy in elderly patients with endometrial cancer. Patterns of relapse, toxicity and quality of life

    Energy Technology Data Exchange (ETDEWEB)

    Huguenin, P.; Baumert, B.; Luetolf, U.M.; Glanzmann, C. [Univ. Hospital Zuerich (Switzerland). Radiation Oncology; Wight, E. [Univ. Hospital Zuerich (Switzerland). Gynecologic Oncology

    1999-07-01

    Purpose: To assess survival, disease-specific survival, acute and late toxicity and quality of life in patients with curable endometrial carcinoma treated with adjuvant or primary radiotherapy at the age {>=}75 years. Patients and methods: In a prospective study, outcome was regularly assessed in 49 patients treated between 1991 and 1995 at a median age of 78.4 years. Radiotherapy was applied using the same concept as in younger patients. Thirty-eight patients received postoperative adjuvant radiotherapy (vaginal insertions only: n=18; external and vaginal insertions: n=17; external radiotherapy only: n=3), 8 patients were treated for a vaginal recurrence. Three patients received primary radiotherapy. Median pelvic dose was 39.6 Gy (ICRU) with 1.8 Gy per fraction (4 fields). Vaginal HDR radiotherapy consisted of 5 times 5 Gy at 0.5 cm depth in cases with no external radiotherapy, and of 3 times 5 Gy in addition to pelvic radiotherapy, respectively. Median follow-up was 3.2 years. The EORTC QLQ-C30 was used for self-assessment of quality of life. Results: Survival and disease-specific survival at 5 years was 64% and 84%, respectively. There was no pelvic or vaginal recurrence in patients with Stage IA to IIB. Patients with positive adnexa and those treated for vaginal recurrence relapsed in 50%. Two patients (4%) did not complete radiotherapy because of severe diarrhea. Grade 4 late complications were observed in 1/38 patients following adjuvant radiotherapy and in 2/8 patients treated for a recurrence. The actuarial rate of Grade 3 to 4 complications was 7% at 3 years. Quality of life was good in most cases and remained constant over time. (orig.) [Deutsch] Ziel: Analyse des Gesamtueberlebens, des tumorspezifischen Ueberlebens, der pelvinen Tumorkontrolle, der Akut- und Spaettoxizitaet sowie der Lebensqualitaet bei Patientinnen, die mit 75 oder mehr Jahren wegen eines Karzinoms des Corpus uteri mit kurativem Ziel bestrahlt wurden. Patienten und Methode: Zwischen

  2. Methotrexate Reduces the Incidence of Severe Acute Graft-versus-Host Disease without Increasing the Risk of Relapse after Reduced-Intensity Allogeneic Stem Cell Transplantation from Unrelated Donors.

    Science.gov (United States)

    Vigouroux, Stéphane; Tabrizi, Reza; Melot, Cyril; Coiffard, Joelle; Lafarge, Xavier; Marit, Gérald; Bouabdallah, Krimo; Pigneux, Arnaud; Leguay, Thibaut; Dilhuydy, Marie-Sarah; Schmitt, Anna; Boiron, Jean-Michel; Milpied, Noël

    2011-01-01

    Optimized prophylaxis against graft-versus-host disease (GVHD) after unrelated reduced-intensity allogeneic transplantation when preceded by a conditioning regimen utilizing antithymocyte globulin (ATG) is poorly defined. To investigate the effects of methotrexate (MTX) in this treatment setting, we conducted a retrospective analysis. Sixty-three patients were selected based on the administration of a total dose of 5 mg/kg of ATG in the conditioning regimen and then separated into either group M+ (n = 39), which received MTX or group M- (n = 24), which did not. All patients received cyclosporine. In the M- and M+ groups, cumulative incidences (CI) of grade III-IV acute GVHD (aGVHD) were 43% and 10%, respectively (P = .002). Multivariate analysis indicated that grade III-IV aGVHD was favored by both the absence of MTX and the provision of a female donor for a male recipient. At 2 years, the M+ and M- groups exhibited, respectively: overall survival of 69% and 40% (P = .06), disease-free survival of 57% and 43% (P = .2), nonrelapse mortality of 20% and 44% (P = .1), and incidence of relapse of 27% and 35% (P = .6). These data suggest that MTX reduces the incidence of severe aGVHD without increasing the risk of relapse but with an accompanying trend toward improved survival after unrelated reduced-intensity transplantation with ATG in the conditioning regimen.

  3. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Hubert Y. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morani, Ajaykumar [Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang, Wei-Lien [Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hess, Kenneth R. [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Paulino, Arnold C. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ludwig, Joseph A. [Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Patrick P. [Department of Orthopedic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Daw, Najat C. [Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mahajan, Anita, E-mail: amahajan@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-06-01

    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

  5. BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

    Science.gov (United States)

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  6. Acute Exercise Enhances the Consolidation of Fear Extinction Memory and Reduces Conditioned Fear Relapse in a Sex-Dependent Manner

    Science.gov (United States)

    Bouchet, Courtney A.; Lloyd, Brian A.; Loetz, Esteban C.; Farmer, Caroline E.; Ostrovskyy, Mykola; Haddad, Natalie; Foright, Rebecca M.; Greenwood, Benjamin N.

    2017-01-01

    Fear extinction-based exposure therapy is the most common behavioral therapy for anxiety and trauma-related disorders, but fear extinction memories are labile and fear tends to return even after successful extinction. The relapse of fear contributes to the poor long-term efficacy of exposure therapy. A single session of voluntary exercise can…

  7. Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia

    NARCIS (Netherlands)

    J. Irving (Julie); A. Enshaei; Parker, C.A. (Catriona A.); R. Sutton; R. Kuiper (Ruud); Erhorn, A. (Amy); L. Minto (L.); N. Venn; T. Law (T.); Yu, J. (Jiangyan); C. Schwab (Claire); Davies, R. (Rosanna); Matheson, E. (Elizabeth); Davies, A. (Alysia); E. Sonneveld (Edwin); M.L. den Boer (Monique); Love, S.B. (Sharon B.); C.J. Harrison (Christine); P.M. Hoogerbrugge (Peter); T. Revesz (Tamas); V. Saha (Vaskar); A.V. Moorman (Anthony)

    2016-01-01

    textabstractSomatic genetic abnormalities are initiators and drivers of disease and have proven clinical utility at initial diagnosis. However, the genetic landscape and its clinical utility at relapse are less well understood and have not been studied comprehensively. We analyzed cytogenetic data f

  8. Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Irving, J.A.; Enshaei, A.; Parker, C.A.; Sutton, R.; Kuiper, R.P.; Erhorn, A.; Minto, L.; Venn, N.C.; Law, T.; Yu, J.; Schwab, C.; Davies, R.; Matheson, E.; Davies, A.; Sonneveld, E.; Boer, M.L. Den; Love, S.B.; Harrison, C.J.; Hoogerbrugge, P.M.; Revesz, T.; Saha, V.; Moorman, A.V.

    2016-01-01

    Somatic genetic abnormalities are initiators and drivers of disease and have proven clinical utility at initial diagnosis. However, the genetic landscape and its clinical utility at relapse are less well understood and have not been studied comprehensively. We analyzed cytogenetic data from 427 chil

  9. VDR and CYP24A1 Expression Analysis in Iranian Relapsing-Remitting Multiple Sclerosis Patients.

    Science.gov (United States)

    Sadeghi, Hashem; Taheri, Mohammad; Sajadi, Elham; Movafagh, Abolfazl; Arsang Jang, Shahram; Sayad, Arezou

    2017-10-01

    Multiple sclerosis (MS) is a common disease of the central nervous system.This disease may be initiated by either vitamin deficiency or triggered by abnormality in CYP24A1 and vitamin D receptor. In this case-control study, the expression of genes encoding vitamin D receptor (VDR) and CYP24A1 in relapsing-remitting MS (RR-MS) patients was compared with normal individuals in the Iranian population. RNA from whole blood of 50 RR-MS patients (HLA-DRB1*15-negative and responders to interferonbeta with a normal vitamin D level) and 50 normal controls was extracted. The levels of CYP24A1 and VDR expression were measured using real-time quantitative polymerase chain reaction. The RR-MS group had a significantly more than 2 times higher expression level of VDR than the normal group (P=0.04). On the other hand, there was a 0.89 times decrease in the expression level of CYP24A1 in RR-MS patients which was not statistically significant. There was no linear correlation between the risk of expanded disability status scale of Kurtzke (EDSS) and the expression level of either CYP24A1 or VDR. In addition, the expression level of CYP24A1 or VDR was not correlated with the duration of the disease. Up-regulation of VDR is likely to happen in RR-MS patients in the Iranian population. We did not observe a gene expression-phenotype correlation for CYP24A1 which may be due to limited statistical power as a result of the small sample size. Although the individuals taking part in this study had normal levels of vitamin D, the increase in VDR expression levels may perhaps be a response to a defect in vitamin D processing. Another possibility is that despite an increase in VDR expression level, factors such as micro-RNAs may result in their deactivation while an increase in VDR expression level can be seen as a compensatory response. Of course, further studies are required to identify the mechanism of action of vitamin D by analyzing genes involved in its signaling pathway, particularly VDR

  10. Pharmacokinetics and excretion of 14C-bendamustine in patients with relapsed or refractory malignancy.

    Science.gov (United States)

    Dubbelman, Anne-Charlotte; Rosing, Hilde; Darwish, Mona; D'Andrea, Denise; Bond, Mary; Hellriegel, Edward; Robertson, Philmore; Beijnen, Jos H; Schellens, Jan H M

    2013-03-01

    Bendamustine is an alkylating agent with clinical activity against a variety of hematologic malignancies and solid tumors. To assess the roles of renal and hepatic drug elimination pathways in the excretion and metabolism of bendamustine, a mass balance study was performed in patients with relapsed or refractory malignancies. A single 60-minute intravenous dose of 120 mg/m(2), 80-95 μCi (14)C-bendamustine hydrochloride was administered to six patients, followed by collection of blood, urine, and fecal samples at specified time points up to day 8 or until the radioactivity of the 24-hour urine and fecal collections was below 1% of the administered dose (whichever was longer). Total radioactivity (TRA) was measured in all samples, and concentrations of unchanged bendamustine and its metabolites γ-hydroxy-bendamustine (M3), N-desmethyl-bendamustine (M4), and dihydroxy bendamustine (HP2) were determined in plasma and urine, using validated liquid chromatography-tandem mass spectrometry methods. The mean recovery of TRA in excreta was 76% of the radiochemical dose. Approximately half of the administered dose was recovered in urine and a quarter in feces. Less than 5% of the administered dose was recovered in urine as unchanged bendamustine. Bendamustine clearance from plasma was rapid, with a half-life of ~40 minutes. Plasma concentrations of M3, M4, and HP2 were very low relative to bendamustine concentrations. Plasma levels of TRA were higher and more sustained as compared with plasma concentrations of bendamustine, M3, M4, and HP2, suggesting the presence of one or more longer-lived (14)C-bendamustine-derived compounds. Fatigue (50%) and vomiting (50%) were the most frequent treatment-related adverse events. A grade 3/4 absolute lymphocyte count decrease occurred in all patients at some point during the study. Bendamustine is extensively metabolized, with subsequent excretion in both urine and feces. Accumulation of bendamustine is not anticipated in cancer

  11. 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.

  12. Lymphoproliferative response after stimulation with soluble leishmania antigen (SLA) as a predictor of visceral leishmaniasis (VL) relapse in HIV+ patients.

    Science.gov (United States)

    Castro, Alicia; Carrillo, Eugenia; San Martín, Juan V; Botana, Laura; Molina, Laura; Matía, Belén; Fernandez, Laura; Horrillo, Luis; Ibarra-Meneses, Ana; Sanchez, Carmen; Ruiz-Giardin, Jose M; Moreno, Javier

    2016-12-01

    The introduction of HAART resulted in the decrease of Leishmania/HIV co-infection cases; nevertheless, the number of relapses remains high and secondary prophylaxis is recommended. However, secondary prophylaxis is not necessary in all patients, and presents a high risk of toxicity and an elevated cost. Our aim was to study whether specific cellular response to Leishmania infantum (measured by cell proliferation response after stimulation with soluble Leishmania antigen (SLA)), could be a useful tool to attempt a secondary prophylaxis withdrawal. In June 2009 an outbreak of leishmaniasis by Leishmania infantum was declared in the southeast of Madrid, and since January 2013, we recruited 10 HIV+ patients that had been treated for visceral leishmaniasis. 6 patients had positive SLA-cell proliferation test. The mean CD4 cell counts of those patients with positive SLA were 140 cel/mm3 and 40 cel/mm3 in those with negative SLA test. 3 patients with positive SLA-cell proliferation test (CD4 count: 336, 307, 625) were not on prophylaxis, and the other 3 patients (CD4 count: 152, 189, 359) were on secondary prophylaxis that was withdrawn after the positive SLA-cell proliferation test with no posterior relapses (mean follow up 60 weeks). From the 4 patients, which had negative SLA-cell proliferation test and continued on prophylaxis, 3 had positive PCR for Leishmania at the end of the follow-up and 2 presented clinical relapses. The performance of SLA-cell proliferation test can be a useful tool that can permit us to try withdrawal of the prophylaxis in Leishmania/HIV co-infected patients with low CD4(+) counts under clinical supervision, diminishing risk of toxicity and cost. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  13. 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.

  14. 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

  15. 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.

  16. Relapse of visceral leishmaniasis in an HIV-infected patient successfully treated with a combination of miltefosine and amphotericin B.

    Science.gov (United States)

    McQuarrie, Shauna; Kasper, Ken; Moffatt, Dana C; Marko, Daniel; Keynan, Yoav

    2015-01-01

    The present report documents a 49-year-old HIV-infected man receiving antiretroviral therapy with a suboptimal immune response and a CD4 count of 95 cells/mm(3), despite virological suppression. Investigation of bone marrow was conducted and yielded a diagnosis of visceral leishmaniasis. The clinical course was complicated by gastrointestinal involvment and relapse occurred after amphotericin B therapy. With the addition of miltefosine, the patient no longer presented with bone marrow amastigotes, and displayed an increased CD4 count and negative Leishmania polymerase chain reaction results. The present case highlights atypical presentation of visceral leishmaniasis, including poor immune reconstitution and gastrointestinal involvement. The high likelihood of relapse and response to combination therapy are illustrated.

  17. Relapse of Visceral Leishmaniasis in an HIV-Infected Patient Successfully Treated with a Combination of Miltefosine and Amphotericin B

    Directory of Open Access Journals (Sweden)

    Shauna McQuarrie

    2015-01-01

    Full Text Available The present report documents a 49-year-old HIV-infected man receiving antiretroviral therapy with a suboptimal immune response and a CD4 count of 95 cells/mm3, despite virological suppression. Investigation of bone marrow was conducted and yielded a diagnosis of visceral leishmaniasis. The clinical course was complicated by gastrointestinal involvment and relapse occurred after amphotericin B therapy. With the addition of miltefosine, the patient no longer presented with bone marrow amastigotes, and displayed an increased CD4 count and negative Leishmania polymerase chain reaction results. The present case highlights atypical presentation of visceral leishmaniasis, including poor immune reconstitution and gastrointestinal involvement. The high likelihood of relapse and response to combination therapy are illustrated.

  18. 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....

  19. Pharmacokinetics and safety of ixazomib plus lenalidomide-dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study

    National Research Council Canada - National Science Library

    Gupta, Neeraj; Goh, Yeow Tee; Min, Chang-Ki; Lee, Jae Hoon; Kim, Kihyun; Wong, Raymond S M; Chim, Chor Sang; Hanley, Michael J; Yang, Huyuan; Venkatakrishnan, Karthik; Hui, Ai-Min; Esseltine, Dixie-Lee; Chng, Wee Joo

    2015-01-01

    ...) in combination with lenalidomide-dexamethasone. This study was conducted to investigate the pharmacokinetic and safety profiles of ixazomib, administered with lenalidomide-dexamethasone, in East Asian patients with relapsed/refractory MM...

