Night-shift work and hematological cancers: a population based case-control study in three Nordic countries.

Science.gov (United States)

Talibov, Madar; Pukkala, Eero; Martinsen, Jan Ivar; Tryggvadottir, Laufey; Weiderpass, Elisabete; Hansen, Johnni

2018-05-01

Objective The aim of this case-control study was to assess the effect of night-shift work on the risk of hematological cancers. Methods The study included 39 371 leukemia, 56 713 non-Hodgkin lymphoma, 9322 Hodgkin lymphoma, and 26 188 multiple myeloma cases diagnosed between 1961 and 2005 in Finland, Sweden, and Iceland. Five controls for each case were selected from the Nordic Occupational Cancer Study (NOCCA) cohort, matched by year of birth, sex and country. Night-shift exposure was assessed by using the NOCCA job-exposure matrix (JEM). Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated from conditional logistic regression models. Results Overall, night work was not associated with a risk of hematological cancers. We observed a small but non-significantly increased risk for leukemia (OR 1.07, 95% CI 0.99-1.16), especially for acute myeloid leukemia (OR 1.15, 95% CI 0.97-1.36) among workers exposed to a high level of cumulative night work exposure. Night work exposure was not associated with lymphatic cancers and multiple myeloma. Conclusion This study did not support associations between night-shift work and hematological cancers.

An Interesting Case of Retropharyngeal Lymph Nodal Metastases in a Case of Iodine-Refractory Thyroid Cancer.

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Harisankar, Chidambaram Natrajan Balasubramanian; Vijayabhaskar, Ramakrishnan

2018-01-01

Metastases to cervical lymph node are fairly common in differentiated thyroid cancer. In iodine-refractory disease, the disease may persist in the thyroid bed, cervical lymph nodes, lungs, or the bones commonly. Retropharyngeal lymph nodal involvement in thyroid cancer is unusual and may even be the presenting complaint. We represent a case of iodine-refractory thyroid cancer with retropharyngeal lymph nodal involvement in addition to lung metastases.

The role of cytokines in development of hematological and immune disorders at radiation therapy for uterine body cancer

International Nuclear Information System (INIS)

Sorochan, P.P.; Prokhach, N.E.; Gromakova, Yi.A.; Krugova, Yi.M.; Sukhyin, V.S.

2013-01-01

The changes in hematological and immune parameters in patients with uterine body cancer were analyzed by the stages of the combined treatment. The rol of cytokines in the development of hematologic and immune disorders was assessed

Amrubicin therapy improves patients with refractory small-cell lung cancer: A single-arm confirmatory Chinese clinical study

Directory of Open Access Journals (Sweden)

Mengli Zheng

2016-09-01

Full Text Available Our objective was to evaluate an open-label, multicenter, single-arm study to appraise whether amrubicin therapy improves patients with refractory small-cell lung cancer in Chinese clinical study. Patients (n=95 with refractory small-cell lung cancer received 3 consecutive days amrubicin therapy for 21 days. Overall response rate of response to amrubicin was 39%. Anemia, febrile neutropenia, thrombocytopenia, hyperglycemia, hyponatremia, infection, elevated serum transaminases levels were appeared, but the incidences of adverse events were very few. Our results suggest amrubicin therapy can improve patients with refractory small-cell lung cancer and may be an effective and safe treatment option.

HIV-associated hematologic malignancies: Experience from a Tertiary Cancer Center in India.

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Reddy, Rakesh; Gogia, Ajay; Kumar, Lalit; Sharma, Atul; Bakhshi, Sameer; Sharma, Mehar C; Mallick, Saumyaranjan; Sahoo, Ranjit

2016-01-01

Data on HIV associated hematologic malignancies is sparse from India. This study attempts to analyze the spectrum and features of this disease at a tertiary cancer center in India. Retrospective study from case records of patients registered with a diagnosis of hematologic malignancy and HIV infection between January 2010 and June 2015. Thirteen cases of HIV associated hematologic malignancies were identified, six of them pediatric. HIV diagnosis was concurrent to diagnosis of cancer in 12 and preceded it in one of them. ECOG PS at presentation was >1 in all of them. All patients, except one, had B symptoms. Six of the patients had bulky disease and six are stage 4. Predominant extranodal disease was seen in 67% of them. NHL accounted for 10 of 13 patients and DLBCL-Germinal center was the most common subtype. Mean CD4+ cell count was 235/μL (range, 32-494). HAART could be given along with chemotherapy to 11 patients. Two-thirds of patients received standard doses of therapy. Chemo-toxicity required hospitalization in 58%. CR was achieved in 45% and 36% had progressive disease with first-line therapy. At the time of last follow up, 3 patients were alive with responsive disease, 2 in CR and 1 in PR. None of the pediatric patients were long time responders. These malignancies were of advanced stage and higher grade. Goal of therapy, in the HAART era, is curative. Pediatric patients had dismal outcome despite good chemotherapy and HAART. There is an urgent need to improve data collection for HIV related cancers in India.

Gastric cancer associated with refractory cytomegalovirus gastritis.

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Ueno, Masayuki; Shimodate, Yuichi; Yamamoto, Shumpei; Yamamoto, Hiroshi; Mizuno, Motowo

2017-12-01

Cytomegalovirus (CMV) sometimes causes gastritis, especially in immunocompromised patients, but whether CMV gastritis promotes the development of gastric cancer is unknown. Here, we report a case of gastric cancer that developed in the presence of CMV gastritis, which had been present for at least 4 years and was refractory to treatment. An 80-year-old woman had noted epigastric discomfort and appetite loss. Esophagogastroduodenoscopy revealed a shallow geographical ulcer extending from the upper body to the pylorus. Histological findings of the biopsy and serology were suggestive of CMV gastritis. Serum anti-Helicobacter pylori antibody test was positive, suggesting co-infection with CMV and H. pylori. Her gastritis was unimproved with repeated antiviral therapy and eradication of H. pylori. Thirty months later, wide-spread gastric cancer had developed. We suggest the possibility that the addition of chronic inflammation of CMV infection to H. pylori-induced gastritis facilitated the development of gastric cancer.

Radioactive iodine-refractory differentiated thyroid cancer: an uncommon but challenging situation

Energy Technology Data Exchange (ETDEWEB)

Schmidt, Angelica; Iglesias, Laura; Schlumberger, Martin J. [Institut Gustave Roussy, Univ. Paris-Saclay, Villejuif (France); Klain, Michele [Univ. Federico II di Napoli (Italy); Pitoia, Fabian [Division of Endocrinology, Hospital de Clinicas, Univ. of Buenos Aires (Argentina)

2017-01-15

Radioiodine (RAI)-refractory thyroid cancer is an uncommon entity, occurring with an estimated incidence of 4-5 cases/year/million people. RAI refractoriness is more frequent in older patients, in those with large metastases, in poorly differentiated thyroid cancer, and in those tumors with high 18-fluorodeoxyglucose uptake on PET/CT. These patients have a 10-year survival rate of less than 10%. In recent years, new therapeutic agents with molecular targets have become available, with multi kinase inhibitors (MKIs) being the most investigated drugs. Two of these compounds, sorafenib and lenvatinib, have shown significant objective response rates and have significantly improved the progression-free survival in the two largest published prospective trials on MKI use. However, no overall survival benefit has been achieved yet. This is probably related to the crossover that occurs in most patients who progress on placebo treatment to the open treatment of these studies. In consequence, the challenge is to correctly identify which patients will benefit from these treatments. It is also crucial to understand the appropriate timing to initiate MKI treatment and when to stop it. The purpose of this article is to define RAI refractoriness, to summarize which therapies are available for this condition, and to review how to select patients who are suitable for them. (author)

Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer

DEFF Research Database (Denmark)

Brose, Marcia S; Nutting, Christopher M; Jarzab, Barbara

2014-01-01

cancer that had progressed within the past 14 months. Adult patients (≥18 years of age) with this type of cancer were enrolled from 77 centres in 18 countries. To be eligible for inclusion, participants had to have at least one measurable lesion by CT or MRI according to Response Evaluation Criteria...... cancer. Adverse events were consistent with the known safety profile of sorafenib. These results suggest that sorafenib is a new treatment option for patients with progressive radioactive iodine-refractory differentiated thyroid cancer. FUNDING: Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals...

Childhood cancer survivorship educational resources in North American pediatric hematology/oncology fellowship training programs: a survey study.

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Nathan, Paul C; Schiffman, Joshua D; Huang, Sujuan; Landier, Wendy; Bhatia, Smita; Eshelman-Kent, Debra; Wright, Jennifer; Oeffinger, Kevin C; Hudson, Melissa M

2011-12-15

Childhood cancer survivors require life-long care by clinicians with an understanding of the specific risks arising from the prior cancer and its therapy. We surveyed North American pediatric hematology/oncology training programs to evaluate their resources and capacity for educating medical trainees about survivorship. An Internet survey was sent to training program directors and long-term follow-up clinic (LTFU) directors at the 56 US and Canadian centers with pediatric hematology/oncology fellowship programs. Perceptions regarding barriers to and optimal methods of delivering survivorship education were compared among training program and LTFU clinic directors. Responses were received from 45/56 institutions of which 37/45 (82%) programs require that pediatric hematology/oncology fellows complete a mandatory rotation focused on survivorship. The rotation is 4 weeks or less in 21 programs. Most (36/45; 80%) offer didactic lectures on survivorship as part of their training curriculum, and these are considered mandatory for pediatric hematology/oncology fellows at 26/36 (72.2%). Only 10 programs (22%) provide training to medical specialty trainees other than pediatric hematology/oncology fellows. Respondents identified lack of time for trainees to spend learning about late effects as the most significant barrier to providing survivorship teaching. LTFU clinic directors were more likely than training program directors to identify lack of interest in survivorship among trainees and survivorship not being a formal or expected part of the fellowship training program as barriers. The results of this survey highlight the need to establish standard training requirements to promote the achievement of basic survivorship competencies by pediatric hematology/oncology fellows. Copyright © 2011 Wiley Periodicals, Inc.

Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer

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Pascoe Abigail C

2012-03-01

Full Text Available Abstract Background The natural history of non-metastatic castrate refractory prostate cancer is unknown and treatment options are limited. We present a retrospective review of 13 patients with locally advanced or high risk prostate cancer, initially treated with hormone monotherapy and then treated with prostate radiation after becoming castration refractory. Findings Median PSA response following prostate radiation was 67.4%. Median time to biochemical progression following radiotherapy was 15 months and to detection of metastatic disease was 18.5 months. Median survival from castration resistance (to date of death or November 2011 was 60 months, with median survival from RT 42 months. Conclusion Prostate radiation appears to be beneficial even in patients with potential micrometastatic disease, which supports the hypothesis that the primary tumour is important in the progression of prostate cancer. These results are an interesting addition to the literature on the biology of prostate cancer especially as this data is unlikely to be available in the future due to combined prostate radiation and androgen deprivation therapy now being the standard of care.

Development of Hemolytic Anemia in a Nivolumab-Treated Patient with Refractory Metastatic Squamous Cell Skin Cancer and Chronic Lymphatic Leukemia

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K.S. Schwab

2016-06-01

Full Text Available Management of patients with metastatic squamous cell skin cancer, refractory to initial therapy with standard chemotherapy and radiation protocols, remains difficult with poor overall prognosis and limited therapeutic options. Recently, promising response rates with nivolumab, a programmed death receptor-1-blocking antibody, in squamous cancer of the head and neck have been demonstrated. Considering the similar histological patterns of squamous cell cancer of the skin and squamous cell cancer of the head and neck, we assumed that nivolumab could also be effective in our patients with refractory metastatic squamous cell cancer of the skin. So far, there have been no clinical data on the therapeutic efficacy of nivolumab in squamous cell skin cancer. We here present a case of a patient with metastatic squamous cell skin cancer refractory to previous therapies, who showed a good response to nivolumab over a period of 5 months, but developed a serious hemolytic crisis under nivolumab treatment after eight applications.

[Nutritional status in patients first hospital admissions service hematology National Cancer Institute].

Science.gov (United States)

Baltazar Luna, E; Omaña Guzmán, L I; Ortiz Hernández, L; Ñamendis-Silva, S A; De Nicola Delfin, L

2013-01-01

To determine the nutritional status of patients admitted to hospital for the first time the hematology service and who have not received treatment for cancer, to know if the nutritional status assessed by the EGS-GP and serum albumin related mortality of patients A longitudinal, prospective, analytical. EGS-Through GP assessed the nutritional status of patients, we used SPSS 19.0 for data analysis. Evaluaron 119 patients, 52.1% female and 47.9% male. The most common diagnosis was non-Hodgkin lymphoma in 43.7%. According to the EGS-GP 50.4% of patients had some degree of malnutrition or was at risk of suffering of which: 31.1% had moderate and 19.3% had severe malnutrition. The 49.6% of patients had an adequate nutritional status. 30.3% of the patients who died, 37% had severe malnutrition and 50% severe decrease in albumin concentration. The prevalence of malnutrition in hematological patients treated at the National Cancer Institute of Mexico that have not received medical treatment was high. There is an association between nutritional status and mortality in this patient group. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

Bone scintigraphy predicts the risk of spinal cord compression in hormone-refractory prostate cancer

International Nuclear Information System (INIS)

Soerdjbalie-Maikoe, Vidija; Pelger, Rob C.M.; Nijeholt, Guus A.B. Lycklama; Arndt, Jan-Willem; Zwinderman, Aeilko H.; Bril, Herman; Papapoulos, Socrates E.; Hamdy, Neveen A.T.

2004-01-01

In prostate cancer, confirmation of metastatic involvement of the skeleton has traditionally been achieved by bone scintigraphy, although the widespread availability of prostate-specific antigen (PSA) measurements has tended to eliminate the need for this investigation. The potential of bone scintigraphy to predict skeletal-related events, particularly spinal cord compression, after the onset of hormone refractoriness has never been investigated. The aim of this study was to establish whether a new method of evaluating bone scintigraphy would offer a better predictive value for this complication of the metastatic process than is achieved with currently available grading methods. We studied 84 patients with hormone-refractory prostate cancer who had undergone bone scintigraphy at the time of hormone escape. Tumour grading and parameters of tumour load (PSA and alkaline phosphatase activity) were available in all patients. The incidence of spinal cord compression was documented and all patients were followed up until death. Bone scintigraphy was evaluated by the conventional Soloway grading and by an additional analysis determining total or partial involvement of individual vertebrae. In contrast to the Soloway method, the new method was able to predict spinal cord compression at various spinal levels. Our data suggest that there is still a place for bone scintigraphy in the management of hormone-refractory prostate cancer. (orig.)

Spanish consensus for the management of patients with advanced radioactive iodine refractory differentiated thyroid cancer.

Science.gov (United States)

Riesco-Eizaguirre, Garcilaso; Galofré, Juan Carlos; Grande, Enrique; Zafón Llopis, Carles; Ramón y Cajal Asensio, Teresa; Navarro González, Elena; Jiménez-Fonseca, Paula; Santamaría Sandi, Javier; Gómez Sáez, José Manuel; Capdevila, Jaume

2016-04-01

Approximately one third of the patients with differentiated thyroid cancer (DTC) who develop structurally-evident metastatic disease are refractory to radioactive iodine (RAI). Most deaths from thyroid cancer occur in these patients. The main objective of this consensus is to address the most controversial aspects of management of these patients. On behalf of the Spanish Society of Endocrinology & Nutrition (SEEN) and the Spanish Group for Orphan and Infrequent Tumors (GETHI), the Spanish Task Force for Thyroid Cancer, consisting of endocrinologists and oncologists, reviewed the relevant literature and prepared a series of clinically relevant questions related to management of advanced RAI-refractory DTC. Ten clinically relevant questions were identified by the task force. In answering to these 10 questions, the task force included recommendations regarding the best definition of refractoriness; the best therapeutic options including watchful waiting, local therapies, and systemic therapy (e.g. kinase inhibitors), when sodium iodide symporter (NIS) restoration may be expected; and how recent advances in molecular biology have increased our understanding of the disease. In response to our appointment as a task force by the SEEN and GHETI, we developed a consensus to help in clinical management of patients with advanced RAI-refractory DTC. We think that this consensus will provide helpful and current recommendations that will help patients with this disorder to get optimal medical care. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

ESHAP chemotherapy is efficient in refractory/relapsed primary central nervous system lymphoma: report of four cases

Directory of Open Access Journals (Sweden)

Ungur R

2015-10-01

Full Text Available Rodica Ungur,1,2 Adrian Tempescul,3 Christian Berthou,3 Cristina Bagacean,1,2 Doinel Radeanu,1 Adriana Muresan,1 Mihnea Zdrenghea1,21Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, 2Department of Hematology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania; 3Department of Clinical Hematology, Institute of Cancerology and Hematology, Brest Teaching Hospital, Brest, FranceAbstract: Primary central nervous system non-Hodgkin’s lymphoma is a rare presentation, almost always of diffuse large B-cell type. Although there is no consensus regarding therapy for this condition, induction regimens are based on high-dose methotrexate and consolidation whole-brain radiotherapy, or, more preferred recently, blood–brain barrier penetrating drugs such as etoposide, cytarabine, and alkylating agents like temozolomide, ifosfamide, and lomustine. We present here four cases of relapsed/refractory primary central nervous system lymphoma treated with ESHAP (etoposide, solumedrol, high-dose cytarabine, and platinum chemotherapy to complete remission, with the eligible patients proceeding to autologous transplantation. We want to draw attention to this interesting, relatively well tolerated, underused therapeutic option, in a setting where treatment options are scarce and evidence-based recommendations are lacking.Keywords: cerebral lymphoma, PCNSL, refractory, relapsed, platinum

Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

Directory of Open Access Journals (Sweden)

Hao Jiqing

2009-03-01

Full Text Available Abstract Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms.

Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

Science.gov (United States)

Wu, Hongyang; Chen, Zhendong; Sun, Guoping; Gu, Kangsheng; Pan, Yueyin; Hao, Jiqing; Du, Yingying; Ning, Jie

2009-01-01

Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms. PMID:19267934

Fertility considerations in young women with hematological malignancies

DEFF Research Database (Denmark)

Jadoul, Pascale; Kim, S Samuel; Andersen, Claus Yding

2012-01-01

The need for practice guidelines for fertility preservation in young women with hematological malignancies has been increased. To develop recommendations, publications relevant to fertility preservation and hematological cancers were identified through a PubMed database search and reviewed...

Nanotechnology applications in hematological malignancies (Review)

Science.gov (United States)

SAMIR, AHMED; ELGAMAL, BASMA M; GABR, HALA; SABAAWY, HATEM E

2015-01-01

A major limitation to current cancer therapies is the development of therapy-related side-effects and dose limiting complications. Moreover, a better understanding of the biology of cancer cells and the mechanisms of resistance to therapy is rapidly developing. The translation of advanced knowledge and discoveries achieved at the molecular level must be supported by advanced diagnostic, therapeutic and delivery technologies to translate these discoveries into useful tools that are essential in achieving progress in the war against cancer. Nanotechnology can play an essential role in this aspect providing a transforming technology that can translate the basic and clinical findings into novel diagnostic, therapeutic and preventive tools useful in different types of cancer. Hematological malignancies represent a specific class of cancer, which attracts special attention in the applications of nanotechnology for cancer diagnosis and treatment. The aim of the present review is to elucidate the emerging applications of nanotechnology in cancer management and describe the potentials of nanotechnology in changing the key fundamental aspects of hematological malignancy diagnosis, treatment and follow-up. PMID:26134389

Body Image Discomfort of Adolescent and Young Adult Hematologic Cancer Survivors.

Science.gov (United States)

Zucchetti, Giulia; Bellini, Simona; Bertolotti, Marina; Bona, Francesca; Biasin, Eleonora; Bertorello, Nicoletta; Tirtei, Elisa; Fagioli, Franca

2017-06-01

This study focuses on body image discomfort (BID) of 50 adolescent and young adult (AYA) hematologic cancer survivors (age range 15-23; 52% males). The study results were obtained through data from a self-report questionnaire: the Body Uneasiness Test. Findings differed according to gender: a greater proportion of females were in the Risk category of impaired body image than males (χ 2  = 5.258, p < 0.05). No significant body image differences were found according to the type of diagnosis or to the length of survival. To manage survivors' BIDs and to improve their quality of life, assessing BID in AYA cancer survivors is important for identifying those who might be in need of additional supportive care or a program.

Successful Treatment of Opioid-Refractory Cancer Pain with Short-Course, Low-Dose Ketamine.

Science.gov (United States)

Waldfogel, Julie M; Nesbit, Suzanne; Cohen, Steven P; Dy, Sydney M

2016-12-01

Opioids remain the mainstay of treatment for severe cancer pain, but up to 20% of patients have persistent or refractory pain despite rapid and aggressive opioid titration, or develop refractory pain after long-term opioid use. In these scenarios, alternative agents and mechanisms for analgesia should be considered. This case report describes a 28-year-old man with metastatic pancreatic neuroendocrine cancer with severe, intractable pain despite high-dose opioids including methadone and a hydromorphone patient-controlled analgesia (PCA). After treatment with short-course, low-dose ketamine, his opioid requirements decreased by 99% and pain ratings by 50%, with the majority of this decrease occurring in the first 48 hours. As this patient's pain and opioid regimen escalated, he likely experienced some component of central sensitization and hyperalgesia. Administration of ketamine reduced opioid consumption by 99% and potentially "reset" neuronal hyperexcitability and reduced pain signaling, allowing for improved pain control.

Quality of life in survivors of hematological malignancies stratified by cancer type, time since diagnosis and stem cell transplantation.

Science.gov (United States)

Esser, Peter; Kuba, Katharina; Mehnert, Anja; Johansen, Christoffer; Hinz, Andreas; Lordick, Florian; Götze, Heide

2018-06-01

Quality of life (QoL) has become an important tool to guide decision making in oncology. Given the heterogeneity among hematological cancer survivors, however, clinicians need comparative data across different subsets. This study recruited survivors of hematological malignancies (≥ 2.5 years after diagnosis) from two German cancer registries. QoL was assessed with the EORTC QLQ-C30. The sample was stratified by cancer type, time since diagnosis, treatment with stem cell transplantation (SCT) and type of SCT. First, levels of QoL were compared across subsamples when controlling for several covariates. Second, we contrasted subsamples with gender- and age-matched population controls obtained from the general population. Of 2001 survivors contacted by mail, 922 (46%) participated in the study. QoL did not significantly differ between the subsamples. All subsamples scored significantly lower in functioning and significantly higher in symptom burden compared to population controls (all p < .001). Almost all of these group effects reached clinically meaningful sizes (Cohen's d ≥ .5). Group differences in global health/QoL were mostly non-significant. Hematological cancer survivors are associated with practically relevant impairments irrespective of differences in central medical characteristics. Nevertheless, survivors seem to evaluate their overall situation as relatively well. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Genomic Testing and Resulting Medical Decisions

Science.gov (United States)

2017-10-03

Cancer of Unknown Origin; Cancer Refractory; Cancer of Stomach; Cancer Head Neck; Cancer of Skin; Cancer, Lung; Cancer Colorectal; Cancer of Esophagus; Cancer, Bladder; Cancer, Uterus; Cancer Cervix; Cancer Liver; Cancer, Kidney; Cancer, Breast; Hematologic Neoplasms

Long-Term Trends in Hematological and Nutritional Status After Gastrectomy for Gastric Cancer.

Science.gov (United States)

Kim, Ji-Hyun; Bae, You-Jin; Jun, Kyong-Hwa; Chin, Hyung-Min

2017-08-01

This study investigated long-term trends in hematological and nutritional parameters after gastrectomy for gastric cancer and evaluated the influence of the reconstruction type on these trends. The medical records of 558 patients who underwent curative gastrectomy with standard lymph node dissection for stage I gastric cancer between January 2006 and December 2013 were reviewed. The hematological and nutritional parameters evaluated included hemoglobin, ferritin, vitamin B 12 , total protein, albumin, total cholesterol, triglyceride, and calcium. The patients were followed up for 6 months postoperatively and then annually until death, cancer recurrence, or follow-up loss. In the long term, ferritin and triglyceride gradually decreased after gastrectomy, while the other parameters decreased slightly or were stable. In the comparisons according to reconstruction type, the Roux-en-Y group had the lowest levels of hemoglobin, ferritin, vitamin B12, total protein, albumin, and total cholesterol beginning 6 months postoperatively compared with the Billroth I and II groups. However, only ferritin and vitamin B 12 had significant differences in the 5-year cumulative incidences of deficiency/reduction according to the reconstruction type, whereas albumin, triglyceride, total cholesterol, and calcium did not. Although malabsorption and malnutrition are common in patients after a gastrectomy, most nutritional parameters were stable or decreased slightly in the long-term and were not markedly influenced by the reconstruction type or extent of gastrectomy. Therefore, for more accurate nutritional assessment after gastrectomy, multidirectional monitoring should be considered rather than simply measuring biochemical parameters.

Meeting the challenge of hematologic malignancies in sub-Saharan Africa

Science.gov (United States)

Wood, William A.; Lee, Stephanie J.; Shea, Thomas C.; Naresh, Kikkeri N.; Kazembe, Peter N.; Casper, Corey; Hesseling, Peter B.; Mitsuyasu, Ronald T.

2012-01-01

Cancer is a leading cause of death and disability in sub-Saharan Africa and will eclipse infectious diseases within the next several decades if current trends continue. Hematologic malignancies, including non-Hodgkin lymphoma, leukemia, Hodgkin lymphoma, and multiple myeloma, account for nearly 10% of the overall cancer burden in the region, and the incidence of non-Hodgkin lymphoma and Hodgkin lymphoma is rapidly increasing as a result of HIV. Despite an increasing burden, mechanisms for diagnosing, treating, and palliating malignant hematologic disorders are inadequate. In this review, we describe the scope of the problem, including the impact of endemic infections, such as HIV, Epstein-Barr virus, malaria, and Kaposi sarcoma–associated herpesvirus. We additionally describe current limitations in hematopathology, chemotherapy, radiotherapy, hematopoietic stem cell transplantation, and supportive care and palliation. We review contemporary treatment and outcomes of hematologic malignancies in the region and outline a clinical service and research agenda, which builds on recent global health successes combating HIV and other infectious diseases. Achieving similar progress against hematologic cancers in sub-Saharan Africa will require the sustained collaboration and advocacy of the entire global cancer community. PMID:22461494

Nanotechnology applications in hematological malignancies (Review).

Science.gov (United States)

Samir, Ahmed; Elgamal, Basma M; Gabr, Hala; Sabaawy, Hatem E

2015-09-01

A major limitation to current cancer therapies is the development of therapy-related side-effects and dose limiting complications. Moreover, a better understanding of the biology of cancer cells and the mechanisms of resistance to therapy is rapidly developing. The translation of advanced knowledge and discoveries achieved at the molecular level must be supported by advanced diagnostic, therapeutic and delivery technologies to translate these discoveries into useful tools that are essential in achieving progress in the war against cancer. Nanotechnology can play an essential role in this aspect providing a transforming technology that can translate the basic and clinical findings into novel diagnostic, therapeutic and preventive tools useful in different types of cancer. Hematological malignancies represent a specific class of cancer, which attracts special attention in the applications of nanotechnology for cancer diagnosis and treatment. The aim of the present review is to elucidate the emerging applications of nanotechnology in cancer management and describe the potentials of nanotechnology in changing the key fundamental aspects of hematological malignancy diagnosis, treatment and follow-up.

[Sport coaching for psychological and social recovery after hematological cancer: An innovative perspective].

Science.gov (United States)

Calvin, Sarah; Blaise, Didier; Ben Soussan, Patrick; Cuvelier, Sarah; Cicut, Nicolas; Caymaris, Laurence; Arnault, Yolande; Onesta, Claude; Dantin, Pierre; Viens, Patrice

2017-10-01

This study is a first step towards the transfer of knowledge and practices between psychological support and performance in elite sport and a patient's "social recovery" in oncology. This proposal brings together people engaged in a variety of healthcare and relationship support roles, and aims to set up a support system beyond the hospital context. It questions the ability of elite sport management and its main actors, the "Great Coaches", to contribute to the support of patients in cancer remission through an onco-coaching approach. This innovative proposal is initiated by a life coaching pilot study designed for hematologic cancer patients in remission after a hematopoietic stem cell transplantation. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Phase II study of concomitant chemoradiotherapy in bulky refractory or chemoresistant relapsed lymphomas

International Nuclear Information System (INIS)

Girinsky, Theodore; Lapusan, Simona; Ribrag, Vincent; Koscielny, Serge; Ferme, Christophe; Carde, Patrice

2005-01-01

Purpose: To evaluate the local efficacy of concomitant chemoradiotherapy in patients with mostly refractory lymphoma. Methods and materials: Patients with refractory or chemoresistant-relapsed lymphoma and bulky life-threatening masses were included in this study. A split course of concomitant radiotherapy and chemotherapy (mostly cisplatin and etoposide) was delivered during a 6-week period. Weekly blood tests and a clinical examination using the Radiation Therapy Oncology Group guidelines were performed to assess acute toxicity. The tumor response was evaluated 1-3 months after treatment and at regular follow-up visits. Results: We enrolled 21 patients in the study between January 1998 and April 2003. Of the 21 patients, 60% had disseminated disease with bulky tumor masses and 85% had refractory lymphoma, of which most had been treated with at least two different chemotherapy regimens before concomitant chemoradiotherapy. Seventy-five percent received regimens containing cisplatinum and etoposide. The median radiation dose was 40 Gy (range, 12-62.5 Gy). Grade 3-4 hematologic toxicity and mucositis was observed in 70% and 30% of cases respectively, without any deaths. The overall response and complete remission rate was 70% and 20%, respectively. The 1-year overall survival and local progression-free survival rate was 20.4% and 54%, respectively. Three patients with localized disease were still alive 16, 33, and 48 months after treatment. Conclusion: Concomitant chemoradiotherapy for refractory or chemoresistant-relapsed lymphoma induced high hematologic toxicity, but seemed adequate for controlling local bulky tumor masses. No toxicity-related death was observed

Efficacy of Self-Expandable Metallic Stent Inserted for Refractory Hemorrhage of Duodenal Cancer

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Takashi Orii

2016-05-01

Full Text Available Because of advances in the technology of gastrointestinal endoscopy and improvements in the quality of stents, it has become routine to place a stent as palliative therapy for malignant gastrointestinal obstruction. On the other hand, stent placement for malignant gastrointestinal hemorrhage has scarcely been reported, although it may be performed for hemorrhage of the esophageal varicose vein. We recently experienced a patient with refractory hemorrhage from an unresectable duodenal cancer who underwent placement of a self-expandable metallic stent (SEMS and thereafter had no recurrence of the hemorrhage. A 46-year-old man underwent laparotomy to radically resect a cancer in the third portion of the duodenum, which invaded widely to the superior mesenteric vein and its branches and was considered unresectable. After stomach-partitioning gastrojejunostomy was performed, chemotherapy was initiated according to the regimen of chemotherapy of far advanced gastric cancer. One year and 4 months after induction of chemotherapy, gastrointestinal hemorrhage occurred. Upper gastrointestinal endoscopy revealed the hemorrhage oozing from the duodenal cancer, and endoscopic hemostasis, such as injection of hypertonic saline epinephrine and argon plasma coagulation, was unsuccessful. Twenty days after emergence of the hemorrhage, an endoscopic covered SEMS was placed with confirmation by fluoroscopy. Immediately after placement of the stent, the tarry stool stopped and the anemia ceased to progress. The recurrence of the hemorrhage has not been confirmed without migration of the stent. SEMS is an effective hemostatic procedure for malignant refractory hemorrhage.

One-unit versus two-unit cord-blood transplantation for hematologic cancers.

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Wagner, John E; Eapen, Mary; Carter, Shelly; Wang, Yanli; Schultz, Kirk R; Wall, Donna A; Bunin, Nancy; Delaney, Colleen; Haut, Paul; Margolis, David; Peres, Edward; Verneris, Michael R; Walters, Mark; Horowitz, Mary M; Kurtzberg, Joanne

2014-10-30

Umbilical-cord blood has been used as the source of hematopoietic stem cells in an estimated 30,000 transplants. The limited number of hematopoietic cells in a single cord-blood unit prevents its use in recipients with larger body mass and results in delayed hematopoietic recovery and higher mortality. Therefore, we hypothesized that the greater numbers of hematopoietic cells in two units of cord blood would be associated with improved outcomes after transplantation. Between December 1, 2006, and February 24, 2012, a total of 224 patients 1 to 21 years of age with hematologic cancer were randomly assigned to undergo double-unit (111 patients) or single-unit (113 patients) cord-blood transplantation after a uniform myeloablative conditioning regimen and immunoprophylaxis for graft-versus-host disease (GVHD). The primary end point was 1-year overall survival. Treatment groups were matched for age, sex, self-reported race (white vs. nonwhite), performance status, degree of donor-recipient HLA matching, and disease type and status at transplantation. The 1-year overall survival rate was 65% (95% confidence interval [CI], 56 to 74) and 73% (95% CI, 63 to 80) among recipients of double and single cord-blood units, respectively (P=0.17). Similar outcomes in the two groups were also observed with respect to the rates of disease-free survival, neutrophil recovery, transplantation-related death, relapse, infections, immunologic reconstitution, and grade II-IV acute GVHD. However, improved platelet recovery and lower incidences of grade III and IV acute and extensive chronic GVHD were observed among recipients of a single cord-blood unit. We found that among children and adolescents with hematologic cancer, survival rates were similar after single-unit and double-unit cord-blood transplantation; however, a single-unit cord-blood transplant was associated with better platelet recovery and a lower risk of GVHD. (Funded by the National Heart, Lung, and Blood Institute and the

T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies

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2017-11-29

Hematologic Malignancy; Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia in Blast Crisis; Anemia, Refractory, With Excess of Blasts; Chronic Myeloproliferative Disease; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Marginal Zone B-cell Lymphoma; Follicular Lymphoma; Lymphoplasmacytic Lymphoma; Mantle-Cell Lymphoma; Prolymphocytic Lymphoma; Large Cell Non-Hodgkin's Lymphoma; Lymphoblastic Lymphoma; Burkitt's Lymphoma; High Grade Non-Hodgkin's Lymphoma

Isotype-specific inhibition of the phosphatidylinositol-3-kinase pathway in hematologic malignancies

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Castillo JJ

2014-02-01

Full Text Available Jorge J Castillo,1 Meera Iyengar,2 Benjamin Kuritzky,2 Kenneth D Bishop2 1Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, 2Division of Hematology and Oncology, Rhode Island Hospital, Providence, RI, USA Abstract: In the last decade, the advent of biological targeted therapies has revolutionized the management of several types of cancer, especially in the realm of hematologic malignancies. One of these pathways, and the center of this review, is the phosphatidylinositol-3-kinase (PI3K pathway. The PI3K pathway seems to play an important role in the pathogenesis and survival advantage in hematologic malignancies, such as leukemia, lymphoma, and myeloma. The objectives of the present review, hence, are to describe the current knowledge on the PI3K pathway and its isoforms, and to summarize preclinical and clinical studies using PI3K inhibitors, focusing on the advances made in hematologic malignancies. Keywords: phosphatidylinositol-3-kinase pathway, inhibitors, leukemia, lymphoma, myeloma

Intracerebroventricular morphine for refractory cancer pain: transitioning to the home setting.

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Adolph, Michael D; Stretanski, Michael F; McGregor, John M; Rawn, Bonnie L; Ross, Patrick M; Benedetti, Costantino

2010-08-01

Refractory cancer pain may be effectively controlled by titrating intracerebroventricular (ICV) preservative-free opioid. In this case report, a continuous infusion of ICV morphine permitted our patient with lung cancer and painful spinal metastases to be discharged to home hospice with family. The approach exploits the high potency of morphine injected into cerebrospinal fluid (CSF). Sterile, injectable, preservative-free morphine is directly infused into CSF through a subcutaneous Ommaya reservoir placed under the scalp by a neurosurgeon, with an attached catheter passed through a burr hole in the skull with its tip in a cerebral ventricle. Although investigators have described home care of patients receiving intraspinal analgesics, no report describes the process of transitioning the patient receiving continuous ICV morphine infusion to the home setting.

Dimethyl sulfoxide and sodium bicarbonate in the treatment of refractory cancer pain.

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Hoang, Ba X; Tran, Dao M; Tran, Hung Q; Nguyen, Phuong T M; Pham, Tuan D; Dang, Hong V T; Ha, Trung V; Tran, Hau D; Hoang, Cuong; Luong, Khue N; Shaw, D Graeme

2011-01-01

Pain is a major concern of cancer patients and a significant problem for therapy. Pain can become a predominant symptom in advanced cancers. In this open-label clinical study, the authors have treated 26 cancer patients who have been declared as terminal without the option of conventional treatment. These patients suffered from high levels of pain that was poorly managed by all available interventional approaches recommended by World Health Organization (WHO) guideline. The results indicate that intravenous infusion of dimethyl sulfoxide (DMSO) and sodium bicarbonate (SB) solution can be a viable, effective, and safe treatment for refractory pain in cancer patients. These patients had pain due to the disease progression and complication of chemotherapy and radiation. Moreover, the preliminary clinical outcome of 96-day follow-up suggests that the application of DMSO and SB solution intravenously could lead to better quality of life for patients with nontreatable terminal cancers. The data of this clinical observation indicates that further research and application of the DMSO and SB combination may help the development of an effective, safe, and inexpensive therapy to manage cancer pain.

Treatment patterns, health state, and health care resource utilization of patients with radioactive iodine refractory differentiated thyroid cancer

International Nuclear Information System (INIS)

Gianoukakis, Andrew G; Flores, Natalia M; Pelletier, Corey L; Forsythe, Anna; Wolfe, Gregory R; Taylor, Matthew H

2016-01-01

Patients with differentiated thyroid cancer (DTC) often respond well to treatment but some become refractory to radioactive iodine (RAI) treatment, and treatment options are limited. Despite the humanistic and economic burden RAI refractory disease imposes on patients, published research concerning treatment patterns and health care resource utilization is sparse. Data were collected from an online retrospective chart review study in the US and five European Union (EU) countries (France, Germany, Italy, Spain, and UK) with physicians recruited from an online panel. Physicians (N=211) provided demographics, disease history, treatment information, and health care resource utilization for one to four of their patients with radioactive iodine refractory differentiated thyroid cancer (RR-DTC). The majority of the patients with RR-DTC (N=623) were female (56%), and their mean age was 58.2 years. In this sample, 63.2% had papillary thyroid cancer and 57.0% were in Stage IV when deemed RAI refractory. Patients with RR-DTC experienced regional recurrence in the thyroid bed/central neck area (25.3%) and had distant metastatic disease (53.6%). At the time data were collected, 50.7% were receiving systemic treatment. Of those, 78.5% were on first-line treatment and 62.7% were receiving multikinase inhibitors. Regional differences for prescribed treatments were observed; the US was more likely to have patients receiving multikinase inhibitors (79.2%) compared with UK (41.2%) and Italy (17.1%). Additional details regarding treatment patterns and resource utilization are discussed. The current study aimed to obtain a greater understanding of RR-DTC treatment globally. These results can assist in the development and implementation of treatment guidelines and ultimately enhance the care of patients with RR-DTC

Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

International Nuclear Information System (INIS)

Rose, Brent S.; Aydogan, Bulent; Liang, Yun; Yeginer, Mete; Hasselle, Michael D.; Dandekar, Virag; Bafana, Rounak; Yashar, Catheryn M.; Mundt, Arno J.; Roeske, John C.; Mell, Loren K.

2011-01-01

Purpose: To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy and to develop a normal tissue complication probability (NTCP) model for HT. Methods and Materials: We tested associations between hematologic nadirs during chemoradiotherapy and the volume of BM receiving ≥10 and 20 Gy (V 10 and V 20 ) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with data from 37 identically treated patients from a previous study, forming a cohort of 81 patients for normal tissue complication probability analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. Results: In the validation cohort, significant negative correlations were observed between white blood cell count nadir and V 10 (regression coefficient (β) = -0.060, p = 0.009) and V 20 (β = -0.044, p = 0.010). In the combined cohort, the (adjusted) β estimates for log (white blood cell) vs. V 10 and V 20 were as follows: -0.022 (p = 0.025) and -0.021 (p = 0.002), respectively. Patients with V 10 ≥ 95% were more likely to experience Grade ≥3 leukopenia (68.8% vs. 24.6%, p 20 > 76% (57.7% vs. 21.8%, p = 0.001). Conclusions: These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V 10 20 < 76% may reduce HT.

Forodesine in the treatment of relapsed/refractory peripheral T-cell lymphoma: an evidence-based review

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Makita S

2018-04-01

Full Text Available Shinichi Makita,1 Akiko Miyagi Maeshima,2 Dai Maruyama,1 Koji Izutsu,1 Kensei Tobinai1 1Department of Hematology, 2Department of Pathology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan Abstract: T-cell lymphoma is a rare hematologic malignancy with an incidence rate between 10% and 20% of that of non-Hodgkin lymphomas. Patients with peripheral T-cell lymphoma (PTCL generally have a poor prognosis when treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP/CHOP-like chemotherapy; once relapse occurs, it is mostly regarded as an incurable disease. To overcome the chemorefractoriness of PTCL, several novel agents have been developed. Since the first approval of pralatrexate, a dihydrofolate reductase inhibitor, for relapsed/refractory PTCL by the US Food and Drug Administration, several new agents, such as romidepsin (histone deacetylase inhibitor, brentuximab vedotin (antibody–drug conjugate targeting CD30, chidamide (histone deacetylase inhibitor, and mogamulizumab (anti-CC chemokine receptor 4 monoclonal antibody, have been approved as a therapeutic option for relapsed/refractory PTCL in several countries, including the US, Europe, China, and Japan. Forodesine is a novel, potent purine nucleoside phosphorylase inhibitor that is effective against T-cell malignancies. Although the clinical development of forodesine was discontinued in the US and Europe, a multicenter Phase I/II study of oral forodesine for relapsed PTCL was recently completed in Japan. The overall response rate was 24% (10 of 41 patients, which included four patients with complete response. In general, the toxicity of forodesine is manageable. As the study met the primary end point, forodesine was approved for the treatment of relapsed/refractory PTCL in Japan in March 2017, which was the first approval of forodesine in the world. As forodesine is an oral formulation, it is more convenient than other novel intravenous agents approved for PTCL

42 CFR 493.941 - Hematology (including routine hematology and coagulation).

Science.gov (United States)

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Hematology (including routine hematology and....941 Hematology (including routine hematology and coagulation). (a) Program content and frequency of challenge. To be approved for proficiency testing for hematology, a program must provide a minimum of five...

Perceptions, attitudes, and experiences of hematology/oncology fellows toward incorporating geriatrics in their training.

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Maggiore, Ronald J; Gorawara-Bhat, Rita; Levine, Stacie K; Dale, William

2014-01-01

The aging of the U.S. population continues to highlight emerging issues in providing care generally for older adults and specifically for older adults with cancer. The majority of patients with cancer in the U.S. are currently 65 years of age or older; therefore, training and research in geriatrics and geriatric oncology are viewed to be integral in meeting the needs of this vulnerable population. Yet, the ways to develop and integrate best geriatrics training within the context of hematology/oncology fellowship remain unclear. Toward this end, the current study seeks to evaluate the prior and current geriatric experiences and perspectives of hematology/oncology fellows. To gain insight into these experiences, focus groups of hematology/oncology fellows were conducted. Emergent themes included: 1) perceived lack of formal geriatric oncology didactics among fellows; 2) a considerable amount of variability exists in pre-fellowship geriatric experiences; 3) shared desire to participate in a geriatric oncology-based clinic; 4) differences across training levels in confidence in managing older adults with cancer; and 5) identification of specific criteria on how best to approach older adults with cancer in a particular clinical scenario. The present findings will help guide future studies in evaluating geriatrics among hematology/oncology fellows across institutions. They will also have implications in the development of geriatrics curricula and competencies specific to hematology/oncology training. © 2013.

Split-Course, High-Dose Palliative Pelvic Radiotherapy for Locally Progressive Hormone-Refractory Prostate Cancer

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Gogna, Nirdosh Kumar, E-mail: kumar_gogna@health.qld.gov.au [Radiation Oncology Services, Mater Centre, Brisbane, Queensland (Australia); Baxi, Siddhartha; Hickey, Brigid; Baumann, Kathryn [Radiation Oncology Services, Mater Centre, Brisbane, Queensland (Australia); Burmeister, Elizabeth [Princess Alexandra Hospital, Brisbane, Queensland (Australia); Holt, Tanya [Radiation Oncology Services, Mater Centre, Brisbane, Queensland (Australia)

2012-06-01

Purpose: Local progression, in patients with hormone-refractory prostate cancer, often causes significant morbidity. Pelvic radiotherapy (RT) provides effective palliation in this setting, with most published studies supporting the use of high-dose regimens. The aim of the present study was to examine the role of split-course hypofractionated RT used at our institution in treating this group of patients. Methods and Materials: A total of 34 men with locoregionally progressive hormone-refractory prostate cancer, treated with a split course of pelvic RT (45-60 Gy in 18-24 fractions) between 2000 and 2008 were analyzed. The primary endpoints were the response rate and actuarial locoregional progression-free survival. Secondary endpoints included overall survival, compliance, and acute and late toxicity. Results: The median age was 71 years (range, 53-88). Treatment resulted in an overall initial response rate of 91%, a median locoregional progression-free survival of 43 months, and median overall survival of 28 months. Compliance was excellent and no significant late toxicity was reported. Conclusions: The split course pelvic RT described has an acceptable toxicity profile, is effective, and compares well with other high-dose palliative regimens that have been previously reported.

Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC).

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Capdevila, Jaume; Trigo, José Manuel; Aller, Javier; Manzano, José Luís; Adrián, Silvia García; Llopis, Carles Zafón; Reig, Òscar; Bohn, Uriel; Cajal, Teresa Ramón Y; Duran-Poveda, Manuel; Astorga, Beatriz González; López-Alfonso, Ana; Martínez, Javier Medina; Porras, Ignacio; Reina, Juan Jose; Palacios, Nuria; Grande, Enrique; Cillán, Elena; Matos, Ignacio; Grau, Juan Jose

2017-10-01

Axitinib, an antiangiogenic multikinase inhibitor (MKI), was evaluated in the compassionate use programme (CUP) in Spain (October 2012-November 2014). 47 patients with advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC, n  = 34) or medullary thyroid cancer (MTC, n  = 13) with documented disease progression were treated with axitinib 5 mg b.i.d. The primary efficacy endpoint was objective response rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Progression-free survival (PFS) and adverse events (AEs) were secondary objectives. Regulatory authorities validated the CUP, and all patients signed informed consent form. Axitinib was administered as first-line therapy in 17 patients (36.2%), as second-line in 18 patients (38.3%) and as third/fourth-line in 12 patients (25.5%). With a median follow-up of 11.5 months (0-24.3), ORR was 27.7% (DTC: 29.4% and MTC: 23.1%) and median PFS was 8.1 months (95% CI: 4.1-12.2) (DTC: 7.4 months (95% CI: 3.1-11.8) and MTC: 9.4 months (95% CI: 4.8-13.9)). Better outcomes were reported with first-line axitinib, with an ORR of 53% and a median PFS of 13.6 months compared with 16.7% and 10.6 months as second-line treatment. Twelve (25.5%) patients required dose reduction to 3 mg b.i.d. All-grade AEs included asthenia (53.2%), diarrhoea (36.2%), hypertension (31.9%) and mucositis (29.8%); grade 3/4 AEs included anorexia (6.4%), diarrhoea (4.3%) and cardiac toxicity (4.3%). Axitinib had a tolerable safety profile and clinically meaningful activity in refractory and progressive thyroid cancer regardless of histology as first-line therapy. To our knowledge, this is the first time that cross-resistance between MKIs is suggested in thyroid cancer, highlighting the importance of prospective sequential clinical studies. © 2017 European Society of Endocrinology.

Risk of Hematologic Malignancies After Radioiodine Treatment of Well-Differentiated Thyroid Cancer.

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Molenaar, Remco J; Sidana, Surbhi; Radivoyevitch, Tomas; Advani, Anjali S; Gerds, Aaron T; Carraway, Hetty E; Angelini, Dana; Kalaycio, Matt; Nazha, Aziz; Adelstein, David J; Nasr, Christian; Maciejewski, Jaroslaw P; Majhail, Navneet S; Sekeres, Mikkael A; Mukherjee, Sudipto

2017-12-18

Purpose To investigate the risk and outcomes of second hematologic malignancies (SHMs) in a population-based cohort of patients with well-differentiated thyroid cancer (WDTC) treated or not with radioactive iodine (RAI). Methods Patients with WDTC were identified from SEER registries. Competing risk regression analysis was performed to calculate the risks of SHMs that occurred after WDTC treatment and outcomes after SHM development were assessed. Results Of 148,215 patients with WDTC, 53% received surgery alone and 47% received RAI. In total, 783 patients developed an SHM after a median interval of 6.5 years (interquartile range, 3.3 to 11.2 years) from WDTC diagnosis. In multivariable analysis, compared with those undergoing thyroidectomy alone, RAI treatment was associated with an increased early risk of developing acute myeloid leukemia (AML; hazard ratio, 1.79; 95% CI, 1.13 to 2.82; P = .01) and chronic myeloid leukemia (CML; hazard ratio, 3.44; 95% CI, 1.87 to 6.36; P < .001). This increased risk of AML and CML after RAI treatment was seen even in low-risk and intermediate-risk WDTC tumors. Occurrence of AML but not CML in patients with WDTC was associated with shorter median overall survival compared with matched controls (8.0 years v 31.0 years; P = .001). In addition, AML developing after RAI trended toward inferior survival compared with matched controls with de novo AML (median overall survival, 1.2 years v 2.9 years; P = .06). Conclusion Patients with WDTC treated with RAI had an increased early risk of developing AML and CML but no other hematologic malignancies. AML that arises after RAI treatment has a poor prognosis. RAI use in patients with WDTC should be limited to patients with high-risk disease features, and patients with WDTC treated with adjuvant RAI should be monitored for myeloid malignancies as part of cancer surveillance.

Retrospective analysis of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide for hormone-refractory prostate cancer.

Science.gov (United States)

Hatano, Koji; Nonomura, Norio; Nishimura, Kazuo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Nakai, Yasutomo; Nakayama, Masashi; Takayama, Hitoshi; Tsujimura, Akira; Okuyama, Akihiko

2011-02-01

To evaluate the clinical utility of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide as a treatment for patients with hormone-refractory prostate cancer. Fifty-seven patients with hormone-refractory prostate cancer were treated with an oral administration of dexamethasone (1.0 mg/day), uracil plus tegafur (400 mg/day) and cyclophosphamide (100 mg/day). The median patient age was 71 years. Sixteen patients had symptomatic bone metastasis, 31 had asymptomatic bone metastasis and 8 showed lymph node metastasis. Eight patients presented with only biochemical progression as evaluated by serum prostate-specific antigen levels. Thirty-six (63%) of 57 patients demonstrated a ≥50% decline in serum prostate-specific antigen levels. The median time to prostate-specific antigen progression was 7.2 months. In patients with a prostate-specific antigen decline of ≥50%, the median time to progression was 13.3 months. With respect to pre-treatment markers, the duration of response to initial hormonal treatment was associated with the time to prostate-specific antigen progression. In 11 of 16 (69%) patients who complained of bone pain, the pain improved and became stable in 5 of those patients (31%). Most adverse events were mild and only three (5%) patients showed neutropenia of Grade 3 or higher. The combination of dexamethasone, uracil plus tegafur and cyclophosphamide is an effective and well tolerated regimen for hormone-refractory prostate cancer. To evaluate the survival benefits, further randomized studies are required.

Hematologic emergencies

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Daniele Vallisa

2012-01-01

Full Text Available In recent years, the surprising progress made in other areas of hematology (advances in the understanding of leukemogenesis, improved transplant techniques has been conspicuously absent in the management of hematologic emergencies. And yet, every step toward greater knowledge, every new treatment option will be of little value unless we are able to manage the acute complications of hematologic diseases. These complications are better defined as hematologic emergencies, and they are characterized by a high rate of mortality. This review is based on a search of the literature that was initially confined to articles published in the journal Hematology from 2000 to 2009. The search was then extended to the Cochrane Library and to Pub Med in February 2010 with the following Keywords emergencies; urgencies; hematology. The same key words were employed in a search of the archives of Blood and the New England Journal of Medicine from 2000 to 2010. The results confirm that hematologic emergencies can be caused by hematologic malignancies as well as by non-neoplastic hematologic diseases. Within the former category; this review examines the causes; manifestations; treatment and prevention of disseminated intravascular coagulation; superior vena caval syndrome; spinal cord compression; tumor lysis syndrome; hyperleukocytosis; and hypercalcemia. We also review emergency situations associated with non-neoplatic haematological diseases; such as thrombotic thrombocytopenic purpura; drug-induced hemolytic anemia; and acute sickle-cell crisis.

Radiotherapy for local progression in patients with hormone-refractory prostate cancer

International Nuclear Information System (INIS)

Furuya, Yuzo; Akakura, Koichiro; Akimoto, Susumu; Ichikawa, Tomohiko; Ito, Haruo

1999-01-01

The aim of the present study was to investigate the effect of radiotherapy on the local progression of hormone-refractory prostate cancer. From 1986 to 1995, 38 patients were diagnosed with local progression without distant progression after hormonal therapy at Chiba University Hospital. Eleven cases were treated with irradiation for local progression. External beam irradiation was delivered to the prostate at a dose of 50-66.6 Gy. In patients treated with radiotherapy, the duration from initial treatment to local recurrence was 6-80 months (mean±SD: 33.9±22.9 months). The follow-up period after irradiation was 7-64 months (mean±SD: 25.4±18.8 months). Three and 5 year cause-specific survival rates from radiotherapy were 46.2 and 23.1%, respectively. Radiotherapy had a marked effect on symptoms associated with local progression and no patients suffered from the symptoms after the radiotherapy. Complications of radiotherapy were limited. In patients with hormone refractory local progression without distant progression, low morbidity, low mortality radiotherapy offers a variable therapy to other palliative treatments because radiotherapy is able to control local symptoms for a long period of time. (author)

Case report: efficacy and tolerability of ketamine in opioid-refractory cancer pain.

Science.gov (United States)

Amin, Priya; Roeland, Eric; Atayee, Rabia

2014-09-01

A 36-year-old female with metastatic breast cancer involving bones, liver, lung, and pleura/chest wall with worsening back pain received weight-based intravenous (IV) ketamine and was transitioned to oral ketamine for cancer-related neuropathic pain. She had responded poorly to outpatient pain regimen of oxycodone sustained and immediate release, hydromorphone, gabapentin, and duloxetine (approximate 480 mg total oral morphine equivalents [OME]), reporting an initial pain score of 10/10. She was started on hydromorphone parenteral patient-controlled analgesia (PCA) bolus dose in addition to her outpatient regimen. Despite escalating doses of opioids and the addition of a lidocaine 5% patch, the patient's pain remained uncontrolled 6 days after admission. On hospital day 7, utilizing a hospital weight-based ketamine protocol, the patient was started on subanesthetic doses of ketamine at 0.2 mg/kg/h (288 mg/24 h) and titrated over 2 days to 0.4 mg/kg/h (576 mg/24 h). Then, a 3-day rotation from intravenous to oral ketamine was initiated, and the patient was discharged on ketamine oral solution, 75 mg every 8 hours. When the patient's dose was increased to 0.4 mg/kg/h, adequate pain relief was charted by the nurse within 120 minutes, "patient pain free and resting comfortably." Her pain continued to be well managed, with an average pain score of 5/10 with the ketamine continuous infusion and sustained with conversion to oral ketamine without any report of side effects. This was a 37% reduction in pain scores. With the patient's stabilized dose of ketamine, opioid requirements decreased by 61.4% (1017.5 mg reduction in total OME). The use of weight-based dosing of IV continuous infusion and transition to oral ketamine was effective and tolerable in the management of opioid-refractory, neuropathic cancer pain. It is hoped that this case report promotes a discussion regarding ketamine dosing in refractory neuropathic cancer pain.

Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

DEFF Research Database (Denmark)

Buch-Hansen, Trine Zeeberg; Bentzen, Lise Nørgaard; Hansen, Steinbjoern

2010-01-01

DGP, maximum of eight courses, until progression or unacceptable toxicity. Docetaxel 75 mg/m(2) was administered intravenously day 1, gemcitabine was given day 1 and 8 in doses increasing from 600 to 1,000 mg/m(2) every third week. Patients had castrate refractory metastatic prostate cancer (CRMPC......), adequate function of liver, kidney and bone marrow; ECOG performance status...

Lenvatinib in Advanced Radioiodine-Refractory Thyroid Cancer - A Retrospective Analysis of the Swiss Lenvatinib Named Patient Program.

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Balmelli, Catharina; Railic, Nikola; Siano, Marco; Feuerlein, Kristin; Cathomas, Richard; Cristina, Valerie; Güthner, Christiane; Zimmermann, Stefan; Weidner, Sabine; Pless, Miklos; Stenner, Frank; Rothschild, Sacha I

2018-01-01

Purpose: Differentiated thyroid cancer (DTC) accounts for approximately 95% of thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has very limited efficacy and is associated with substantial toxicity. With increasing knowledge of the molecular pathogenesis of DTC, novel targeted therapies have been developed. Lenvatinib is a tyrosine kinase inhibitor (TKI) with promising clinical activity based on the randomized phase III SELECT trial. In Switzerland, a Named Patient Program (NPP) was installed to bridge the time gap to Swissmedic approval. Here, we report the results from the Swiss Lenvatinib NPP including patients with metastatic RAI-refractory DTC. Methods: Main inclusion criteria for the Swiss NPP were RAI-refractory DTC, documented disease progression, Eastern Cooperative Oncology Group (ECOG) performance status 0-3. The number of previous therapies was not limited. The Swiss Lenvatinib NPP was initiated in June 2014 and was closed in October 2015 with the approval of the drug. Results: Between June 2014 and October 2015, 13 patients with a median age of 72 years have been enrolled. Most patients (69%) had at least one prior systemic therapy, mainly sorafenib. 31% of patients showed a PR and 31% SD. Median progression free survival was 7.2 months and the median overall survival was 22.7 months. Dose reduction due to adverse events was necessary in 7 patients (53%). At the time of analysis 6 patients (47%) were still on treatment with a median time on treatment of 9.98 months. Conclusions: Our results show that lenvatinib has reasonable clinical activity in unselected patients with RAI-refractory thyroid cancer with nearly two-third of patients showing clinical benefit. The toxicity profile of lenvatinib is manageable.

The European Hematology Association Roadmap for European Hematology Research

DEFF Research Database (Denmark)

Engert, Andreas; Balduini, Carlo; Brand, Anneke

2016-01-01

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology...... research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness...... of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology...