  20. Doctors’ views of disulfiram and their response to relapse in alcohol-dependent patients, Free State, 2009

    Directory of Open Access Journals (Sweden)

    Paulina M. van Zyl

    2016-03-01

    Full Text Available Background: Disulfiram is the oldest and best known drug to prevent relapse after detoxification from alcohol. Effective use of the drug is dependent on stringent monitoring and high levels of external motivation. Doctors’ perceptions about the drug have not been investigated extensively.Aim: We investigated the perceptions and practices of doctors involved in relapse prevention in alcoholics with regard to disulfiram and their response to relapse.Setting: The study population consisted of 60 doctors from the Free State Province, involved in the follow-up of alcoholics across various work settings.Methods: A cross-sectional descriptive study design was used, and data collection involved the use of a questionnaire and semi-structured interviews. Quantitative results are presented in figures and percentages to provide a background for the qualitative findings that are clustered in themes.Results: A quarter of participants did not prescribe disulfiram, another quarter prescribed disulfiram routinely after detoxification, and half of them prescribed it for selected cases only. Subject to affordability, selection of disulfiram was mainly determined by the perceived level of the patient’s motivation. External motivation sometimes took the form of threats of bodily harm or death caused by drinking. Some participants regarded relapse as confirmation of poor motivation and even a valid reason for terminating the doctor-patient relationship.Conclusion: Doctors perceive disulfiram as a psychological tool to induce motivation through creating fear of drinking. Failure and success are perceived as related to the level of motivation. These perceptions could be unfair as biological factors in inter-patient variability in response are ignored.

  1. Doctors’ views of disulfiram and their response to relapse in alcohol-dependent patients, Free State, 2009

    Science.gov (United States)

    2016-01-01

    Background Disulfiram is the oldest and best known drug to prevent relapse after detoxification from alcohol. Effective use of the drug is dependent on stringent monitoring and high levels of external motivation. Doctors’ perceptions about the drug have not been investigated extensively. Aim We investigated the perceptions and practices of doctors involved in relapse prevention in alcoholics with regard to disulfiram and their response to relapse. Setting The study population consisted of 60 doctors from the Free State Province, involved in the follow-up of alcoholics across various work settings. Methods A cross-sectional descriptive study design was used, and data collection involved the use of a questionnaire and semi-structured interviews. Quantitative results are presented in figures and percentages to provide a background for the qualitative findings that are clustered in themes. Results A quarter of participants did not prescribe disulfiram, another quarter prescribed disulfiram routinely after detoxification, and half of them prescribed it for selected cases only. Subject to affordability, selection of disulfiram was mainly determined by the perceived level of the patient’s motivation. External motivation sometimes took the form of threats of bodily harm or death caused by drinking. Some participants regarded relapse as confirmation of poor motivation and even a valid reason for terminating the doctor-patient relationship. Conclusion Doctors perceive disulfiram as a psychological tool to induce motivation through creating fear of drinking. Failure and success are perceived as related to the level of motivation. These perceptions could be unfair as biological factors in inter-patient variability in response are ignored. PMID:27380787

  2. Altered activity of plasma hemopexin in patients with minimal change disease in relapse

    NARCIS (Netherlands)

    Bakker, WW; van Dael, CML; Pierik, LJWM; van Wijk, JAE; Nauta, J; Borghuis, T; Kapojos, JJ

    2005-01-01

    Since an active isoform of plasma hemopexin (Hx) has been proposed to be a potential effector molecule in minimal change disease (MCD), we tested plasma and urine samples from subjects with MCD in relapse (n =18) or in remission (n =23) (after treatment with prednisolone) for presence or activity of

  3. Pattern of follow-up care and early relapse detection in breast cancer patients

    NARCIS (Netherlands)

    Geurts, S.M.E.; Vegt, de F.; Siesling, S.; Flobbe, K.; Aben, K.K.H.; Heiden-van der Loo, van der M.; Verbeek, A.L.M.; Dijck, van J.A.A.M.; Tjan-Heijnen, V.C.G.

    2012-01-01

    Routine breast cancer follow-up aims at detecting second primary breast cancers and loco regional recurrences preclinically. We studied breast cancer follow-up practice and mode of relapse detection during the first 5 years of follow-up to determine the efficiency of the follow-up schedule. The Neth

  4. Review article: the association of diet with onset and relapse in patients with inflammatory bowel disease

    NARCIS (Netherlands)

    Spooren, C.E.G.M.; Pierik, M.; Zeegers, M.P.A.; Feskens, E.J.M.; Masclee, A.A.M.

    2013-01-01

    Background The role of diet in inflammatory bowel disease (IBD) is supported by migration studies and increasing incidences in line with Westernisation. Aim To give a complete overview of studies associating habitual diet with the onset or relapses in ulcerative colitis (UC) or Crohn's disease (CD).

  5. A single high dose of idarubicin combined with high-dose ARA-C for treatment of first relapse in childhood 'high-risk' acute lymphoblastic leukaemia: a study of the AIEOP group.

    Science.gov (United States)

    Testi, Anna Maria; Del Giudice, Ilaria; Arcese, William; Moleti, Maria Luisa; Giona, Fiorina; Basso, Giuseppe; Biondi, Andrea; Conter, Valentino; Messina, Chiara; Rondelli, Roberto; Micozzi, Alessandra; Micalizzi, Concetta; Barisone, Elena; Locatelli, Franco; Dini, Giorgio; Aricò, Maurizio; Casale, Fiorina; Comis, Margherita; Ladogana, Saverio; Lippi, Alma; Mura, Rossella; Pinta, Marie France; Santoro, Nicola; Valsecchi, Maria Grazia; Masera, Giuseppe; Mandelli, Franco

    2002-09-01

    The outcome of children with acute lymphoblastic leukaemia (ALL) and early relapse remains unsatisfactory. In January 1995, the AIEOP (Associazione Italiana di Oncologia ed Ematologia Pediatrica) group opened a trial for children with ALL in first isolated or combined bone marrow relapse defined at high risk according to the length of first remission and the immunophenotype. The treatment plan included the combination of a single high-dose idarubicin and high-dose cytarabine as induction therapy followed by an intensive consolidation and stem cell transplant (SCT). In total, 100 children from 16 Italian centres were enrolled; 80 out of the 99 evaluable patients (81%) achieved second complete remission; eight (8%) died during induction and 11 (11%) failed to respond. A total of 42 out of the 80 responders (52.5%) received a SCT: 19 from an identical sibling, 11 from a matched unrelated donor and 12 from umbilical cord blood cells. The estimated 4-year overall survival and event-free survival were 25% and 21% respectively. Disease-free survival at 4 years was 25.8% for the 80 responders. At 4 years, 39 out of 100 children remain alive, with 27 of them free of leukaemia. This induction therapy has shown antileukaemic efficacy with acceptable toxicity; moreover, all responders proved eligible for intensive consolidation.

  6. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2012-09-01

    al., “The effects of induced hypogonadism on arterial stiffness , body composi- tion, and metabolic parameters in males with prostate cancer ,” The...Phase 2 Trial of 177Lu Radiolabeled Monoclonal Antibody J591in Patients with High-Risk Castrate Biochemically Relapsed Prostate Cancer PRINCIPAL...NUMBER in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer 5b. GRANT NUMBER W81XWH-09-1-0596 5c. PROGRAM ELEMENT NUMBER

  7. Acute portal vein thrombosis due to chronic relapsing pancreatitis: a fistula between a pancreatic pseudocyst and the splenic vein.

    Science.gov (United States)

    Kikuchi, Masahiro; Nishizaki, Yasuhiro; Tsuruya, Kota; Hamada, Ikuko; Higashi, Toru; Sakuma, Keiko; Shiozawa, Hirokazu; Aoki, Jun; Nagashima, Rena; Koizumi, Jun; Arase, Yoshitaka; Shiraishi, Koichi; Matsushima, Masashi; Mine, Tetsuya

    2014-02-01

    Portal vein thrombosis (PVT) is a relatively common complication in patients with liver cirrhosis, but several other causes might play an important role in PVT pathogenesis. We present a case of alcoholic chronic pancreatitis complicated by acute extensive PVT. The patient was managed conservatively with danaparoid sodium at first, but the thrombosis gradually extended. We then tried radiological intervention using the direct transhepatic and transjugular intrahepatic postsystemic shunt approaches. Although we were able to successfully catheterize the percutaneous transhepatic portal vein (PTP), we could not achieve recanalization of the portal vein. Therefore, PTP catheterization and systemic intravenous infusion of urokinase and heparin was performed to prevent further progression of the thrombosis and cavernous transformation was finally achieved. Computed tomography (CT) and magnetic resonance cholangiopancreatography revealed a pancreatic stone which had possibly induced dilatation of the tail duct and formation of a pancreatic pseudocyst and caused intractable pancreatitis. We performed endoscopic retrograde cholangiopancreatography and placed a stent in the pancreatic duct, which completely cured the pancreatitis. Retrospectively, the previous CT with curved multi-planar reconstruction was reviewed and a fistula was detected between the pancreatic pseudocyst and splenic vein. We concluded that the etiology of the PVT was not only inflammatory extension from pancreatitis but also a fistula between the pancreatic duct and the splenic vein.

  8. Extended intrathecal methotrexate may replace cranial irradiation for prevention of CNS relapse in children with intermediate-risk acute lymphoblastic leukemia treated with Berlin-Frankfurt-Münster-based intensive chemotherapy. The Associazione Italiana di Ematologia ed Oncologia Pediatrica.

    Science.gov (United States)

    Conter, V; Aricò, M; Valsecchi, M G; Rizzari, C; Testi, A M; Messina, C; Mori, P G; Miniero, R; Colella, R; Basso, G

    1995-10-01

    To assess the effect of treatment intensification and that of extended intrathecal methotrexate substitution for cranial irradiation in intermediate-risk acute lymphoblastic leukemia (ALL) children treated with a Berlin-Frankfurt-Münster (BFM)-based intensive chemotherapy. Three hundred ninety-six children with non-B-ALL were enrolled onto the Associazione Italiana di Ematologia ed Oncologic Pediatrica (AIEOP) ALL 88 study. Standard risk (SR) included patients with low tumor burden (BFM risk index [RI], or = 0.8 but less than 1.2; and high risk (HR) were those with an RI > or = 1.2 or CNS involvement at diagnosis. The treatment schedule was a modified version of the ALL-BFM 86 study. CNS-directed treatment consisted of high-dose methotrexate (HD-MTX; 5 g/m2 for four courses) plus intrathecal methotrexate (IT-MTX; nine doses); IR patients additionally received extended IT-MTX (nine doses during continuation therapy); cranial irradiation was given only to HR patients. Of the 375 (94.7%) children who achieved remission, 1.3% had an adverse event other than relapse. The estimated event-free survival (EFS) at 6 years was 66.6% (SE 2.4) overall; 80.7% (4.5) in the SR patients, 77.5% (3.9) in the IR patients, and 54.5% (3.7) in the HR patients. Relapse occurred in 107 children (27.0%). Isolated CNS relapse occurred in 20 children (5.0%): 5 (6.3%) in the SR group, 1 (0.8%) in the IR group, and 14 (7.1%) in the HR group. The estimated 6-year CNS leukemia-free survival was 94.6% (1.2) overall: 93.5% (2.8) in the SR group, 99.1% (0.9) in the IR group, and 92.3% (2.0) in the HR group. Cranial irradiation may be omitted safely in IR ALL patients treated with BFM-based intensive chemotherapy when extended intrathecal chemotherapy is given. Because the CNS disease control was less complete in the SR group, these data challenge the effectiveness of HD-MTX for protection from CNS disease and support the protective role of extended intrathecal chemotherapy.

  9. Fas and Bcl-2 Expression on T Lymphocyte Subsets in the Peripheral Blood of Relapsing Patients with Condyloma Acuminatum

    Institute of Scientific and Technical Information of China (English)

    顾军; 范清源; 高春芳; 代夫; 郑茂荣

    2003-01-01

    Objective: To study the expression of Fas and Bcl-2 proteins on T lymphocyte subsets in the peripheral blood of relapsing patients with condyloma acuminatum(CA) and healthy controls.Methods: Flow cytometry (permeabization and staining procedure with conjugated antibodies) was used.Results: We observed that the expression of Fas protein on CD4+ T lymphocyte subset of CA patients was significantly higher than that of healthy controls( P<0.01 ).Conclusions: Increased expression of Fas proteinon CD4+ T lymphocyte subset may be a cause of de-creased percentage of CD4+ T lymphocyte subset. This induces the increased ratio of CD4+/CD8+.

  10. A Randomized Phase II Study of Linsitinib (OSI-906) Versus Topotecan in Patients With Relapsed Small-Cell Lung Cancer

    Science.gov (United States)

    Otterson, Gregory A.; Dowlati, Afshin; Traynor, Anne M.; Horn, Leora; Owonikoko, Taofeek K.; Ross, Helen J.; Hann, Christine L.; Abu Hejleh, Taher; Nieva, Jorge; Zhao, Xiuhua; Schell, Michael; Sullivan, Daniel M.

    2016-01-01

    Lessons Learned Targeted therapy options for SCLC patients are limited; no agent, thus far, has resulted in a strategy promising enough to progress to phase III trials. Linsitinib, a potent insulin growth factor-1-receptor tyrosine kinase inhibitor, may be one agent with activity against SCLC. Despite lack of a reliable predictive biomarker in this disease, which may have partly contributed to the negative outcome reported here, linsitinib, although safe, showed no clinical activity in unselected, relapsed SCLC patients. Background. Treatment of relapsed small-cell lung cancer (SCLC) remains suboptimal. Insulin growth factor-1 receptor (IGF-1R) signaling plays a role in growth, survival, and chemoresistance in SCLC. Linsitinib is a potent IGF-1R tyrosine kinase inhibitor that potentially may be active against SCLC. Methods. In this phase II study, 8 eligible patients were randomly assigned in a 1:2 ratio to topotecan (1.5 mg/m2 intravenously or 2.3 mg/m2 orally, daily for 5 days for 4 cycles) or linsitinib (150 mg orally twice daily until progression). The primary endpoint was progression-free survival. Patients with relapsed SCLC, platinum sensitive or resistant, performance status (PS) 0–2, and adequate hematologic, renal, and hepatic function were enrolled. Patients with diabetes, cirrhosis, and those taking insulinotropic agents were excluded. Crossover to linsitinib was allowed at progression. Results. Fifteen patients received topotecan (8 resistant, 3 with PS 2) and 29 received linsitinib (16 resistant, 5 with PS 2). Two partial responses were observed with topotecan. Only 4 of 15 patients with topotecan and 1 of 29 with linsitinib achieved stable disease. Median progression-free survival was 3.0 (95% confidence interval [CI], 1.5–3.6) and 1.2 (95% CI, 1.1–1.4) months for topotecan and linsitinib, respectively (p = .0001). Median survival was 5.3 (95% CI, 2.2–7.6) and 3.4 (95% CI, 1.8–5.6) months for topotecan and linsitinib, respectively (p = .71

  11. Successful treatment of post-transplant relapsed acute myeloid leukemia with FLT3 internal tandem duplication using the combination of induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine. Report of three cases.

    Science.gov (United States)

    Campregher, Paulo Vidal; Mattos, Vinicius Renan Pinto de; Salvino, Marco Aurélio; Santos, Fabio Pires de Souza; Hamerschlak, Nelson

    2017-07-24

    Acute myeloid leukemia is a hematopoietic stem cell neoplastic disease associated with high morbidity and mortality. The presence of FLT3 internal tandem duplication mutations leads to high rates of relapse and decreased overall survival. Patients with FLT3 internal tandem duplication are normally treated with hematopoietic stem cell transplantation in first complete remission. Nevertheless, the incidence of post-transplant relapse is considerable in this group of patients, and the management of this clinical condition is challenging. The report describes the outcomes of patients with FLT3 internal tandem duplication positive acute myeloid leukemia who relapsed after allogeneic hematopoietic stem cell transplantation and were treated with the combination of re-induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine. Three cases are described and all patients achieved prolonged complete remission with the combined therapy. The combination of induction chemotherapy followed by donor lymphocyte infusion, and the maintenance with azacitidine and sorafenib can be effective approaches in the treatment of post-hematopoietic stem cell transplant and relapsed FLT3 internal tandem duplication positive acute myeloid leukemia patients. This strategy should be further explored in the context of clinical trials. RESUMO A leucemia mieloide aguda é uma doença neoplásica de células-tronco hematopoiéticas com alta morbimortalidade. A presença de mutações de duplicação em tandem de FLT3 leva a altas taxas de recorrência e a menor sobrevida global. Os pacientes com duplicação em tandem de FLT3 são normalmente tratados com transplante de células-tronco hematopoiéticas na primeira remissão completa. No entanto, a incidência de recidiva pós-transplante é considerável neste grupo de pacientes, e a conduta, nestes casos, é um desafio. O relato descreve os resultados do tratamento de pacientes com leucemia mieloide aguda positiva e duplicação em

  12. Lamivudine plus adefovir is a good option for chronic hepatitis B patients with viral relapse after cessation of lamivudine treatment

    Directory of Open Access Journals (Sweden)

    Zhang Yong

    2011-08-01

    Full Text Available Abstract Aim Currently, there is no consensus on the retreatment recommendation of chronic hepatitis B (CHB patients with viral rebound after cessation of treatment. In the search of reasonable treatment, we compared the efficacy and safety of adefovir (ADV plus lamivudine (LAM and LAM alone for the retreatment of patients with viral relapse but without genotypic resistance after cessation of LAM. Methods This is a prospective controlled study, and a total of 53 hepatitis B e antigen (HBeAg-positive patients with viral rebound but without resistance were received either LAM plus ADV or LAM alone treatment. Results After 1-year treatment, more patients who received LAM plus ADV than those who received LAM alone had ALT normalization (84% versus 53.6%, P = 0.018 or HBV DNA levels below 1000 copies/mL (80% versus 42.9%, P Conclusions Patients treated with LAM plus ADV exhibited significantly greater virological, biochemical and serological responses compared with LAM alone. These data suggested that combination of LAM plus ADV would be a good option for the retreatment of CHB patients with viral relapse after cessation of LAM.

  13. Nuclear corepressor 1 expression predicts response to first-line endocrine therapy for breast cancer patients on relapse

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhen-huan; Hiroko Yamashita; Tatsuya Toyama; Yutaka Yamamoto; Teru Kawasoe; Mutsuko Ibusuki; Saori Tomita; Hiroshi Sugiura; Shunzo Kobayashi; Yoshitaka Fujii; Hirotaka Iwase

    2009-01-01

    Background Estrogen receptor alpha(ER a)is the most important endocrine therapy responsiveness predictor for women with breast cancer.The accuracy of the prediction of the response to endocrine therapy was thought to be affected by involving the estrogen receptor coregulatory proteins and cross-talk between ER and other growth factor-signaling networks.Nuclear corepressor 1(NCOR1)is one of the ERa transcription repressor.The objective of the study is to investigate the expression of NCOR1 at the protein level and pursue its predictive value for breast cancer endocrine therapy.Methods In the present study,the level of expression of NCOR1 protein has been assessed by immunohistochemistry in 104 cases of invasive carcinoma of the breast.Associations between NCOR1 protein expression and different clinicopathological factors and survival were sought.Results It was found that NCOR1 was expressed at significantly higher levels in responsive patients treated with endocrine therapy as first-line treatment on relapse.Responsive patients also had a significantly longer post-relapse survival and overall survival.No NCOR1 expression difference was found between patient by age,tumor size,lymph node status,different histological grade groups and human epidermal growth factor receptor 2(HER2)status.Multivariate analysis showed that NCOR1 is an independent prognostic factor for over-all survival.Conclusions In breast cancer,NCOR1 protein expression level predicts response to endocrine therapy as first-line treatment for breast cancer patients on relapse and NCOR1 protein level assay may increase the accuracy in the endocrine treatment determination and,therefore,improving the patients survival.

  14. Anti-inflammatory nutritional intervention in patients with relapsing-remitting and primary-progressive multiple sclerosis: A pilot study.

    Science.gov (United States)

    Riccio, Paolo; Rossano, Rocco; Larocca, Marilena; Trotta, Vincenzo; Mennella, Ilario; Vitaglione, Paola; Ettorre, Michele; Graverini, Antonio; De Santis, Alessandro; Di Monte, Elisabetta; Coniglio, Maria Gabriella

    2016-03-01

    The aim of this work was to assess the influence of nutritional intervention on inflammatory status and wellness in people with multiple sclerosis. To this end, in a seven-month pilot study we investigated the effects of a calorie-restricted, semi-vegetarian diet and administration of vitamin D and other dietary supplements (fish oil, lipoic acid, omega-3 polyunsaturated fatty acids, resveratrol and multivitamin complex) in 33 patients with relapsing-remitting multiple sclerosis and 10 patients with primary-progressive multiple sclerosis. At 0/3/6 months, patients had neurological examination, filled questionnaires and underwent anthropometric measurements and biochemical analyses. Serum fatty acids and vitamin D levels were measured as markers of dietary compliance and nutritional efficacy of treatment, whereas serum gelatinase levels were analyzed as markers of inflammatory status. All patients had insufficient levels of vitamin D at baseline, but their values did not ameliorate following a weekly administration of 5000  IU, and rather decreased over time. Conversely, omega-3 polyunsaturated fatty acids increased already after three months, even under dietary restriction only. Co-treatment with interferon-beta in relapsing-remitting multiple sclerosis was irrelevant to vitamin D levels. After six months nutritional treatment, no significant changes in neurological signs were observed in any group. However, serum levels of the activated isoforms of gelatinase matrix metalloproteinase-9 decreased by 59% in primary-progressive multiple sclerosis and by 51% in relapsing-remitting multiple sclerosis patients under nutritional intervention, including dietary supplements. This study indicates that a healthy nutritional intervention is well accepted by people with multiple sclerosis and may ameliorate their physical and inflammatory status.

  15. Anti-inflammatory nutritional intervention in patients with relapsing-remitting and primary-progressive multiple sclerosis: A pilot study

    Science.gov (United States)

    Rossano, Rocco; Larocca, Marilena; Trotta, Vincenzo; Mennella, Ilario; Vitaglione, Paola; Ettorre, Michele; Graverini, Antonio; De Santis, Alessandro; Di Monte, Elisabetta; Coniglio, Maria Gabriella

    2016-01-01

    The aim of this work was to assess the influence of nutritional intervention on inflammatory status and wellness in people with multiple sclerosis. To this end, in a seven-month pilot study we investigated the effects of a calorie-restricted, semi-vegetarian diet and administration of vitamin D and other dietary supplements (fish oil, lipoic acid, omega-3 polyunsaturated fatty acids, resveratrol and multivitamin complex) in 33 patients with relapsing-remitting multiple sclerosis and 10 patients with primary-progressive multiple sclerosis. At 0/3/6 months, patients had neurological examination, filled questionnaires and underwent anthropometric measurements and biochemical analyses. Serum fatty acids and vitamin D levels were measured as markers of dietary compliance and nutritional efficacy of treatment, whereas serum gelatinase levels were analyzed as markers of inflammatory status. All patients had insufficient levels of vitamin D at baseline, but their values did not ameliorate following a weekly administration of 5000  IU, and rather decreased over time. Conversely, omega-3 polyunsaturated fatty acids increased already after three months, even under dietary restriction only. Co-treatment with interferon-beta in relapsing-remitting multiple sclerosis was irrelevant to vitamin D levels. After six months nutritional treatment, no significant changes in neurological signs were observed in any group. However, serum levels of the activated isoforms of gelatinase matrix metalloproteinase-9 decreased by 59% in primary-progressive multiple sclerosis and by 51% in relapsing-remitting multiple sclerosis patients under nutritional intervention, including dietary supplements. This study indicates that a healthy nutritional intervention is well accepted by people with multiple sclerosis and may ameliorate their physical and inflammatory status. PMID:26785711

  16. Metodologia diagnóstica e tratamento da recaída após transplante de medula óssea em paciente com leucemia promielocítica aguda Diagnostic methodology and treatment of relapse after bone marrow transplantation in a patient with acute promyelocitic leukemia

    Directory of Open Access Journals (Sweden)

    Ronald Pallotta

    2000-12-01

    fundamental manner. The early diagnosis of relapse is sustented by the ability to detect the minimal residual disease. The methodology using flowcitometry, conventional cytogenetic, fluorescence in situ hybridization (FISH and polymerase chain reaction (PCR allow the diagnosis of these residual clone that are responsible for relapse. L.M.S.O., 54 year old lady, was diagnosed with promyelocitic leukemia (AML M3 in 1997. She was submitted to an autologous bone marrow transplantation in 09/01/98 as consolidation therapy. Two years after the transplant she was diagnosed with a molecular relapse by RT-PCR sequentially performed. The use of all-trans-retinoic acid (ATRA was able to induce a new molecular remission. The mechanism of action of ATRA to induce remission in AML M3 is not well established. This drug can be use in relapse. In the case that was presented, the early diagnosis that leaded to this good result happened because of a well planned post transplant evaluation. These variables of selection, conditioning and follow up should be well studied to plan an adequate and prolonged post transplant follow up, allowing better results with the procedure.

  17. [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.

  18. Genomic profiling of pediatric acute myeloid leukemia reveals a changing mutational landscape from disease diagnosis to relapse | Office of Cancer Genomics

    Science.gov (United States)

    The genomic and clinical information used to develop and implement therapeutic approaches for AML originated primarily from adult patients and has been generalized to patients with pediatric AML. However, age-specific molecular alterations are becoming more evident and may signify the need to age-stratify treatment regimens. The NCI/COG TARGET-AML initiative employed whole exome capture sequencing (WXS) to interrogate the genomic landscape of matched trios representing specimens collected upon diagnosis, remission, and relapse from 20 cases of de novo childhood AML.

  19. Outpatient-Based Therapy of Oral Fludarabine and Subcutaneous Alemtuzumab for Asian Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    William Y. K. Hwang

    2009-01-01

    Full Text Available Background. Intravenous alemtuzumab and fludarabine are effective in combination for the treatment of chronic lymphocytic leukemia (CLL, but require hospital visits for intravenous injection. We performed a pilot study to assess the safety and efficacy of outpatient-based oral fludarabine with subcutaneous alemtuzumab (OFSA for the treatment of relapsed/refractory CLL. Results. Depending on their response, patients were given two to six 28-day cycles of subcutaneous alemtuzumab 30 mg on days 1,3, and 5 and oral fludarabine 40 mg/m2/day for 5 days. Median patient age was 74. The lymphocyte counts of all five patients fell after the 1st cycle of treatment and reached normal/low levels on completion of 2 to 6 cycles of therapy. Platelet counts and hemoglobin were unaffected. All five patients achieved complete hematological remission, while two attained minimal residual disease negativity on 4-color flow cytometry. Conclusions. Our OFSA regimen was effective in elderly Asian patients with relapsed/refractory CLL, and it should be investigated further.

  20. Risk factors for visceral leishmaniasis relapse in immunocompetent patients following treatment with 20 mg/kg liposomal amphotericin B (Ambisome in Bihar, India.

    Directory of Open Access Journals (Sweden)

    Sakib Burza

    Full Text Available BACKGROUND: A proportion of all immunocompetent patients treated for visceral leishmaniasis (VL are known to relapse; however, the risk factors for relapse are not well understood. With the support of the Rajendra Memorial Research Institute (RMRI, Médecins Sans Frontières (MSF implemented a program in Bihar, India, using intravenous liposomal amphotericin B (Ambisome as a first-line treatment for VL. The aim of this study was to identify risk factors for VL relapse by examining the characteristics of immunocompetent patients who relapsed following this regimen. METHODS AND PRINCIPAL FINDINGS: This is an observational retrospective cohort study of all VL patients treated by the MSF program from July 2007 to August 2012. Intravenous Ambisome was administered to 8749 patients with VL in four doses of 5 mg/kg (for a total dose of 20 mg/kg over 4-10 days, depending on the severity of disease. Out of 8588 patients not known to be HIV-positive, 8537 (99.4% were discharged as initial cures, 24 (0.3% defaulted, and 27 (0.3% died during or immediately after treatment. In total, 1.4% (n = 119 of the initial cured patients re-attended the programme with parasitologically confirmed VL relapse, with a median time to relapse of 10.1 months. Male sex, age <5 years and ≥45 years, a decrease in spleen size at time of discharge of ≤0.5 cm/day, and a shorter duration of symptoms prior to seeking treatment were significantly associated with relapse. Spleen size at admission, hemoglobin level, nutritional status, and previous history of relapse were not associated with relapse. CONCLUSIONS: This is the largest cohort of VL patients treated with Ambisome worldwide. The risk factors for relapse included male sex, age <5 and ≥45 years, a smaller decrease in splenomegaly at discharge, and a shorter duration of symptoms prior to seeking treatment. The majority of relapses in this cohort occurred 6-12 months following treatment, suggesting that a 1-year follow

  1. [Acute confusion in the geriatric patient].

    Science.gov (United States)

    Zanocchi, M; Vallero, F; Norelli, L; Zaccagna, B; Spada, S; Fabris, F

    1998-05-01

    During 1996, 585 patients, aged 55 to 96, were admitted into hospital at the Geriatric Department of Ospedale Maggiore (Turin). Acute confusion was seen in 22.2% of these patients who tended to have more serious clinical condition, were more likely to have chronic cognitive impairment, were treated with a greater number of drugs and suffered more from immobility with pressure ulcer. The confusional state, manifested at admission to Geriatric department, was mostly related with the patient's clinical severity, while the one which developed during hospital stay was linked to situations of physical frailty, as pressure ulcer and low albumin values. The most frequent causes of acute confusional state were acute infectious diseases, heart failure, gastro-intestinal bleeding with secondary anaemia, stroke and dehydration. In many cases the very cause of the acute confusional state could not be identified. Falls, more than 31 days length of stay in hospital and death were more frequent in patients suffering from confusional state. Chronic cognitive impairment, functional dependence, clinical severity and treatment involving a great number of drugs, are the main contributing factors in this syndrome. Thus, a multi-dimensional evaluation which takes into account both clinical-functional and socio-economical aspects, is useful for a correct preventive and diagnostic approach of acute confusional state.

  2. 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

    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...... 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...... 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...

  3. Cognitive impairment in patients suffering from relapsing-remitting multiple sclerosis with EDSS < or = 3.5.

    Science.gov (United States)

    Ruggieri, R M; Palermo, R; Vitello, G; Gennuso, M; Settipani, N; Piccoli, F

    2003-11-01

    Previous papers have mainly demonstrated the presence and the frequency of cognitive impairment in patients suffering from relapsing-remitting multiple sclerosis. The purpose of this study was to investigate subjects with the relapsing-remitting form of the disease and mild clinical disability (EDSS Aphasie Test (AAT). They also underwent Clinical Depression Scale (CDQ) and State-Trait Anxiety Inventory (STAI). The results show the presence of significant memory impairment on both WMS (P = 0.000) and BVRT (P = 0.000) in patients compared with controls. Patients were also impaired in abstract reasoning and problem-solving deficit (KT P = 0.003; RCPM P = 0.000) and in FR (P = 0.019). Cognitive decline correlated with illness duration (r = 0.761), but was independent of EDSS (r = 0.085). Cognitive decline was present even when physical disability was not yet severe, but it was mild and did not limit patients' ability to work. The cognitive impairment outlined was of the subcortical type and correlated with illness duration. This study emphasizes the importance of cognitive examination in clinical practice. It is suggested that a complete neurological examination include tests on memory and abstract reasoning.

  4. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with acute lymphoblastic leukemia in a second remission after an isolated central nervous system relapse: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research.

    Science.gov (United States)

    Eapen, M; Zhang, M-J; Devidas, M; Raetz, E; Barredo, J C; Ritchey, A K; Godder, K; Grupp, S; Lewis, V A; Malloy, K; Carroll, W L; Davies, S M; Camitta, B M

    2008-02-01

    In children with acute lymphoblastic leukemia (ALL) with isolated central nervous system (CNS) relapse and a human leucocyte antigen (HLA)-matched sibling, the optimal treatment after attaining second remission is unknown. We compared outcomes in 149 patients enrolled on chemotherapy trials and 60 HLA-matched sibling transplants, treated in 1990-2000. All patients achieved a second complete remission. Groups were similar, except the chemotherapy recipients were younger at diagnosis, less likely to have T-cell ALL and had longer duration (> or = 18 months) first remission. To adjust for time-to-transplant bias, left-truncated Cox's regression models were constructed. Relapse rates were similar after chemotherapy and transplantation. In both treatment groups, relapse rates were higher in older children (11-17 years; RR 2.81, P=0.002) and shorter first remission (< 18 months; RR 3.89, P<0.001). Treatment-related mortality rates were higher after transplantation (RR 4.28, P=0.001). The 8-year probabilities of leukemia-free survival adjusted for age and duration of first remission were similar after chemotherapy with irradiation and transplantation (66 and 58%, respectively). In the absence of an advantage for one treatment option over another, the data support use of either intensive chemotherapy with irradiation or HLA-matched sibling transplantation with total body irradiation containing conditioning regimen for children with ALL in second remission after an isolated CNS relapse.