New developments in the management of relapsed/refractory multiple myeloma – the role of ixazomib

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Richardson PG

2017-08-01

Full Text Available Paul G Richardson,1 Shaji Kumar,2 Jacob P Laubach,1 Claudia Paba-Prada,1 Neeraj Gupta,3 Deborah Berg,3 Helgi van de Velde,3 Philippe Moreau4 1Division of Hematologic Malignancy, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA; 2Division of Hematology, Mayo Clinic, Rochester, MN, USA; 3Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA; 4Hematology Department, University Hospital Hotel-Dieu, Nantes, France Abstract: Ixazomib is the first oral proteasome inhibitor to be approved, in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was on the basis of results from the phase 3, double-blind, placebo-controlled TOURMALINE-MM1 study, which demonstrated a 35% improvement in progression-free survival with the all-oral combination of ixazomib plus lenalidomide–dexamethasone versus lenalidomide–dexamethasone alone (median: 20.6 vs 14.7 months; hazard ratio: 0.74, p=0.012; median follow-up 14.7 months. The addition of ixazomib to the lenalidomide–dexamethasone regimen was associated with limited additional toxicity and had no adverse impact on patient-reported quality of life. Common grade ≥3 adverse events with ixazomib include gastrointestinal adverse events, rash, and thrombocytopenia. Here, we review the efficacy, safety, pharmacokinetics, and patient-reported quality of life data seen with ixazomib, and discuss the role of this oral agent in the treatment of patients with relapsed/refractory multiple myeloma, including in patients with high-risk cytogenetic abnormalities and those with multiple prior therapies. Keywords: ixazomib, multiple myeloma, proteasome inhibitor, clinical, efficacy, tolerability, pharmacokinetics 

Ketamine, as adjuvant analgesics for patients with refractory cancer pain, does affect IL-2/IFN-γ expression of T cells in vitro?

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Zhou, Naibao; Fu, Zhijian; Li, Hao; Wang, Kaiguo

2017-01-01

Abstract Background: Ketamine has been used as an analgesic adjuvant with morphine in the treatment of refractory cancer pain recently. But both morphine and ketamine have been reported to produce a number of immunomodulatory effects. The current study was performed to assess whether the concentration of ketamine, as adjuvant analgesics for patient with refractory cancer pain, was related to its effect on T cells interleukin-2 (IL-2)/interferon-γ (IFN-γ) expression in vitro. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood of patients with refractory cancer pain over a Ficoll-Hypaque density gradient. T cells were isolated from by positive selection using anti-CD3 beads. T cells were then treated with vehicle (C group), morphine (200 ng/mL, M group), morphine (200 ng/mL), and different dose of ketamine (100, 200, 1000 ng/mL; MK1, MK5, MK10 group) for 24 hours before stimulation with anti-CD3 and anti-CD28. Then supernatant IL-2 and IFN-γ protein analysis, quantitative reverse transcription polymerase chain reaction (RT-PCR) for IL-2 and IFN-γ were done. Results: There were no significant difference of supernatant IL-2 and IFN-γ among C group, M group, and MK1 group, but the mRNA of M group and MK1 group were decreased compared with C group (P ketamine dose-dependently suppressed IL-2 and IFN-γ of activated T lymphocyte of patients with refractory cancer pain in vitro, but the inhibitory action of low dose ketamine could be neglected. PMID:28422864

Ruxolitinib in steroid refractory graft-vs.-host disease: a case report

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Enrico Maffini

2016-08-01

Full Text Available Abstract Background Allogeneic hematopoietic stem cell transplantation (HSCT is potentially curative in a variety of hematological malignancies. Graft-vs.-host disease (GvHD remains a life-threatening complication. Standard treatment is high-dose (HD corticosteroids. Steroid-refractory (SR GvHD is associated with poor prognosis. At present, second-line treatment is ill-defined and includes a number of agents. Novel insights into the pathophysiology of acute GvHD (aGvHD highlight the relevant role of the host inflammatory response governed by several kinase families, including Janus kinases (JAK1/2. Ruxolitinib, a JAK1/2 inhibitor approved for intermediate-2/high-risk myelofibrosis, was recently employed in SR-GvHD with encouraging overall response rates. Clinical experience however remains limited. Case presentation A 51-year-old male with refractory anemia with excess blast type-2 underwent a myeloablative allogeneic HSCT from a 9/10 HLA-matched unrelated donor after conditioning with busulfan and cyclophosphamide. GvHD prophylaxis consisted of cyclosporine, methotrexate, and thymoglobulin. CD34+ cells/kg infused were 8.69 × 106 kg. On day 29, the patient developed overall grade IV aGvHD with biopsy proven stage IV gastrointestinal (GI GvHD refractory to HD corticosteroids. Patient conditions rapidly deteriorated and became critical despite the addition of mycophenolate mofetil and budesonide. On day 33, Ruxolitinib was started, and on day 39 the patient clinical conditions gradually improved. Complete resolution of aGvHD was also confirmed by histology on day 54. Conclusions At 5 months from HSCT, the patient is well and in continuous hematological complete remission without flare of GvHD. Ruxolitinib was discontinued on day 156. Ruxolitinib is feasible and effective in SR-aGvHD though large prospective clinical trials are warranted.

Survival From Childhood Hematological Malignancies in Denmark

DEFF Research Database (Denmark)

Erdmann, Friederike; Winther, Jeanette Falck; Dalton, Susanne Oksbjerg

2016-01-01

BACKGROUND: Due to diverse findings as to the role of family factors for childhood cancer survival even within Europe, we explored a nationwide, register-based cohort of Danish children with hematological malignancies. METHODS: All children born between 1973 and 2006 and diagnosed with a hematolo...

An exploratory study of the relation of population density and agricultural activity to hematologic malignancies in North Dakota.

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Watkins, Patricia L; Watkins, John M

2013-02-01

Established risk factors for hematologic cancers include exposure to ionizing radiation, organic solvents, and genetic mutation; however, the potential roles of environmental and sociological factors are not well explored. As North Dakota engages in significant agricultural activity, the present investigation seeks to determine whether an association exists between the incidence of hematologic cancers and either population density or agricultural occupation for residents of south central North Dakota. The present study is a retrospective analysis. Cases of hematologic malignancies and associated pre-malignant conditions were collected from the regional Central North Dakota Cancer Registry, and analysis of study-specific demographic factors was performed. Significantly higher incidence of hematologic cancers and pre-malignant disorders was associated with residence in an "urban" county and rural city/town. Within the latter designation, there was a higher rate of self-reported agricultural occupation (40% vs 10%, P Dakota supports the need for more detailed prospective research centered on agricultural exposures.

Impact of Bone Marrow Radiation Dose on Acute Hematologic Toxicity in Cervical Cancer: Principal Component Analysis on High Dimensional Data

International Nuclear Information System (INIS)

Yun Liang; Messer, Karen; Rose, Brent S.; Lewis, John H.; Jiang, Steve B.; Yashar, Catheryn M.; Mundt, Arno J.; Mell, Loren K.

2010-01-01

Purpose: To study the effects of increasing pelvic bone marrow (BM) radiation dose on acute hematologic toxicity in patients undergoing chemoradiotherapy, using a novel modeling approach to preserve the local spatial dose information. Methods and Materials: The study included 37 cervical cancer patients treated with concurrent weekly cisplatin and pelvic radiation therapy. The white blood cell count nadir during treatment was used as the indicator for acute hematologic toxicity. Pelvic BM radiation dose distributions were standardized across patients by registering the pelvic BM volumes to a common template, followed by dose remapping using deformable image registration, resulting in a dose array. Principal component (PC) analysis was applied to the dose array, and the significant eigenvectors were identified by linear regression on the PCs. The coefficients for PC regression and significant eigenvectors were represented in three dimensions to identify critical BM subregions where dose accumulation is associated with hematologic toxicity. Results: We identified five PCs associated with acute hematologic toxicity. PC analysis regression modeling explained a high proportion of the variation in acute hematologicity (adjusted R 2 , 0.49). Three-dimensional rendering of a linear combination of the significant eigenvectors revealed patterns consistent with anatomical distributions of hematopoietically active BM. Conclusions: We have developed a novel approach that preserves spatial dose information to model effects of radiation dose on toxicity, which may be useful in optimizing radiation techniques to avoid critical subregions of normal tissues. Further validation of this approach in a large cohort is ongoing.

CURRENT POSSIBILITIES OF TREATMENT FOR VISCERAL METASTASES IN PATIENTS WITH METASTATIC CASTRATION-REFRACTORY PROSTATE CANCER

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A. V. Govorov

2014-07-01

Full Text Available Medications increasing the survival of patients with metastatic castration-refractory prostate cancer (CRPC are lacking today. In the past 3 years, in the pharmaceutical market there have been a few novel drugs to treat progressive prostate cancer. Abiraterone acetate is an androgen synthesis inhibitor, which is also used to increase the survival of patients with metastatic CRPC that progresses after chemotherapy. The results of treatment for metastatic CRPC depend on a number of factors. Visceral metastases are poor predictors of the course of the disease. The results of abiraterone acetate treatment were analyzed in CRPC patients with visceral metastases.

Total-Body Irradiation and Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

Science.gov (United States)

2017-12-11

Adult Acute Myeloid Leukemia in Remission; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndrome; Childhood Renal Cell Carcinoma; Chronic Myelomonocytic Leukemia; Clear Cell Renal Cell Carcinoma; de Novo Myelodysplastic Syndrome; Metastatic Renal Cell Cancer; Previously Treated Myelodysplastic Syndrome; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Renal Medullary Carcinoma; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Hematologic Nadirs During Chemoradiation for Anal Cancer: Temporal Characterization and Dosimetric Predictors

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Lee, Andrew Y.; Golden, Daniel W. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Bazan, Jose G. [Department of Radiation Oncology, The Ohio State University, Columbus, Ohio (United States); Kopec, Malgorzata; Pelizzari, Charles A. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Aggarwal, Sonya; Chang, Daniel T. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States)

2017-02-01

Purpose: Pelvic bone marrow (BM) constraints may offer a means to reduce the toxicity commonly associated with chemoradiation for anal cancer. We conducted a bi-institutional analysis of dose-volume metrics in a time-sensitive fashion to devise practical metrics to minimize hematologic toxicity. Methods and Materials: Fifty-six anal cancer patients from 2 institutions received definitive radiation therapy (median primary dose of 54 Gy) using intensity modulated radiation therapy (IMRT, n=49) or 3-dimensional (3D) conformal therapy (n=7) with concurrent 5-fluorouracil (5-FU) and mitomycin C. Weekly blood counts were retrospectively plotted to characterize the time course of cytopenias. Dose-volume parameters were correlated with blood counts at a standardized time point to identify predictors of initial blood count nadirs. Results: Leukocytes, neutrophils, and platelets reached a nadir at week 3 of treatment. Smaller volumes of the pelvic BM correlated most strongly with lower week 3 blood counts, more so than age, sex, body mass index (BMI), or dose metrics. Patients who had ≥750 cc of pelvic BM spared from doses of ≥30 Gy had 0% grade 3+ leukopenia or neutropenia at week 3. Higher V40 Gy to the lower pelvic BM (LP V40) also correlated with cytopenia. Patients with an LP V40 >23% had higher rates of grade 3+ leukopenia (29% vs 4%, P=.02), grade 3+ neutropenia (33% vs 8%, P=.04), and grade 2+ thrombocytopenia (32% vs 7%, P=.04) at week 3. On multivariate analysis, pelvic BM volume and LP V40 remained associated with leukocyte count, and all marrow subsite volumes remained associated with neutrophil counts at week 3 (P<.1). Conclusions: Larger pelvic BM volumes correlate with less severe leukocyte and neutrophil nadirs, suggesting that larger total “marrow reserve” can mitigate cytopenias. Sparing a critical marrow reserve and limiting the V40 Gy to the lower pelvis may reduce the risk of hematologic toxicity.

Single center experience with total body irradiation and melphalan (TBI-MEL) myeloablative conditioning regimen for allogeneic stem cell transplantation (SCT) in patients with refractory hematologic malignancies.

Science.gov (United States)

Bhatnagar, Bhavana; Rapoport, Aaron P; Fang, Hong-Bin; Ilyas, Can; Marangoz, Deniz; Akbulut, Vinil; Ruehle, Kathleen; Badros, Ashraf; Yanovich, Saul; Akpek, Görgün

2014-04-01

We retrospectively evaluated the tolerability and efficacy of fractionated total body irradiation (TBI) (1,200 cGy) and melphalan (MEL) (100-110 mg/m(2)) myeloablative conditioning in 48 patients with nonremission AML (n = 14), ALL (n = 10), NHL (n = 18), and other refractory hematologic malignancies (n = 6) who received allogeneic stem cell transplantation (SCT) between 2002 and 2011. Median age was 48 years (22 to 68); 14 out of 26 leukemia patients (54 %) had circulating blasts at transplant, 20 (50 %) evaluable patients had poor-risk cytogenetics, 12 (25 %) had prior SCT, and 10 (21 %) received stem cells from a mismatch donor. All patients received tacrolimus with or without methotrexate for GVHD prophylaxis. At the time of analysis, 13 patients (27 %) were alive and disease free. Engraftment was complete in all patients. The median time to ANC recovery (>500) was 12 days (range, 6-28). The most common grade III and IV toxicities were mucositis and infections. Eighteen patients (43 %) developed grade II-IV acute GVHD, and eight (26 %) had extensive chronic GVHD. Of 44 evaluable patients for response, 28 (64 %) achieved a complete remission (CR), and seven (15 %) had a partial remission after the transplant. With a median follow-up of 30 months (4 to 124 months) for surviving patients, the cumulative incidence of relapse was 45 % at 1 year, and the probability of overall survival (OS) at 5 years was 22.5 %. Multivariate analysis showed that platelet count (500 IU/L) at SCT were associated with relapse. Age less than 53 years and CR after SCT were associated with better OS. Our data suggest that TBI-MEL can result in CR in two thirds, durable remission in one third, and 5-year survival in about one quarter of patients with nonremission hematologic malignancies. Further studies with TBI-MEL in standard risk transplant patients are warranted.

Clinical approach to circumvention of multidrug resistance in refractory leukemic patients: association of cyclosporin A with etoposide.

Science.gov (United States)

Maia, R C; Carriço, M K; Klumb, C E; Noronha, H; Coelho, A M; Vasconcelos, F C; Ruimanek, V M

1997-12-01

Alternative therapy for refractory leukemic patients is being increasingly adopted. Circumvention of multidrug resistance represents a strategy that has been taken into account when conventional chemotherapy failed. In this work a group of 15 refractory, heavily pretreated, patients was enrolled in a circumvention protocol including etoposide (ETO) and cyclosporin A (CSA). All patients received etoposide prior to this schedule. Toxicity to circumvention protocol was acceptable and only one serious side-effect was observed. Two hematological clinical responses were seen, both of which were positive to P-glycoprotein immunostaining and exhibited in vitro modulation by CSA in cultures using the thymidine incorporation assay. Three out of four patients negative for P-glycoprotein achieved a minor response. Three out of six clinical failures were also negative for Pgp immunostaining one of which exhibited sinergistic effect between ETO and CSA. Our study suggests that hematological response to ETO and CSA association can be obtained in intensely pretreated leukemic patients. Several factors may affect the response such as clinical status before this therapy. Additionally, it also suggests that not all CSA effects on the combination ETO-CSA can be attributed to Pgp modulation.

An "off-the-shelf" fratricide-resistant CAR-T for the treatment of T cell hematologic malignancies.

Science.gov (United States)

Cooper, Matthew L; Choi, Jaebok; Staser, Karl; Ritchey, Julie K; Devenport, Jessica M; Eckardt, Kayla; Rettig, Michael P; Wang, Bing; Eissenberg, Linda G; Ghobadi, Armin; Gehrs, Leah N; Prior, Julie L; Achilefu, Samuel; Miller, Christopher A; Fronick, Catrina C; O'Neal, Julie; Gao, Feng; Weinstock, David M; Gutierrez, Alejandro; Fulton, Robert S; DiPersio, John F

2018-02-20

T cell malignancies represent a group of hematologic cancers with high rates of relapse and mortality in patients for whom no effective targeted therapies exist. The shared expression of target antigens between chimeric antigen receptor (CAR) T cells and malignant T cells has limited the development of CAR-T because of unintended CAR-T fratricide and an inability to harvest sufficient autologous T cells. Here, we describe a fratricide-resistant "off-the-shelf" CAR-T (or UCART7) that targets CD7+ T cell malignancies and, through CRISPR/Cas9 gene editing, lacks both CD7 and T cell receptor alpha chain (TRAC) expression. UCART7 demonstrates efficacy against human T cell acute lymphoblastic leukemia (T-ALL) cell lines and primary T-ALL in vitro and in vivo without the induction of xenogeneic GvHD. Fratricide-resistant, allo-tolerant "off-the-shelf" CAR-T represents a strategy for treatment of relapsed and refractory T-ALL and non-Hodgkin's T cell lymphoma without a requirement for autologous T cells.

BMC Blood Disorders becomes BMC Hematology: evolving along with the hematology field

OpenAIRE

Chap, Christna

2013-01-01

This Editorial marks the launch of BMC Hematology, formerly known as BMC Blood Disorders, within the BMC series of journals published by BioMed Central. The scope of BMC Hematology encompasses basic, experimental and clinical research related to hematology. In this Editorial we will discuss the rationale behind this relaunch and how, as an open access journal providing unrestricted and free access to scientific and scholarly work, BMC Hematology will help disseminate research in the hematolog...

BMC Blood Disorders becomes BMC Hematology: evolving along with the hematology field.

Science.gov (United States)

Chap, Christna

2013-04-10

This Editorial marks the launch of BMC Hematology, formerly known as BMC Blood Disorders, within the BMC series of journals published by BioMed Central. The scope of BMC Hematology encompasses basic, experimental and clinical research related to hematology. In this Editorial we will discuss the rationale behind this relaunch and how, as an open access journal providing unrestricted and free access to scientific and scholarly work, BMC Hematology will help disseminate research in the hematology field in a freely-accessible manner.

Multicenter Retrospective Analysis of the Effectiveness and Safety of Rituximab in Korean Patients with Refractory Systemic Lupus Erythematosus

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So-Young Bang

2012-01-01

Full Text Available Objective. Although two recent randomized placebo-controlled trials of rituximab (RTX failed to demonstrate efficacy in systemic lupus erythematosus (SLE, clinicians continue to use off-label RTX for cases refractory to current treatments. We evaluated the effectiveness and safety of rituximab for patients with refractory SLE in Korea. Methods. We retrospectively analyzed multicenter patients treated with RTX in Korea. Results. 39 SLE patients treated with RTX were included in the following manner: lupus nephritis 43.6%, hematologic 33.3%, arthritis 7.8%, myositis 7.8%, and others 7.7%. All patients had responded poorly to at least one conventional immunosuppressive agent (mean 2.5 ± 1.1, cyclophosphamide 43.6%, mycophenolate mofetil 48.7%, and other drugs before RTX. Clinical improvements (complete or partial remission occurred in patients with renal disease, hematologic disease, arthritis, myositis, and other manifestations at 6 months after RTX. The SLEDAI score was significantly decreased from 10.8±7.1 at baseline to 6.7±4.0 at 6 months, 6.2±4.1 at 12 months, and 5.5±3.6 at 24 months after RTX (P<0.05. Among 28 clinical responders, 4 patients experienced a relapse of disease at 25±4 months. Infections were noted in 3 patients (7.7%. Conclusion. RTX could be an effective and relatively safe therapeutic option in patients with severe refractory SLE until novel B-cell depletion therapy is available.

Adjuvant chemotherapy and risk of gastrointestinal, hematologic, and cardiac toxicities in elderly patients with stage III colon cancer.

Science.gov (United States)

Hu, Chung-Yuan; Chan, Wenyaw; Delclos, George P; Du, Xianglin L

2012-06-01

Randomized trials have established the effectiveness of 5-fluorouracil-based adjuvant chemotherapy for stage III resectable colon cancer but the toxicity has not been well established outside the trial setting. The objective of this study was to estimate the risk of various toxicity-related endpoints among the elderly patients. Patients diagnosed with stage III colon cancer in 1991 to 2005 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Chemotherapy use within 3 months after tumor resection was identified from submitted claims. We reported the 3-month cumulative incidence rate (CIR) for gastrointestinal and hematologic toxicities. The risk of ischemic heart disease in relation to chemotherapy use and length was assessed using Cox regression models, stratified by age and comorbidity subgroups. Of the 12,099 patients, 63.9% (n=7740) received adjuvant chemotherapy. Common gastrointestinal and hematologic toxicities among chemotherapy group include volume depletion disorder (CIR=9.1%), agranulocytosis (CIR=3.4%), diarrhea (CIR=2.4%), nausea and vomiting (CIR=2.3%). Chemotherapy use was significantly associated with the onset of these toxicities [hazard ratio (HR)=2.76; 95% confidence interval (95% CI)=2.42-3.15]. The risk of ischemic heart disease was slightly associated with chemotherapy use (HR=1.08, 95% CI=0.96-1.22), but significant only among patients aged colon cancer. On account of the effects of these side effects on treatment discontinuation, rehospitalization, and overall health status, some close monitoring and preventive measures may be emphasized to maximize the benefits of adjuvant chemotherapy.

Trisomy 19 as the sole chromosomal anomaly in hematologic neoplasms.

Science.gov (United States)

Johansson, B; Billström, R; Mauritzson, N; Mitelman, F

1994-05-01

Trisomy 19 was found as the sole chromosomal aberration in three hematologic malignancies: one chronic myelomonocytic leukemia and two cases of of immunophenotypically immature acute myeloid leukemia (AML). A compilation of previously published hematologic neoplasms with +19 as the only change reveals that this anomaly is strongly associated with myeloid malignancies; 25 of 31 cases have been myelodysplastic syndromes (MDS) or AML. Eight of the 11 MDS cases have been either refractory anemia (RA) or RA with excess of blasts, and four of the 14 AML cases have had preleukemic myelodysplastic cases phase, with the +19 accruing during the time of leukemic transformation. The AML cases have, in general, been either or early maturation arrest, i.e. undifferentiated or AML-M1/M2, or of myelomonocytic-monoblastic origin, i.e., AML-M4/M5. None of the MDS or AML cases with +19 had had a previous history of radio- or chemotherapy. We conclude that trisomy 19, as the sole anomaly, is a characteristic abnormality in de novo myeloid malignancies. No clinical features seem to characterize patients with +19 AML and MDS and the prognostic impact of the aberration remains to be elucidated.

Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review.

Science.gov (United States)

Moloudizargari, Milad; Mortaz, Esmaeil; Asghari, Mohammad Hossein; Adcock, Ian M; Redegeld, Frank A; Garssen, Johan

2018-02-20

Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both in vitro and in vivo , following a partially selective manner. They also increase the efficacy of chemotherapeutic agents by increasing the sensitivity of different cell lines to specific anti-neoplastic drugs. Various mechanisms have been proposed for the anti-cancer effects of these omega-3 PUFAs; however, the exact mechanisms still remain unknown. While numerous studies have investigated the effects of DHA and EPA on solid tumors and the responsible mechanisms, there is no consensus regarding the effects and mechanisms of action of these two FAs in hematological malignancies. Here, we performed a systematic review of the beneficial effects of EPA and DHA on hematological cell lines as well as the findings of related in vivo studies and clinical trials. We summarize the key underlying mechanisms and the therapeutic potential of these PUFAs in the treatment of hematological cancers. Differential expression of apoptosis-regulating genes and Glutathione peroxidase 4 (Gp-x4), varying abilities of different cancerous and healthy cells to metabolize EPA into its more active metabolites and to uptake PUFAS are among the major factors that determine the sensitivity of cells to DHA and EPA. Considering the abundance of data on the safety of these FAs and their proven anti-cancer effects in hematological cell lines and the lack of related human studies, further research is warranted to find ways of exploiting the anticancer effects of DHA and EPA in clinical settings both in isolation and in combination with other therapeutic regimens.

Associations between dyadic coping and supportive care needs: findings from a study with hematologic cancer patients and their partners.

Science.gov (United States)

Weißflog, Gregor; Hönig, Klaus; Gündel, Harald; Lang, Dirk; Niederwieser, Dietger; Döhner, Hartmut; Vogelhuber, Martin; Mehnert, Anja; Ernst, Jochen

2017-05-01

The way couples mutually cope with hematologic cancer is likely to influence their levels of supportive care needs (SCN). Therefore, this study evaluated the levels of dyadic coping (DC) and SCN and the concurrent associations between both variables. Three hundred thirty patients with a hematologic malignancy (63% male) and their partners completed the dyadic coping inventory (DCI) and the supportive care needs survey (SCNS-SF-34-G). The levels of dyadic coping (DC) and supportive care needs (SCN) were compared with representative validation samples. Correlational analyses and actor-partner interdependence models (APIM) were calculated to estimate the association between DC and SCN. Partners' stress communication of cancer patients (as part of DC) was decreased in contrast to that of a non-cancer sample. The perception of partners' delegated DC was higher (both with a moderate effect size of g ≥ |0.50|). SCN of patients and partners were lower in the dimensions health system/information and physical problems/daily living in contrast to those of a cancer patients' validation sample (both with a small effect of g ≥ |0.20|). Higher perceptions of partners' negative DC were associated with higher SCN for both patients and partners. The same was true for patients' own stress communication and SCN, but only for the patients. Sociodemographic and illness-related factors were only partially related with the SCN of patients and partners. In order to diminish SCN of patients and partners, a possible way is to strengthen the quality of the dyadic relation. Due to its associations with elevated SCN, stress communication and negative dyadic coping behaviours may be useful targets for psychosocial interventions.

Acute hematologic emergencies in oncology

International Nuclear Information System (INIS)

Kristof, L.

2012-01-01

Malignant disease and its treatment are often being complicated by development of serious and at times life-threatening emergencies. Early recognition and treatment of these acute events are important to reduce morbidity and mortality in cancer patients. The following article provides an overview of several hematologic emergencies, which occur due abnormal hemopoiesis (e.g. hyperleukocytosis, anemia, thrombocytopenia), abnormal hemo stasis (e.g. hemorrhage, pulmonary embolism, disseminated intravascular coagulation), or are related to blood products transfusions (transfuse reactions). (author)

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

OpenAIRE

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

2002-01-01

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

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

Directory of Open Access Journals (Sweden)

Li Y

2017-11-01

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

The European Hematology Association Roadmap for European Hematology Research : A consensus document

NARCIS (Netherlands)

Engert, Andreas; Balduini, Carlo; Brand, Anneke; Coiffier, Bertrand; Cordonnier, Catherine; Döhner, Hartmut; de Wit, Thom Duyvené; Eichinger, Sabine; Fibbe, Willem; Green, Tony; de Haas, Fleur; Iolascon, Achille; Jaffredo, Thierry; Rodeghiero, Francesco; Salles, Gilles; Schuringa, Jan Jacob

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology

Maspin Enhances the Anticancer Activity of Curcumin in Hormone-refractory Prostate Cancer Cells.

Science.gov (United States)

Cheng, Wan-Li; Huang, Chien-Yu; Tai, Cheng-Jeng; Chang, Yu-Jia; Hung, Chin-Sheng

2018-02-01

Androgen deprivation therapy remains the principal treatment for patients with advanced prostate cancer, though, most patients will eventually develop hormone-refractory prostate cancer (HRPC). Androgen ablation mediated maspin-induction has been identified in cancer patients. However, the role of maspin on the anticancer activity of curcumin derived from turmeric (Curcuma longa) in HRPC cells has not been elucidated. The anticancer action of curcumin in hormone-independent prostate cancer cells (DU145, and PC-3) was determined by measures of cell survival rate. The cause of maspin silencing on the anti-tumor abilities of curcumin in PC-3 cells was evaluated by measures of cell survival rate, cell-cycle distribution, and apoptosis signaling analysis. Our present study showed that PC-3 cells (with higher maspin expression) were more sensitive than DU145 cells to curcumin treatment (with lower maspin expression). RNA interference-mediated maspin silencing reduced curcumin sensitivity of PC-3 cells, as evidenced by reduced apoptotic cell death. After exposure to curcumin, maspin-knockdown cells showed lower expression levels of pro-apoptotic proteins, Bad and Bax, as compared with control cells. Maspin can enhance the sensitivity of HRPC cells to curcumin treatment. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Early hematologic changes during prostate cancer radiotherapy predictive for late urinary and bowel toxicity

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Pinkawa, Michael; Djukic, Victoria; Klotz, Jens; Holy, Richard; Eble, Michael J. [RWTH Aachen University, Department of Radiation Oncology, Aachen (Germany); Ribbing, Carolina [RWTH Aachen University, Department of Diagnostic and Interventional Radiology, Aachen (Germany)

2015-10-15

The primary objective of the study was to identify early hematologic changes predictive for radiotherapy (RT)-associated genitourinary and gastrointestinal toxicity. In a group of 91 prostate cancer patients presenting for primary (n = 51) or postoperative (n = 40) curative RT, blood samples (blood count, acute phase proteins, and cytokines) were analyzed before (T1), three times during (T2-T4), and 6-8 weeks after (T5) radiotherapy. Before RT (baseline), on the last day (acute toxicity), a median of 2 months and 16 months (late toxicity) after RT, patients responded to a validated questionnaire (Expanded Prostate Cancer Index Composite). Acute score changes > 20 points and late changes > 10 points were considered clinically relevant. Radiotherapy resulted in significant changes of hematologic parameters, with the largest effect on lymphocytes (mean decrease of 31-45 %) and significant dependence on target volume. C-reactive protein (CRP) elevation > 5 mg/l and hemoglobin level decrease ≥ 5 G/1 at T2 were found to be independently predictive for acute urinary toxicity (p < 0.01, respectively). CRP elevation was predominantly detected in primary prostate RT (p = 0.02). Early lymphocyte level elevation ≥ 0.3G/l at T2 was protective against late urinary and bowel toxicity (p = 0.02, respectively). Other significant predictive factors for late bowel toxicity were decreasing hemoglobin levels (cut-off ≥ 5 G/l) at T2 (p = 0.04); changes of TNF-α (tumor necrosis factor; p = 0.03) and ferritin levels (p = 0.02) at T5. All patients with late bowel toxicity had interleukin (IL)-6 levels < 1.5 ng/l at T2 (63 % without; p = 0.01). Early hematologic changes during prostate cancer radiotherapy are predictive for late urinary and bowel toxicity. (orig.) [German] Das primaere Ziel der Studie war die Identifikation von fruehen haematologischen Veraenderungen mit praediktiver Bedeutung fuer radiotherapieassoziierte genitourinale und gastrointestinale Toxizitaet. In einer

Determinants of hematology-oncology trainees' postfellowship career pathways with a focus on nonmalignant hematology

Science.gov (United States)

Jenkins, Sarah; Mikhael, Joseph; Gitlin, Scott D.