  5. Anesthesia for the acute abdomen patient.

    Science.gov (United States)

    Hofmeister, Erik H

    2003-02-01

    Patients with acute abdomen often have marked physiologic and pathologic changes, making anesthesia both challenging and potentially hazardous for the patient. A thorough understanding of the pathophysiologic mechanisms of cardiovascular function under anesthesia and selection of appropriate anesthetic protocols are critical to a successful anesthetic outcome. The goal is to produce anesthesia while minimizing depression of the cardiovascular system. Monitoring and management of acid-base and cardiovascular function serve to ensure appropriate oxygen delivery to the tissues during anesthesia. Postoperative management can significantly influence patient outcome following anesthesic recovery, and must therefore be considered in the anesthetic plan. Finally, pain management in all patients is an important aspect of case management, and should not be overlooked. This article serves to educate the clinician in the above-described areas in regard to the acute abdomen patient.

  6. Efficacy of lenalidomide in relapsed/refractory chronic lymphocytic leukemia patient: a systematic review and meta-analysis.

    Science.gov (United States)

    Liang, Liang; Zhao, Ming; Zhu, Yuan-Chao; Hu, Xin; Yang, Li-Ping; Liu, Hui

    2016-09-01

    Therapeutic results of relapsed/refractory chronic lymphocytic leukemia (CLL) are very disappointing at present. Lenalidomide has been proved to be effective for relapsed/refractory CLL as a single agent or in combination with various chemo-immunotherapeutic regimens. However, current clinical experience in its usage is still limited. Because of existing considerable variability in different studies, a systematic review and meta-analysis was conducted to describe overall response rate (ORR) of lenalidomide in patients with relapsed/refractory CLL. Pooled estimate of cumulative prevalence of total ORR was 42.23 % (95 % confidence interval [CI], 32.49-52.61 %), while pooled ORR in regimen with lenalidomide plus anti-CD20 monoclonal antibody (mAbs) and lenalidomide mono-therapy were 60.01 % (95 % CI, 53.86-65.86 %) and 24.38 % (95 % CI, 16.15-35.06 %), respectively. There was no significant difference between L + R (lenalidomide plus rituximab) group and L + O (lenalidomide plus ofatumumab) group, with pooled ORR of 66.38 % (95 % CI, 57.96-73.87 %) and 57.40 % (95 % CI, 46.46-67.65 %), respectively. When co-administrated with anti-CD20 mAbs, dosage of lenalidomide was not the key factor of ORR in combination therapy. Pooled ORR of patient with high-risk cytogenetic in L + anti-CD20 mAbs group was 56.74 % (95 % CI, 45.53-67.30 %). In comparison with patients without high-risk cytogenetic receiving the same treatment regimen, no significant difference was observed, with relative risk (RR) of 0.87 (95 % CI 0.68-1.11). Our finding demonstrated that lenalidomide plus anti-CD20 mAbs could be an efficient therapy regimen for relapsed/refractory CLL patients, especially for those with high-risk cytogenetic factor.

  7. Acute respiratory failure in scrub typhus patients

    Directory of Open Access Journals (Sweden)

    Jyoti Narayan Sahoo

    2016-01-01

    Full Text Available Respiratory failure is a serious complication of scrub typhus. In this prospective study, all patients with a diagnosis of scrub typhus were included from a single center Intensive Care Unit (ICU. Demographic, clinical characteristics, laboratory, and imaging parameters of these patients at the time of ICU admission were compared. Of the 55 scrub typhus patients, 27 (49% had an acute respiratory failure. Seventeen patients had acute respiratory distress syndrome, and ten had cardiogenic pulmonary edema. Respiratory supported patients were older had significant chronic lungs disease and high severity illness scores (Acute Physiology and Chronic Health Evaluation-II and Sequential Organ Failure Assessment score. At ICU admission, these patients presented with more deranged laboratory markers, including high bilirubin, high creatine kinase, high lactate, metabolic acidosis, low serum albumin, and presence of ascites. The average ICU and hospital stay were 4.27 ± 2.74 and 6.53 ± 3.52 days, respectively, in the respiratory supported group. Three patients died in respiratory failure group, while only one patient died in nonrespiratory failure group.

  8. Molecular detection of minimal residual disease is a strong predictive factor of relapse in childhood B-lineage acute lymphoblastic leukemia with medium risk features. A case control study of the International BFM study group

    NARCIS (Netherlands)

    Biondi, A; Valsecchi, MG; Seriu, T; D'Aniello, E; Willemse, MJ; Fasching, K; Pannunzio, A; Gadner, H; Schrappe, M; Kamps, WA; Bartram, CR; van Dongen, JJM; Panzer-Grumayer, ER

    2000-01-01

    The medium-risk B cell precursor acute lymphoblastic leukemia (ALL) accounts for 50-60% of total childhood ALL and comprises the largest number of relapses still unpredictable with diagnostic criteria. To evaluate the prognostic impact of minimal residual disease (MRD) in this specific group, a case

  9. Changes of the MS functional composite and EDSS during and after treatment of relapses with methylprednisolone in patients with multiple sclerosis.

    Science.gov (United States)

    Patzold, T; Schwengelbeck, M; Ossege, L-M; Malin, J-P; Sindern, E

    2002-03-01

    The Multiple Sclerosis Functional Composite (MSFC) comprises quantitative functional measures of leg, hand/arm and cognitive function. We examined the responsiveness of the MSFC compared with the Expanded Disability Status Scale (EDSS) during treatment of relapses in patients with multiple sclerosis (MS). 27 patients received 1000 mg intravenous methylprednisolone (i.v.-MP) for 5 days, followed by oral methylprednisolone for 14 days. The MSFC and the EDSS-score were assessed on day 0, before the first corticosteroid treatment, on day 5, after the last course of i.v. MP, and on day 20 after the treatment was finished. Before the first administration of the MSFC, patients were trained for the paced auditory addition test (PASAT) performing three test trials. In order to analyse practice effects, 10 MS patients without an acute exacerbation were tested three times under the same conditions as the treated group. The median EDSS-score was 2.5 in both groups. On day 5 it remained unchanged in all treated patients, on day 20 a decrease of 0.5 EDSS point occurred in five patients, and in two patients an improvement with a decrease of more than 0.5 point was observed. There was no statistically significant difference between the EDSS-scores on day 0, 5 and 20. The mean MSFC-score in the treated group was -0.14 +/- 0.63 on day 0, 0.17 +/- 0.66 on day 5, and 0.42 +/- 0.59 on day 20. On the last study day, 26 patients improved compared with day 0. The differences between the MSFC-scores at the three points of time were statistically significant for the treated group (P EDSS.

  10. Post-remission treatment with allogeneic stem cell transplantation in patients aged 60 years and older with acute myeloid leukaemia : a time-dependent analysis

    NARCIS (Netherlands)

    Versluis, Jurjen; Hazenberg, Carin L. E.; Passweg, Jakob R.; van Putten, Wim L. J.; Maertens, Johan; Biemond, Bart J.; Theobald, Matthias; Graux, Carlos; Kuball, Jurgen; Schouten, Harry C.; Pabst, Thomas; Lowenberg, Bob; Ossenkoppele, Gert; Vellenga, Edo; Cornelissen, Jan J.

    2015-01-01

    Background Acute myeloid leukaemia mainly affects elderly people, with a median age at diagnosis of around 70 years. Although about 50-60% of patients enter first complete remission upon intensive induction chemotherapy, relapse remains high and overall outcomes are disappointing. Therefore, effecti

  11. Clinical significance of CD56 expression in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens

    NARCIS (Netherlands)

    Montesinos, Pau; Rayon, Chelo; Vellenga, Edo; Brunet, Salut; Gonzalez, Jose; Gonzalez, Marcos; Holowiecka, Aleksandra; Esteve, Jordi; Bergua, Juan; Gonzalez, Jose D.; Rivas, Concha; Tormo, Mar; Rubio, Vicente; Bueno, Javier; Manso, Felix; Milone, Gustavo; de la Serna, Javier; Perez, Inmaculada; Perez-Encinas, Manuel; Krsnik, Isabel; Ribera, Josep M.; Escoda, Lourdes; Lowenberg, Bob; Sanz, Miguel A.

    2011-01-01

    The expression of CD56 antigen in acute promyelocytic leukemia (APL) blasts has been associated with short remission duration and extramedullary relapse. We investigated the clinical significance of CD56 expression in a large series of patients with APL treated with all-trans retinoic acid and anthr

  12. Clinical significance of CD56 expression in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens

    NARCIS (Netherlands)

    Montesinos, Pau; Rayon, Chelo; Vellenga, Edo; Brunet, Salut; Gonzalez, Jose; Gonzalez, Marcos; Holowiecka, Aleksandra; Esteve, Jordi; Bergua, Juan; Gonzalez, Jose D.; Rivas, Concha; Tormo, Mar; Rubio, Vicente; Bueno, Javier; Manso, Felix; Milone, Gustavo; de la Serna, Javier; Perez, Inmaculada; Perez-Encinas, Manuel; Krsnik, Isabel; Ribera, Josep M.; Escoda, Lourdes; Lowenberg, Bob; Sanz, Miguel A.

    2011-01-01

    The expression of CD56 antigen in acute promyelocytic leukemia (APL) blasts has been associated with short remission duration and extramedullary relapse. We investigated the clinical significance of CD56 expression in a large series of patients with APL treated with all-trans retinoic acid and

  13. Acute hepatitis C in patients receiving hemodialysis.

    Science.gov (United States)

    Griveas, I; Germanidis, G; Visvardis, G; Morice, Y; Perelson, A S; Pawlotsky, J M; Papadopoulou, D

    2007-01-01

    Hepatitis C virus (HCV) infection is frequent in patients with end-stage renal disease treated by chronic dialysis, with a prevalence varying from 10-65% according to the geographical data. The prevalence is significantly associated with the duration of dialysis and the number of transfused blood products[1,2] and has dramatically declined with efficient blood screening.[3] We studied patients with acute HCV infection in a dialysis unit. The diagnosis was based on both anti-HCV detection and HCV-RNA detection. Other virological tools including HCV genotype determination was also used to tailor treatment to the individual patient and determine its efficacy for a one-year follow-up period. Seventeen patients (7 male and 10 female, mean age: 63.7 +/- 11.6 SD) with acute hepatitis C were enrolled to our study. All of them were followed up for a period of one year after the diagnosis was established. Phylogenetic analysis distinguished two separate HCV subtypes 1b, which were both responsible for this acute infection (see Figure 1). These types did not differ in their behavior on the clinical situation of our patients, as confirmed by the fact that in both groups of patients, there was only one patient who presented with acute illness. Six patients of our study group, three months after the acute infection, received pegylated interferon (Peg-IFNa2a) 135 mug for a six-month period. Four of them responded very well to therapy and at the first determination HCV RNA was below the cutoff point. One of our patients with very high HCV levels (HCV RNA > 50,000,000 IU/mL), despite receiving the same therapy, did not respond well and developed cirrhosis. In conclusion, it is clear from our experience that better information is needed about the current incidence, prevalence, and risk factors for HCV infection in dialysis patients. Algorithms for the diagnosis and management of hepatitis C should be developed by academic societies. Routine screening for hepatitis C also would allow

  14. Acute Stroke Management in Patients Taking Dabigatran

    NARCIS (Netherlands)

    Brouns, Raf; Van Hooff, Robbert-Jan; De Smedt, Ann; Moens, Maarten; De Raedt, Sylvie; Uyttenboogaart, Maarten; Luijckx, Gert-Jan; Jochmans, Kristin; De Keyser, Jacques

    Dabigatran etexilate is emerging as an alternative for vitamin K antagonists, but evidence-based guidelines for management of intracerebral hemorrhage and acute ischemic stroke in patients taking this drug are nonexistent. This review summarizes current knowledge on key pharmacological features and

  15. Pressure sore prevention in acutely ill patients.

    Science.gov (United States)

    James, H

    1997-03-01

    A wide range of factors affect the skin's ability to withstand pressure, friction and shear. Clinically validated pressure-relieving equipment is essential to prevent pressure sores in acutely ill patients. A successful pressure sore prevention strategy depends on sufficient resource allocation, appropriate levels and types of preventive equipment and evaluation.

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

    DEFF Research Database (Denmark)

    Spelman, Tim; Meyniel, Claire; Rojas, Juan Ignacio

    2016-01-01

    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. CONCLUSION: 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...

  17. Energy expenditure of acutely ill hospitalised patients

    Directory of Open Access Journals (Sweden)

    Gariballa Salah

    2006-03-01

    Full Text Available Abstract Objective To measure energy expenditure of acutely ill elderly patients in hospital and following discharge in the community. Design Sixty-three consecutive hospitalised acutely ill elderly patients were recruited. Eight patients were studied to assess the reliability of the Delta Tract Machine as a measure of energy expenditure; 35 patients had their energy expenditure studied in hospital on two occasions and 20 patients had their energy expenditure measured in hospital and at 6 weeks in the community Results Men had higher basal energy expenditure (BMR values compared to women however the difference was not statistically significant [Men, mean (SD 1405 (321 Kcal, women 1238 (322 kcal; mean difference (95% CI 166 kcal (-17 to 531, p = 0.075]. After adjusting for age, gender and body mass index both medication and C-reactive protein (CRP, concentrations showed significant correlation with measured energy expenditure in hospital, (r = -0.36, "p Conclusion Tissue inflammation and medications were associated with change in measured energy expenditure in acutely ill patients.

  18. [Nutrition for elderly acute stroke patients].

    Science.gov (United States)

    Ha, Lisa; Iversen, Per Ole; Hauge, Truls

    2008-09-11

    Elderly people have an increased risk of malnutrition due to biological and physiological changes and underlying disease. Almost 90% of the stroke patients are older than 65 years, and the consequences of acute stroke may lead to additional nutritional problems. This paper reviews nutritional therapy for stroke patients. PubMed was searched (non-systematically) for prospective cohort studies of occurrence, diagnostics and consequences of undernutrition in stroke patients. Randomized trials were examined to identify clinical effects of oral protein and energy supplements or tube feeding on nutritional status and intake, functional status, infections, length of stay, quality of life and mortality. 8-35% of stroke patients are undernourished. Body weight is one of the most important parameters for assessment of nutritional status. Dysphagia occurs in up to 80% of patients with acute stroke and increases the risk of undernutrition, which again leads to prolonged length of stay, reduced functional status and poorer survival. Early nasogastric tube feeding does not increase the risk of pneumonia and may improve survival after six months. Oral supplements lead to a significantly improved nutritional intake in undernourished stroke patients, as well as improved nutritional status and survival in undernourished elderly. Nutritional treatment can improve the clinical outcome after an acute stroke, provided that there are good procedures for follow-up and monitoring of the treatment.

  19. Natalizumab reduces relapse clinical severity and improves relapse recovery in MS.

    Science.gov (United States)

    Lublin, Fred D; Cutter, Gary; Giovannoni, Gavin; Pace, Amy; Campbell, Nolan R; Belachew, Shibeshih

    2014-11-01

    Compare relapse clinical severity, post-relapse residual disability, and the probability of confirmed complete recovery from relapse between patients who relapsed during natalizumab (n=183/627 [29%]) and placebo (n=176/315 [56%]) treatments in the AFFIRM trial. In this post-hoc analysis, relapse clinical severity and residual disability were defined by change in Expanded Disability Status Scale (EDSS) score occurring between pre-relapse and at-relapse assessment and between pre-relapse and post-relapse assessment, respectively. Patients were considered completely recovered from relapse when their post-relapse EDSS score was less than or equal to their pre-relapse EDSS score, and this was maintained for 12 or 24 weeks. At relapse, an increase in EDSS score of ≥0.5 points occurred in 71% of natalizumab and 84% of placebo patients (P=0.0088); an increase of ≥1.0 point occurred in 49% of natalizumab and 61% of placebo patients (P=0.0349) (mean increase in EDSS at relapse: natalizumab=0.77; placebo=1.09; P=0.0044). After relapse, residual disability of ≥0.5 EDSS points remained in 31% of natalizumab and 45% of placebo patients (P=0.0136) (mean post-relapse residual EDSS increase: natalizumab=0.06; placebo=0.28; P=0.0170). In patients with an increase in EDSS of ≥0.5 or ≥1.0 during relapse, natalizumab increased the probability of 12-week confirmed complete recovery from relapse by 55% (hazard ratio [HR]=1.554; P=0.0161) and 67% (HR=1.673; P=0.0319) compared to placebo, respectively. In AFFIRM, natalizumab treatment decreased the clinical severity of relapses and improved recovery from disability induced by relapses. These beneficial effects would limit the step-wise accumulation of disability. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML

    Science.gov (United States)

    2017-08-21

    Relapsed Acute Lymphoblastic Leukemia (ALL); Refractory Acute Lymphoblastic Leukemia (ALL); Relapsed Acute Myelogenous Leukemia (AML); Refractory Acute Myelogenous Leukemia (AML); Relapsed Mixed Lineage Leukemia; Refractory Mixed Lineage Leukemia; Relapsed Biphenotypic Leukemia; Refractory Biphenotypic Leukemia; Chronic Myelogenous Leukemia (CML) in Blast Crisis

  1. Leptin enhances the release of cytokines by peripheral blood mononuclear cells from acute multiple sclerosis patients

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To explore the effect of leptin on cytokine production by PBMCs obtained from MS patients either in acute (relapse) or in stable (nonrelapse) phase of disease. Methods PBMCs were collected from 25 untreated acute MS patients, 11 stable MS patients and 20 healthy controls. PBMCs were cultured either with RPMI-1640 alone or with leptin (1.25 nmol/ml), phytohemagglutinin (PHA) ( 100 μg/ml), and leptin + PHA. 72 h later the supernate of the culture medium were collected and stored at -70℃. The pro-inflammatory cytokine (IFN-γ) concentration were determined using an enzyme-linked immunosorbent assay ( ELISA), and the anti-inflammatory cytokine (IL-4) concentration were investigated by radioimmunity methods. Results Our data showed that leptin induced IFN-γproduction by PBMCs of patients in an acute phase of disease but not in a stable phase or in healthy controls. Moreover, we found that PHA induced IL-4 production by PBMCs of patients in an acute phase of disease, but leptin inhibited this ability of PHA. Conclusion Leptin can affect on pro- and anti-inflammatory cytokine production by PBMCs collected from MS patients, may be this connected with leptin increase the susceptiveness of MS.

  2. Acute myeloid leukemia in the pregnant patient.

    Science.gov (United States)

    Thomas, Xavier

    2015-08-01

    Although acute myeloid leukemia (AML) mostly occurs in older patients, it could be seen in women of childbearing age. It is therefore not surprising that in some patients, the management of AML will be complicated by a coexistent pregnancy. However, the association of leukemia and pregnancy is uncommon. Its incidence is estimated to be 1 in 75,000-100,000 pregnancies. During pregnancy, most leukemias are acute: two-thirds are myeloid and one-third are lymphoblastic. There is no standard approach for this clinical dilemma, in part because of variables such as the type of AML, the seriousness of the symptoms, and the patient's personal beliefs. In many cases, the diagnostic workup has to be altered because of the pregnancy, and often available treatments have varying risks to the fetus. While chemotherapy is reported to have some risks during the first trimester, it is admitted that it can be administered safely during the second and the third trimesters.

  3. Gerstmann'S syndrome in acute stroke patients.

    Science.gov (United States)

    Zukic, Sanela; Mrkonjic, Zamir; Sinanovic, Osman; Vidovic, Mirjana; Kojic, Biljana

    2012-12-01

    Gerstmann in 1924. observed in a few patients a concomitant impairment in discriminating their own fingers, writing by hand, distinguishing left from right and performing calculations. He claimed that this tetrad of symptoms constituted a syndromal entity, assigned it to a lesion of the dominant parietal lobe. Since than, Gerstmann`s syndrome (GS) was enigma for neuropsychologists. The aim of this study was to analyze frequency and clinical features of GS among acute stroke patients. We prospectively analyzed 194 acute stroke patients (average age 65±11.06 years, male 113 (58.2%), female 81 (41.8%) hospitalized at department of Neurology, University Clinical Center tuzla, during the six mounths in 2010. For clinical assessment of agraphia, alexia and acalculia we used Minessota test for differential diagnosis of aphasia's. Among these acute stroke patients, 59 (30.40%) had alexia, agraphia and acalculia or different combinations of these disorders. two patients (3.4%) had agraphia and acalculia associated with other part of tetrad of GS: fi nger agnosia and left-right disorientation. they both where men, right handed, and cranial computed tomography scan showed ischemic lesion in the left parietal and left temporoparietal lobe. Gerstmann`s syndrome is rare clinical entity, and has the high value in localization and the lesion is mainly localized to angular gyrus of the dominant hemisphere.

  4. Expression and activity of breast cancer resistance protein (BCRP) in de novo and relapsed acute myeloid leukemia

    NARCIS (Netherlands)

    Vellenga, E; Scheffer, GL; Muller, M; Bates, SE; Scheper, RJ; de Vries, EGE

    2002-01-01

    Overexpression of the breast cancer resistance protein (BCRP) efflux pump In human cancer cell lines results in resistance to a variety of cytostatic agents. The aim of this study was to analyze BCRP protein expression and activity In acute myeloid leukemia (AML) samples and to determine whether it

  5. 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

  6. ¿Tiene utilidad el tratamiento preoperatorio con ácido ursodeoxicólico en la reducción de las recidivas en la pancreatitis aguda biliar? Is pre-operative treatment with ursodeoxycholic acid useful in reducing relapses in acute biliary pancreatitis?

    Directory of Open Access Journals (Sweden)

    F. Borda

    2003-08-01

    Full Text Available En el presente trabajo se ha valorado la posible reducción de la tasa de recidivas en la pancreatitis aguda biliar mediante el tratamiento con ácido ursodeoxicólico (AUC entre el episodio de pancreatitis y el momento de la colecistectomía. Se estudiaron 72 primeros episodios consecutivos de pancreatitis aguda biliar, en pacientes no colecistectomizados, seguidos hasta la cirugía. Los casos se dividieron en grupo A (n = 30, tratados al alta con AUC 10 mg/kg/día, hasta la cirugía, y grupo B o control (n = 42. Se evaluaron las diferencias entre ambos grupos en cuanto a características del paciente, gravedad de la pancreatitis, características de la litiasis y demora hasta la cirugía. Analizamos las recidivas de la pancreatitis entre los grupos con y sin AUC. En el grupo con AUC comparamos la duración del tratamiento entre los pacientes con y sin recidiva de la pancreatitis. Los dos grupos no mostraron diferencias significativas en cuanto a ninguno de los parámetros estudiados. Registramos 7/30 (23,3% recidivas en el grupo AUC, frente a 9/42 (21,4% recidivas en el control (p = 0,85. Dentro del grupo AUC, la duración del tratamiento fue similar entre los casos que recidivaron: 4,9±4,5 meses y los no recidivados: 4,4±1,9 meses (p = 0,78. En nuestra experiencia, el empleo de AUC hasta el momento de la colecistectomía no reduce la incidencia de recidiva en los pacientes tras un primer episodio de pancreatitis aguda biliar. La duración del tratamiento con AUC tampoco parece relacionarse con la aparición o no de recidivas.In the present paper, we evaluate the possible reduction in the rate of relapses in acute biliary pancreatitis through treatment with ursodeoxycholic acid (UCA, between the episode of pancreatitis and the moment of cholecystectomy. We studied 72 consecutive first episodes of acute biliary pancreatitis, in patients who had not yet undergone colecistectomy, followed up until surgery. The cases were divided into group A (n

  7. EDSS Change Relates to Physical HRQoL While Relapse Occurrence Relates to Overall HRQoL in Patients with Multiple Sclerosis Receiving Subcutaneous Interferon β -1a.

    Science.gov (United States)

    Vickrey, Barbara G; Lee, Liesly; Moore, Fraser; Moriarty, Patrick

    2015-01-01

    Objective. To compare patterns of associations of changes in mental and physical health dimensions of health-related quality of life (HRQoL) over time with relapse occurrence and changes in Expanded Disability Status Scale (EDSS) scores in patients with relapsing multiple sclerosis (RMS). Methods. This 24-month, phase IV, observational study enrolled 334 patients with RMS who received interferon β-1a 44 μg or 22 μg subcutaneously three times weekly. At each 6-month visit, patients completed the Multiple Sclerosis Quality of Life-54 (MSQOL-54) and site investigators assessed EDSS and recorded relapse occurrence. A generalized linear model procedure was used for multivariable analyses (per protocol) that explored unique associations of EDSS score change and relapse occurrence with MSQOL-54 physical health composite score (PCS) and mental health composite score (MCS). Results. HRQoL improved over 2 years among those who completed the study. Occurrence of ≥1 relapse was significantly associated with lower MSQOL-54 PCS and MCS. Changes in EDSS score were significantly associated with MSQOL-54 PCS, but not MCS. Conclusions. HRQoL assessments, particularly those that examine mental health, may provide information on the general health status of patients with RMS that would not be recognized using traditional clinician-assessed measures of disease severity and activity. This trial is registered with ClinicalTrials.gov; identifier: NCT01141751.

  8. EDSS Change Relates to Physical HRQoL While Relapse Occurrence Relates to Overall HRQoL in Patients with Multiple Sclerosis Receiving Subcutaneous Interferon β-1a

    Directory of Open Access Journals (Sweden)

    Barbara G. Vickrey

    2015-01-01

    Full Text Available Objective. To compare patterns of associations of changes in mental and physical health dimensions of health-related quality of life (HRQoL over time with relapse occurrence and changes in Expanded Disability Status Scale (EDSS scores in patients with relapsing multiple sclerosis (RMS. Methods. This 24-month, phase IV, observational study enrolled 334 patients with RMS who received interferon β-1a 44 μg or 22 μg subcutaneously three times weekly. At each 6-month visit, patients completed the Multiple Sclerosis Quality of Life-54 (MSQOL-54 and site investigators assessed EDSS and recorded relapse occurrence. A generalized linear model procedure was used for multivariable analyses (per protocol that explored unique associations of EDSS score change and relapse occurrence with MSQOL-54 physical health composite score (PCS and mental health composite score (MCS. Results. HRQoL improved over 2 years among those who completed the study. Occurrence of ≥1 relapse was significantly associated with lower MSQOL-54 PCS and MCS. Changes in EDSS score were significantly associated with MSQOL-54 PCS, but not MCS. Conclusions. HRQoL assessments, particularly those that examine mental health, may provide information on the general health status of patients with RMS that would not be recognized using traditional clinician-assessed measures of disease severity and activity. This trial is registered with ClinicalTrials.gov; identifier: NCT01141751.

  9. Oncological outcomes in patients with stage I testicular seminoma and nonseminoma: pathological risk factors for relapse and feasibility of surveillance after orchiectomy.

    Science.gov (United States)

    Kobayashi, Kazuhiro; Saito, Toshihiro; Kitamura, Yasuo; Nobushita, Tomohiro; Kawasaki, Takashi; Hara, Noboru; Takahashi, Kota

    2013-04-08

    Surveillance after orchiectomy has recently been a management option in patients with stage I seminoma, while it remains controversial in those with stage I nonseminoma, and the risk factor associated with relapse is still a matter of concern in both entities. This study was performed to explore pathological risk factors for post-orchiectomy relapse in patients with stage I seminoma and nonseminoma, and to assess oncological outcomes in those managed with surveillance. In this single institution study, 118 and 40 consecutive patients with stage I seminoma and nonseminoma were reviewed, respectively. Of the 118 patients with stage I seminoma, 56 and one received adjuvant radiotherapy and chemotherapy, respectively, and 61 were managed with surveillance. Of the 40 men with stage I nonseminoma, 4 underwent adjuvant chemotherapy and 36 were managed with surveillance. No patient had cause-specific death during the mean observation period of 104 and 99 months in men with seminoma and nonseminoma, respectively. In men with stage I seminoma, 1 (1.7%) receiving radiotherapy and 4 (6.6%) men managed with surveillance had disease relapse; the 10-year relapse-free survival (RFS) rate was 93.4% in men managed with surveillance, and their RFS was not different from that in patients receiving adjuvant radiotherapy (log rank P=0.15). Patients with tunica albuginea involvement showed a poorer RFS than those without (10-year RFS rate 80.0% vs. 94.1%), although the difference was of borderline significance (P=0.09). In men with stage I nonseminoma, 9 (22.5%) patients experienced relapse. Patients with lymphovascular invasion seemingly had a poorer RFS than those without; 40.0% and 18.7% of the patients with and without lymphovascular invasion had disease relapse, respectively, although the difference was not significant (log rank P=0.17). In both men with stage I seminoma and nonseminoma, surveillance after orchiectomy is a feasible option. However, disease extension through tunica

  10. Respiratory insufficiency and dynamic hyperinflation after rigid bronchoscopy in a patient with relapsing polychondritis -a case report-.

    Science.gov (United States)

    Ahn, Hyun-Joo; Kim, Jie Ae; Yang, Mikyung; Lee, Eun Kyung

    2013-12-01

    Relapsing polychondritis (RP) is an uncommon disease that is characterized by inflammation and destruction of cartilaginous structures. When tracheobronchial tree is involved, respiratory obstructive symptoms can occur. A 35-year-old man, with a previous diagnosis of RP, was scheduled for rigid bronchoscopy to relieve dyspnea, caused by subglottic stenosis. After laser splitting of the subglottic web, the spontaneous respiration of the patient was insufficient, and hypercarbia developed progressively even with assisted ventilation. After 20 minutes of aggressive hyperventilation to reduce end-tidal CO2 level, sudden extreme tachycardia and hypotension developed. Ventilation rate was reduced and prolonged expiration time was allowed to alleviate a near-tampon status from dynamic hyperinflation. After the hemodynamic status was stabilized, the patient was transferred to the ICU for mechanical ventilation. He received ICU care for 30 days, and now, he was on supportive care on a ward, considering Y stent insertion to prevent luminal collapse from tracheobronchomalacia.

  11. Relapsing pityriasis rosea.

    Science.gov (United States)

    Drago, Francesco; Ciccarese, Giulia; Rebora, Alfredo; Parodi, Aurora

    2014-01-01

    To assess the prevalence of relapses of pityriasis rosea (PR), a retrospective cohort study investigated all PR cases diagnosed in Genoa between 2000 and 2013 and followed them up to today. Of 570 cases, 21 (3.7%) relapsed. Most of them had a single episode, but 4 had two episodes and 2 had three episodes. The herald patch was always absent, size and number of the lesions were reduced, and duration was shorter than that of the primary episodes. Constitutional symptoms were present, though less severe than in the primary eruption. Most recurrences occurred within 1 year (16/21, 76.2%). Men outnumbered women and the mean age of the relapsing patients (20.3 years) was higher than that for the primary episode. A pathogenetic hypothesis is provided: since PR is associated with reactivation of human herpesvirus 6/7, a parallelism with other typical reactivating human herpesviruses (varicella zoster virus and Epstein-Barr virus) has been established.

  12. Surgical acute abdomen in elderly patients.

    Directory of Open Access Journals (Sweden)

    Itengré Ouédraogo

    2004-08-01

    Full Text Available Fundaments : The surgical acute abdomen usually is the most frequent cause of abdominal surgery of urgency in t he old one, with the high mortality in spite of the modern surgical technologies. Objective: To evaluate the surgery of the surgical acute abdomen in the old one. Method: Appears a prospectivo descriptive study that includes 102 patients of 60 years or more who underwent surgery at the ¨Dr Gustavo Aldereguía Lima¨ University Hospital of Cienfuegos with this diagnostic. The primary data were obtained from clinical cards of the patients and the daily clinical observation until the debit. Results: The patients presented an average age of 74 years, being the most frequent causes of the syndrome intestinal obstruction (32,4%, the biliary tract affections (22,5%, and acute appendicitis (21,6%. The most frequent symptom was abdominal pain (96,08%, and we noticed tachycardia in 80,4%. Postoperating complications in 47,06% of the patients appeared and was observed a mortality of 26,5% with statistically significant relation with the age, ASA classification, surgical risk, time of evolution and the surgical time. The peritonitis heads the direct causes of death.