2018-01-01

Nonmalignant hematologic conditions are extremely prevalent and contribute significantly to the global burden of disease. The US health care system may soon face a shortage of specialists in nonmalignant hematology. We sought to identify factors that lead hematology-oncology fellows to pursue (or not to pursue) careers in nonmalignant hematology. Cross-sectional, web-based survey distributed to 149 graduates of a hematology-oncology fellowship program at a large academic medical center between 1998 and 2016. Eighty-six out of 149 graduates responded (57.7%); most (59 [68.6%]) practice at an academic medical center. Respondents spend a mean of 61% of their time in clinical practice, 23.7% conducting research, 5.2% in education, and 5.2% in administration. Those in clinical practice spend a mean of 52.1% of their time in solid tumor oncology, 37.5% in hematologic malignancies, and 10% in nonmalignant hematology; only 1 spent >50% of time practicing nonmalignant hematology. Factors most significantly affecting choice of patient population included clinical experience during fellowship and intellectual stimulation of the patient population/disease type. Factors that could have most significantly influenced a decision to spend more time in nonmalignant hematology included increased exposure/access to role models and mentors and opportunities for better career growth/advancement. Fellowship graduates spend >50% of their time in clinical practice, but almost none spend a significant amount of time practicing nonmalignant hematology. Given the growing number of patients with nonmalignant hematologic conditions and a possible future provider shortage, medical trainees should be encouraged to pursue careers in nonmalignant hematology. PMID:29463548

The European Hematology Association Roadmap for European Hematology Research: a consensus document.

Science.gov (United States)

Engert, Andreas; Balduini, Carlo; Brand, Anneke; Coiffier, Bertrand; Cordonnier, Catherine; Döhner, Hartmut; de Wit, Thom Duyvené; Eichinger, Sabine; Fibbe, Willem; Green, Tony; de Haas, Fleur; Iolascon, Achille; Jaffredo, Thierry; Rodeghiero, Francesco; Salles, Gilles; Schuringa, Jan Jacob

2016-02-01

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap.The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders.The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. Copyright© Ferrata Storti Foundation.

Hematology

International Nuclear Information System (INIS)

Konrad, H.

1976-01-01

The latest state of nuclear medical functional diagnostics in hematology is reviewed. In addition to methods for determining the blood volume, iron kinetics, the survival time of erythrocytes as well as resorption and serum levels of vitamin B 12 kinetic investigations of thrombocytes, granulocytes, lymphocytes, and the spleen with the aid of radioisotopes are described in detail. Also included are tables with data about radiation doses to patients due to medical application of radioisotopes as well as a compilation of physical properties of radioisotopes which are used in hematological diagnosis such as 59 Fe, 51 Cr, 131 I, 125 I, 58 Co, 57 Co, 32 P, 3 H, sup(99m)Tc, 113 In. Finally, radiopharmaceuticals for hematological diagnostics are listed, which are commercially available in the German Democratic Republic. The booklet is intended for physicians working in outpatient departments and hospitals

Ketamine, as adjuvant analgesics for patients with refractory cancer pain, does affect IL-2/IFN-γ expression of T cells in vitro?: A prospective, randomized, double-blind study.

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Zhou, Naibao; Fu, Zhijian; Li, Hao; Wang, Kaiguo

2017-04-01

Ketamine has been used as an analgesic adjuvant with morphine in the treatment of refractory cancer pain recently. But both morphine and ketamine have been reported to produce a number of immunomodulatory effects. The current study was performed to assess whether the concentration of ketamine, as adjuvant analgesics for patient with refractory cancer pain, was related to its effect on T cells interleukin-2 (IL-2)/interferon-γ (IFN-γ) expression in vitro. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood of patients with refractory cancer pain over a Ficoll-Hypaque density gradient. T cells were isolated from by positive selection using anti-CD3 beads. T cells were then treated with vehicle (C group), morphine (200 ng/mL, M group), morphine (200 ng/mL), and different dose of ketamine (100, 200, 1000 ng/mL; MK1, MK5, MK10 group) for 24 hours before stimulation with anti-CD3 and anti-CD28. Then supernatant IL-2 and IFN-γ protein analysis, quantitative reverse transcription polymerase chain reaction (RT-PCR) for IL-2 and IFN-γ were done. There were no significant difference of supernatant IL-2 and IFN-γ among C group, M group, and MK1 group, but the mRNA of M group and MK1 group were decreased compared with C group (P ketamine dose-dependently suppressed IL-2 and IFN-γ of activated T lymphocyte of patients with refractory cancer pain in vitro, but the inhibitory action of low dose ketamine could be neglected.

Hormonotherapy and chemotherapy in hormone refractory prostate cancer

International Nuclear Information System (INIS)

Droz, J.

2004-01-01

The median survival of patients with metastatic prostate cancer is 3 years, though it is only one year when the tumor is hormone refractory (HRPC). The number of possible problems is great, but the major one is pain. The number of therapeutics is also great. They have only palliative and symptomatic impact. Early hormone suppression in patients with advanced disease may have slight survival impact. Thus, a general scheme of management can be proposed, based on several principles: 1- Early hormone suppression is proposed is metastatic prostate cancer. Hormone suppression is castration or LH-RH agonist. 2- Powerful tools must be used to measure palliative impact: pain and analgesic scales, quality of life evaluation. PSA decrease may only be a surrogate of clinical response evaluation. 3- After first line hormone suppression, indication of further hormone therapy, chemotherapy and radio pharmaceutics is based only on symptomatic progression. It is not based on tumor progression as measured by PSA increase or metastasis evolution, because it is well established that, till now, treatment has only palliative effect. 4- Management of local problems (urinary obstruction, fracture, nerve compression) must be done depending on the situation. 4- Patients must be clearly informed of the palliative end-points, of the therapeutic tools, of the current side effects and goals of treatments. The strategy must be prospectively explained at the early beginning of treatment. Chemotherapy has become a standard treatment in HRPC because it has shown palliative improvement (Mitoxantrone studies), and more recently survival improvement (Docetaxel studies). However new drugs are under development. It will be focussed on drugs acting on EGF-receptor, endothelin-A, proteasome and V EGF. Practical management of HRPC will be discussed

Immunomodulatory therapy in refractory/recurrent ovarian cancer

Directory of Open Access Journals (Sweden)

Chao-Yu Chen

2015-04-01

Conclusion: IMT alone or add-on to palliative/salvage chemotherapy for refractory/recurrent EOC achieves a substantial disease stabilizing rate without severe toxicity, which might be a potential option in selected patients. The ALC 1 month after IMT could be an early indicator to disease stabilization.

Incidence and risk of hematologic toxicities in cancer patients treated with regorafenib.

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Zhao, Bin; Zhao, Hong

2017-11-07

Regorafenib, an oral vascular endothelial growth factor receptor tyrosine-kinase inhibitor, has been approved for the treatment of several malignancies. As a non-traditional cytotoxic chemotherapeutic agent, regorafenib is often associated with hematologic toxicities. Here we searched PubMed and Embase up to June 2017 for relevant clinical trials. Eligible studies include trials in which subjects treated with 160 mg of regorafenib daily during the first 21 days of each 28-day cycle, and adequate safety data profile reporting thrombocytopenia, anemia, neutropenia and leucopenia. Statistical analyses were conducted to calculate the overall incidences, relative risks (RRs) and their 95% confidence intervals (CIs). A total of 2,341 subjects from 16 trials were included in the present studies. The incidences of regorafenib associated all-grade and high-grade hematologic toxicities were: thrombocytopenia, 22% and 3%; anemia, 20% and 3%; neutropenia, 10% and 2%, and leucopenia, 13% and 2%, respectively. Regorafenib-treated subjects had a significant increased risk of all-grade (RR=6.35; 95% CI, 3.19-12.64) and high-grade (RR=6.27; 95% CI, 1.69-23.26) thrombocytopenia, all-grade (RR=2.76; 95% CI, 1.63-4.68) and high-grade (RR=5.38; 95% CI, 1.60-18.06) anemia. Our results suggested that regorafenib therapy was associated with significantly increased risks of hematological toxicities, and hematologic monitoring at regular intervals should be advised to clinician.

[Precision medicine: A major step forward in specific situations, a myth in refractory cancers?

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Albin, Nicolas; Mc Leer, Anne; Sakhri, Linda

2018-04-01

In recent years, high-throughput sequencing techniques have been developed for cancerology and many clinical trials are currently structured around biomarkers that can guide specific treatment choices. This approach is characteristic of precision medicine, which is actually a concept initiated several decades ago with, for example, retinoic acid in promyelocytic leukemia. This paper will review the different types of molecular alterations and « -omics » biological analyses, bioinformatics tools, coupled drug/biomarkers already validated, the ethical issues of whole genomic sequencing of an individual as part of an inclusion in a clinical trial and finally the first results of precision medicine trials. The AcSé crizotinib program, supported by the Inca (french Cancer National Institute), is emblematic of a success of this personalized medicine illustrated by 4 points: the discovery of a cohort of patients with lung cancer with a ROS1 rearrangement characteristic of a sensitivity to crizotinib, a rapid availability of this innovation through the implementation of a temporary recommendation for use (ANSM), the obtention of a conditional marketing authorization by the pharmaceutical industry and finally, financial assumption of responsibility by French social security (HAS), despite preliminary and non-comparative data. In the case of cancers refractory to standard chemotherapy, and regarding our system of access to drugs illustrated by the PROFILER clinical trial, this approach allows the access to a therapeutic drug targeting specific biomarkers only in 7% of patients included. This does not bode well for efficient treatment and even less for survival. Allowing patients to be included in trials that identify molecular targets by molecular screening, and not being able to propose the drug of interest is a traumatic event for those patients who live in the hope of an immediate future. In refractory disease we must rethink precision medicine in a more humanistic

Preclinical Medical Student Hematology/Oncology Education Environment.

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Zumberg, Marc S; Broudy, Virginia C; Bengtson, Elizabeth M; Gitlin, Scott D

2015-12-01

To better prepare medical students to care for patients in today's changing health-care environment as they transition to continuing their education as residents, many US medical schools have been reviewing and modifying their curricula and are considering integration of newer adult learning techniques, including team-based learning, flipped classrooms, and other active learning approaches (Assoc Am Med Coll. 2014). Directors of hematology/oncology (H/O) courses requested an assessment of today's H/O education environment to help them respond to the ongoing changes in the education content and environment that will be necessary to meet this goal. Several recommendations for the improvement of cancer education resulted from American Association for Cancer Education's (ACCE's) "Cancer Education Survey II" including a call for medical schools to evaluate the effectiveness of current teaching methods in achieving cancer education objectives (Chamberlain et al. J Cancer Educ 7(2):105-114.2014). To understand the current environment and resources used in medical student preclinical H/O courses, an Internet-based, Survey Monkey®-formatted, questionnaire focusing on nine topic areas was distributed to 130 United States Hematology/Oncology Course Directors (HOCDs). HOCDs represent a diverse group of individuals who work in variably supportive environments and who are variably satisfied with their position. Several aspects of these courses remain relatively unchanged from previous assessments, including a predominance of traditional lectures, small group sessions, and examinations that are either written or computer-based. Newer technology, including web-based reproduction of lectures, virtual microscopes, and availability of additional web-based content has been introduced into these courses. A variety of learner evaluation and course assessment approaches are used. The ultimate effectiveness and impact of these changes needs to be determined.

Identification of compounds that selectively target highly chemotherapy refractory neuroblastoma cancer stem cells.

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Díaz-Carballo, David; Acikelli, Ali Haydar; Bardenheuer, Walter; Gustmann, Sebastian; Malak, Sascha; Stoll, Raphael; Kedziorski, Thorsten; Nazif, Mhd Ali; Jastrow, Holger; Wennemuth, Gunter; Dammann, Philip; Feigel, Martin; Strumberg, Dirk

2014-09-01

Relapse of cancer months or years after an apparently successful therapy is probably caused by cancer stem cells (CSCs) due to their intrinsic features like dormant periods, radiorefraction, and acquired multidrug resistance (MDR) phenotypes, among other mechanisms of cellular drug evasiveness. Thus, the lack of currently efficacious interventions remains a major problem in the treatment of malignancies, together with the inability of existing drugs to destroy specifically CSCs. Neuroblastomas per se are highly chemotherapy-refractory extracranial tumors in infants with very low survival rates. So far, no effective cytostatics against this kind of tumors are clinically available. Therefore, we have put much effort into the development of agents to efficiently combat this malignancy. For this purpose, we tested several compounds isolated from Cuban propolis on induced CSCs (iCSC) derived from LAN-1 neuroblastoma cells which expressed several characteristics of tumor-initiating cells both in in-vitro and in-vivo models. Some small molecules such as flavonoids and polycyclic polyprenylated acylphloroglucinols (PPAP) were isolated using successive RT-HPLC cycles and identified employing mass spectrometry and NMR spectroscopic techniques. Their cytotoxicity was first screened in sensitive cell systems by MTT proliferation assays and afterwards studied in less sensitive neuroblastoma iCSC models. We found several compounds with considerable anti-iCSC activity, most of them belonging to the PPAP class. The majority of the compounds act in a pleiotropic manner on the molecular biology of tumors although their specific targets remain unclear. Nevertheless, two substances, one of them a flavonoid, induced a strong disruption of tubulin polymerization. In addition, an unknown compound strongly inhibited replicative enzymes like toposimerases I/II and DNA polymerase. Here, we report for the first time cytotoxic activities of small molecules isolated from Caribbean propolis

Hematology

International Nuclear Information System (INIS)

Price, D.C.; Ries, C.

1975-01-01

This paper reviews the wide variety of radioisotopic techniques available to pediatricians in hematologic evaluation of their patients, with comments on the tracer techniques, and an indication of some new territory in splenic evaluation and nonradioactive tracers which may prove to be of considerable interest in the future. The only differences in applying these techniques to the pediatric population, compared with the adult population, lie in the different spectrum of hematologic diseases under consideration in this age group and the greater sensitivity to problems of radiation exposure which the pediatrician and the nuclear medicine physician must have in administering the isotopes in vivo. With these considerations in mind, the usefulness of such radioisotopic techniques in the evaluation of pediatric hematologic disease remains unquestionable. Radiopharmaceuticals and the radiation doses associated with the various procedures are listed. It is hoped in the future that fluorescent excitation techniques will replace at least s []me of the radioisotope techniques, obviating all considerations of patient irradiation in such instances. (auth)

Intravenous flurbiprofen axetil enhances analgesic effect of opioids in patients with refractory cancer pain by increasing plasma β-endorphin.

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Wu, Ting-Ting; Wang, Zhi-Gang; Ou, Wu-Ling; Wang, Jun; Yao, Guo-Qing; Yang, Bo; Rao, Zhi-Guo; Gao, Jian-Fei; Zhang, Bi-Cheng

2014-01-01

The study aimed to investigate the analgesic effect of a combination of intravenous flurbiprofen axetil and opioids, and evaluate the relationship between refractory pain relief and plasma β-endorphin levels in cancer patients. A total of 120 cancer patients was randomly divided into two groups, 60 patients took orally morphine sulfate sustained-release tablets in group A, and another 60 patients receiving the combination treatment of intravenous flurbiprofen axetil and opioid drugs in group B. After 7 days, pain relief, quality of life improvement and side effects were evaluated. Furthermore, plasma β-endorphin levels were measured by radioimmunoassay. With the combination treatment of intravenous intravenous flurbiprofen axetil and opioids, the total effective rate of pain relief rose to 91.4%, as compared to 82.1% when morphine sulfate sustained-release tablet was used alone. Compared with that of group A, the analgesic effect increased in group B (p=0.031). Moreover, satisfactory pain relief was associated with a significant increase in plasma β-endorphin levels. After the treatment, plasma β-endorphin level in group B was 62.4±13.5 pg/ml, which was higher than that in group A (45.8±11.2 pg/ml) (pflurbiprofen axetil and opioids can enhance the analgesic effect of opioid drugs by increasing plasma β-endorphin levels, which would offer a selected and reliable strategy for refractory cancer pain treatment.

Telomere Shortening in Hematological Malignancies with Tetraploidization—A Mechanism for Chromosomal Instability?

Directory of Open Access Journals (Sweden)

Eigil Kjeldsen

2017-11-01

Full Text Available Aneuploidy, the presence of an abnormal number of chromosomes in a cell, is one of the most obvious differences between normal and cancer cells. There is, however, debate on how aneuploid cells arise and whether or not they are a cause or a consequence of tumorigenesis. Further, it is important to distinguish aneuploidy (the “state” of the karyotype from chromosomal instability (CIN; the “rate” of karyotypic change. Although CIN leads to aneuploidy, not all aneuploid cells exhibit CIN. One proposed route to aneuploid cells is through an unstable tetraploid intermediate because tetraploidy promotes chromosomal aberrations and tumorigenesis. Tetraploidy or near-tetraploidy (T/NT (81–103 chromosomes karyotypes with or without additional structural abnormalities have been reported in acute leukemia, T-cell and B-cell lymphomas, and solid tumors. In solid tumors it has been shown that tetraploidization can occur in response to loss of telomere protection in the early stages of tumorigenesis in colon cancer, Barrett’s esophagus, and breast and cervical cancers. In hematological malignancies T/NT karyotypes are rare and the role of telomere dysfunction for the induction of tetraploidization is less well characterized. To further our understanding of possible telomere dysfunction as a mechanism for tetrapolydization in hematological cancers we here characterized the chromosomal complement and measured the telomere content by interphase nuclei quantitative fluorescence in situ hybridization (iQFISH in seven hematological cancer patients with T/NT karyotypes, and after cytogenetic remission. The patients were identified after a search in our local cytogenetic registry in the 5-year period between June 2012 and May 2017 among more than 12,000 analyzed adult patients in this period. One advantage of measuring telomere content by iQFISH is that it is a single-cell analysis so that the telomere content can be distinguished between normal karyotype

Italian real life experience with ibrutinib: results of a large observational study on 77 relapsed/refractory mantle cell lymphoma.

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Broccoli, Alessandro; Casadei, Beatrice; Morigi, Alice; Sottotetti, Federico; Gotti, Manuel; Spina, Michele; Volpetti, Stefano; Ferrero, Simone; Spina, Francesco; Pisani, Francesco; Merli, Michele; Visco, Carlo; Paolini, Rossella; Zilioli, Vittorio Ruggero; Baldini, Luca; Di Renzo, Nicola; Tosi, Patrizia; Cascavilla, Nicola; Molica, Stefano; Ilariucci, Fiorella; Rigolin, Gian Matteo; D'Alò, Francesco; Vanazzi, Anna; Santambrogio, Elisa; Marasca, Roberto; Mastrullo, Lucia; Castellino, Claudia; Desabbata, Giovanni; Scortechini, Ilaria; Trentin, Livio; Morello, Lucia; Argnani, Lisa; Zinzani, Pier Luigi

2018-05-04

Although sometimes presenting as an indolent lymphoma, mantle cell lymphoma (MCL) is an aggressive disease, hardly curable with standard chemo-immunotherapy. Current approaches have greatly improved patients' outcomes, nevertheless the disease is still characterized by high relapse rates. Before approval by EMA, Italian patients with relapsed/refractory MCL were granted ibrutinib early access through a Named Patient Program (NPP). An observational, retrospective, multicenter study was conducted. Seventy-seven heavily pretreated patients were enrolled. At the end of therapy there were 14 complete responses and 14 partial responses, leading to an overall response rate of 36.4%. At 40 months overall survival was 37.8% and progression free survival was 30%; disease free survival was 78.6% at 4 years: 11/14 patients are in continuous complete response with a median of 36 months of follow up. Hematological toxicities were manageable, and main extra-hematological toxicities were diarrhea (9.4%) and lung infections (9.0%). Overall, 4 (5.2%) atrial fibrillations and 3 (3.9%) hemorrhagic syndromes occurred. In conclusions, thrombocytopenia, diarrhea and lung infections are the relevant adverse events to be clinically focused on; regarding effectiveness, ibrutinib is confirmed to be a valid option for refractory/relapsed MCL also in a clinical setting mimicking the real world.

Anti-cancer vaccine therapy for hematologic malignancies: An evolving era.

Science.gov (United States)

Nahas, Myrna R; Rosenblatt, Jacalyn; Lazarus, Hillard M; Avigan, David

2018-02-15

The potential promise of therapeutic vaccination as effective therapy for hematologic malignancies is supported by the observation that allogeneic hematopoietic cell transplantation is curative for a subset of patients due to the graft-versus-tumor effect mediated by alloreactive lymphocytes. Tumor vaccines are being explored as a therapeutic strategy to re-educate host immunity to recognize and target malignant cells through the activation and expansion of effector cell populations. Via several mechanisms, tumor cells induce T cell dysfunction and senescence, amplifying and maintaining tumor cell immunosuppressive effects, resulting in failure of clinical trials of tumor vaccines and adoptive T cell therapies. The fundamental premise of successful vaccine design involves the introduction of tumor-associated antigens in the context of effective antigen presentation so that tolerance can be reversed and a productive response can be generated. With the increasing understanding of the role of both the tumor and tumor microenvironment in fostering immune tolerance, vaccine therapy is being explored in the context of immunomodulatory therapies. The most effective strategy may be to use combination therapies such as anti-cancer vaccines with checkpoint blockade to target critical aspects of this environment in an effort to prevent the re-establishment of tumor tolerance while limiting toxicity associated with autoimmunity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Battling the hematological malignancies: the 200 years' war.

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Lichtman, Marshall A

2008-02-01

The delineation of the hematological malignancies began near the end of the first third of the 19th century with the recognition of the similarity among cases with lymph node tumors and an enlarged spleen (Hodgkin's disease). Descriptions of chronic and acute leukemia and myeloma followed thereafter. In the first years of the 20th century the discovery of x-radiation permitted palliative orthovoltage radiation therapy of Hodgkin's disease. Following World War II, legitimate drug therapy for the hematological malignancies was introduced: nitrogen mustard, adrenocorticotropic hormone and cortisone acetate, and anti-folic acid derivatives, initially aminopterin. Today, about 14 classes of drugs (different mechanisms of action) and >50 individual agents are being used, with others under study. Several examples of agents targeting specific transcription factors or oncoproteins have been introduced. Despite remarkable progress, including the ability to cure acute leukemia in about 70% of children, cure several genetic variants of acute myelogenous leukemia in younger adults, cure some cases of lymphoma in children and younger adults, and induce prolonged remission in many affected persons, the majority of patients face an uncertain outcome and shortened life. Thus, we have much to do in the next several decades. The significant hurdles we must overcome include: the apparent infrequency of an exogenous cause that can be avoided, the exponential increase in incidence rates with age and the dramatic negative effect of aging on the results of treatment, the challenge of one trillion or more disseminated cancer cells among which are a smaller population of cancer stem cells, the profound genetic diversity of the hematological malignancies (apparently hundreds of unique genetic primary lesions), the redundant growth and survival pathways defining the cancer phenotype, the decreasing market for pharmaceutical companies as therapy becomes more specific (fewer target patients

Thoracic Vertebral Body Irradiation Contributes to Acute Hematologic Toxicity During Chemoradiation Therapy for Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Deek, Matthew P.; Benenati, Brian [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Kim, Sinae [Department of Biostatistics, School of Public Health, Rutgers University, Piscataway, New Jersey (United States); Biometrics Division, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Chen, Ting; Ahmed, Inaya; Zou, Wei [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Aisner, Joseph [Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States)

2016-01-01

Purpose: To determine the relationships between radiation doses to the thoracic bone marrow and declines in blood cell counts in non-small cell lung cancer (NSCLC) patients treated with chemoradiation therapy (CRT). Methods and Materials: We included 52 patients with NSCLC treated with definitive concurrent carboplatin–paclitaxel and RT. Dose-volume histogram (DVH) parameters for the thoracic vertebrae (TV), sternum, scapulae, clavicles, and ribs were assessed for associations with changes in blood counts during the course of CRT. Linear and logistic regression analyses were performed to identify associations between hematologic nadirs and DVH parameters. A DVH parameter of Vx was the percentage of the total organ volume exceeding x radiation dose. Results: Grade ≥3 hematologic toxicity including neutropenia developed in 21% (n=11), leukopenia in 42% (n=22), anemia in 6% (n=3), and throbocytopenia in 2% (n=1) of patients. Greater RT dose to the TV was associated with higher risk of grade ≥3 leukopenia across multiple DVH parameters, including TV V{sub 20} (TVV) (odds ratio [OR] 1.06; P=.025), TVV{sub 30} (OR 1.07; P=.013), and mean vertebral dose (MVD) (OR 1.13; P=.026). On multiple regression analysis, TVV{sub 30} (β = −0.004; P=.018) and TVV{sub 20} (β = −0.003; P=.048) were associated with white blood cell nadir. Additional bone marrow sites (scapulae, clavicles, and ribs) did not affect hematologic toxicity. A 20% chance of grade ≥3 leukopenia was associated with a MVD of 13.5 Gy and a TTV{sub 30} of 28%. Cutoff values to avoid grade ≥3 leukopenia were MVD ≤23.9 Gy, TVV{sub 20} ≤56.0%, and TVV{sub 30} ≤52.1%. Conclusions: Hematologic toxicity is associated with greater RT doses to the TV during CRT for NSCLC. Sparing of the TV using advanced radiation techniques may improve tolerance of CRT and result in improved tolerance of concurrent chemotherapy.

Radiation Therapy and Late Mortality From Second Sarcoma, Carcinoma, and Hematological Malignancies After a Solid Cancer in Childhood

International Nuclear Information System (INIS)

Tukenova, Markhaba; Guibout, Catherine; Hawkins, Mike; Quiniou, Eric; Mousannif, Abddedahir; Pacquement, Helene; Winter, David; Bridier, Andre; Lefkopoulos, Dimitri; Oberlin, Odile; Diallo, Ibrahima; Vathaire, Florent de

2011-01-01

Purpose: To compare patterns of long-term deaths due to secondary carcinomas, sarcomas, and hematological malignancies occurring after childhood cancer in a cohort of patients followed over a median of 28 years. Methods and Materials: The study included 4,230 patients treated at eight institutions, who were at least 5-year survivors of a first cancer, representing 105,670 person-years of observation. Complete clinical, chemotherapeutic, and radiotherapeutic data were recorded, and the integral radiation dose was estimated for 2,701 of the 2,948 patients who had received radiotherapy. The integral dose was estimated for the volume inside the beam edges. The causes of death obtained from death certificates were validated. Results: In total, 134 events were due to second malignant neoplasm(s) (SMN). We found that the standardized mortality ratio decreased with increasing follow-up for second carcinomas and sarcomas, whereas the absolute excess risk (AER) increased for a second carcinoma but decreased for second sarcomas. There was no clear variation in SMN and AER for hematological malignancies. We found a significant dose-response relationship between the radiation dose received and the mortality rate due to a second sarcoma and carcinoma. The risk of death due to carcinoma and sarcoma as SMN was 5.2-fold and 12.5-fold higher, respectively, in patients who had received a radiation dose exceeding 150 joules. Conclusions: Among patients who had received radiotherapy, only those having received the highest integral radiation dose actually had a higher risk of dying of a second carcinoma or sarcoma.

Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

International Nuclear Information System (INIS)

Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others

2005-01-01

Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20∼70 mg) immediately prior to administration of therapeutic dose (51.4∼152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted

Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

Energy Technology Data Exchange (ETDEWEB)

Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others [Korea University Medical School, Seoul (Korea, Republic of)

2005-07-01

Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20{approx}70 mg) immediately prior to administration of therapeutic dose (51.4{approx}152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted.

Rate of primary refractory disease in B and T-cell non-Hodgkin's lymphoma: correlation with long-term survival.

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Corrado Tarella

Full Text Available BACKGROUND: Primary refractory disease is a main challenge in the management of non-Hodgkin's Lymphoma (NHL. This survey was performed to define the rate of refractory disease to first-line therapy in B and T-cell NHL subtypes and the long-term survival of primary refractory compared to primary responsive patients. METHODS: Medical records were reviewed of 3,106 patients who had undergone primary treatment for NHL between 1982 and 2012, at the Hematology Centers of Torino and Bergamo, Italy. Primary treatment included CHOP or CHOP-like regimens (63.2%, intensive therapy with autograft (16.9%, or other therapies (19.9%. Among B-cell NHL, 1,356 (47.8% received first-line chemotherapy with rituximab. Refractory disease was defined as stable/progressive disease, or transient response with disease progression within six months. RESULTS: Overall, 690 (22.2% patients showed primary refractory disease, with a higher incidence amongst T-cell compared to B-cell NHL (41.9% vs. 20.5%, respectively, p<0.001. Several other clinico-pathological factors at presentation were variably associated with refractory disease, including histological aggressive disease, unfavorable clinical presentation, Bone Marrow involvement, low lymphocyte/monocyte ration and male gender. Amongst B-cell NHL, the addition of rituximab was associated with a marked reduction of refractory disease (13.6% vs. 26.7% for non-supplemented chemotherapy, p<0.001. Overall, primary responsive patients had a median survival of 19.8 years, compared to 1.3 yr. for refractory patients. A prolonged survival was consistently observed in all primary responsive patients regardless of the histology. The long life expectancy of primary responsive patients was documented in both series managed before and after 2.000. Response to first line therapy resulted by far the most predictive factor for long-term outcome (HR for primary refractory disease: 16.52, p<0.001. CONCLUSION: Chemosensitivity to primary

Molecular-targeted therapy for chemotherapy-refractory gastric cancer: a case report and literature review.