  13. Immunological effects of donor lymphocyte infusion in patients with chronic myelogenous leukemia relapsing after bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Castro F.A.

    2004-01-01

    Full Text Available Allogeneic bone marrow transplantation (alloBMT is the only curative therapy for chronic myelogenous leukemia (CML. This success is explained by the delivery of high doses of antineoplastic agents followed by the rescue of marrow function and the induction of graft-versus-leukemia reaction mediated by allogeneic lymphocytes against host tumor cells. This reaction can also be induced by donor lymphocyte infusion (DLI producing remission in most patients with CML who relapse after alloBMT. The immunological mechanisms involved in DLI therapy are poorly understood. We studied five CML patients in the chronic phase, who received DLI after relapsing from an HLA-identical BMT. Using flow cytometry we evaluated cellular activation and apoptosis, NK cytotoxicity, lymphocytes producing cytokines (IL-2, IL-4 and IFN-gamma, and unstimulated (in vivo lymphocyte proliferation. In three CML patients who achieved hematological and/or cytogenetic remission after DLI we observed an increase of the percent of activation markers on T and NK cells (CD3/DR, CD3/CD25 and CD56/DR, of lymphocytes producing IL-2 and IFN-gamma, of NK activity, and of in vivo lymphocyte proliferation. These changes were not observed consistently in two of the five patients who did not achieve complete remission with DLI. The percent of apoptotic markers (Fas, FasL and Bcl-2 on lymphocytes and CD34-positive cells did not change after DLI throughout the different study periods. Taken together, these preliminary results suggest that the therapeutic effect of DLI in the chronic phase of CML is mediated by classic cytotoxic and proliferative events involving T and NK cells but not by the Fas pathway of apoptosis.

  14. Triglyceride levels and apolipoprotein E polymorphism in patients with acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Radka Ivanova; Susana Puerta; Alfonso Garrido; Ignacio Cueto; Ana Ferro; María José Ariza; Andrés Cobos; Pedro González-Santos; Pedro Valdivielso

    2012-01-01

    BACKGROUND: Hypertriglyceridemia is an unusual cause of acute pancreatitis and sometimes considered to be an epiphenomenon. This study aimed to investigate the clinical and analytical features and the APOE genotypes in patients with acute pancreatitis and severe hypertriglyceridemia. METHODS: We undertook a one-year, prospective study of patients with acute pancreatitis whose first laboratory analysis on admission to the emergency department included measurement of serum triglycerides. The APOE genotype was determined and the patients answered an established questionnaire within the first 24 hours concerning their alcohol consumption, the presence of co-morbidities and any medications being taken. The patients' progression, etiological diagnosis, hospital stay and clinical and radiological severity were all recorded. RESULTS: Hypertriglyceridemia was responsible for 7 of 133 cases of pancreatitis (5%); the remaining cases were of biliary (53%), idiopathic (26%), alcoholic (11%) or other (5%) origin. Compared with these remaining cases, the patients with hypertriglyceridemia were significantly younger, had more relapses, and more often had diabetes mellitus. They usually consumed alcohol or consumed it excessively on the days before admission. Also, the ε4 allele of the APOE gene was more common in this group (P CONCLUSION: One of 20 episodes of acute pancreatitis is caused by hypertriglyceridemia and it is linked to genetic (ε4 allele) and comorbid factors such as diabetes and, especially, alcohol consumption.

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

    Energy Technology Data Exchange (ETDEWEB)

    Tseng, Yolanda D., E-mail: ydt2@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Chen, Yu-Hui [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Catalano, Paul J. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts (United States); Ng, Andrea [Department of Radiation Oncology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States)

    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

  16. Analysis of associated factors for remission and relapse in proliferative and membranous lupus nephritis patients: a 4-year follow-up study

    Institute of Scientific and Technical Information of China (English)

    戚超君

    2014-01-01

    Objective To explore the related factors of remission and relapse in lupus nephritis(LN)patients.Methods A retrospective study was conducted for proliferation and membrane LN patients diagnosed from 2003 to 2010.Their clinical,laboratory and pathological parameters were collected.According to the response to treatment,they were divided into 3

  17. Corpus Callosum Function in Verbal Dichotic Listening: Inferences from a Longitudinal Follow-Up of Relapsing-Remitting Multiple Sclerosis Patients

    Science.gov (United States)

    Gadea, Marien; Marti-Bonmati, Luis; Arana, Estanislao; Espert, Raul; Salvador, Alicia; Casanova, Bonaventura

    2009-01-01

    This study conducted a follow-up of 13 early-onset slightly disabled Relapsing-Remitting Multiple Sclerosis (RRMS) patients within an year, evaluating both CC area measurements in a midsagittal Magnetic Resonance (MR) image, and Dichotic Listening (DL) testing with stop consonant vowel (C-V) syllables. Patients showed a significant progressive…

  18. THE TOLERABILITY OF CONTINUOUS INTRAVENOUS-INFUSION OF INTERLEUKIN-3 AFTER DHAP CHEMOTHERAPY IN PATIENTS WITH RELAPSED MALIGNANT-LYMPHOMA - A PHASE-I STUDY

    NARCIS (Netherlands)

    RAEMAEKERS, JMM; VANIMHOFF, GW; VERDONCK, LF; HESSELS, JA; FIBBE, WE

    1993-01-01

    The objective of this phase-I study was to establish the maximum tolerable dose of recombinant human interleukin-3 (rhIL-3) after salvage chemotherapy in patients with malignant lymphoma. Twenty-one patients with relapsed Hodgkin's disease or intermediate/high-grade non-Hodgkin's lymphoma received r

  19. Fatal Bacillus cereus endocarditis masquerading as an anthrax-like infection in a patient with acute lymphoblastic leukemia: case report.

    Science.gov (United States)

    Cone, Lawrence A; Dreisbach, Luke; Potts, Barbara E; Comess, Barbara E; Burleigh, William A

    2005-01-01

    A 38-year-old male farm worker with relapsing acute lymphoblastic leukemia spontaneously developed an ulcerating ulcer on his anterior thigh which was surrounded by a non-tender area of erythema. Bacillus cereus was isolated from the ulcer and blood, and the patient received intravenous penicillin and vancomycin for one week. When sensitivity studies were returned he was treated with gatifloxacin orally. After two weeks of combined antimicrobial therapy and negative blood cultures, the patient received combination chemotherapy with vincristine, prednisone, doxorubicin and cyclophosphamide. He was hospitalized a day after completing chemotherapy with neutropenic sepsis due to B. cereus. He received similar antimicrobial therapy as previously, but died three days later. At autopsy, the patient was found to have acute mitral valve endocarditis and bilateral brain abscesses. This was the first case of B. cereus endocarditis reported in a patient with acute lymphoblastic leukemia.

  20. Comprehensive genomic analysis reveals FLT3 activation and a therapeutic strategy for a patient with relapsed adult B-lymphoblastic leukemia.

    Science.gov (United States)

    Griffith, Malachi; Griffith, Obi L; Krysiak, Kilannin; Skidmore, Zachary L; Christopher, Matthew J; Klco, Jeffery M; Ramu, Avinash; Lamprecht, Tamara L; Wagner, Alex H; Campbell, Katie M; Lesurf, Robert; Hundal, Jasreet; Zhang, Jin; Spies, Nicholas C; Ainscough, Benjamin J; Larson, David E; Heath, Sharon E; Fronick, Catrina; O'Laughlin, Shelly; Fulton, Robert S; Magrini, Vincent; McGrath, Sean; Smith, Scott M; Miller, Christopher A; Maher, Christopher A; Payton, Jacqueline E; Walker, Jason R; Eldred, James M; Walter, Matthew J; Link, Daniel C; Graubert, Timothy A; Westervelt, Peter; Kulkarni, Shashikant; DiPersio, John F; Mardis, Elaine R; Wilson, Richard K; Ley, Timothy J

    2016-07-01

    The genomic events responsible for the pathogenesis of relapsed adult B-lymphoblastic leukemia (B-ALL) are not yet clear. We performed integrative analysis of whole-genome, whole-exome, custom capture, whole-transcriptome (RNA-seq), and locus-specific genomic assays across nine time points from a patient with primary de novo B-ALL. Comprehensive genome and transcriptome characterization revealed a dramatic tumor evolution during progression, yielding a tumor with complex clonal architecture at second relapse. We observed and validated point mutations in EP300 and NF1, a highly expressed EP300-ZNF384 gene fusion, a microdeletion in IKZF1, a focal deletion affecting SETD2, and large deletions affecting RB1, PAX5, NF1, and ETV6. Although the genome analysis revealed events of potential biological relevance, no clinically actionable treatment options were evident at the time of the second relapse. However, transcriptome analysis identified aberrant overexpression of the targetable protein kinase encoded by the FLT3 gene. Although the patient had refractory disease after salvage therapy for the second relapse, treatment with the FLT3 inhibitor sunitinib rapidly induced a near complete molecular response, permitting the patient to proceed to a matched-unrelated donor stem cell transplantation. The patient remains in complete remission more than 4 years later. Analysis of this patient's relapse genome revealed an unexpected, actionable therapeutic target that led to a specific therapy associated with a rapid clinical response. For some patients with relapsed or refractory cancers, this approach may indicate a novel therapeutic intervention that could alter outcome.

  1. Outcomes for newly diagnosed patients with acute myeloid leukemia dosed on actual or adjusted body weight.

    Science.gov (United States)

    Bray, Whitney M; Bivona, Cory; Rockey, Michelle; Henry, Dave; Grauer, Dennis; Abhyankar, Sunil; Aljitawi, Omar; Ganguly, Siddhartha; McGuirk, Joseph; Singh, Anurag; Lin, Tara L

    2015-10-01

    Data from solid tumor malignancies suggest that actual body weight (ABW) dosing improves overall outcomes. There is the potential to compromise efficacy when chemotherapy dosages are reduced, but the impact of dose adjustment on clinical response and toxicity in hematologic malignancies is unknown. The purpose of this study was to evaluate the outcomes of utilizing a percent of ABW for acute myeloid leukemia (AML) induction chemotherapy dosing. This retrospective, single-center study included 146 patients who received 7 + 3 induction (cytarabine and anthracycline) for treatment of AML. Study design evaluated the relationship between percentage of ABW dosing and complete response (CR) rates in patients newly diagnosed with AML. Percentage of ABW dosing did not influence CR rates in patients undergoing induction chemotherapy for AML (p = 0.83); nor did it influence rate of death at 30 days or relapse at 6 months (p = 0.94). When comparing patients dosed at 90-100 % of ABW compared to ABW, CR rates were not significantly different in patients classified as poor risk (p = 0.907). All favorable risk category patients obtained CR. Preemptive dose reductions for obesity did not influence CR rates for patients with AML undergoing induction chemotherapy and did not influence the composite endpoint of death at 30 days or disease relapse at 6 months.

  2. Epidemiology of acute otitis in pediatric patients

    Directory of Open Access Journals (Sweden)

    Maddalena Perotti

    2011-03-01

    Full Text Available Introduction. Acute otitis is one of the most common pediatric infectious diseases that requires an accurate diagnosis in order to direct appropriate therapy to reduce the risk of complications. In this study pathogens collected from pediatric patients and their antibiotic susceptibility patterns were evaluated. Methods. Between May 2009 and May 2010, 739 samples (swabs taken from nasopharynx in case of acute otitis media and/or from ears in case of acute external otitis, collected from 680 patients, suffering of otalgia, admitted to the emergency department of our Hospital were studied.The specimens were submitted for routine bacterial cultures and the susceptibility tests were performed according to Clinical Laboratory Standards. Nitrocefin was used to detect ß-lactamase activity. Results. 316 samples (42.8% of 739 were negative, 102 (13.8% were positive for Streptococcus pneumoniae, 97 (13.1% for Moraxella catarrhalis, 68 (9.2% for Haemophilus influenzae, 62 (8.4% for Pseudomonas aeruginosa, 49 (6.6% for Staphylococcus aureus, 36 (4.9% for Streptococcus pyogenes, 5 (0.7% for Gram negative and 4 (0.5% for Candida spp. Antibiotic susceptibility tests showed that amikacin, ceftazidime, ciprofloxacin, imipenem, meropenem and piperacillin/tazobactam were active against all Gram negative strains isolated.We found one strain of MRSA. Of 102 Streptococcus pneumoniae, 5 (4.9% were penicillin resistant and 25 (24.5% were erythromycin resistant, showing the prevalence of constitutive phenotype (80%. All M. catarrhalis strains were ß-lactamase producers while all H. influenzae were ß-lactamase negatives. Conclusions. The prevalent etiological agents in pediatric acute otitis are S. pneumoniae, M. catharralis, and H. influenzae, as reported in literature. In external acute otitis P. aeruginosa prevails in particular in summer.

  3. {sup 11}C-Choline PET/CT detects the site of relapse in the majority of prostate cancer patients showing biochemical recurrence after EBRT

    Energy Technology Data Exchange (ETDEWEB)

    Ceci, Francesco; Graziani, Tiziano; Lodi, Filippo; Fanti, Stefano [University of Bologna, Service of Nuclear Medicine, Policlinico S. Orsola Malpighi, Bologna (Italy); Castellucci, Paolo [University of Bologna, Service of Nuclear Medicine, Policlinico S. Orsola Malpighi, Bologna (Italy); Azienda Ospedaliero-Unversitaria di Bologna Policlinico Sant' Orsola-Malpighi, UO di Medicina Nucleare, PAD. 30, Bologna (Italy); Schiavina, Riccardo; Brunocilla, Eugenio; Martorana, Giuseppe [University of Bologna, Department of Urology, Policlinico S. Orsola Malpighi, Bologna (Italy); Mazzarotto, Renzo; Ntreta, Maria [University of Bologna, Service of Radiotherapy, Policlinico S. Orsola Malpighi, Bologna (Italy)

    2014-05-15

    The aim of this retrospective study was to evaluate the usefulness and the detection rate of {sup 11}C-choline PET/CT in a population of patients with prostate cancer (PC), exclusively treated with external beam radiotherapy (EBRT) as primary treatment, who showed biochemical relapse. We enrolled 140 patients showing a serum PSA level >2 ng/mL (mean 8.6 ng/mL, median 5 ng/mL, range 2 - 60 ng/mL). All patients had been treated with EBRT to the prostate gland and prostatic fossa with doses ranging from 70 to 76 Gy in low-risk patients (T1/T2 and/or serum PSA <10 ng/mL) and escalating to >76 Gy (range 76 - 81 Gy) in high-risk patients (T3/T4 and/or serum PSA >10 ng/mL). Of the 140 patients, 53 were receiving androgen deprivation therapy at the time of the scan. All positive {sup 11}C-choline PET/CT findings were validated by transrectal ultrasound-guided biopsy or at least 12 months of follow-up with contrast-enhanced CT, MR, bone scintigraphy or a repeated {sup 11}C-choline PET/CT scan. The relationships between the detection rate of {sup 11}C-choline PET/CT and the factors PSA level, PSA kinetics, Gleason score, age, time to relapse and SUVmax in patients with positive findings were analysed. {sup 11}C-Choline PET/CT detected the site of relapse in 123 of the 140 patients with a detection rate of 87.8 % (46 patients showed local relapse, 31 showed local and distant relapse, and 46 showed only distant relapse). In patients with relapse the mean serum PSA level was 9.08 ng/mL (median 5.1 ng/mL, range 2 - 60 ng/mL), the mean PSA doubling time was 5.6 months (median 3.5 months, range 0.4 - 48 months), and the mean PSA velocity was 15 ng/mL/year (median 8.8 ng/mL/year, range 0.4 - 87 ng/mL/year). Of the 123 patients with relapse, 77 (62.6 %) showed distant relapse with/without local relapse, and of these 77, 31 (40.2 %) showed oligometastatic disease (one or two distant lesions: lymph node lesions only in 16, bone lesions only in 14, and lymph node lesions and bone

  4. 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

  5. Role of Salvage Radiation Therapy for Patients With Relapsed or Refractory Hodgkin Lymphoma Who Failed Autologous Stem Cell Transplant

    Energy Technology Data Exchange (ETDEWEB)

    Goda, Jayant S. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Massey, Christine [Department of Biostatistics, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Kuruvilla, John [Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Gospodarowicz, Mary K.; Wells, Woodrow; Hodgson, David C.; Sun, Alexander [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Keating, Armand; Crump, Michael [Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Tsang, Richard W., E-mail: richard.tsang@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada)

    2012-11-01

    Purpose: To analyze, through chart review, the efficacy of salvage radiation therapy (sRT) for relapsed or progressive Hodgkin lymphoma (HL) patients who failed autologous stem cell transplant (ASCT). Patients and Methods: Among 347 patients with recurrent/refractory HL who received ASCT from 1986-2006, 163 had post-ASCT progression or relapse. Of these, 56 received sRT and form the basis of this report. Median age at sRT was 30 years (range, 17-59 years). Disease was confined to lymph nodes in 27 patients, whereas 24 had both nodal and extranodal disease. Salvage radiation therapy alone was given in 34 patients (61%), and sRT plus chemotherapy was given in 22 (39%). Median interval from ASCT to sRT was 0.8 years (range, 0.1-5.6 years). The median dose was 35 Gy (range, 8-40.3 Gy). The sRT technique was extended-field in 14 patients (25%) and involved-field in 42 (75%). Results: The median follow-up from sRT was 31.3 months (range, 0.2-205.5 months). Overall response rate was 84% (complete response: 36%; partial response: 48%). The median overall survival was 40.8 months (95% confidence interval, 34.2-56.3 months). The 5-year overall survival was 29% (95% confidence interval, 14%-44%). The 2-year progression-free survival (PFS) was 16%; the 2-year local PFS was 65%, whereas the 2-year systemic PFS was 17%. The 1-year PFS was higher in patients in whom all diseased sites were irradiated (49%) compared with those in whom only the symptomatic site was treated (22%, P=.07). Among 20 alive patients, 5 were disease free (at 6.4, 6.8, 7.4, 7.9, and 17.1 years). Conclusion: For patients with HL who fail ASCT, a selective use of RT provides a durable local control rate of 65% at 2 years and should be considered as part of the standard management plan for the palliation of incurable HL. Occasionally irradiation of truly localized disease can lead to long-term survival.

  6. Fatal Relapse of Myelodysplastic Syndrome in a Patient with HIV/Hepatitis C Coinfection Treated with Simeprevir/Sofosbuvir.

    Science.gov (United States)

    Diejomaoh, Efemena Michael; Gathe, Joseph Clayton; Mayberry, Carl Craig; Clemmons, John Benjamin; Miguel, Bernie; Glombicki, Alan; Daquioag, Benjamin

    2017-01-01

    Registrational studies and observational cohorts clearly suggest sustained virologic response (SVR) rates in HIV-/hepatitis C-coinfected patients are similar to monoinfected patients when utilizing interferon-free regimens, and this can be accomplished with agents that are well tolerated with minimal adverse events. These randomized trials that led to the approval of several of our new direct-acting antiviral agents, however, specifically excluded patients who had significant comorbidities and none to our knowledge accepted patients with a history of cancer. Therefore, the effect of treatment of active hepatitis C in such patients and the effect on preexisting neoplasia are relatively unknown. We prospectively followed a 62-year-old male coinfected with HIV/hepatitis C who had a history of anal squamous cell carcinoma, prostate carcinoma, renal cell carcinoma all clinically cured and a myelodysplastic syndrome that was in remission. The patient achieved an SVR of hepatitis C with simeprevir/sofosbuvir without ribavirin and died shortly thereafter of a fatal relapse of his previously clinically controlled myelodysplastic syndrome.

  7. Acute kidney injury in the pregnant patient.

    Science.gov (United States)

    Nwoko, Rosemary; Plecas, Darko; Garovic, Vesna D

    2012-12-01

    Acute kidney injury (AKI) is costly and is associated with increased mortality and morbidity. An understanding of the renal physiologic changes that occur during pregnancy is essential for proper evaluation, diagnosis, and management of AKI. As in the general population, AKI can occur from prerenal, intrinsic, and post-renal causes. Major causes of pre-renal azotemia include hyperemesis gravidarum and uterine hemorrhage in the setting of placental abruption. Intrinsic etiologies include infections from acute pyelonephritis and septic abortion, bilateral cortical necrosis, and acute tubular necrosis. Particular attention should be paid to specific conditions that lead to AKI during the second and third trimesters, such as preeclampsia, HELLP syndrome, acute fatty liver of pregnancy, and TTP-HUS. For each of these disorders, delivery of the fetus is the recommended therapeutic option, with additional therapies indicated for each specific disease entity. An understanding of the various etiologies of AKI in the pregnant patient is key to the appropriate clinical management, prevention of adverse maternal outcomes, and safe delivery of the fetus. In pregnant women with pre-existing kidney disease, the degree of renal dysfunction is the major determining factor of pregnancy outcomes, which may further be complicated by a prior history of hypertension.

  8. Relapse and hospitalization in patients with schizophrenia and bipolar disorder at the St Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia: a comparative quantitative cross-sectional study.

    Science.gov (United States)

    Ayano, Getnet; Duko, Bereket

    2017-01-01

    Relapse and hospital admission are common among, and carry a heavy burden in, patients with schizophrenia and bipolar disorder. The aim of this study was to assess the risk of relapse and hospitalizations in patients with schizophrenia and bipolar disorder at the St Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia. A hospital-based comparative cross-sectional study was conducted in June 2016. Systematic random sampling technique was used to recruit 521 (260 schizophrenia cases and 261 bipolar disorder cases) study participants. Face-to-face interviews were conducted by trained psychiatry professionals. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria and Structured Clinical Interview of DSM-IV (SCID) were used. The risk of relapse and hospitalizations was slightly higher in patients with bipolar disorder than in patients with schizophrenia. A majority of schizophrenic (213 [81.92%]) and bipolar (215 [82.37%]) patients had a history of hospital admission, and 228 (87.69%) schizophrenic and 230 (88.12%) bipolar patients had a history of relapse. Patients who had a history of hospitalizations also had co-occurring substance use disorders compared to those who had no history of hospitalizations for schizophrenia (81.5% vs 37.9%) and bipolar disorder (82.56% vs 38.2%), respectively. Similarly, those patients who had a history of relapse had high comorbid substance use disorders than those who had no history of relapse for both schizophrenia (87.88% vs 47.37%) and bipolar disorder (88.37% vs 47.19%), respectively. It is vital that, in the local context, mental health professionals strengthen their therapeutic relationships with patients and their caregivers. This might enable patients and their caregivers to express their needs and concerns to them, as well as help to plan proper interventions for patients. Attention needs to be given to screening for comorbid substance use disorders in patients with

  9. Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias

    Science.gov (United States)

    2010-09-21

    Myelodysplastic Syndrome; Acute Myeloid Leukemia; Myeloproliferative Disorders; Acute Lymphocytic Leukemia; Acute Promyelocytic Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia; Myelofibrosis; Chronic Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia

  10. Frequency and Prognostic Relevance of FLT3 Mutations in Saudi Acute Myeloid Leukemia Patients

    Directory of Open Access Journals (Sweden)

    Ghaleb Elyamany

    2014-01-01

    Full Text Available The Fms-like tyrosine kinase-3 (FLT3 is a receptor tyrosine kinase that plays a key role in cell survival, proliferation, and differentiation of hematopoietic stem cells. Mutations of FLT3 were first described in 1997 and account for the most frequent molecular mutations in acute myeloid leukemia (AML. AML patients with FLT3 internal tandem duplication (ITD mutations have poor cure rates the prognostic significance of point mutations; tyrosine kinase domain (TKD is still unclear. We analyzed the frequency of FLT3 mutations (ITD and D835 in patients with AML at diagnosis; no sufficient data currently exist regarding FLT3 mutations in Saudi AML patients. This study was aimed at evaluating the frequency of FLT3 mutations in patients with AML and its significance for prognosis. The frequency of FLT3 mutations in our study (18.56% was lower than many of the reported studies, FLT3-ITD mutations were observed in 14.4%, and FLT3-TKD in 4.1%, of 97 newly diagnosed AML patients (82 adult and 15 pediatric. Our data show significant increase of FLT3 mutations in male more than female (13 male, 5 female. Our results support the view that FLT3-ITD mutation has strong prognostic factor in AML patients and is associated with high rate of relapse, and high leucocytes and blast count at diagnosis and relapse.

  11. Early assessment of minimal residual disease identifies patients at very high relapse risk in NPM-ALK-positive anaplastic large-cell lymphoma.

    Science.gov (United States)

    Damm-Welk, Christine; Mussolin, Lara; Zimmermann, Martin; Pillon, Marta; Klapper, Wolfram; Oschlies, Ilske; d'Amore, Emanuele S G; Reiter, Alfred; Woessmann, Wilhelm; Rosolen, Angelo

    2014-01-16

    Detection of minimal disseminated disease (MDD) at diagnosis correlates with relapse risk in children with anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL). We investigated whether minimal residual disease (MRD) positivity by qualitative reverse-transcriptase polymerase chain reaction (RT-PCR) for Nucleophosmin (NPM)-ALK during treatment identifies patients at the highest relapse risk. Blood and/or bone marrow of 180 patients with NPM-ALK-positive ALCL treated with Berlin-Frankfurt-Münster-type protocols were screened for NPM-ALK transcripts at diagnosis; 103 were found to be MDD-positive. MRD before the second therapy course could be evaluated in 52 MDD-positive patients. MRD positivity correlated with uncommon histology. The cumulative incidence of relapses (CIR) of 26 MDD-positive/MRD-positive patients (81% ± 8%) was significantly higher than the CIR of 26 MDD-positive/MRD-negative (31% ± 9%) and 77 MDD-negative patients (15% ± 5%) (P NPM-ALK-positive ALCL identifies patients with a very high relapse risk and inferior survival.

  12. Weight-based combination therapy with peginterferon alpha-2b and ribavirin for Naïve, relapser and non-responder patients with chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    Fernando Lopes Gonçales Jr.

    2006-10-01

    Full Text Available Combination therapy with pegylated interferon and ribavirin is considered the new standard therapy for naïve patients with chronic hepatitis C. We evaluated the efficacy and safety of treatment with weight-based peginterferon alpha-2b (1.5 mg/kg per week plus ribavirin (800-1,200 mg/day for 48 weeks in naïve, relapser and non-responder (to previous treatment with interferon plus ribavirin patients with chronic hepatitis C. Sixty-seven naïve, 26 relapser and 40 non-responder patients were enrolled. The overall sustained virological response (SVR for the intention-to-treat population was 54% for naïve, 62% for relapser and 38% for non-responder patients. In the naïve subgroup, SVR was significantly higher in patients with the non-1 genotype (67% compared to those with genotype 1 (45%. In relapsers and non-responders, SVR was, respectively, 69% and 24% in patients with genotype 1 and 43% and 73% in those with genotype non-1. There were no significant differences in SVR rates among the three body weight ranges ( 85 kg in any of the subgroups. Early virological response (EVR was reached by 78%, 81% and 58% of naïve, relapser and non-responder patients, respectively, and among those with EVR, 63%, 67% and 61%, respectively, subsequently achieved SVR. All of the non-responder patients who did not have EVR reached SVR. Treatment was discontinued in 13% of the patients, due to loss to follow-up, hematological abnormalities or depression.

  13. Acute Respiratory Distress Syndrome in Obstetric Patients

    Directory of Open Access Journals (Sweden)

    S. V. Galushka

    2007-01-01

    Full Text Available Objective: to define the specific features of the course of acute respiratory distress syndrome (ARDS in puer-peras with a complicated postpartum period. Subjects and methods. Sixty-seven puerperas with ARDS were examined. Group 1 included 27 puerperas with postpartum ARDS; Group 2 comprised 10 puerperas who had been treated in an intensive care and died; Group 3 consisted of nonobstetric patients with ARDS of various genesis (a control group. Results. In obstetric patients, the baseline oxygenation index was significantly lower than that in the control group. However, Group 1 patients showed a rapid increase in PaO2/FiO2 on days 3—4 of treatment. In the control group, the changes occurred later — on days 5—6. The baseline alveolar-arterial oxygen difference was significantly higher in the obstetric patients than that in the controls. In Group 1, AaDpO2 drastically decreased on days 3—4, which took place in parallel with an increase in the oxygenation index. At the beginning of the study, pulmonary shunting was high in the group of survivors, deceased, and controls. In Group 1, the shunting decreased on days 3—4 whereas in the control group this index normalized later — only by days 6—7. In Group 1, compliance remained lower throughout the observation, but on day 7 there was a significant difference in this index between the deceased, survivors, and controls. Conclusion. Thus, more severe baseline pulmonary gas exchange abnormalities are observed in obstetric patients than in general surgical and traumatological patients; the oxygenation index, alveolar-arterial oxygen difference, and pulmonary shunting index more rapidly change in patients with severe obstetric disease in its favorable course than in general surgical and traumatological patients; throughout the observation, thoracopulmonary compliance was less in obstetric patients than in the controls. Key words: acute respiratory distress syndrome, puerperium.

  14. Acute pain management in burn patients

    DEFF Research Database (Denmark)

    Gamst-Jensen, Hejdi; Vedel, Pernille Nygaard; Lindberg-Larsen, Viktoria Oline

    2014-01-01

    management addresses and alleviates these complications. The aim of our study was to compare clinical guidelines for pain management in burn patients in selected European and non-European countries. We included pediatric guidelines due to the high rate of children in burn units. METHOD: The study had...... patients. The most highly recommended guidelines provided clear and accurate recommendations for the nursing and medical staff on pain management in burn patients. We recommend the use of a validated appraisal tool such as the AGREE instrument to provide more consistent and evidence-based care to burn......OBJECTIVE: Burn patients suffer excruciating pain due to their injuries and procedures related to surgery, wound care, and mobilization. Acute Stress Disorder, Post-Traumatic Stress Disorder, chronic pain and depression are highly prevalent among survivors of severe burns. Evidence-based pain...

  15. ACUTE-PANCREATITIS IN A PATIENT WITH FAMILIAL BENIGN HYPERCALCEMIA

    NARCIS (Netherlands)

    VANHAEFTEN, TW; HOOGENBERG, K; VANESSEN, LH

    1994-01-01

    A patient with familial benign hypercalcaemia (FBH) who developed relapsing pancreatitis is presented. She underwent distal partial pancreas resection with surgical removal of pancreatic duct stones, and a pancreaticojejunostomy. No further causes for the pancreatitis were found. The present case is

  16. Acute renal failure in Yemeni patients

    Directory of Open Access Journals (Sweden)

    Muhamed Al Rohani

    2011-01-01

    Full Text Available Acute renal failure (ARF is defined as a rapid decrease in the glomerular filtration rate, occurring over a period of hours to days. The Science and Technology University Hospital, Sana′a, is a referral hospital that caters to patients from all parts of Yemen. The aim of this study is to have a deeper overview about the epidemiological status of ARF in Yemeni patients and to identify the major causes of ARF in this country. We studied 203 patients with ARF over a period of 24 months. We found that tropical infectious diseases constituted the major causes of ARF, seen in 45.3% of the patients. Malaria was the most important and dominant infectious disease causing ARF. Hypotension secondary to infection or cardiac failure was seen in 28.6% of the patients. Obstructive nephropathy due to urolithiasis or prostate enlargement was the cause of ARF in a small number of patients. ARF was a part of multi-organ failure in 19.7% of the patients, and was accompanied by a high mortality rate. Majority of the patients were managed conservatively, and only 39.9% required dialysis. Our study suggests that early detection of renal failure helps improve the outcome and return of renal function to normal. Mortality was high in patients with malaria and in those with associated hepatocellular failure.