Science.gov (United States)

Kuo, Hung-Yang; Yeh, Kun-Huei

2014-07-01

The prognosis of advanced gastric cancer (AGC) remains poor despite therapeutic advances in recent decades. Several recent positive phase III trials established the efficacy of second-line chemotherapy for metastatic gastric cancer in prolonging overall survival. However, malnutrition and poor performance of AGC in late stages usually preclude such patients from intensive treatment. Many targeted-therapies failed to show a significant survival benefit in AGC, but have regained attention after the positive result of ramucirumab was announced last year. Among all targeted agents, only trastuzumab, a monoclonal antibody against Human epidermal growth factor receptor-2 (HER2) protein, has been proven as having survival benefit by addition to first-line chemotherapy. Herein we reported a patient who benefited from adding trastuzumab to the same second-line combination chemotherapy (paclitaxel, 5-fluorouracil, and leucovorin) upon progression of bulky liver metastases. At least five months of progression-free survival were achieved without any additional toxicity. We also reviewed literature of molecularly-targeted therapy for chemotherapy-refractory gastric cancer, including several large phase III trials (REGARD, GRANITE-1, EXPAND, and REAL-3) published in 2013-2014. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

External Beam Radiotherapy for Clinically Localized Hormone-Refractory Prostate Cancer: Clinical Significance of Nadir Prostate-Specific Antigen Value Within 12 Months

International Nuclear Information System (INIS)

Ogawa, Kazuhiko; Nakamura, Katsumasa; Sasaki, Tomonari; Onishi, Hiroshi; Koizumi, Masahiko; Shioyama, Yoshiyuki; Araya, Masayuki; Mukumoto, Nobutaka M.S.; Mitsumori, Michihide; Teshima, Teruki

2009-01-01

Purpose: To analyze retrospectively the results of external beam radiotherapy for clinically localized hormone-refractory prostate cancer and investigate the clinical significance of nadir prostate-specific antigen (PSA) value within 12 months (nPSA12) as an early estimate of clinical outcomes after radiotherapy. Methods and Materials: Eighty-four patients with localized hormone-refractory prostate cancer treated with external beam radiotherapy were retrospectively reviewed. The total radiation doses ranged from 30 to 76 Gy (median, 66 Gy), and the median follow-up period for all 84 patients was 26.9 months (range, 2.7-77.3 months). Results: The 3-year actuarial overall survival, progression-free survival (PFS), and local control rates in all 84 patients after radiotherapy were 67%, 61%, and 93%, respectively. Although distant metastases and/or regional lymph node metastases developed in 34 patients (40%) after radiotherapy, local progression was observed in only 5 patients (6%). Of all 84 patients, the median nPSA12 in patients with clinical failure and in patients without clinical failure was 3.1 ng/mL and 0.5 ng/mL, respectively. When dividing patients according to low (<0.5 ng/mL) and high (≥0.5 ng/mL) nPSA12 levels, the 3-year PFS rate in patients with low nPSA12 and in those with high nPSA12 was 96% and 44%, respectively (p < 0.0001). In univariate analysis, nPSA12 and pretreatment PSA value had a significant impact on PFS, and in multivariate analysis nPSA12 alone was an independent prognostic factor for PFS after radiotherapy. Conclusions: External beam radiotherapy had an excellent local control rate for clinically localized hormone-refractory prostate cancer, and nPSA12 was predictive of clinical outcomes after radiotherapy.

Value of innovation in hematologic malignancies: a systematic review of published cost-effectiveness analyses.

Science.gov (United States)

Saret, Cayla J; Winn, Aaron N; Shah, Gunjan; Parsons, Susan K; Lin, Pei-Jung; Cohen, Joshua T; Neumann, Peter J

2015-03-19

We analyzed cost-effectiveness studies related to hematologic malignancies from the Tufts Medical Center Cost-Effectiveness Analysis Registry (www.cearegistry.org), focusing on studies of innovative therapies. Studies that met inclusion criteria were categorized by 4 cancer types (chronic myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and multiple myeloma) and 9 treatment agents (interferon-α, alemtuzumab, bendamustine, bortezomib, dasatinib, imatinib, lenalidomide, rituximab alone or in combination, and thalidomide). We examined study characteristics and stratified cost-effectiveness ratios by type of cancer, treatment, funder, and year of study publication. Twenty-nine studies published in the years 1996-2012 (including 44 cost-effectiveness ratios) met inclusion criteria, 22 (76%) of which were industry funded. Most ratios fell below $50,000 per quality-adjusted life-years (QALY) (73%) and $100,000/QALY (86%). Industry-funded studies (n = 22) reported a lower median ratio ($26,000/QALY) than others (n = 7; $33,000/QALY), although the difference was not statistically significant. Published data suggest that innovative treatments for hematologic malignancies may provide reasonable value for money. © 2015 by The American Society of Hematology.

The JAK2V617F and CALR exon 9 mutations are shared immunogenic neoantigens in hematological malignancy

DEFF Research Database (Denmark)

Holmstrom, Morten Orebo; Hasselbalch, Hans Carl; Andersen, Mads Hald

2017-01-01

Approximately 90% of patients with the hematological malignancies termed the chronic myeloproliferative neoplasms harbor either the JAK2V617F-mutation or CALR exon 9 mutation. Both of these are recognized by T-cells, which make the mutations ideal targets for cancer immune therapy as they are sha......Approximately 90% of patients with the hematological malignancies termed the chronic myeloproliferative neoplasms harbor either the JAK2V617F-mutation or CALR exon 9 mutation. Both of these are recognized by T-cells, which make the mutations ideal targets for cancer immune therapy...

REPTILE HEMATOLOGY

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Nejra Hadžimusić

2013-03-01

Full Text Available Determination of the number of circulating blood cells is of a great importance in clinical diagnosis. However, in some species, such as birds and reptiles, it is not possible to determine the number of individual blood cells using standard automated equipment, because of the specific morphological characteristics. For this reason, recognition of individual cell elements is crucial during hematological examination. Key words: Hematology, reptiles, blood cell morphology

Management of acute perianal sepsis in neutropenic patients with hematological malignancy.

Science.gov (United States)

Baker, B; Al-Salman, M; Daoud, F

2014-04-01

In neutropenic patients with acute perianal sepsis in the setting of hematological malignancy, the classical clinical features of abscess formation are lacking. Additionally, the role of surgical intervention is not well established. In this review, we discuss the challenges and controversy regarding diagnosis and optimal management when clear surgical guidelines are absent. In the literature, there is great diversity in the surgical approach to these patients, which leads to a high percentage of diagnostic errors, risks of complications, and unnecessary interventions. We review the literature and assess whether surgical intervention produces better outcomes than a non-surgical approach. Studies published on perianal sepsis in neutropenic cancer patients were identified by searching PubMed using the following key words: "perianal sepsis/abscesses, anorectal sepsis/abscess, neutropenia, hematological malignancy, cancer". No randomized or prospective studies on the management of acute perianal sepsis in hematological malignancies were found. The largest retrospective study and most comprehensive clinical data demonstrated that 42% of patients were treated successfully without surgical intervention and without morbidity or mortality related to treatment chosen. Small retrospective studies advocated surgical intervention, while the majority of successes were in a non-operative treatment. It is difficult to formulate a conclusion given the small retrospective series on management of neutropenic patients with hematological malignancies. While there is no evidence mandating a routine surgical approach in this category of patients, non-surgical management including careful follow-up to determine whether the patient's condition is deteriorating or treatment has failed is an acceptable approach in selected patients without pathognomonic features of abscess. Comprehensive and well-designed prospective studies are needed to firmly establish the guidelines of treatment

Landscape of early clinical trials for childhood and adolescence cancer in Spain.

Science.gov (United States)

Bautista, F; Gallego, S; Cañete, A; Mora, J; Diaz de Heredia, C; Cruz, O; Fernández, J M; Rives, S; Madero, L; Castel, V; Cela, M E; Ramírez, G; Sábado, C; Acha, T; Astigarraga, I; Sastre, A; Muñoz, A; Guibelalde, M; Moreno, L

2016-07-01

Despite numerous advances, survival remains dismal for children and adolescents with poor prognosis cancers or those who relapse or are refractory to first line treatment. There is, therefore, a major unmet need for new drugs. Recent advances in the knowledge of molecular tumor biology open the door to more adapted therapies according to individual alterations. Promising results in the adult anticancer drug development have not yet been translated into clinical practice. We report the activity in early pediatric oncology trials in Spain. All members of the Spanish Society of Pediatric Hematology Oncology (SEHOP) were contacted to obtain information about early trials open in each center. 22 phase I and II trials were open as of May 2015: 15 for solid tumors (68 %) and 7 for hematological malignancies (32 %). Fourteen (64 %) were industry sponsored. Since 2010, four centers have joined the Innovative Therapies For Children With Cancer, an international consortium whose aim is developing novel therapies for pediatric cancers. A substantial number of studies have opened in these 5 years, improving the portfolio of trials for children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents and their benefits. Clinical trials are the way to evaluate new drugs, avoiding the use of off-label drugs that carry significant risks. The Spanish pediatric oncology community through the SEHOP is committed to develop and participate in collaborative academic trials, to favor the advancement and optimization of existing therapies in pediatric cancer.

Paraneoplastic hematological, biochemical, and hemostatic abnormalities in female dogs with mammary neoplasms

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Naila C.B. Duda

Full Text Available ABSTRACT: Paraneoplastic laboratory abnormalities are identified in several types of cancers in dogs and cats. In veterinary medicine, particularly in mammary cancer, there are few studies that correlate abnormal laboratory findings with tumor type and staging. The aim of this study was to evaluate hematological, biochemical, and hemostatic abnormalities and correlate them with mammary tumor staging in female dogs with mammary cancer. Blood samples from 24 female dogs were evaluated, and the hematological, biochemical, and hemostatic parameters were correlated with tumor staging obtained by physical examination, imaging exams, and histopathological surgical biopsies. The groups were organized according to tumor staging: group 1 (stages I and II, group 2 (stage III, and group 3 (stages IV and V. Anemia, neutrophilic leukocytosis, monocytosis, eosinophilia, thrombocytosis, hypoalbuminemia, hypocalcemia, hypoglycemia, and low blood urea were observed. The variables MCHC, TPP, and RDW were correlated with tumor staging with no clinical relevance. Thrombin time and fibrinogen were significant between the groups in the coagulation test, being associated with tumor staging. The findings suggest influence of the proinflammatory cytokines released during tumor growth.

Beneficial Treatment Management with Trifluridine/Tipiracil in a Patient with Metastatic Colorectal Cancer and Pronounced Hematological Event History during Previous Treatments

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Volker Kaechele

2018-01-01

Full Text Available Trifluridine/tipiracil (FTD/TPI significantly improves overall survival in patients with metastatic colorectal cancer (mCRC. The most common treatment-related event (grade ≥3 was hematological toxicity. We here report long-term disease-stabilizing FTD/TPI treatment of an mCRC patient (KRAS wild-type, ECOG performance status 1 at baseline and at the end of FTD/TPI therapy with multifocal synchronous metastases and a longstanding history of extensive hematological events during previous treatments. Finally, this 62-year-old male patient was treated for 10 months with FTD/TPI by consecutive alteration of treatment parameters: (i initial daily dose reduction to 80 mg (72% of the recommended dose, (ii 20 days dose delay, (iii a second and later third dose reduction to 70 mg and 60 mg (about 64% and 55%, respectively, of the recommended dose, and (iv 30 µg per day of granulocyte colony-stimulating factor administration first for 3 days, and later for 5 days, for each treatment cycle.

Hope, Quality of Life, and Benefit From Treatment in Women Having Chemotherapy for Platinum-Resistant/Refractory Recurrent Ovarian Cancer: The Gynecologic Cancer Intergroup Symptom Benefit Study

OpenAIRE

Sjoquist, Katrin M.; Friedlander, Michael L.; O'Connell, Rachel L.; Voysey, Merryn; King, Madeleine T.; Stockler, Martin R.; Oza, Amit M.; Gillies, Kim; Martyn, Julie K.; Butow, Phyllis N.

2013-01-01

Chemotherapy for platinum-resistant/refractory ovarian cancer is motivated by the hope of benefit. Trait hope and expectation of symptom benefit from chemotherapy appear to be distinct and independent of quality of life and depression. Hope did not appear to affect perceived efficacy of chemotherapy in alleviating symptoms, but women whose expectation of symptom benefit from chemotherapy was not fulfilled were more likely to have scores indicative of depression.

Chromosomal differences between acute nonlymphocytic leukemia in patients with prior solid tumors and prior hematologic malignancies. A study of 14 cases with prior breast cancer

International Nuclear Information System (INIS)

Mamuris, Z.; Dumont, J.; Dutrillaux, B.; Aurias, A.

1989-01-01

A cytogenetic study of 14 patients with secondary acute nonlymphocytic leukemia (S-ANLL) with prior treatment for breast cancer is reported. The chromosomes recurrently involved in numerical or structural anomalies are chromosomes 7, 5, 17, and 11, in decreasing order of frequency. The distribution of the anomalies detected in this sample of patients is similar to that observed in published cases with prior breast or other solid tumors, though anomalies of chromosome 11 were not pointed out, but it significantly differs from that of the S-ANLL with prior hematologic malignancies. This difference is principally due to a higher involvement of chromosome 7 in patients with prior hematologic malignancies and of chromosomes 11 and 17 in patients with prior solid tumors. A genetic determinism involving abnormal recessive alleles located on chromosomes 5, 7, 11, and 17 uncovered by deletions of the normal homologs may be a cause of S-ANLL. The difference between patients with prior hematologic malignancies or solid tumors may be explained by different constitutional mutations of recessive genes in the two groups of patients

The effects of combination of Eurycoma longifolia Jack ethanolic extract and doxorubicine on hematological profile in rats given by 7,12-dimethylbenz(a)anthracene

Science.gov (United States)

Nurani, L. H.; Mursyidi, A.; Widyarini, S.; Rohman, A.

2017-11-01

Doxorubicin (Dox) is known as anticancer drug commonly used for cancer treatment. Eurycoma longifolia Jack or Pasakbumi was reported to have chemopreventive effect. In cancer patients, there are some dysfunctions of blood parameter, therefore some hematologic tests are needed to monitor cancer patients. In this study, the effects of combination of ethanolic extract of E. longifolia Jack (EEE) and Dox on hematologic profiles were investigated in rats injected by DMBA. Rats were divided into eight groups. Group I was normal group; Group II, rats were treated with extract dose 100 mg/kgbw; Groups III, IV, V, VI, VII and VIII, rats were treated with Dox, DMBA, DMBA+Dox, DMBA+EEE, DMBA+Dox +EEE, and Dox+EEE, respectively. DMBA administration orally was conducted twice a week for 5 weeks. At 16th week of treatments, bloods were taken from orbitalis sinus for hematologicals profile (levels of Hb, erytrocyte, hematocrite, leukocyte, MCV, MCH, and differencial leucocyte count) measurements. These data were analyzed by one way ANOVA followed by LSD test. DMBA administration significantly decreased the hematological profiles compared to the normal group, except in lymphocyte level. Rats treated with extract and extract+Dox were able to increase the hematological profile compared to rats given by DMBA only. Based on these findings it can be concluded that the combination of EEE and Dox potentially increase hematological profile of rats given by DMBA.

Nutritional Assessment of Children With Hematological Malignancies and Their Subsequent Tolerance to Chemotherapy

OpenAIRE

Linga, Vijay Gandhi; Shreedhara, A. K.; Rau, A. T. K.; Rau, Aarathi

2012-01-01

Background: Our research goals were to assess the prevalence of malnutrition in children with cancer, observe malnutrition's effect on tolerance to chemotherapy, and establish malnutrition at onset as one of the prognostic factors in children with hematological malignancies.

Modern approaches for management of the refractory immune thrombocytopenia in pregnancy

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Davydova Iu.

2017-01-01

Full Text Available Background. Thrombocytopenia per se is one of the hematological diseases, which demands the repeated thrombocytes infusion. The last tendencies in the management of this disease show the enhanced amount of the necessary thrombocytes doses for treatment and the worldwide trend for the declining of donors. Considerably to these facts the new approaches for the thrombocytopenia treatment have been organized within last two decades. One of them is the finding of the safe, appropriate and effective growth factor for platelets, which could significantly improve the level of thrombocytes. The article describes the case of refractory ITP management in pregnancy. ITP diagnosed at 26 weeks of gestation, the platelet number at the time of diagnostics 20000. The other bone marrow disorders excluded by bone marrow biopsy. The in-patient of the High Risk Pregnancy Department (Obstetric Issues of the Extragenital Pathology from the 28 weeks of pregnancy. Modern approaches for treatment of ITP was describe in the article. Pregnant received therapy according to the latest guidelines. Delivery in term of 33–34 weeks. Integrated treatment of thrombocytopenia. Conclusions. The refractory ITP is a rare disease and could be occasionally seen during pregnancy, but the hemorrhagic complications could be extremely harmful for both mother and child and demand the preterm pregnancy termination. The management of refractory ITP during pregnancy should be performed according to the International recommendations for the thrombocytopenia treatment with all the reserve of the medications. The positive result of the ITP management and perinatal and obstetric outcomes has been achieved through the use of the entire arsenal of drugs, correct tactics of delivery with hemorrhage prevention be using the 4 T strategy and the adequate doses of the tranexamic acid (sangera and rhTPO (Emaplug (Yuriya-Farm, Ukraine. It was the first implementation of the subcutaneous rhTPO in

Metronomic Treatment with Low-Dose Trofosfamide Leads to a Long-Term Remission in a Patient with Docetaxel-Refractory Advanced Metastatic Prostate Cancer

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Jochen Greiner

2010-01-01

Full Text Available The treatment of metastatic prostate cancer patients refractory to androgen withdrawal and docetaxel therapy is currently discouraging and new therapeutic approaches are vastly needed. Here, we report a long-term remission over one year in a 68-year-old patient with metastatic docetaxel-refractory prostate cancer employing low-dose trofosfamide. The patient suffered from distant failure with several bone lesions and lymph node metastases depicted by a (11 C-Choline positron emission tomography/computerized tomography (PET/CT. After initiation of trofosfamide 100 mg taken orally once a day we observed a steadily decreasing PSA value from initial 46.6 down to 2.1 g/l. The Choline-PET/CT was repeated after 10 months of continuous therapy and demonstrated a partial remission of the bone lesions and a regression of all involved lymph nodes but one. Taken together we found an astonishing and durable activity of the alkylating agent trofosfamide given in a metronomic fashion. We rate the side effects as low and state an excellent therapeutic ratio of this drug in our patient.

Eligibility of real-world patients with chemo-refractory, K-RAS wild-type, metastatic colorectal cancer for palliative intent regorafenib monotherapy.

Science.gov (United States)

Angeles, Arkhjamil; Hung, Wayne; Cheung, Winson Y

2018-06-23

The CORRECT trial demonstrated survival benefits with regorafenib monotherapy in patients with treatment-refractory, metastatic colorectal cancer (mCRC). However, the trial's stringent eligibility criteria for regorafenib may limit its external validity. We aimed to examine treatment attrition rates and eligibility for regorafenib in routine practice. We identified patients at the British Columbia Cancer Agency diagnosed with mCRC who demonstrated disease progression or intolerable toxicity on 2 or more lines of systemic therapy. During the study timeframe, panitumumab and cetuximab were only used in the chemo-refractory setting. Data on clinicopathologic variables and patient outcomes were ascertained and analyzed. Eligibility was determined using the CORRECT trial criteria. A total of 391 patients were identified, among whom only 39% were eligible for regorafenib: 35% in the panitumumab group and 51% in the cetuximab group. The main reasons for ineligibility in all patients were Eastern Cooperative Oncology Group Performance Status (ECOG PS) > 1 (69%), an elevated total bilirubin (21%), and thromboembolic events in the past 6 months (10%). No difference in eligibility for regorafenib was observed between patients previously receiving panitumumab or cetuximab (P = 0.914; 95% CI 0.550-1.951). Kaplan-Meier analyses showed that regorafenib-eligible compared to regorafenib-ineligible patients had an increased median overall survival of 5.3 versus 2.1 months, respectively (P < 0.001). However, Cox proportional hazard analyses showed that only ECOG PS rather than trial eligibility was correlated with outcomes. The strict eligibility criteria disqualify most patients with treatment-refractory mCRC for regorafenib therapy. Future trials should broaden the eligibility criteria to improve external validity.

Slagging gasifier refractories. A new pathway to longer refractory life

Energy Technology Data Exchange (ETDEWEB)

Schnake, Mark [Harbinson-Walker Refractories Company, Mexico, MO (United States)

2013-07-01

Solid fuel slagging gasification to convert coal or petroleum coke feedstocks into syngas has rapidly evolved over the last 25 years. The gasifier is a high temperature, high pressure reaction chamber. Operating temperatures are between 1250 and 1575 C. Pressures will be between 20.4 and 68 atm. Syngas has been typically used for chemical feedstocks, fuel for power plants, or for steam and hydrogen generation in other industrial applications. Ash which comes from the solid fuel during gasification has many impurities. It melts during the gasifier reactor operation forming a liquid that penetrates the refractory lining. Given time, the refractory will wear away from thermal spalling, structural spalling, or overheating of the refractory. In some cases, all three wear mechanisms are seen in the same gasifier lining. Industry users have identified refractory life as one major limiting factor in worldwide use of this technology. Users have stated if the refractory liner can increase on-line availability of the gasifier operation, more industry acceptance of this technology is possible. Harbison-Walker Refractories Company will review destructive factors affecting lining life and discuss new refractory materials that have dramatically increased gasifier lining life and reliability. New refractory materials will be presented and supported by field trial results and post mortem analysis.

High Chromosome Number in hematological cancer cell lines is a Negative Predictor of Response to the inhibition of Aurora B and C by GSK1070916

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Hardwicke Mary

2011-07-01

Full Text Available Abstract Background Aurora kinases play critical roles in mitosis and are being evaluated as therapeutic targets in cancer. GSK1070916 is a potent, selective, ATP competitive inhibitor of Aurora kinase B and C. Translation of predictive biomarkers to the clinic can benefit patients by identifying the tumors that are more likely to respond to therapies, especially novel inhibitors such as GSK1070916. Methods 59 Hematological cancer-derived cell lines were used as models for response where in vitro sensitivity to GSK1070916 was based on both time and degree of cell death. The response data was analyzed along with karyotype, transcriptomics and somatic mutation profiles to determine predictors of response. Results 20 cell lines were sensitive and 39 were resistant to treatment with GSK1070916. High chromosome number was more prevalent in resistant cell lines (p-value = 0.0098, Fisher Exact Test. Greater resistance was also found in cell lines harboring polyploid subpopulations (p-value = 0.00014, Unpaired t-test. A review of NOTCH1 mutations in T-ALL cell lines showed an association between NOTCH1 mutation status and chromosome number (p-value = 0.0066, Fisher Exact Test. Conclusions High chromosome number associated with resistance to the inhibition of Aurora B and C suggests cells with a mechanism to bypass the high ploidy checkpoint are resistant to GSK1070916. High chromosome number, a hallmark trait of many late stage hematological malignancies, varies in prevalence among hematological malignancy subtypes. The high frequency and relative ease of measurement make high chromosome number a viable negative predictive marker for GSK1070916.

Myeloid derived suppressor cells as therapeutic target in hematological malignancies

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Kim eDe Veirman

2014-12-01

Full Text Available Myeloid derived suppressor cells (MDSC are a heterogeneous population of immature myeloid cells that accumulate during pathological conditions such as cancer and are associated with a poor clinical outcome. MDSC expansion hampers the host anti-tumor immune response by inhibition of T cell proliferation, cytokine secretion and recruitment of regulatory T cells. In addition, MDSC exert non-immunological functions including the promotion of angiogenesis, tumor invasion and metastasis. Recent years, MDSC are considered as a potential target in solid tumors and hematological malignancies to enhance the effects of currently used immune modulating agents. This review focuses on the characteristics, distribution, functions, cell-cell interactions and targeting of MDSC in hematological malignancies including multiple myeloma, lymphoma and leukemia.

The european hematology association roadmap for european hematology research : A consensus document

NARCIS (Netherlands)

A. Engert (Andreas); C.L. Balduini (Carlo); A. Brand (Anneke); B. Coiffier (Bertrand); C. Cordonnier (Charlotte); H. Döhner (Hartmut); De Wit, T.D. (Thom Duyvené); Eichinger, S. (Sabine); W.E. Fibbe (Willem); Green, T. (Tony); De Haas, F. (Fleur); A. Iolascon (Achille); T. Jaffredo (Thierry); F. Rodeghiero (Francesco); G. Salles (Gilles); J.J. Schuringa (Jan Jacob)

2016-01-01

textabstractThe European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European

Hematological evaluation of splenomegaly

International Nuclear Information System (INIS)

Ali, N.; Anwar, M.; Ayyub, M.; Ejaz, A.; Nadeem, M.; Qureshi, A.H.; Qamar, M.A.

2004-01-01

Objective: To find out the relative frequency of clinical conditions associated with splenomegaly that require hematological evaluation in our set up. Subjects and Methods: Patients of either gender or all age groups with palpable spleen was included. Patients with splenomegaly due to liver disease, malarial parasites on thick or thin blood film, positive Widal test, or positive blood cultures were excluded from study. Patients were initially evaluated with clinical history, microscopic examination of blood smear, and blood counts. Depending upon provisional diagnosis bone marrow examination or investigations for hemolytic anemia were performed. Results: One hundred patients were received. Seventy-eight patients were adults and 22 patients were of pediatric age group. In the adults, hematological malignancies were seen in 37%, malarial parasites in bone marrow in 20.5%, megaloblastic anemia in 13%, bacterial infections in 9%, hemolytic anemia in 9%, tropical splenomegaly in 5%, and positive bone marrow culture for salmonella in 6.5%. In children, hematological evaluation revealed hematological malignancies in 18%, beta thalassaemia in 55%, other hemolytic anemias in 13.5%, congenital sideroblastic anemia in 4.5%, and storage disorder in 9%. Conclusion: Hematological workup is informative in most of the cases. Bone marrow examination is the key investigation, hematological malignancies constituted 37% of the adult and 18% of pediatric age group patients. Hemolytic anemia constituted 68% of pediatric age group. (author)

Distribution and features of hematological malignancies in Eastern Morocco: a retrospective multicenter study over 5?years

OpenAIRE

Elidrissi Errahhali, Mounia; Elidrissi Errahhali, Manal; Boulouiz, Redouane; Ouarzane, Meryem; Bellaoui, Mohammed

2016-01-01

Background Hematological malignancies (HM) are a public health problem. The pattern and distribution of diagnosed hematological cancers vary depending on age, sex, geography, and ethnicity suggesting the involvement of genetic and environmental factors for the development of these diseases. To our knowledge, there is no published report on HM in the case of Eastern Morocco. In this report we present for the first time the overall pattern of HM for this region. Methods Retrospective descriptiv...

The association between COX-2 polymorphisms and hematologic toxicity in patients with advanced non-small-cell lung cancer treated with platinum-based chemotherapy.

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Fei Zhou

Full Text Available BACKGROUND AND OBJECTIVE: Overexpression of COX-2 is proved to contribute to tumor promotion and carcinogenesis through stimulating cell proliferation, inhibiting apoptosis and enhancing the invasiveness of cancer cells. Apoptosis-related molecules are potential predictive markers for survival and toxicity in platinum treatment. This study aimed at investigating the association between COX-2 polymorphisms and the occurrence of grade 3 or 4 toxicity in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy. MATERIALS AND METHODS: Two hundred and twelve patients with inoperable stage IIIB-IV NSCLC received first-line chemotherapy between 2007 and 2009 were recruited in this study. Four functional COX-2 polymorphisms were genotyped by PCR-based restriction fragment length polymorphism (RFLP methods. RESULTS: The incidence of grade 3 or 4 hematologic toxicity was significantly higher in G allele carriers of the COX-2 rs689466 (-1195G/A polymorphism compared with wild-type homozygotes AA (P value = 0.008; odds ratio, 2.47; 95% confidence internal, 1.26-4.84 and the significance still existed after the Bonferroni correction. Statistically significant difference was also found in grade 3 or 4 leukopenia (P value = 0.010; OR = 2.82; 95%CI = 1.28-6.20. No other significant association was observed between genotype and toxicity in the study. The haplotype analysis showed that the haplotype AGG was associated with a reduced risk of grade 3 or 4 hematologic and leukopenia toxicity (P value = 0.009; OR = 0.59; 95%CI = 0.39-0.88 and P value = 0.025; OR = 0.61; 95%CI = 0.39-0.94, respectively while the haplotype GGG was associated with an increased risk of grade 3 or 4 hematologic and leukopenia toxicity (P value = 0.009; OR = 1.71; 95%CI = 1.14-2.56 and P value = 0.025; OR = 1.65; 95%CI  = 1.06-2.57, respectively. CONCLUSION: This investigation for the first time

Combination of Intensive Chemotherapy and Anticancer Vaccines in the Treatment of Human Malignancies: The Hematological Experience

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Knut Liseth

2010-01-01

Full Text Available In vitro studies have demonstrated that cancer-specific T cell cytotoxicity can be induced both ex vivo and in vivo, but this therapeutic strategy should probably be used as an integrated part of a cancer treatment regimen. Initial chemotherapy should be administered to reduce the cancer cell burden and disease-induced immune defects. This could be followed by autologous stem cell transplantation that is a safe procedure including both high-dose disease-directed chemotherapy and the possibility for ex vivo enrichment of the immunocompetent graft cells. The most intensive conventional chemotherapy and stem cell transplantation are used especially in the treatment of aggressive hematologic malignancies; both strategies induce T cell defects that may last for several months but cancer-specific T cell reactivity is maintained after both procedures. Enhancement of anticancer T cell cytotoxicity is possible but posttransplant vaccination therapy should probably be combined with optimalisation of immunoregulatory networks. Such combinatory regimens should be suitable for patients with aggressive hematological malignancies and probably also for other cancer patients.

A novel antibody-drug conjugate targeting SAIL for the treatment of hematologic malignancies.

Science.gov (United States)

Kim, S Y; Theunissen, J-W; Balibalos, J; Liao-Chan, S; Babcock, M C; Wong, T; Cairns, B; Gonzalez, D; van der Horst, E H; Perez, M; Levashova, Z; Chinn, L; D'Alessio, J A; Flory, M; Bermudez, A; Jackson, D Y; Ha, E; Monteon, J; Bruhns, M F; Chen, G; Migone, T-S

2015-05-29

Although several new therapeutic approaches have improved outcomes in the treatment of hematologic malignancies, unmet need persists in acute myeloid leukemia (AML), multiple myeloma (MM) and non-Hodgkin's lymphoma. Here we describe the proteomic identification of a novel cancer target, SAIL (Surface Antigen In Leukemia), whose expression is observed in AML, MM, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). While SAIL is widely expressed in CLL, AML, MM, DLBCL and FL patient samples, expression in cancer cell lines is mostly limited to cells of AML origin. We evaluated the antitumor activity of anti-SAIL monoclonal antibodies, 7-1C and 67-7A, conjugated to monomethyl auristatin F. Following internalization, anti-SAIL antibody-drug conjugates (ADCs) exhibited subnanomolar IC50 values against AML cell lines in vitro. In pharmacology studies employing AML cell line xenografts, anti-SAIL ADCs resulted in significant tumor growth inhibition. The restricted expression profile of this target in normal tissues, the high prevalence in different types of hematologic cancers and the observed preclinical activity support the clinical development of SAIL-targeted ADCs.

High alumina refractories

International Nuclear Information System (INIS)

Simao, L.C.; Lopes, A.B.; Galvao Filho, N.B.; Souza, R.B. de

1989-01-01

High alumina refractories with 92 to 96.5% Al 2 O 3 were produced using brown and white fused as aggregate. Those refractories present only alumina-α and mullite as crystalline mineralogical phase. Other physical and chemical characteristics are similar to the ones found in refractories produced in Brazil, Japan and U.S.A. The most important physical and chemical tests used for the characterization of the raw materials and refractories, complemented by those realized at high temperatures, plus X-ray Difractometry and optical microscopy are presented, besides the refractory formulation and main parameters of production [pt

Interpretation of erythrocyte histograms obtained from automated hematology analyzers in hematologic diseases

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Ali Maleki

2015-12-01

Full Text Available Background: Presently, the graphical data of blood cells (histograms and cytograms or/ scattergrams that they are usually available in all modern automated hematology analyzers are an integral a part of automated complete blood count (CBC. To find incorrect results from automated hematology analyzer and establish the samples that require additional analysis, Laboratory employees will use those data for quality control of obtaining results, to assist identification of complex and troublesome cases. Methods: During this descriptive analytic study, in addition to erythrocyte graphs from variety of patients, referring from March 2013 to Feb 2014 to our clinical laboratory, Zagros Hospital, Kermanshah, Iran, are given, the papers published in relevant literature as well as available published manuals of automatic blood cell counters were used. articles related to the key words of erythrocyte graphs and relevant literature as well as available published manuals of automatic blood cell counters were searched from valid databases such as Springer Link, google scholar, Pubmed and Sciencedirect. Then, the articles related to erythrogram, erythrocyte histogram and hematology analyzer graphs are involved in diagnosis of hematological disorder were searched and selected for this study. Results: Histograms and different automated CBC parameter become abnormal in various pathologic conditions, and can present important clues for diagnosis and treatment of hematologic and non-hematologic disorders. In several instances, these histograms have characteristic appearances in an exceedingly wide range of pathological conditions. In some hematologic disorders like iron deficiency or megaloblastic anemia, a sequential histogram can clearly show the progressive treatment and management. Conclusion: These graphical data are often accompanied by other automated CBC parameter and microscopic examination of peripheral blood smears (PBS, and can help in monitoring and

New developments in the treatment of HER2-positive breast cancer

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Nahta R

2012-05-01

Full Text Available Rita NahtaDepartments of Pharmacology and Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USAAbstract: Approximately 20%–30% of metastatic breast cancers show increased expression of the human epidermal growth factor receptor-2 (HER2 tyrosine kinase. Two HER2-specific therapies are currently approved for clinical treatment of patients with HER2-overexpressing metastatic breast cancer. Trastuzumab is a monoclonal antibody against HER2 and is approved for first-line treatment of HER2-positive metastatic breast cancer. Lapatinib is a small molecule dual inhibitor of epidermal growth factor receptor and HER2 tyrosine kinases, and is approved for trastuzumab-refractory disease. Although trastuzumab is a highly effective therapy for patients with HER2-overexpressing metastatic breast cancer, a significant number of patients in the initial clinical trials of trastuzumab monotherapy showed resistance to trastuzumab-based therapy. Further, among those who did respond, the initial trials indicated that the median time to progression was less than 1 year. Similarly, lapatinib is effective in a subset of trastuzumab-refractory cases, but the majority of patients display resistance. This review discusses the multiple molecular mechanisms of resistance that have been proposed in the literature. In addition, novel agents that are being tested for efficacy against HER2-positive breast cancer, including the antibodies pertuzumab and trastuzumab-DM1 and the immunotoxin affitoxin, are reviewed. The introduction of trastuzumab has revolutionized the clinical care of patients with HER2-positive metastatic breast cancer and has resulted in dramatic reductions in recurrences of early-stage HER2-positive breast cancer. The development and implementation of gene- and protein-based assays that measure potential molecular predictors of trastuzumab resistance will allow individualization of HER2-targeted therapeutic approaches

Invasive fungal diseases in children with hematologic disorders

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Ünsal Günay

2009-12-01

Full Text Available Objective: Fungal infection is a significant problem, causing of infective deaths of leukemic patients. The situation in developing countries is not well documented. The purpose of this study was characterizing IFD by analyzing data retrospectively to determine the incidence, predisposing factors, diagnostic methods, efficacy of treatment, and the outcome in pediatric patients with hematological disorders. Materials and Methods: There were 160 children with leukemia (22 AML, 129 ALL and 9 with aplastic anemia (AA. The diagnostic criteria for IFD were defined according to the EORTC/MSG, 2008. IFD was classified as proven or probable. Empiric antifungal treatment with L-AmB was commenced by day 5-7 of persistent fever. Patients with invasive aspergillosis (IA who were refractory to primary treatment were commenced on voriconazole (VCZ. Salvage therapy as combination of VCZ and caspofungin was given to those with progressive infection. Results: The incidence of IFD was found 23 (14.3%. 19 with leukemia (14 ALL, 5 AML and 4 with aplastic anemia were diagnosed as IFD. IA was the dominant cause of infection (n=17 and the rest (n: 6 had candidiasis. Ten children had “proven” infection and 13 children were defined as “probable”. The most frequent site of infection was lungs. In our series, the most frequently used diagnostic methods were clinical findings (100% and radiologic methods (84%. The success rate of treatment for candidiasis and IA were found 60%, 71% respectively. IFD related death rate was found 30%.Conclusion: IFD is still a major morbidity and mortality reason in children with hematologic disorders. However, the availability of new antifungal treatments and diagnostic tests will improve the survival rates in these children.

Comparison of survival of adolescents and young adults with hematologic malignancies in Osaka, Japan.

Science.gov (United States)

Nakata-Yamada, Kayo; Inoue, Masami; Ioka, Akiko; Ito, Yuri; Tabuchi, Takahiro; Miyashiro, Isao; Masaie, Hiroaki; Ishikawa, Jun; Hino, Masayuki; Tsukuma, Hideaki

2016-01-01

The survival gap between adolescents and young adults (AYAs) with hematological malignancies persists in many countries. To determine to what extent it does in Japan, we investigated survival and treatment regimens in 211 Japanese AYAs (15-29 years) in the Osaka Cancer Registry diagnosed during 2001-2005 with hematological malignancies, and compared adolescents (15-19 years) with young adults (20-29 years). AYAs with acute lymphoblastic leukemia (ALL) had a poor 5-year survival (44%), particularly young adults (29% vs. 64% in adolescents, p = 0.01). Additional investigation for patients with ALL revealed that only 19% of young adults were treated with pediatric treatment regimens compared with 45% of adolescents (p = 0.05). Our data indicate that we need to focus on young adults with ALL and to consider establishing appropriate cancer care system and guidelines for them in Japan.

Using [18F]Fluorothymidine Imaged With Positron Emission Tomography to Quantify and Reduce Hematologic Toxicity Due to Chemoradiation Therapy for Pelvic Cancer Patients

International Nuclear Information System (INIS)

McGuire, Sarah M.; Bhatia, Sudershan K.; Sun, Wenqing; Jacobson, Geraldine M.; Menda, Yusuf; Ponto, Laura L.; Smith, Brian J.; Gross, Brandie A.; Bayouth, John E.; Sunderland, John J.; Graham, Michael M.; Buatti, John M.

2016-01-01

Purpose: The purpose of the present prospective clinical trial was to determine the efficacy of [ 18 F]fluorothymidine (FLT)-identified active bone marrow sparing for pelvic cancer patients by correlating the FLT uptake change during and after chemoradiation therapy with hematologic toxicity. Methods and Materials: Simulation FLT positron emission tomography (PET) images were used to spare pelvic bone marrow using intensity modulated radiation therapy (IMRT BMS) for 32 patients with pelvic cancer. FLT PET scans taken during chemoradiation therapy after 1 and 2 weeks and 30 days and 1 year after completion of chemoradiation therapy were used to evaluate the acute and chronic dose response of pelvic bone marrow. Complete blood counts were recorded at each imaging point to correlate the FLT uptake change with systemic hematologic toxicity. Results: IMRT BMS plans significantly reduced the dose to the pelvic regions identified with FLT uptake compared with control IMRT plans (P<.001, paired t test). Radiation doses of 4 Gy caused an ∼50% decrease in FLT uptake in the pelvic bone marrow after either 1 or 2 weeks of chemoradiation therapy. Additionally, subjects with more FLT-identified bone marrow exposed to ≥4 Gy after 1 week developed grade 2 leukopenia sooner than subjects with less marrow exposed to ≥4 Gy (P<.05, Cox regression analysis). Apparent bone marrow recovery at 30 days after therapy was not maintained 1 year after chemotherapy. The FLT uptake in the pelvic bone marrow regions that received >35 Gy was 18.8% ± 1.8% greater at 30 days after therapy than at 1 year after therapy. The white blood cell, platelet, lymphocyte, and neutrophil counts at 1 year after therapy were all lower than the pretherapy levels (P<.05, paired t test). Conclusions: IMRT BMS plans reduced the dose to FLT-identified pelvic bone marrow for pelvic cancer patients. However, reducing hematologic toxicity is challenging owing to the acute radiation sensitivity (∼4

Dose-escalated total body irradiation and autologous stem cell transplantation for refractory hematologic malignancy

International Nuclear Information System (INIS)

McAfee, Steven L.; Powell, Simon N.; Colby, Christine; Spitzer, Thomas R.

2002-01-01

Purpose: To evaluate the feasibility of dose escalation of total body irradiation (TBI) above the previously reported maximally tolerated dose, we have undertaken a Phase I-II trial of dose-escalated TBI with autologous peripheral blood stem cell transplantation (PBSCT) for chemotherapy-refractory lymphoma. Methods and Materials: Nine lymphoma patients with primary refractory disease (PRD) or in resistant relapse (RR) received dose-escalated TBI and PBSCT. The three dose levels of fractionated TBI (200 cGy twice daily) were 1,600 cGy, 1,800 cGy, and 2,000 cGy. Lung blocks were used to reduce the TBI transmission dose by 50%, and the chest wall dose was supplemented to the prescribed dose using electrons. Shielding of the kidneys was performed to keep the maximal renal dose at 1,600 cGy. Three patients, two with non-Hodgkin's lymphoma (NHL) in RR and one with PRD Hodgkin's disease, received 1,600 cGy + PBSCT, three patients (two NHL in RR, one PRD) received 1,800 cGy + PBSCT, and three patients with NHL (two in RR, one PRD) received 2,000 cGy + PBSCT. Results: Toxicities associated with this high-dose TBI regimen included reversible hepatic veno-occlusive disease in 1 patient, Grade 2 mucositis requiring narcotic analgesics in 8 patients, and neurologic toxicities consisting of a symmetrical sensory neuropathy (n=4) and Lhermitte's syndrome (n=1). Interstitial pneumonitis developed in 1 patient who received 1,800 cGy after receiving recombinant α-interferon (with exacerbation after rechallenge with interferon). Six (66%) patients achieved a response. Four (44%) patients achieved complete responses, three of which were of a duration greater than 1 year, and 2 (22%) patients achieved a partial response. One patient remains disease-free more than 5 years posttransplant. Corticosteroid-induced gastritis and postoperative infection resulted in the death of 1 patient in complete response, 429 days posttransplant. Conclusion: TBI in a dose range 1,600-2,000 cGy as

Is there an association with constitutional structural chromosomal abnormalities and hematologic neoplastic process? A short review.

Science.gov (United States)

Panani, Anna D

2009-04-01

The occasional observation of constitutional chromosomal abnormalities in patients with a malignant disease has led to a number of studies on their potential role in cancer development. Investigations of families with hereditary cancers and constitutional chromosomal abnormalities have been key observations leading to the molecular identification of specific genes implicated in tumorigenesis. Large studies have been reported on the incidence of constitutional chromosomal aberrations in patients with hematologic malignancies, but they could not confirm an increased risk for hematologic malignancy among carriers of structural chromosomal changes. However, it is of particular interest that constitutional structural aberrations with breakpoints similar to leukemia-associated specific breakpoints have been reported in patients with hematologic malignancies. Because of insufficient data, it remains still unclear if these aberrations represent random events or are associated with malignancy. There has been a substantial discussion about mechanisms involved in constitutional structural chromosomal changes in the literature. The documentation of more patients with constitutional structural chromosomal changes could be of major importance. Most importantly, the molecular investigation of chromosomal regions involved in rearrangements could give useful information on the genetic events underlying constitutional anomalies, contributing to isolation of genes important in the development of the neoplastic process. Regarding constitutional anomalies in patients with hematologic disorders, a survey of the cytogenetic data of our cytogenetics unit is herein also presented.

Merits of using andalusite-based refractories compared to bauxite-based refractories

OpenAIRE

Nyoka, M.; Brazier, D.; Courtney, T.; Parry, R.A.

2013-01-01

Historically bauxite-based refractories have been used in applications where andalusite-based refractories could work. Bauxite-based refractories were chosen over andalusite-based refractories mainly because of the availability of low-cost Chinese bauxite and also because many furnaces were designed by international companies that cannot easily access high-quality products. Currently, the availability of low-cost bauxite is under threat as a result of high export duties and tariffs as well as...

Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase III study design.

Science.gov (United States)

Pujade-Lauraine, Eric; Fujiwara, Keiichi; Dychter, Samuel S; Devgan, Geeta; Monk, Bradley J

2018-03-27

Avelumab is a human anti-PD-L1 checkpoint inhibitor with clinical activity in multiple solid tumors. Here, we describe the rationale and design for JAVELIN Ovarian 200 (NCT02580058), the first randomized Phase III trial to evaluate the role of checkpoint inhibition in women with ovarian cancer. This three-arm trial is comparing avelumab administered alone or in combination with pegylated liposomal doxorubicin versus pegylated liposomal doxorubicin alone in patients with platinum-resistant/refractory recurrent ovarian, fallopian tube or peritoneal cancer. Eligible patients are not preselected based on PD-L1 expression and may have received up to three prior lines of chemotherapy for platinum-sensitive disease, but none for resistant disease. Overall survival and progression-free survival are primary end points, and secondary end points include biomarker evaluations and pharmacokinetics.

42 CFR 493.1215 - Condition: Hematology.

Science.gov (United States)

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Hematology. 493.1215 Section 493.1215 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1215 Condition: Hematology. If the laboratory provides services in the specialty of Hematology, the...

Hematologic Toxicity in RTOG 0418: A Phase 2 Study of Postoperative IMRT for Gynecologic Cancer

International Nuclear Information System (INIS)

Klopp, Ann H.; Moughan, Jennifer; Portelance, Lorraine; Miller, Brigitte E.; Salehpour, Mohammad R.; Hildebrandt, Evangeline; Nuanjing, Jenny; D'Souza, David; Souhami, Luis; Small, William; Gaur, Rakesh; Jhingran, Anuja

2013-01-01

Purpose: Intensity modulated radiation therapy (IMRT), compared with conventional 4-field treatment, can reduce the volume of bone marrow irradiated. Pelvic bone marrow sparing has produced a clinically significant reduction in hematologic toxicity (HT). This analysis investigated HT in Radiation Therapy Oncology Group (RTOG) 0418, a prospective study to test the feasibility of delivering postoperative IMRT for cervical and endometrial cancer in a multiinstitutional setting. Methods and Materials: Patients in the RTOG 0418 study were treated with postoperative IMRT to 50.4 Gy to the pelvic lymphatics and vagina. Endometrial cancer patients received IMRT alone, whereas patients with cervical cancer received IMRT and weekly cisplatin (40 mg/m 2 ). Pelvic bone marrow was defined within the treatment field by using a computed tomography density-based autocontouring algorithm. The volume of bone marrow receiving 10, 20, 30, and 40 Gy and the median dose to bone marrow were correlated with HT, graded by Common Terminology Criteria for Adverse Events, version 3.0, criteria. Results: Eighty-three patients were eligible for analysis (43 with endometrial cancer and 40 with cervical cancer). Patients with cervical cancer treated with weekly cisplatin and pelvic IMRT had grades 1-5 HT (23%, 33%, 25%, 0%, and 0% of patients, respectively). Among patients with cervical cancer, 83% received 5 or more cycles of cisplatin, and 90% received at least 4 cycles of cisplatin. The median percentage volume of bone marrow receiving 10, 20, 30, and 40 Gy in all 83 patients, respectively, was 96%, 84%, 61%, and 37%. Among cervical cancer patients with a V40 >37%, 75% had grade 2 or higher HT compared with 40% of patients with a V40 less than or equal to 37% (P =.025). Cervical cancer patients with a median bone marrow dose of >34.2 Gy also had higher rates of grade ≥2 HT than did those with a dose of ≤34.2 Gy (74% vs 43%, P=.049). Conclusions: Pelvic IMRT with weekly cisplatin is

Hematologic Toxicity in RTOG 0418: A Phase 2 Study of Postoperative IMRT for Gynecologic Cancer

Energy Technology Data Exchange (ETDEWEB)

Klopp, Ann H., E-mail: aklopp@mdanderson.org [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Moughan, Jennifer [RTOG Statistical Center, Philadelphia, Pennsylvania (United States); Portelance, Lorraine [Sylvester Comprehensive Cancer Center, Miami, Florida (United States); Miller, Brigitte E. [Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina (United States); Salehpour, Mohammad R.; Hildebrandt, Evangeline; Nuanjing, Jenny [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); D' Souza, David [London Regional Cancer Center, University of Western Ontario, London, Ontario (Canada); Souhami, Luis [Sylvester Comprehensive Cancer Center, Miami, Florida (United States); Small, William [Northwestern Memorial Hospital, Chicago, Illinois (United States); Gaur, Rakesh [St. Luke' s Cancer Institute, Kansas City, Missouri (United States); Jhingran, Anuja [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2013-05-01

Purpose: Intensity modulated radiation therapy (IMRT), compared with conventional 4-field treatment, can reduce the volume of bone marrow irradiated. Pelvic bone marrow sparing has produced a clinically significant reduction in hematologic toxicity (HT). This analysis investigated HT in Radiation Therapy Oncology Group (RTOG) 0418, a prospective study to test the feasibility of delivering postoperative IMRT for cervical and endometrial cancer in a multiinstitutional setting. Methods and Materials: Patients in the RTOG 0418 study were treated with postoperative IMRT to 50.4 Gy to the pelvic lymphatics and vagina. Endometrial cancer patients received IMRT alone, whereas patients with cervical cancer received IMRT and weekly cisplatin (40 mg/m{sup 2}). Pelvic bone marrow was defined within the treatment field by using a computed tomography density-based autocontouring algorithm. The volume of bone marrow receiving 10, 20, 30, and 40 Gy and the median dose to bone marrow were correlated with HT, graded by Common Terminology Criteria for Adverse Events, version 3.0, criteria. Results: Eighty-three patients were eligible for analysis (43 with endometrial cancer and 40 with cervical cancer). Patients with cervical cancer treated with weekly cisplatin and pelvic IMRT had grades 1-5 HT (23%, 33%, 25%, 0%, and 0% of patients, respectively). Among patients with cervical cancer, 83% received 5 or more cycles of cisplatin, and 90% received at least 4 cycles of cisplatin. The median percentage volume of bone marrow receiving 10, 20, 30, and 40 Gy in all 83 patients, respectively, was 96%, 84%, 61%, and 37%. Among cervical cancer patients with a V40 >37%, 75% had grade 2 or higher HT compared with 40% of patients with a V40 less than or equal to 37% (P =.025). Cervical cancer patients with a median bone marrow dose of >34.2 Gy also had higher rates of grade ≥2 HT than did those with a dose of ≤34.2 Gy (74% vs 43%, P=.049). Conclusions: Pelvic IMRT with weekly cisplatin is

Medical versus surgical treatment for refractory or recurrent peptic ulcer.

Science.gov (United States)

Gurusamy, Kurinchi Selvan; Pallari, Elena

2016-03-29

authors do not state whether these were recurrent or refractory ulcers. It appears that the participants did not have previous complications such as bleeding or perforation. Of the 77 included participants, 37 participants continued to have medical therapy while 40 participants received surgical therapy (antrectomy with or without vagotomy; subtotal gastrectomy with or without vagotomy; vagotomy; pyloroplasty and suture of the ulcer; suture or closure of ulcer without vagotomy or excision of the ulcer; proximal gastric or parietal cell vagotomy alone; suture or closure of the ulcer with proximal gastric or parietal cell vagotomy). Whether to use medical or surgical treatment was determined by participant's or treating physician's preference.The study authors reported that two participants in the medical treatment group (2 out of 37; 5.4%) had gastric cancer, which was identified by repeated biopsy. They did not report the proportion of participants who had gastric cancer in the surgical treatment group. They also did not report the implications of the delayed diagnosis of gastric cancer in the medical treatment group. They did not report any other outcomes of interest for this review (that is health-related quality of life (using any validated scale), adverse events and serious adverse events, peptic ulcer bleeding, peptic ulcer perforation, abdominal pain, and long-term mortality). We found no studies that provide the relative benefits and harms of medical versus surgical treatment for recurrent or refractory peptic ulcers. Studies that evaluate the natural history of recurrent and refractory peptic ulcers are urgently required to determine whether randomised controlled trials comparing medical versus surgical management in patients with recurrent or refractory peptic ulcers or both are necessary. Such studies will also provide information for the design of such randomised controlled trials. A minimum follow-up of two to three years will allow the calculation of the

42 CFR 493.849 - Condition: Hematology.

Science.gov (United States)

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Hematology. 493.849 Section 493.849 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.849 Condition: Hematology. The specialty of hematology, for the purpose of proficiency...

CD20-based Immunotherapy of B-cell Derived Hematologic Malignancies.

Science.gov (United States)

Shanehbandi, Dariush; Majidi, Jafar; Kazemi, Tohid; Baradaran, Behzad; Aghebati-Maleki, Leili

2017-01-01

CD20 is a surface antigen, which is expressed at certain stages of B-cell differentiation. Targeting the CD20-positive B-cells with therapeutic monoclonal antibodies (MAbs) has been an effectual strategy in the treatment of hematologic malignancies such as non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Initial success with Rituximab (RTX) has encouraged the creation and development of more effective CD20 based therapeutics. However, treatment with conventional MAbs has not been adequate to overcome the problems such as refractory/ relapsed disease. In this regard, new generations of MAbs with enhanced affinity or improved anti-tumor properties have been developed. CD20 directed therapeutics have heterogeneous features and mechanisms of action. Hence, having sufficient knowledge on the immunological and molecular aspects of CD20 based cancer therapy is necessary for predicting the clinical outcomes and taking the necessary measures. An extensive search was performed in PubMed and similar databases for peer-reviewed articles concerning the biology, function and characteristics of CD20 molecule as well as the mechanisms of action and evolutionary process of CD20 targeting agents. This review provides information about the current situation of CD20 targeting immunotherapeutics including MAbs, bispecific antibodies (which exert multiple functions or involve Tcells in tumor elimination) and CAR T-cells (engineered T-cells armed with chimeric antigen receptors). Moreover, limitations, challenges and available solutions regarding the application of CD20 targeting treatments are addressed. Utilization of CD20-targeted therapeutics, due to their diverse properties, requires special considerations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Regorafenib Versus Trifluridine/Tipiracil for Refractory Metastatic Colorectal Cancer: A Retrospective Comparison.

Science.gov (United States)

Masuishi, Toshiki; Taniguchi, Hiroya; Hamauchi, Satoshi; Komori, Azusa; Kito, Yosuke; Narita, Yukiya; Tsushima, Takahiro; Ishihara, Makoto; Todaka, Akiko; Tanaka, Tsutomu; Yokota, Tomoya; Kadowaki, Shigenori; Machida, Nozomu; Ura, Takashi; Fukutomi, Akira; Ando, Masashi; Onozawa, Yusuke; Tajika, Masahiro; Yasui, Hirofumi; Muro, Kei; Mori, Keita; Yamazaki, Kentaro

2017-06-01

Regorafenib and trifluridine/tipiracil (TAS-102) both prolong survival for patients with refractory metastatic colorectal cancer. However, it is unclear which drug should be administered first. We retrospectively evaluated the data from patients who had received regorafenib or TAS-102 at 2 institutions from May 2013 to March 2015. The inclusion criteria were disease refractory or intolerant to fluoropyrimidines, oxaliplatin, irinotecan, anti-vascular endothelial growth factor antibodies, and anti-epidermal growth factor receptor (EGFR) antibodies (if KRAS exon 2 wild-type), and no previous treatment with regorafenib or TAS-102. A total of 146 and 54 patients received regorafenib and TAS-102, respectively. The baseline characteristics were similar between the 2 groups, except for a history of irinotecan and anti-EGFR therapy and high alkaline phosphatase levels. The median progression-free survival and overall survival were 2.1 months and 6.7 months, respectively, with regorafenib and 2.1 months and 6.5 months, respectively, with TAS-102 (progression-free survival hazard ratio 1.20, P = .27; overall survival hazard ratio, 1.01, P = .97). The analysis of overall survival for patients after the approval of TAS-102 in Japan was similar to the overall survival for the entire population. The frequency of hand-foot syndrome and increased aspartate aminotransferase, alanine aminotransferase, and bilirubin levels was higher and the frequency of neutropenia, leukopenia, anemia, nausea, and febrile neutropenia was lower with regorafenib than with TAS-102. No remarkable differences were found in the efficacy and safety of TAS-102 between patients with and without previous regorafenib and vice versa. Regorafenib and TAS-102 had similar efficacy but resulted in different toxicities, which could guide the agent choice. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies

International Nuclear Information System (INIS)

Kim, S Y; Theunissen, J-W; Balibalos, J; Liao-Chan, S; Babcock, M C

2015-01-01

Although several new therapeutic approaches have improved outcomes in the treatment of hematologic malignancies, unmet need persists in acute myeloid leukemia (AML), multiple myeloma (MM) and non-Hodgkin's lymphoma. Here we describe the proteomic identification of a novel cancer target, SAIL (Surface Antigen In Leukemia), whose expression is observed in AML, MM, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). While SAIL is widely expressed in CLL, AML, MM, DLBCL and FL patient samples, expression in cancer cell lines is mostly limited to cells of AML origin. We evaluated the antitumor activity of anti-SAIL monoclonal antibodies, 7-1C and 67-7A, conjugated to monomethyl auristatin F. Following internalization, anti-SAIL antibody–drug conjugates (ADCs) exhibited subnanomolar IC 50 values against AML cell lines in vitro. In pharmacology studies employing AML cell line xenografts, anti-SAIL ADCs resulted in significant tumor growth inhibition. The restricted expression profile of this target in normal tissues, the high prevalence in different types of hematologic cancers and the observed preclinical activity support the clinical development of SAIL-targeted ADCs

A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies

Science.gov (United States)

Kim, S Y; Theunissen, J-W; Balibalos, J; Liao-Chan, S; Babcock, M C; Wong, T; Cairns, B; Gonzalez, D; van der Horst, E H; Perez, M; Levashova, Z; Chinn, L; D‘Alessio, J A; Flory, M; Bermudez, A; Jackson, D Y; Ha, E; Monteon, J; Bruhns, M F; Chen, G; Migone, T-S

2015-01-01

Although several new therapeutic approaches have improved outcomes in the treatment of hematologic malignancies, unmet need persists in acute myeloid leukemia (AML), multiple myeloma (MM) and non-Hodgkin's lymphoma. Here we describe the proteomic identification of a novel cancer target, SAIL (Surface Antigen In Leukemia), whose expression is observed in AML, MM, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). While SAIL is widely expressed in CLL, AML, MM, DLBCL and FL patient samples, expression in cancer cell lines is mostly limited to cells of AML origin. We evaluated the antitumor activity of anti-SAIL monoclonal antibodies, 7-1C and 67-7A, conjugated to monomethyl auristatin F. Following internalization, anti-SAIL antibody–drug conjugates (ADCs) exhibited subnanomolar IC50 values against AML cell lines in vitro. In pharmacology studies employing AML cell line xenografts, anti-SAIL ADCs resulted in significant tumor growth inhibition. The restricted expression profile of this target in normal tissues, the high prevalence in different types of hematologic cancers and the observed preclinical activity support the clinical development of SAIL-targeted ADCs. PMID:26024286

[Current Status and Challenges of CAR-T Immunotherapy in Hematologic Malignancies -Review].