  17. Radioimmunotherapy with {sup 131}I-Rituximab in a Patient with Diffuse Large B-Cell Lymphoma Relapsed After Treatment with {sup 90}Y-Ibritumomab Tiuxetan

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Geon Wook; Kang, Hye Jin; Shin, Dongyeop; Gu, Ha Ra; Choi, Hong Seok; Lim, Sang Moo [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    2013-12-15

    We report a case that demonstrates the efficacy of radioimmunotherapy (RIT) with radioiodinated rituximab ({sup 131}I-rituximab) for relapsed diffuse large B-cell lymphoma (DLBCL). A 79-year-old male patient with DLBCL initially achieved a complete response (CR) after six cycles of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. However, the lymphoma relapsed 20 months later. Although the patient had achieved a second and a third CR after two cycles of {sup 90}Y-ibritumomab tiuxetan, he experienced a third relapse approximately 3 years later. Between March and June 2011, the patient received three cycles of {sup 131}I-rituximab. Although he had achieved partial response after the second cycle, the disease progressed after the third cycle, and the total progression. Free survival was thus 5 months. The patient suffered only relatively mild toxicity (grade 1 thrombocytopenia) during treatment. RIT with {sup 131}I-rituximab is therefore potentially effective in patients with relapsed DLBCL, even after the failure of {sup 90}Y-ibritumomab tiuxetan therapy.

  18. Treatment with lenalidomide (Revlimid®), cyclophosphamide (Endoxan®) and prednisone (REP) in relapsed/refractory multiple myeloma patients: results of a single centre retrospective study.

    Science.gov (United States)

    Zelis, N; Devos, T; Dierickx, D; Janssens, A; Raddoux, J; Verhoef, G; Delforge, M

    2014-04-01

    Lenalidomide (Revlimid®) combined with intermittent dexamethasone (the RD regimen) is one of the current standards for treatment of patients with relapsed/refractory multiple myeloma (MM). However, since the disease in the majority of patients will become resistant to RD, or treatment with RD needs to be discontinued due to side effects, we evaluated the combination lenalidomide, low-dose oral cyclophosphamide, with prednisone (REP) in patients with relapsed/refractory MM previously exposed to RD. For this purpose, we performed a single centre retrospective study of the efficacy of REP in 19 patients with relapsed/refractory MM. Overall response rate (partial response or better) with REP was 68% compared with 83% with RD, but with a shorter time to response with the triplet REP. Time to progression after REP was 6 months. Overall the REP regimen was better tolerated compared to RD. We conclude that the REP regimen is an effective treatment regimen for patients with relapsed/refractory MM with good tolerance, warranting further exploration in prospective randomized trials.

  19. 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.

  20. Response to Therapeutic Plasma Exchange as a Rescue Treatment in Clinically Isolated Syndromes and Acute Worsening of Multiple Sclerosis: A Retrospective Analysis of 90 Patients.

    Directory of Open Access Journals (Sweden)

    Johannes Ehler

    Full Text Available Experience with therapeutic plasma exchange (TPE for acute relapses in clinically isolated syndrome (CIS or multiple sclerosis (MS patients has been derived from small and inhomogeneous patient populations so far. In the present study, we retrospectively evaluated features associated with TPE response in a larger cohort of CIS and MS patients with acute worsening of disease.Ninety CIS and MS patients with acute relapses or acute worsening of symptoms were firstly treated with TPE. The population consisted of 62 women and 28 men with a median age of 38 years (range 18-69 years.Primary endpoint was the clinical response to TPE, focused on the functional improvement of the target neurologic deficit. Secondary endpoint was an improvement in expanded disability status scale (EDSS scoring.A clinical response to TPE was observed in 65 out of 90 patients (72.2%, with marked improvement in 18 (20.0% and moderate improvement in 47 out of 90 patients (52.2%. The median EDSS was reduced from 3.75 before to 3.0 after TPE (p = 0.001. Response to TPE was significantly more frequent in patients with relapsing courses of disease (CIS, RR-MS, p = 0.001, no disease modifying drugs (p = 0.017, gadolinium-positive (Gd+ MRI lesions (p = 0.001 and EDSS ≤ 5.0 before TPE (p = 0.014. In the multiple logistic regression analysis only the detection of Gd+ MRI lesions was significantly altered (p = 0.004.Clinical response to TPE was achieved in the majority of our patients. We identified clinical and diagnostic features in CIS and MS relapses that might be helpful to identify patients responding to TPE. Gd+ MRI lesions before treatment were the best predictor of the response to TPE in our cohort.

  1. Clinical Feature and Prognostic Factors for Relapse of Acute Disseminated Encephalomyelitis in Children%急性播散性脑脊髓炎患儿的临床特征及复发因素

    Institute of Scientific and Technical Information of China (English)

    杨斌; 江亮亮; 叶小飞; 何远知; 王成月; 赵忠礼; 张志明

    2011-01-01

    目的 探讨儿童急性播散性脑脊髓炎(ADEM)的临床特征及复发因素.方法 2003年2月-2009年12月,本院神经内科共收治符合ADEM诊断标准并完成随访的48例患儿,分析其临床资料、实验室检查、神经影像学特征及随访结果,总结其临床特征及复发因素.结果 48例ADEM患儿中,男22例,女26例;发病年龄1岁1个月~12岁6个月,中位年龄 6.3岁.发病前驱期有感染症状31例(占65%),疫苗接种史4例(占8%),无明显诱因13例(占27%).临床主要以运动障碍(46例)、精神障碍(21例)、头痛头晕(21例)及意识障碍(15例)为主要表现.MRI以皮质下白质、半卵圆中心、侧脑室周围、基底核、脑干及脊髓损害为主,呈点片状或稍长T1、长T2信号.8例为第2次复发或多次复发.其复发与视神经症状、头颅MRI上显示幕上和幕下病灶同时存在、脊髓病灶及视觉诱发电位异常有关.随访结果:34例完全缓解,无任何神经系统后遗症;8例复发;14例遗留神经功能缺损,主要以运动障碍为主.结论 儿童ADEM临床表现多样,视神经损害及磁共振成像显示病灶的部位对复发的判断有一定的临床价值.ADEM长期预后大多良好,少数患儿遗留神经功能缺损.%Objective To explore the clinical feature and prognostic factors for relapse of acute disseminated encephalomyelitis (ADEM) in children. Methods Forty -eight patients with ADEM in the Department of Neurology of Anhui Provincial Children's Hospital from Feb. 2003 to Dec. 2009 were selected, their clinical data, laboratory examination and neuroimaging character were analyzed, and the clinical feature and prognostic factors for relapse were summarized. Results All the 48 cases included 22 boys and 26 girls, the onset age was from 1 year and 1 month to 12 years and 6 months,median age was 6.3 years old. Among the 48 ADEM children,31 cases (65%) showed infection symptoms in the prodromal period,4 cases (8%) had received

  2. Hepatitis B surface antigen quantification at hepatitis B e antigen seroconversion predicts virological relapse after the cessation of entecavir treatment in hepatitis B e antigen-positive patients

    Directory of Open Access Journals (Sweden)

    Yuan-wang Qiu

    2016-02-01

    Conclusions: HBsAg levels can help guide the timing of cessation of ETV treatment. HBsAg levels of 2.5 log10 IU/ml at HBeAg seroconversion may be a useful marker to predict virological relapse after the cessation of ETV treatment in HBeAg-positive CHB patients.

  3. 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 r...

  4. Mouth and genital ulcers with inflamed cartilage: MAGIC syndrome. Five patients with features of relapsing polychondritis and Behçet's disease.

    Science.gov (United States)

    Firestein, G S; Gruber, H E; Weisman, M H; Zvaifler, N J; Barber, J; O'Duffy, J D

    1985-07-01

    Five patients with features of coexistent relapsing polychondritis and Behçet's disease are described. Review of the literature supports the overlap of the clinical manifestations of these two conditions. A common immunologic abnormality is likely, and elastin is cited as a possible target antigen. The "mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome" is the proposed name for this entity.

  5. Improvement of health-related quality of life in relapsing remitting multiple sclerosis patients after 2 years of treatment with intramuscular interferon-beta-1a.

    NARCIS (Netherlands)

    Jongen, P.J.H.; Sindic, C.; Carton, H.; Zwanikken, C.P.; Lemmens, W.A.J.G.; Borm, G.F.

    2010-01-01

    In patients with relapsing remitting multiple sclerosis (RRMS), the effect of interferon-beta (INFb) on health-related quality of life (HR-QoL) is not firmly documented. The objective of this study is to assess HR-QoL during 2 years of treatment with intramuscular INFb and its correlation with disab

  6. An approach for conjugation of 177 Lu- DOTA-SCN- Rituximab (BioSim & its evaluation for radioimmunotherapy of relapsed & refractory B-cell non Hodgkins lymphoma patients

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    Parul Thakral

    2014-01-01

    Interpretation & conclusions: A favourable radiochemical purity, stability and biodistribution of the radiolabelled immunoconjugate indicate that clinical trials for evaluation of toxicity and efficacy of 177 Lu-DOTA-antiCD20 antibody-Rituximab (BioSim in patients of relapsed and refractory non Hodgkin′s lymphoma can be considered.

  7. Acute myocardial infarction in the obstetric patient.

    Science.gov (United States)

    Firoz, Tabassum; Magee, Laura A

    2012-06-01

    Acute myocardial infraction (AMI) in the obstetric patient is a rare event, although the incidence is rising due to advancing maternal age and pre-existing cardiac risk factors and medical co-morbidities. While atherosclerotic disease is the leading cause of AMI, coronary artery dissection is an important consideration in pregnancy and in the postpartum period. The physiological changes of pregnancy as well as pregnancy-specific risk factors can predispose the obstetric patient to AMI. Diagnosis of AMI can be challenging as symptoms may be atypical. Furthermore, diagnostic tests must be interpreted in the context of pregnancy. While the overall management of the obstetric patient with AMI is similar to that outside of pregnancy, drug therapy requires modification as some medications may be contraindicated in pregnancy and breastfeeding. There is limited information about prognosis and risk stratification but it is anticipated that future studies will address this issue.

  8. Acute coronary syndromes in patients with HIV

    Science.gov (United States)

    Seecheran, Valmiki K.; Giddings, Stanley L.

    2017-01-01

    Highly active antiretroviral treatment (HAART) has considerably increased the life expectancy of patients infected with HIV. Coronary artery disease is a leading cause of mortality in patients infected with HIV. This is primarily attributed to their increased survival, HAART-induced metabolic derangements, and to HIV itself. The pathophysiology of atherosclerosis in HIV is both multifactorial and complex – involving direct endothelial injury and dysfunction, hypercoagulability, and a significant contribution from traditional cardiac risk factors. The advent of HAART has since heralded a remarkable improvement in outcomes, but at the expense of other unforeseen issues. It is thus of paramount importance to swiftly recognize and manage acute coronary syndromes in HIV-infected patients to attenuate adverse complications, which should translate into improved clinical outcomes. PMID:27845996

  9. Chemotherapy versus radiotherapy in early-stage Hodgkin's disease: evidence of a more difficult rescue for patients relapsed after chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Cimino, G.; Cartoni, C. (Univ. ' ' La Sapienza' ' , Rome (Italy). Dept. of Human Biopathology); Biti, G.P.; Magrini, S.M. (Florence Univ. (Italy))

    1992-08-01

    Six cycles of mechloretamine, vincristine, procarbazine and prednisone (MOPP) chemotherapy were randomly compared with extended field radiotherapy (RT) in 89 adult patients with pathological stage I-II A Hodgkin's disease (HD). 45 patients received RT and 44 were treated with MOPP. Complete remission (CR) was obtained in all patients in the RT group and in 40 of 44 in the MOPP group. 12 patients relapsed in both groups. 10 out of 44 patients treated with MOPP died of HD, compared with only 2 in the RT group. 3 more patients died in the MOPP group following the occurrence of second cancers. 11 out of the 12 (96%) patients relapsing after RT achieved a second CR, compared with 6 out of the 12 (50%) patients relapsing after MOPP. With a median follow-up of more than 8 years, overall survival of patients was significantly better for RT compared with MOPP; 93 and 56% respectively (P < 0.001). The authors conclude RT alone remains the treatment of choice for adult patients with early-stage HD with favourable prognosis. (Author).

  10. A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies

    DEFF Research Database (Denmark)

    Ziemssen, Tjalf; Bajenaru, Ovidiu A; Carrá, Adriana;

    2014-01-01

    .32 (95 % CI 0.26-0.40; p disability was halted, as the Kurtzke Expanded Disability Status Scale (EDSS) scores remained stable. Patients improved significantly (p ...Studies suggest that patients with relapsing-remitting multiple sclerosis (RRMS) who do not benefit from other disease-modifying treatments (DMTs) may benefit from converting to glatiramer acetate (GA). COPTIMIZE was a 24-month observational study designed to assess the disease course of patients...

  11. TH1/TH2 Cytokine profile in relapsing-remitting multiple sclerosis patients treated with Glatiramer acetate or Natalizumab

    Directory of Open Access Journals (Sweden)

    Oreja-Guevara Celia

    2012-09-01

    Full Text Available Abstract Background The balance between T helper cells Th2- and Th1-related cytokines plays a key role in multiple sclerosis (MS. A shift from a Th1 towards a Th2 cytokine profile could have a beneficial effect on the clinical course of the disease. The objective of this study was to assess Th2/Th1 cytokine profile in relapsing-remitting MS (RRMS patients receiving an immunosuppressive treatment with natalizumab (NAT, or an immunomodulatory treatment with glatiramer acetate (GA after one year of treatment. Methods This was an observational cross-sectional study. All consecutive patients diagnosed with RRMS who had received GA or NAT for 12 months were included in the study. We determined serum levels of Th1 and Th2 cytokines (interleukin [IL]-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, monocyte chemotactic protein [MCP]-1, tumor-necrosis factor [TNF]-α, interferon [IFN]-γ and granulocyte macrophage colony stimulating factor [GM-CSF] by flow cytometry. Th2/Th1 bias was defined based on the ratio of IL-4, IL-5, IL-6 or IL-10 Th2 cytokines and proinflammatory INF-γ or TNF-α Th1 cytokines. Results Eleven patients under treatment with NAT and 12 patients treated with GA were evaluated. RRMS patients treated with NAT showed significantly higher levels of IL-6 (p  Conclusion In conclusion, our findings suggest that GA promotes a superior Th2-biased anti-inflammatory response as compared with NAT in the systemic circulation of RRMS patients. Future studies with larger cohorts will determine whether this immune Th2 shift in GA patients is associated with a beneficial effect on disease outcome.

  12. The impact of health anxiety in patients with relapsing remitting multiple sclerosis: Misperception, misattribution and quality of life.

    Science.gov (United States)

    Hayter, Aimee L; Salkovskis, Paul M; Silber, Eli; Morris, Robin G

    2016-11-01

    Multiple sclerosis (MS) is a progressive disease with an unpredictable prognosis. Previous studies have reported health anxiety within the MS population. This study examines the effect of health anxiety on MS patients' quality of life (QoL) and evaluates the potential contribution of cognitive factors in maintaining health anxiety. A total of 84 patients with relapsing remitting multiple sclerosis (RRMS) were screened for health anxiety. From this sample, a group with relatively high and another group with low anxiety (n = 21 in each group) were identified. A further 21 healthy controls were recruited for comparison. A measure of QoL was then completed. Cognitive biases were investigated by measuring perception and attribution of common bodily symptoms as well as appraisal of performance on neuropsychological and physical fatigue tests. The high health anxiety group reported poorer QoL relative to the other groups, independent of level of disability. They were also more likely to misattribute common bodily changes to MS, and perceive their (objectively intact) performance on tests of cognition and fatigue as being impaired, attributing the cause of impairment to MS. Health anxiety may be a factor in mediating the psychosocial impact of MS. Skilled psychological treatment which changes misperception and misattribution may significantly benefit patients with MS and elevated health anxiety. Clinical implications Health anxiety impacts on quality of life in patients with MS even when disability and other measures of psychological distress are taken into account. High levels of health anxiety distort perceptions of symptoms in patients with MS in line with the predictions made by the cognitive model of health anxiety. Limitations of study This study is limited to patients with RRMS within the relatively early stages of their disease and is based on a small sample size. Health anxiety is correlated with measures of generalized anxiety, depression, and worry,