Science.gov (United States)

Cheng, Xin; Wang, Ya-Jie; Feng, Shuai; Wu, Ya-Yun; Yang, Tong-Hua; Lai, Xun

2018-04-01

The chimeric antigen receptor (CAR) T cell therapy has gradually became a new trend in the treatment of refractory and relapsed hematologic malignancies by developing for 30 years. With the exciting development of genetic engineering, CAR-T technology has subjected to 4 generations of innovation. Structure of CAR-T started from a single signal molecule to 2 or more than 2 co-stimulatory molecules, and then coding the CAR gene or promoter. CAR-T can specifically recognize tumor antigens, and does not be restricted by major histocompatibility complex (MHC), thus making a breakthrough in clinical treatment. In this review, the history, structure and mechanism of action of CAR-T, as well as the current status and challenges of CAR-T immunotherapy in acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia and multiple myeloma are summarized.

Using [{sup 18}F]Fluorothymidine Imaged With Positron Emission Tomography to Quantify and Reduce Hematologic Toxicity Due to Chemoradiation Therapy for Pelvic Cancer Patients

Energy Technology Data Exchange (ETDEWEB)

McGuire, Sarah M., E-mail: sarah-mcguire@uiowa.edu [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Bhatia, Sudershan K.; Sun, Wenqing [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Jacobson, Geraldine M. [Department of Radiation Oncology, West Virginia University, Morgantown, West Virginia (United States); Menda, Yusuf; Ponto, Laura L. [Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Smith, Brian J. [Department of Biostatistics, University of Iowa College of Public Health, Iowa City, Iowa (United States); Gross, Brandie A. [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Bayouth, John E. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Sunderland, John J.; Graham, Michael M. [Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Buatti, John M. [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States)

2016-09-01

Purpose: The purpose of the present prospective clinical trial was to determine the efficacy of [{sup 18}F]fluorothymidine (FLT)-identified active bone marrow sparing for pelvic cancer patients by correlating the FLT uptake change during and after chemoradiation therapy with hematologic toxicity. Methods and Materials: Simulation FLT positron emission tomography (PET) images were used to spare pelvic bone marrow using intensity modulated radiation therapy (IMRT BMS) for 32 patients with pelvic cancer. FLT PET scans taken during chemoradiation therapy after 1 and 2 weeks and 30 days and 1 year after completion of chemoradiation therapy were used to evaluate the acute and chronic dose response of pelvic bone marrow. Complete blood counts were recorded at each imaging point to correlate the FLT uptake change with systemic hematologic toxicity. Results: IMRT BMS plans significantly reduced the dose to the pelvic regions identified with FLT uptake compared with control IMRT plans (P<.001, paired t test). Radiation doses of 4 Gy caused an ∼50% decrease in FLT uptake in the pelvic bone marrow after either 1 or 2 weeks of chemoradiation therapy. Additionally, subjects with more FLT-identified bone marrow exposed to ≥4 Gy after 1 week developed grade 2 leukopenia sooner than subjects with less marrow exposed to ≥4 Gy (P<.05, Cox regression analysis). Apparent bone marrow recovery at 30 days after therapy was not maintained 1 year after chemotherapy. The FLT uptake in the pelvic bone marrow regions that received >35 Gy was 18.8% ± 1.8% greater at 30 days after therapy than at 1 year after therapy. The white blood cell, platelet, lymphocyte, and neutrophil counts at 1 year after therapy were all lower than the pretherapy levels (P<.05, paired t test). Conclusions: IMRT BMS plans reduced the dose to FLT-identified pelvic bone marrow for pelvic cancer patients. However, reducing hematologic toxicity is challenging owing to the acute radiation sensitivity

Correlation Between Radiation Dose to 18F-FDG-PET Defined Active Bone Marrow Subregions and Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

International Nuclear Information System (INIS)

Rose, Brent S.; Liang Yun; Lau, Steven K.; Jensen, Lindsay G.; Yashar, Catheryn M.; Hoh, Carl K.; Mell, Loren K.

2012-01-01

Purpose: To test the hypothesis that radiation dose to 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET)-defined active bone marrow (BM ACT ) subregions is correlated with hematologic toxicity in cervical cancer patients treated with chemoradiotherapy. Methods and Materials: The conditions of 26 women with cervical cancer who underwent 18 F-FDG-PET before treatment with concurrent cisplatin and intensity-modulated radiation therapy were analyzed. BM ACT was defined as the subregion of total bone marrow (BM TOT ) with a standardized uptake value (SUV) equal to or above the mean for that individual. Inactive bone marrow (BM INACT ) was defined as BM TOT − BM ACT . Generalized linear modeling was used to test the correlation between BM ACT and BM INACT dose–volume metrics and hematologic nadirs, particularly white blood cell count (WBC) and absolute neutrophil count (ANC). Results: Increased BM ACT mean dose was significantly associated with decreased log(WBC) nadir (β = −0.04; 95% CI, −0.07to −0.01; p = 0.009), decreased log(ANC) nadir (β = −0.05; 95% CI, −0.08 to −0.02; p = 0.006), decreased hemoglobin nadir (β = −0.16; 95% CI, −0.27 to −0.05; p = 0.010), and decreased platelet nadir (β = −6.16; 95% CI, −9.37 to −2.96; p INACT mean dose and log(WBC) nadir (β = −0.01; 95% CI, −0.06 to 0.05; p = 0.84), log(ANC) nadir (β = −0.03; 95% CI, −0.10 to 0.04; p = 0.40), hemoglobin nadir (β = −0.09; 95% CI, −0.31 to 0.14; p = 0.452), or platelet nadir (β = −3.47; 95% CI, −10.44 to 3.50; p = 0.339). Conclusions: Irradiation of BM subregions with higher 18 F-FDG-PET activity was associated with hematologic toxicity, supporting the hypothesis that reducing dose to BM ACT subregions could mitigate hematologic toxicity. Future investigation should seek to confirm these findings and to identify optimal SUV thresholds to define BM ACT .

Reptile Hematology.

Science.gov (United States)

Sykes, John M; Klaphake, Eric

2015-09-01

The basic principles of hematology used in mammalian medicine can be applied to reptiles. The appearances of the blood cells are significantly different from those seen in most mammals, and vary with taxa and staining method used. Many causes for abnormalities of the reptilian hemogram are similar to those for mammals, although additional factors such as venipuncture site, season, hibernation status, captivity status, and environmental factors can also affect values, making interpretation of hematologic results challenging. Values in an individual should be compared with reference ranges specific to that species, gender, and environmental conditions when available. Copyright © 2015 Elsevier Inc. All rights reserved.

High-doses of proton pump inhibitors in refractory gastro-intestinal cancer: A case series and the state of art.

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Falcone, Rosa; Roberto, Michela; D'Antonio, Chiara; Romiti, Adriana; Milano, Annalisa; Onesti, Concetta Elisa; Marchetti, Paolo; Fais, Stefano

2016-12-01

In recent years, proton pump inhibitors (PPIs) have been investigated at high-dose to modulate tumour microenvironment acidification thus restoring chemotherapeutic sensitivity. Moreover, several clinical data supports the role of cytotoxic drugs at low-dose continuously delivered as anticancer therapy. Clinical records of three patients affected with gastrointestinal cancer refractory to standard treatments, who had received a combination of high-dose rabeprazole and metronomic chemotherapy were reviewed. The first case, a 78-year-old man was treated for lung metastasis from colon adenocarcinoma. The second case, a 73-year-old man was treated for metastatic rectal cancer to the liver. The third one, a 68-year-old man, underwent the combination regimen for colon cancer with lung, liver and peritoneal metastases. Despite the failure of previous standard chemotherapy for metastatic disease, good clinical outcome was shown in these patients treated with an unconventional association of high-dose PPIs and metronomic chemotherapy. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Development of the family symptom inventory: a psychosocial screener for children with hematology/oncology conditions.

Science.gov (United States)

Karlson, Cynthia W; Haynes, Stacey; Faith, Melissa A; Elkin, Thomas D; Smith, Maria L; Megason, Gail

2015-03-01

A growing body of literature has begun to underscore the importance of integrating family-based comprehensive psychological screening into standard medical care for children with oncology and hematology conditions. There are no known family-based measures designed to screen for clinically significant emotional and behavioral concerns in pediatric oncology and hematology patients. The aim of this study was to develop and evaluate the Family Symptom Inventory (FSI), a brief screener of patient and family member psychological symptoms. The FSI also screens for common comorbid physical symptoms (pain and sleep disturbance) and is designed for use at any point during treatment and follow-up. A total of 488 caregivers completed the FSI during regular hematology/oncology visits for 193 cancer, 219 sickle cell disease, and 76 hematology pediatric patients. Exploratory factor analysis, confirmatory factor analysis, and tests of reliability and preliminary validity were conducted. Exploratory factor analysis suggested a 34-item, 4-factor solution, which was confirmed in an independent sample using confirmatory factor analysis (factor loadings=0.49 to 0.88). The FSI demonstrated good internal reliability (α's=0.86 to 0.92) and good preliminary validity. Regular psychosocial screening throughout the course of treatment and follow-up may lead to improved quality of care for children with oncology and hematology conditions.

Exploring communication difficulties in pediatric hematology: oncology nurses.

Science.gov (United States)

Citak, Ebru Akgun; Toruner, Ebru Kilicarslan; Gunes, Nebahat Bora

2013-01-01

Communication plays an important role for the well being of patients, families and also health care professionals in cancer care. Conversely, ineffective communication may cause depression, increased anxiety, hopelessness and decreased of quality life for patients, families and also nurses. This study aimed to explore communication difficulties of pediatric hematology/oncology nurses with patients and their families, as well as their suggestions about communication difficulties. It was conducted in a pediatric hematology/oncology hospital in Ankara, Turkey. Qualitative data were collected by focus groups, with 21 pediatric hematology/oncology nursing staff from three groups. Content analysis was used for data analysis. Findings were grouped in three main categories. The first category concerned communication difficulties, assessing problems in responding to questions, ineffective communication and conflicts with the patient's families. The second was about the effects of communication difficulties on nurses and the last main category involved suggestions for empowering nurses with communication difficulties, the theme being related to institutional issues. Nurses experience communication difficulties with children and their families during long hospital stays. Communication difficulties particularly increase during crisis periods, like at the time of first diagnosis, relapse, the terminal stage or on days with special meaning such as holidays. The results obtained indicate that pediatric nurses and the child/family need to be supported, especially during crisis periods. Feeling of empowerment in communication will improve the quality of care by reducing the feelings of exhaustion and incompetence in nurses.

Refractory Materials for Flame Deflector Protection System Corrosion Control: Refractory Ceramics Literature Survey

Science.gov (United States)

Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Curran, Jerome P.; Kolody, Mark; Perusich, Stephen; Whitten, Mary C.; Trejo, David; Zidek, Jason; Sampson, Jeffrey W.;

Refractory vasculitis

NARCIS (Netherlands)

Rutgers, Bram; Kallenberg, Cees G. M.

Refractory vasculitis occurs in 4-5% of patients with anti-neutrophil cytoplasmic antibody associated vasculitis (AAV). Differences between therapies used for refractory disease are mostly reflected in the percentages of complete and partial remissions, but also in the number of serious side

A Phase II Trial of 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) in Patients with Hormone-Refractory Metastatic Prostate Cancer

Science.gov (United States)

Heath, Elisabeth I.; Hillman, David W.; Vaishampayan, Ulka; Sheng, Shijie; Sarkar, Fazlul; Harper, Felicity; Gaskins, Melvin; Pitot, Henry C.; Tan, Winston; Ivy, S. Percy; Pili, Roberto; Carducci, Michael A.; Liu, Glenn

2011-01-01

Purpose 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin antibiotic with anti-proliferative activity in several mouse xenograft models including prostate cancer models. A two-stage phase II study was conducted to assess the activity and toxicity profile of 17-AAG administered to patients with metastatic, hormone-refractory prostate cancer. Experimental Design Patients with at least one prior systemic therapy and a rising PSA were eligible. Patients received 17-AAG at a dose of 300 mg/m2 IV weekly for three out of four weeks. The primary objective was to assess the PSA response. Secondary objectives were to determine overall survival, to assess toxicity, to measure IL-6, IL-8 and maspin levels and quality of life. Results Fifteen eligible patients were enrolled. The median age was 68 years and the median PSA was 261 ng/mL. Patients received 17-AAG for a median number of 2 cycles. Severe adverse events included: grade 3 fatigue (4 pts), grade 3 lymphopenia (2 pts) and grade 3 back pain (2 pts). The median PSA progression free survival was 1.8 months (95% CI: 1.3–3.4 months). The six-month overall survival was 71% (95% CI: 52%–100%). Conclusion 17-AAG did not show any activity with regards to PSA response. Due to insufficient PSA response, enrollment was stopped at end of first stage per study design. The most significant severe toxicity was grade 3 fatigue. Further evaluation of 17-AAG at a dose of 300 mg/m2 IV weekly as a single agent in patients with metastatic, hormone-refractory prostate cancer who received at least one prior systemic therapy is not warranted. PMID:19047126

Epigenetic mechanisms in the initiation of hematological malignancies

Directory of Open Access Journals (Sweden)

Ali Maleki

2011-10-01

Full Text Available Background: Cancer development is not restricted to the genetic changes, but also to epigenetic changes. Epigenetic processes are very important in the development of hematological malignancies. The main epigenetic alterations are aberrations in DNA methylation, post-translational modifications of histones, chromatin remodeling and microRNAs patterns, and these are associated with tumor genesis. All the various cellular pathways contributing to the neoplastic phenotype are affected by epigenetic genes in cancer. These pathways can be explored as biomarkers in clinical use for early detection of disease, malignancy classification and response to treatment with classical chemotherapy agents and epigenetic drugs. Materials and Method: A literature review was performed using PUBMED from 1985 to 2008. Cross referencing of discovered articles was also reviewed.Results: In chronic lymphocytic leukemia, regional hypermethylation of gene promoters leads to gene silencing. Many of these genes have tumor suppressor phenotypes. In myelodysplastic syndrome (MDS, CDKN2B (alias, P15, a cyclin-dependent kinase inhibitor that negatively regulates the cell cycle, has been shown to be hypermethylated in marrow stem (CD34+ cells in patients with MDS. At present both Vidaza and Decitabine (DNA methyltransferase inhibitors are approved for the treatment of MDS.Conclusion: Unlike mutations or deletions, DNA hypermethylation and histone deacetylation are potentially reversible by pharmacological inhibition, therefore those epigenetic changes have been recognized as promising novel therapeutic targets in hematopoietic malignances. In this review, we discussed molecular mechanisms of epigenetics, epigenetic changes in hematological malignancies and epigenetic based treatments

Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis

DEFF Research Database (Denmark)

De Roock, Wendy; Claes, Bart; Bernasconi, David

2010-01-01

with KRAS wild-type tumours still do not respond. We studied the effect of other downstream mutations on the efficacy of cetuximab in, to our knowledge, the largest cohort to date of patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab plus chemotherapy in the pre...

21 CFR 864.8625 - Hematology quality control mixture.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hematology quality control mixture. 864.8625 Section 864.8625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8625 Hematology...

Hematological dosimetry

International Nuclear Information System (INIS)

Fluery-Herard, A.

1991-01-01

The principles of hematological dosimetry after acute or protracted whole-body irradiation are reviewed. In both cases, over-exposure is never homogeneous and the clinical consequences, viz medullary aplasia, are directly associated with the mean absorbed dose and the seriousness and location of the overexposure. The main hematological data required to assess the seriousness of exposure are the following: repeated blood analysis, blood precursor cultures, as indicators of whole-body exposure; bone marrow puncture, medullary precursor cultures and medullary scintigraphy as indicators of the importance of a local over-exposure and capacity for spontaneous repair. These paraclinical investigations, which are essential for diagnosis and dosimetry, are also used for surveillance and for the main therapeutic issues [fr

Overview of pediatric oncology and hematology in Myanmar

Directory of Open Access Journals (Sweden)

Jay Halbert

2014-01-01

Full Text Available Myanmar is a country in southeast Asia in political, economic and healthcare transition. There are currently only two pediatric oncology centers serving a population of almost 19 million children. An estimated 85-92% of children with cancer are undiagnosed or not receiving treatment. Abandonment of treatment is as high as 60%. Although a number of chemotherapy agents are available, difficulties remain concerning treatment costs, quality control and the availability of supportive care. Radiotherapy services are also limited and not usually included in pediatric protocols. Healthcare professional training, improved diagnostics, strategies to tackle abandonment of treatment and the development of a parents′ support group are major priorities. Local and international partnerships including a recent partnership with world child cancer are essential in the interim to support the development of pediatric oncology and hematology in Myanmar. A unique opportunity exists to support the development of preventive, diagnostic, curative and palliative care for children′s cancer in Myanmar from the outset.

Self-regulatory fatigue in hematologic malignancies: impact on quality of life, coping, and adherence to medical recommendations.

Science.gov (United States)

Solberg Nes, Lise; Ehlers, Shawna L; Patten, Christi A; Gastineau, Dennis A

2013-03-01

Hematopoietic stem cell transplantation (HSCT) is an intensive cancer therapy entailing numerous physical, emotional, cognitive, and practical challenges. Patients' ability to adjust and cope with such challenges may depend on their ability to exert control over cognitive, emotional, and behavioral processes, that is, ability to self-regulate. Self-regulatory capacity is a limited resource that can be depleted or fatigued (i.e., "self-regulatory fatigue"), particularly in the context of stressful life events such as cancer diagnosis and treatment. This is one of the first studies to examine self-regulatory fatigue in a cancer population. The current study aimed to (1) extract items for a specific scale of self-regulatory capacity and (2) examine the impact of such capacity on adaptation in patients with hematologic malignancies preparing for HSCT. Factor analysis of four existing scales gauging psychological adjustment and well-being in 314 patients preparing for HSCT (63% male and 89% Caucasian) identified 23 items (α = 0.85) related to self-regulatory control or fatigue. This measure was then examined using existing clinical data obtained from 178 patients (57% male and 91% Caucasian) undergoing treatment for hematologic malignancies in relationship to quality of life, coping, and self-reported adherence to physicians' recommendations. Controlling for pain severity, physical fatigue, and depression, self-regulatory fatigue scores were incrementally associated with decreased quality of life, use of avoidance coping strategies, and decreased adherence to physicians' recommendations. These results emphasize the potential role of self-regulatory capacity in coping with and adjusting to hematologic cancers and future research is warranted.

Pharmacotherapy for Refractory and Super-Refractory Status Epilepticus in Adults.

Science.gov (United States)

Holtkamp, Martin

2018-03-01

Patients with prolonged seizures that do not respond to intravenous benzodiazepines and a second-line anticonvulsant suffer from refractory status epilepticus and those with seizures that do not respond to continuous intravenous anesthetic anticonvulsants suffer from super-refractory status epilepticus. Both conditions are associated with significant morbidity and mortality. A strict pharmacological treatment regimen is urgently required, but the level of evidence for the available drugs is very low. Refractory complex focal status epilepticus generally does not require anesthetics, but all intravenous non-anesthetizing anticonvulsants may be used. Most descriptive data are available for levetiracetam, phenytoin and valproate. Refractory generalized convulsive status epilepticus is a life-threatening emergency, and long-term clinical consequences are eminent. Administration of intravenous anesthetics is mandatory, and drugs acting at the inhibitory gamma-aminobutyric acid (GABA) A receptor such as midazolam, propofol and thiopental/pentobarbital are recommended without preference for one of those. One in five patients with anesthetic treatment does not respond and has super-refractory status epilepticus. With sustained seizure activity, excitatory N-methyl-d-aspartate (NMDA) receptors are increasingly expressed post-synaptically. Ketamine is an antagonist at this receptor and may prove efficient in some patients at later stages. Neurosteroids such as allopregnanolone increase sensitivity at GABA A receptors; a Phase 1/2 trial demonstrated safety and tolerability, but randomized controlled data failed to demonstrate efficacy. Adjunct ketogenic diet may contribute to termination of difficult-to-treat status epilepticus. Randomized controlled trials are needed to increase evidence for treatment of refractory and super-refractory status epilepticus, but there are multiple obstacles for realization. Hitherto, prospective multicenter registries for pharmacological

Palliative radiotherapy for local progression of hormone refractory stage D2 prostate cancer

International Nuclear Information System (INIS)

Kawakami, Satoru; Kawai, Tsuneo; Yonese, Junji; Yamauchi, Tamio; Ishibashi, Keiichiro; Ueda, Tomohiro

1993-01-01

From 1970 to 1992, 10 patients with hormone refractory stage D2 adenocarcinoma of the prostate presenting themselves with urinary retention and/or gross hematuria were treated by palliative irradiation for local progression at Cancer Institute Hospital. External beam irradiation was delivered to the primary lesion at dose of 38 Gy to one patient and 30∼27 Gy to seven patients. Five of these patients in whom an urethral catheter had been indwelt were able to void without difficulty following the treatment. Of four patients with severe hematuria resulting from vesical tamponade, none had hematuria after the treatment. These effect lasted until patients' death or more than 11 months follow-up. In other 2 patients, irradiation had to be discontinued at dose less than 20 Gy because of deteriorated general conditions and no significant effect. Complications of the treatment were minimal. These results indicate that the optimal dose of local palliative irradiation is around 30 Gy. Irradiation is a good choice for palliation of locally progressive hormone refactory prostate cancer in view of its certain and long-lasting effect, low invasiveness and minimal complications. When to institute palliative irradiation is one of the most important question in order to secure a good quality of life of patients. From our experiences, it is our belief that if local progression is symptomatic, palliative irradiation should be initiated as soon as possible. (author)

CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia.

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Davila, Marco L; Brentjens, Renier J

2016-10-01

Immunotherapy has demonstrated significant potential for the treatment of patients with chemotherapy-resistant hematologic malignancies and solid tumors. One type of immunotherapy involves the adoptive transfer of T cells that have been genetically modified with a chimeric antigen receptor (CAR) to target a tumor. These hybrid proteins are composed of the antigen-binding domains of an antibody fused to T-cell receptor signaling machinery. CAR T cells that target CD19 recently have made the jump from the laboratory to the clinic, and the results have been remarkable. CD19-targeted CAR T cells have induced complete remissions of disease in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), who have an expected complete response rate of 30% in response to chemotherapy. The high efficacy of CAR T cells in B-ALL suggests that regulatory approval of this therapy for this routinely fatal leukemia is on the horizon. We review the preclinical development of CAR T cells and their early clinical application for lymphoma. We also provide a comprehensive analysis of the use of CAR T cells in patients with B-ALL. In addition, we discuss the unique toxicities associated with this therapy and the management schemes that have been developed.

Hematological adverse effects in breast cancer patients treated with cyclin-dependent kinase 4 and 6 inhibitors: a systematic review and meta-analysis.

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Kassem, Loay; Shohdy, Kyrillus S; Lasheen, Shaimaa; Abdel-Rahman, Omar; Bachelot, Thomas

2018-01-01

The introduction of specific cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors significantly improved progression-free survival in hormone receptor-positive metastatic breast cancer. CDK 4/6 inhibitors induce cell cycle arrest via liberating the tumor suppressor retinoblastoma protein from CDK4/6 inhibitory effect. Preliminary studies suggested an increase in the hematological toxicities which might affect the quality of life in such palliative setting. We searched PubMed, ASCO, ESMO and San Antonio meeting databases for randomized phase II/III trials in metastatic breast cancer receiving CDK4/6 inhibitors with safety data provided on the incidence of hematological adverse effects. Our search identified 1012 citations that were screened for relevance. Thirty-six studies were found to be potentially eligible. After excluding the ineligible studies, six studies were deemed to be eligible for meta-analysis. The risk ratio (RR) was 11.31 [95% confidence interval (CI) 8.06-15.87; p < 0.0001] for all-grade leucopenia, 14.86 (95% CI 11.37-19.41; p < 0.0001) for all-grade neutropenia, 9.04 (95% CI 3.78-21.63; p < 0.0001) for all-grade thrombocytopenia and 3.57 (95% CI 2.65-4.81; p < 0.0001) for all-grade anemia. The RR for grade 3/4 leucopenia was 33.86 (95% CI 14.59-78.57; p < 0.0001), for grade 3/4 neutropenia was 44.00 (95% CI 24.72-78.33; p < 0.0001), for grade 3/4 thrombocytopenia was 5.70 (95% CI 2.03-16.01; p = 0.001) and for grade 3/4 anemia was 2.80 (95% CI 1.45-5.41; p = 0.002). There was no significant increase in the RR of febrile neutropenia with RR of 3.29 (95% CI 0.93-11.57; p = 0.06). Our analysis provides evidence that the use of CDK 4/6 inhibitors is associated with an increased risk of all-grade and high-grade hematological adverse events, which seems to be a class-effect, but not of febrile neutropenia compared with hormonal therapy alone.

Pattern of hematological malignancies in adolescents and young adults in Bangladesh.

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Hasan, Md Mahbub; Raheem, Enayetur; Sultana, Tanvira Afroze; Hossain, Mohammad Sorowar

2017-12-01

The adolescent and young adult (AYA) age group (15-39 years) bears distinct characteristics in terms of cancer biology, long-term health and treatment-related complications and psychosocial aspects. The overall scenario of cancer including hematological malignancies (HMs) is largely unknown in Bangladesh, where a significant proportion of people (44% of total population) belong to AYA age group. This study aims to describe the patterns of HM among AYA in the context of Bangladesh METHODS: Two previously published datasets (on hematological malignancies and childhood and adolescent cancer) were merged to construct a comprehensive dataset focusing exclusively on HMs in AYA age group. Univariate descriptive statistics were calculated and bivariate association were tested using Pearson's Chi-square test. A total of 2144 diagnosed HM related cases over a period of 2007-2014 were analyzed. Acute myeloid leukemia (AML) was the most frequent HM (35.1%) in AYAs, which was followed by acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) constituting 22.7% and 20.8%, respectively. Among lymphomas, Non-Hodgkin lymphoma (NHL) constituted 13.9% of all HMs while 4.6% was for Hodgkin's lymphoma (HL). This is the first attempt to provide a glimpse on the pattern and distribution of HMs among AYA in Bangladesh. Future studies are essential to get a better insight on the epidemiology, biology, potential risk factors and treatment outcomes for the AYA age group. Copyright © 2017 Elsevier Ltd. All rights reserved.

American Society of Pediatric Hematology/Oncology

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... Learn More Explore career opportunities in pediatric hematology/oncology Visit the ASPHO Career Center. Learn More Join ... Privacy Policy » © The American Society of Pediatric Hematology/Oncology

Invasive Aspergillosis in Hematological Patients.

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Kimura, Shun-Ichi

2016-01-01

Invasive aspergillosis (IA) is still one of the leading causes of morbidity and mortality in hematological patients, although its outcome has been improving. Prolonged and profound neutropenia in patients receiving intensive chemotherapy for acute leukemia and stem cell transplantation is a major risk factor for IA. Allogeneic stem cell transplant recipients with graft-versus-host disease and corticosteroid use are also at high risk. Management in a protective environment with high efficiency particular air (HEPA) filter is generally recommended to prevent aspergillosis in patients with prolonged and profound neutropenia. Antifungal prophylaxis against Aspergillus species should be considered in patients with past history of aspergillosis or colonization of Aspergillus species, at facilities with high incidence of IA and those without a protective environment. Early diagnosis and prompt antifungal treatment is important to improve outcome. Imaging studies such as computed tomography and biomarkers such as galactomannan antigen and β-D-glucan are useful for early diagnosis. Empirical antifungal treatment based on persistent or recurrent fever during neutropenia despite broad-spectrum antibiotic therapy is generally recommended in high-risk patients. Alternatively, a preemptive treatment strategy has recently been proposed in the context of progress in the early diagnosis of IA based on the results of imaging studies and biomarkers. Voriconazole is recommended for initial therapy for IA. Liposomal amphotericin B is considered as alternative initial therapy. Combination antifungal therapy of echinocandin with voriconazole or liposomal amphotericin B could be a choice for refractory cases.

Autoradiographic study of corrosion of refractories

International Nuclear Information System (INIS)

Lisenenkova, S.B.; Kucheryavyi, M.N.; Bursteva, T.A.

1988-01-01

A comparative study was made of the character of the interaction between a container-glass melt consisting of sodium calcium silicate and refractories in various furnace sections using an autoradiographic method. Static tests were conducted on specimens of the following refractories: chrome-aluminum-zircon, Bakor 41, corundum, a high alumina refractory, and a refractory based on tin dioxide. The specimens were activated by calcium 45. Autoradiography and photomicrography indicated that an intrinsic feature of all refractories was that calcium from the melt penetrated the refractories along the weak link; for fused-cast refractories, the glass phase; and for sintered refractories, through the binder and cracks

Artificial intelligence in hematology.

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Zini, Gina

2005-10-01

Artificial intelligence (AI) is a computer based science which aims to simulate human brain faculties using a computational system. A brief history of this new science goes from the creation of the first artificial neuron in 1943 to the first artificial neural network application to genetic algorithms. The potential for a similar technology in medicine has immediately been identified by scientists and researchers. The possibility to store and process all medical knowledge has made this technology very attractive to assist or even surpass clinicians in reaching a diagnosis. Applications of AI in medicine include devices applied to clinical diagnosis in neurology and cardiopulmonary diseases, as well as the use of expert or knowledge-based systems in routine clinical use for diagnosis, therapeutic management and for prognostic evaluation. Biological applications include genome sequencing or DNA gene expression microarrays, modeling gene networks, analysis and clustering of gene expression data, pattern recognition in DNA and proteins, protein structure prediction. In the field of hematology the first devices based on AI have been applied to the routine laboratory data management. New tools concern the differential diagnosis in specific diseases such as anemias, thalassemias and leukemias, based on neural networks trained with data from peripheral blood analysis. A revolution in cancer diagnosis, including the diagnosis of hematological malignancies, has been the introduction of the first microarray based and bioinformatic approach for molecular diagnosis: a systematic approach based on the monitoring of simultaneous expression of thousands of genes using DNA microarray, independently of previous biological knowledge, analysed using AI devices. Using gene profiling, the traditional diagnostic pathways move from clinical to molecular based diagnostic systems.

Patients' reflections on communication in the second-opinion hematology-oncology consultation.

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Goldman, Roberta E; Sullivan, Amy; Back, Anthony L; Alexander, Stewart C; Matsuyama, Robin K; Lee, Stephanie J

2009-07-01

The nature of communication between patients and their second-opinion hematology consultants may be very different in these one-time consultations than for those that are within long-term relationships. This study explored patients' perceptions of their second-opinion hematology-oncology consultation to investigate physician-patient communication in malignant disease at a critical juncture in cancer patients' care and decision-making. In-depth telephone interviews with a subset of 20 patients from a larger study, following their subspecialty hematology consultations. Most patients wanted to contribute to the consultation agenda, but were unable to do so. Patients sought expert and honest advice delivered with empathy, though most did not expect the consultant to directly address their emotions. They wanted the physician to apply his/her knowledge to the specifics of their individual cases, and were disappointed and distrustful when physicians cited only general prognostic statistics. In contrast, physicians' consideration of the unique elements of patients' cases, and demonstrations of empathy and respect made patients' feel positively about the encounter, regardless of the prognosis. Patients provided concrete recommendations for physician and patient behaviors to enhance the consultation. Consideration of these recommendations may result in more effective communication and increased patient satisfaction with medical visits.

Successful treatment of refractory hepatic lymphorrhea after gastrectomy for early gastric cancer, using surgical ligation and subsequent OK-432 (Picibanil) sclerotherapy.

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Tanaka, Kouji; Ohmori, Yukinari; Mohri, Yasuhiko; Tonouchi, Hitoshi; Suematsu, Mina; Taguchi, Yukiko; Adachi, Yukihiko; Kusunoki, Masato

2004-01-01

Postoperative hepatic lymphorrhea is a very rare complication after abdominal surgery. Hepatic lymphorrhea, not containing chyle, involves an internal lymph fistula between the lymphatic channels toward the cisterna chyli and the peritoneal cavity. Over the past 20 years, 17 cases have been reported in Japan. Here, we report a further case, of a patient with successfully treated intractable hepatic lymphorrhea following gastrectomy for early gastric cancer. We review 18 cases, including the present case, with respect to the management of postoperative lymphorrhea refractory to conventional medical treatment.

The multicenter experience with bendamustine in the treatment of relapsed and refractory multiple myeloma

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S. V. Voloshin

2015-01-01

Full Text Available Relapsed and refractory (R/R multiple myeloma (MM constitutes a specific and unmet medical need. Median survival ranges from as little as 6 to 9 months, and responses to treatment are characteristically short. In patients with R/R MM after therapy of bortezomib and/or immunomodulators a bendamustine-based treatment can be used as “salvage”.In this retrospective analysis we have identified 32 patients with R/R MM by means of case research, have been bendamustine-based treated at Hematological Clinics of Russian Federation since 2011. Median age was 67 (43–81 years, the female/male ratio was 2.5:1. After in median 2 (1–7 lines of prior therapy patients received in median 3 (1–9 cycles of bendamustine-based therapy. Bendamustine dosage was 70–120 mg/m2 /day on 2 days of each 28-day cycle until progressive disease or intolerability. Overall rate response was 56.2 %: 21.9 % partial response, stable disease 34.4 %. Median time to progression was 5.3 (0.8–18.0 months and median overall survival was 25.4 (0.8–47.1 months. Hematologic toxicity was in 53.2 % of patients.

Leveraging cancer genome information in hematologic malignancies.

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Rampal, Raajit; Levine, Ross L

2013-05-20

The use of candidate gene and genome-wide discovery studies in the last several years has led to an expansion of our knowledge of the spectrum of recurrent, somatic disease alleles, which contribute to the pathogenesis of hematologic malignancies. Notably, these studies have also begun to fundamentally change our ability to develop informative prognostic schema that inform outcome and therapeutic response, yielding substantive insights into mechanisms of hematopoietic transformation in different tissue compartments. Although these studies have already had important biologic and translational impact, significant challenges remain in systematically applying these findings to clinical decision making and in implementing new technologies for genetic analysis into clinical practice to inform real-time decision making. Here, we review recent major genetic advances in myeloid and lymphoid malignancies, the impact of these findings on prognostic models, our understanding of disease initiation and evolution, and the implication of genomic discoveries on clinical decision making. Finally, we discuss general concepts in genetic modeling and the current state-of-the-art technology used in genetic investigation.

Palliative radiotherapy for local progression of hormone refractory stage D2 prostate cancer

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Kawakami, Satoru; Kawai, Tsuneo; Yonese, Junji; Yamauchi, Tamio; Ishibashi, Keiichiro; Ueda, Tomohiro (Japanese Foundation for Cancer Research, Tokyo (Japan). Hospital)

1993-09-01

From 1970 to 1992, 10 patients with hormone refractory stage D2 adenocarcinoma of the prostate presenting themselves with urinary retention and/or gross hematuria were treated by palliative irradiation for local progression at Cancer Institute Hospital. External beam irradiation was delivered to the primary lesion at dose of 38 Gy to one patient and 30[approx]27 Gy to seven patients. Five of these patients in whom an urethral catheter had been indwelt were able to void without difficulty following the treatment. Of four patients with severe hematuria resulting from vesical tamponade, none had hematuria after the treatment. These effect lasted until patients' death or more than 11 months follow-up. In other 2 patients, irradiation had to be discontinued at dose less than 20 Gy because of deteriorated general conditions and no significant effect. Complications of the treatment were minimal. These results indicate that the optimal dose of local palliative irradiation is around 30 Gy. Irradiation is a good choice for palliation of locally progressive hormone refactory prostate cancer in view of its certain and long-lasting effect, low invasiveness and minimal complications. When to institute palliative irradiation is one of the most important question in order to secure a good quality of life of patients. From our experiences, it is our belief that if local progression is symptomatic, palliative irradiation should be initiated as soon as possible. (author).

High prevalence of malnutrition among patients with solid non-hematological tumors as found by using skinfold and circumference measurements

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Adriana Garófolo

Full Text Available CONTEXT AND OBJECTIVE: Malnutrition in cancer patients has many causes. Nutritional status is usually assessed from weight/height indices. These present limitations for the nutritional assessment of cancer patients: their weights include tumor mass, and lean mass changes are not reflected in weight/height indices. The objective was to evaluate differences between two anthropometric methods and compare deficits, in non-hematological tumor patients and hematological disease patients. DESIGN AND SETTING: Cross-sectional study at Instituto de Oncologia Pediátrica, Universidade Federal de São Paulo. METHODS: Children and adolescents were evaluated between March 1998 and January 2000. Traditional anthropometric measurements were obtained in the first month of treatment (induction therapy, by weight-for-height (W/H using z-scores index for children and body mass index (BMI for adolescents. Body composition evaluations consisted of specific anthropometric measurements: triceps skinfold thickness (TSFT, mid-upper arm circumference (MUAC and arm muscle circumference (AMC. Data were analyzed to compare nutritional assessment methods for diagnosing malnutrition prevalence. The chi-squared test was used for comparative analyses between tumor patients and hematological disease patients. RESULTS: Analysis was done on 127 patients with complete data. Higher percentages of deficits were found among tumor patients, by W/H z-scores or BMI and by MUAC and AMC. Higher percentages of deficits were shown by TSFT (40.2% and MUAC (35.4% than by W/H z-scores or BMI (18.9%. CONCLUSION: Non-hematological tumor patients presented higher malnutrition prevalence than did hematological disease patients. Body composition measurements by TSFT and MUAC detected more patients with malnutrition than did W/H or BMI.

Brief assessment of priority symptoms in hormone refractory prostate cancer: The FACT Advanced Prostate Symptom Index (FAPSI

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Banik Donald

2003-11-01

Full Text Available Abstract Background The objective of this study was to construct and validate a brief, clinically-relevant symptom index for advanced prostate cancer. Methods Questions were extracted from a commonly-used multi-dimensional cancer quality of life instrument with prostate-specific items, the Functional Assessment of Cancer Therapy-Prostate (FACT-P. Surveys of disease-related symptoms were presented to an international sample of 44 expert physicians. Each expert narrowed the list to no more than five of the most important symptoms or concerns to monitor when assessing the value of treatment for advanced prostate cancer. Symptoms/concerns endorsed at a frequency greater than chance probability (17% were retained for the symptom index and called the FACT Advanced Prostate Symptom Index-8 (FAPSI-8: pain (three items, fatigue, weight loss, urinary difficulties (two items, and concern about the condition becoming worse. The FAPSI-8 was validated using data from a clinical trial of 288 men being treated for hormone refractory prostate cancer. Results The FAPSI-8 showed good internal consistency (r = 0.67–0.80; association with existing FACT scales (e.g., FACT-P, Physical Well-being, Functional Well-being; r = 0.44–0.85, p Conclusions This project produced a reliable and valid list of the eight most important clinician-rated targets of drug therapy for advanced prostate cancer. These questions perform comparably to the longer derivative questionnaire. Examination of patient agreement with this priority list and the extent to which changes in these 8 targets are related to meaningful clinical benefit to the patient are important next steps for future research.

Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: Challenges and Clinical Applications

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Hamid R. Mirzaei

2017-12-01

Full Text Available Adoptive cellular immunotherapy (ACT employing engineered T lymphocytes expressing chimeric antigen receptors (CARs has demonstrated promising antitumor effects in advanced hematologic cancers, such as relapsed or refractory acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma, supporting the translation of ACT to non-hematological malignancies. Although CAR T cell therapy has made remarkable strides in the treatment of patients with certain hematological cancers, in solid tumors success has been limited likely due to heterogeneous antigen expression, immunosuppressive networks in the tumor microenvironment limiting CAR T cell function and persistence, and suboptimal trafficking to solid tumors. Here, we outline specific approaches to overcome barriers to CAR T cell effectiveness in the context of the tumor microenvironment and offer our perspective on how expanding the use of CAR T cells in solid tumors may require modifications in CAR T cell design. We anticipate these modifications will further expand CAR T cell therapy in clinical practice.

DKK1 is a potential novel mediator of cisplatin-refractoriness in non-small cell lung cancer cell lines

International Nuclear Information System (INIS)

Salim, Hogir; Zong, Dali; Hååg, Petra; Novak, Metka; Mörk, Birgitta; Lewensohn, Rolf; Lundholm, Lovisa; Viktorsson, Kristina

2015-01-01

Platinum compounds are the mainstay of chemotherapy for lung cancer. Unfortunately treatment failure remains a critical issue since about 60 % of all non-small cell lung cancer (NSCLC) patients display intrinsic platinum resistance. We analyzed global gene expression profiles of NSCLC clones surviving a pulse treatment with cisplatin and mapped deregulated signaling networks in silico by Ingenuity Pathway Analysis (IPA). Further validation was done using siRNA. The pooled cisplatin-surviving NSCLC clones from each of the biological replicates demonstrated heterogeneous gene expression patterns both in terms of the number and the identity of the altered genes. Genes involved in Wnt signaling pathway (Dickkopf-1, DKK1), DNA repair machinery (XRCC2) and cell-cell/cell-matrix interaction (FMN1, LGALS9) were among the top deregulated genes by microarray in these replicates and were validated by q-RT-PCR. We focused on DKK1 which previously was reported to be overexpressed in NSCLC patients. IPA network analysis revealed coordinate up-regulation of several DKK1 transcriptional regulators (TCF4, EZH2, DNAJB6 and HDAC2) in cisplatin-surviving clones from that biological replicate. Knockdown of DKK1 by siRNA sensitized for cisplatin in two different NSCLC cell lines and in ovarian A2780 cells, but not in the A2780 cis subline made resistant to cisplatin by chronic exposure, suggesting a role of DKK1 in intrinsic but not acquired platinum refractoriness. We identified DKK1 as a possible marker of a cisplatin-refractory phenotype and as a potential novel therapeutic target to improve platinum response of NSCLC cells. The online version of this article (doi:10.1186/s12885-015-1635-9) contains supplementary material, which is available to authorized users

Allergic conditions and risk of hematological malignancies in adults: a cohort study

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Schwartzbaum Judith

2004-11-01

Full Text Available Abstract Background Two contradictory hypotheses have been proposed to explain the relationship between allergic conditions and malignancies, the immune surveillance hypothesis and the antigenic stimulation hypothesis. The former advocates that allergic conditions may be protective against development of cancer, whereas the latter proposes an increased risk. This relationship has been studied in several case-control studies, but only in a few cohort studies. Methods The association between allergic conditions and risk of developing leukemia, Hodgkin's disease, non-Hodgkin's lymphoma and myeloma was investigated in a cohort of 16,539 Swedish twins born 1886–1925. Prospectively collected, self-reported information about allergic conditions such as asthma, hay fever or eczema was obtained through questionnaires administered in 1967. The cohort was followed 1969–99 and cancer incidence was ascertained from the Swedish Cancer Registry. Results Hives and asthma tended to increase the risk of leukemia (relative risk [RR] = 2.1, 95% Confidence Interval [CI] 1.0–4.5 and RR = 1.6, 95% CI 0.8–3.5, respectively. There was also an indication of an increased risk of non-Hodgkin's lymphoma associated with eczema during childhood (RR = 2.3, 95% CI 1.0–5.3. Conclusion In contrast to most previous studies, our results do not indicate a protective effect of allergic conditions on the risk of developing hematological malignancies. Rather, they suggest that allergic conditions might increase the risk of some hematological malignancies.

Central venous catheter-related infections in hematology and oncology: 2012 updated guidelines on diagnosis, management and prevention by the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology.

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Hentrich, M; Schalk, E; Schmidt-Hieber, M; Chaberny, I; Mousset, S; Buchheidt, D; Ruhnke, M; Penack, O; Salwender, H; Wolf, H-H; Christopeit, M; Neumann, S; Maschmeyer, G; Karthaus, M

2014-05-01

Cancer patients are at increased risk for central venous catheter-related infections (CRIs). Thus, a comprehensive, practical and evidence-based guideline on CRI in patients with malignancies is warranted. A panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) has developed a guideline on CRI in cancer patients. Literature searches of the PubMed, Medline and Cochrane databases were carried out and consensus discussions were held. Recommendations on diagnosis, management and prevention of CRI in cancer patients are made, and the strength of the recommendation and the level of evidence are presented. This guideline is an evidence-based approach to the diagnosis, management and prevention of CRI in cancer patients.

Verification and quality control of routine hematology analyzers.

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Vis, J Y; Huisman, A

2016-05-01

Verification of hematology analyzers (automated blood cell counters) is mandatory before new hematology analyzers may be used in routine clinical care. The verification process consists of several items which comprise among others: precision, accuracy, comparability, carryover, background and linearity throughout the expected range of results. Yet, which standard should be met or which verification limit be used is at the discretion of the laboratory specialist. This paper offers practical guidance on verification and quality control of automated hematology analyzers and provides an expert opinion on the performance standard that should be met by the contemporary generation of hematology analyzers. Therefore (i) the state-of-the-art performance of hematology analyzers for complete blood count parameters is summarized, (ii) considerations, challenges, and pitfalls concerning the development of a verification plan are discussed, (iii) guidance is given regarding the establishment of reference intervals, and (iv) different methods on quality control of hematology analyzers are reviewed. © 2016 John Wiley & Sons Ltd.

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

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

2017-12-01

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

Epigenetics in Cancer: A Hematological Perspective.

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Maximilian Stahl

2016-10-01

Full Text Available For several decades, we have known that epigenetic regulation is disrupted in cancer. Recently, an increasing body of data suggests epigenetics might be an intersection of current cancer research trends: next generation sequencing, immunology, metabolomics, and cell aging. The new emphasis on epigenetics is also related to the increasing production of drugs capable of interfering with epigenetic mechanisms and able to trigger clinical responses in even advanced phase patients. In this review, we will use myeloid malignancies as proof of concept examples of how epigenetic mechanisms can trigger or promote oncogenesis. We will also show how epigenetic mechanisms are related to genetic aberrations, and how they affect other systems, like immune response. Finally, we will show how we can try to influence the fate of cancer cells with epigenetic therapy.

Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group.

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Buckstein, Rena; Kuruvilla, John; Chua, Neil; Lee, Christina; Macdonald, David A; Al-Tourah, Abdulwahab J; Foo, Alison H; Walsh, Wendy; Ivy, S Percy; Crump, Michael; Eisenhauer, Elizabeth A

2011-05-01

There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3-4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity.

Propensity Score Analysis of Regorafenib Versus Trifluridine/Tipiracil in Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapy (REGOTAS): A Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study.

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Moriwaki, Toshikazu; Fukuoka, Shota; Taniguchi, Hiroya; Takashima, Atsuo; Kumekawa, Yusuke; Kajiwara, Takeshi; Yamazaki, Kentaro; Esaki, Taito; Makiyama, Chinatsu; Denda, Tadamichi; Satake, Hironaga; Suto, Takeshi; Sugimoto, Naotoshi; Enomoto, Masanobu; Ishikawa, Toshiaki; Kashiwada, Tomomi; Sugiyama, Masahiko; Komatsu, Yoshito; Okuyama, Hiroyuki; Baba, Eishi; Sakai, Daisuke; Watanabe, Tomoki; Tamura, Takao; Yamashita, Kimihiro; Gosho, Masahiko; Shimada, Yasuhiro

2018-01-01

This study compared the efficacy of regorafenib and trifluridine/tipiracil (TFTD) in patients with metastatic colorectal cancer (mCRC) who are refractory to standard chemotherapy, because despite their clinical approval, it still remains unclear which of these two drugs should be used as initial treatment. The clinical data of patients with mCRC who were treated with regorafenib or TFTD and those of drug-naive patients, between June 2014 and September 2015, were retrospectively collected from 24 institutions in Japan. Overall survival (OS) was evaluated using the Cox's proportional hazard models based on propensity score adjustment for baseline characteristics. A total of 550 patients (223 patients in the regorafenib group and 327 patients in the TFTD group) met all criteria. The median OS was 7.9 months (95% confidence interval [CI], 6.8-9.2) in the regorafenib group and 7.4 months (95% CI, 6.6-8.3) in the TFTD group. The propensity score adjusted analysis showed that OS was similar between the two groups (adjusted hazard ratio [HR], 0.96; 95% CI, 0.78-1.18). In the subgroup analysis, a significant interaction with age was observed. Regorafenib showed favorable survival in patients aged regorafenib and TFTD was observed in patients with mCRC. Although the choice of the drug by age might affect survival, a clearly predictive biomarker to distinguish the two drugs should be identified in further studies. Previous studies of patients with metastatic colorectal cancer refractory to standard chemotherapy had demonstrated that both regorafenib and trifluridine/tipiracil could result in increased overall survival compared with placebo, but there are no head-to-head trials. This large, multicenter, observational study retrospectively compared the efficacy of regorafenib and trifluridine/tipiracil in 550 patients with metastatic colorectal cancer refractory to standard chemotherapy who had access to both drugs. Although no difference in overall survival was found between

Microarray Gene Expression Analysis to Evaluate Cell Type Specific Expression of Targets Relevant for Immunotherapy of Hematological Malignancies.

Directory of Open Access Journals (Sweden)

M J Pont

Full Text Available Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate potential efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. We performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN-γ to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlations between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage-restricted expression as potential targets for immunotherapy of hematological cancers.

42 CFR 493.1269 - Standard: Hematology.

Science.gov (United States)

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Standard: Hematology. 493.1269 Section 493.1269 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1269 Standard: Hematology. (a) For manual cell counts performed using a hemocytometer— (1...

Serodiagnosis of celiac disease in children referred for evaluation of anemia: A pediatric hematology unit′s experience

Directory of Open Access Journals (Sweden)

Deepak Bansal

2011-01-01

Full Text Available Background: Children presenting with typical clinical features of celiac disease (CD are diagnosed relatively easily, however, diagnosis remains challenging and is often delayed when they present with ′difficult to treat anemia′ without overt gastrointestinal manifestations. Index study was undertaken to report profile of patients referred to pediatric hematology unit with ′difficult anemia′ who subsequently were diagnosed with CD. Materials and Methods: The records of 83 patients (1988-2008 with CD were scrutinized retrospectively who had presented with predominant hematological manifestations. Results: CD was confirmed histologically in 31 (37%, while 52 (63% were diagnosed by serology alone. The mean age at diagnosis was 8.0 ± 2.8 years. The mean duration of symptom-diagnosis interval was 40.9 ± 30.6 months. Eighty-one (98% children had anemia (Hb < 11 g/dl and 55 (66% had received iron supplements without discernible benefit. Thirty-nine (47% patients received a blood transfusion. Thirty-six (43% patients did not have diarrhea. Majority of the patients had either a microcytic-hypochromic (48% or dimorphic (43% anemia. Twenty-four (33% had thrombocytosis, while 5 (7% had thrombocytopenia. Mean duration of follow-up for patients on roll in the clinic for more than six months was 17.7 ± 20.9 months. Conclusion: Pediatricians and hematologists need to be aware of the extra-intestinal manifestations of CD. Prolonged duration of symptoms and a diagnosis at a relatively older age is striking in children presenting with predominantly hematological manifestations. Investigations for CD are recommended in children presenting with iron deficiency anemia refractory to hematinics or who have coexisting growth retardation. Necessity for biopsy in overtly symptomatic cases is discussed.

Bleeding frequency and characteristics among hematologic malignancy inpatient rehabilitation patients with severe thrombocytopenia.

Science.gov (United States)

Fu, Jack B; Tennison, Jegy M; Rutzen-Lopez, Isabel M; Silver, Julie K; Morishita, Shinichiro; Dibaj, Seyedeh S; Bruera, Eduardo

2018-03-28

To identify the frequency and characteristics of bleeding complications during acute inpatient rehabilitation of hematologic malignancy patients with severe thrombocytopenia. Retrospective descriptive analysis. Comprehensive cancer center acute inpatient rehabilitation unit. Consecutive hematologic malignancy patients with a platelet count of less than or equal to 20,000/microliter (μL) on the day of acute inpatient rehabilitation admission from 1/1/2005 through 8/31/2016. Medical records were retrospectively analyzed for demographic, laboratory, and medical data. Patients were rehabilitated using the institutional exercise guidelines for thrombocytopenic patients. Bleeding events noted in the medical record. Out of 135 acute inpatient rehabilitation admissions, 133 unique patients were analyzed with a total of 851 inpatient rehabilitation days. The mean platelet count was 14,000/μL on the day of admission and 22,000/μL over the course of the rehabilitation admission. There were 252 days of inpatient rehabilitation where patients had less than 10,000/μL platelets. A total of 97 bleeding events were documented in 77/135 (57%) admissions. Of the 97 bleeding events, 72 (74%), 14 (14%), and 11 (11%) were considered to be of low, medium, and high severity, respectively. There were 4/97 (4%) bleeding events that were highly likely attributable to physical activity but only 1/4 was considered high severity. Bleeding rates were .09, .08, .17, and .37 for > 20,000, 15-20,000, 10-15,000, and rehabilitation in severely thrombocytopenic hematologic cancer patients. Bleeding rates increased with lower platelet counts. However, using the exercise guidelines for severely thrombocytopenic patients, the risk of severe exercise-related bleeding events was low.

Determination of the most appropriate method for extrapolating overall survival data from a placebo-controlled clinical trial of lenvatinib for progressive, radioiodine-refractory differentiated thyroid cancer

Directory of Open Access Journals (Sweden)

Tremblay G

2016-06-01

Full Text Available Gabriel Tremblay,1 Christopher Livings,2 Lydia Crowe,2 Venediktos Kapetanakis,2 Andrew Briggs3 1Global Health Economics and Health Technology Assessment, Eisai Inc., Woodcliff Lake, NJ, USA; 2Health Economics, Decision Resources Group, Bicester, Oxfordshire, 3Health Economics and Health Technology Assessment, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK Background: Cost-effectiveness models for the treatment of long-term conditions often require information on survival beyond the period of available data. Objectives: This paper aims to identify a robust and reliable method for the extrapolation of overall survival (OS in patients with radioiodine-refractory differentiated thyroid cancer receiving lenvatinib or placebo. Methods: Data from 392 patients (lenvatinib: 261, placebo: 131 from the SELECT trial are used over a 34-month period of follow-up. A previously published criterion-based approach is employed to ascertain credible estimates of OS beyond the trial data. Parametric models with and without a treatment covariate and piecewise models are used to extrapolate OS, and a holistic approach, where a series of statistical and visual tests are considered collectively, is taken in determining the most appropriate extrapolation model. Results: A piecewise model, in which the Kaplan–Meier survivor function is used over the trial period and an extrapolated tail is based on the Exponential distribution, is identified as the optimal model. Conclusion: In the absence of long-term survival estimates from clinical trials, survival estimates often need to be extrapolated from the available data. The use of a systematic method based on a priori determined selection criteria provides a transparent approach and reduces the risk of bias. The extrapolated OS estimates will be used to investigate the potential long-term benefits of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer patients and

Refractoriness in human atria

DEFF Research Database (Denmark)

Skibsbye, Lasse; Jespersen, Thomas; Christ, Torsten

2016-01-01

BACKGROUND: Refractoriness of cardiac cells limits maximum frequency of electrical activity and protects the heart from tonic contractions. Short refractory periods support major arrhythmogenic substrates and augmentation of refractoriness is therefore seen as a main mechanism of antiarrhythmic...... drugs. Cardiomyocyte excitability depends on availability of sodium channels, which involves both time- and voltage-dependent recovery from inactivation. This study therefore aims to characterise how sodium channel inactivation affects refractoriness in human atria. METHODS AND RESULTS: Steady......-state activation and inactivation parameters of sodium channels measured in vitro in isolated human atrial cardiomyocytes were used to parameterise a mathematical human atrial cell model. Action potential data were acquired from human atrial trabeculae of patients in either sinus rhythm or chronic atrial...

Nanodiamonds enhance therapeutic efficacy of doxorubicin in treating metastatic hormone-refractory prostate cancer.

Science.gov (United States)

Salaam, Amanee D; Hwang, Patrick T J; Poonawalla, Aliza; Green, Hadiyah N; Jun, Ho-wook; Dean, Derrick

2014-10-24

Enhancing therapeutic efficacy is essential for successful treatment of chemoresistant cancers such as metastatic hormone-refractory prostate cancer (HRPC). To improve the efficacy of doxorubicin (DOX) for treating chemoresistant disease, the feasibility of using nanodiamond (ND) particles was investigated. Utilizing the pH responsive properties of ND, a novel protocol for complexing NDs and DOX was developed using a pH 8.5 coupling buffer. The DOX loading efficiency, loading on the NDs, and pH responsive release characteristics were determined utilizing UV-Visible spectroscopy. The effects of the ND-DOX on HRPC cell line PC3 were evaluated with MTS and live/dead cell viability assays. ND-DOX displayed exceptional loading efficiency (95.7%) and drug loading on NDs (23.9 wt%) with optimal release at pH 4 (80%). In comparison to treatment with DOX alone, cell death significantly increased when cells were treated with ND-DOX complexes demonstrating a 50% improvement in DOX efficacy. Of the tested treatments, ND-DOX with 2.4 μg mL(-1) DOX exhibited superior efficacy (60% cell death). ND-DOX with 1.2 μg mL(-1) DOX achieved 42% cell death, which was comparable to cell death in response to 2.4 μg mL(-1) of free DOX, suggesting that NDs aid in decreasing the DOX dose necessary to achieve a chemotherapeutic efficacy. Due to its enhanced efficacy, ND-DOX can be used to successfully treat HRPC and potentially decrease the clinical side effects of DOX.

Oral microflora in children with hematologic malignancies

Directory of Open Access Journals (Sweden)

M. F. Vecherkovskaya

2015-06-01

Full Text Available The goal was a comprehensive study of oral microflora in healthy children and those with hematologic malignancies, based on the analysis of mixed microbial biofilms composition, isolation and identification of new previously unknown microorganisms. The material was obtained in children with hematological diseases in remission, 2–10 years aged, and for the control group from St. Petersburg schoolchildren and in kindergartens. We used microbiological, biochemical and molecular genetic methods, including electron microscopy, proteomic analysis, sequencing and complete genome annotation. Microorganisms of 23 genera isolated as pure cultures and identified by biochemical activity from mixed microbial biofilm derived from saliva of healthy and sick children. In microflora of children with hematologic malignancies a previously unknown type of streptococci with a large number of antibiotic resistance genes was revealed. Differences in oral microbiota composition of healthy children and children with hematological diseases in remission were revealed. The microbiota of children with hematologic malignancies contains more genes controlling antibiotic resistance. Also, it was observed previously unknown bacterium of the genus Streptococcus.

Oral microflora in children with hematologic malignancies

Directory of Open Access Journals (Sweden)

M. F. Vecherkovskaya

2015-01-01

Full Text Available The goal was a comprehensive study of oral microflora in healthy children and those with hematologic malignancies, based on the analysis of mixed microbial biofilms composition, isolation and identification of new previously unknown microorganisms. The material was obtained in children with hematological diseases in remission, 2–10 years aged, and for the control group from St. Petersburg schoolchildren and in kindergartens. We used microbiological, biochemical and molecular genetic methods, including electron microscopy, proteomic analysis, sequencing and complete genome annotation. Microorganisms of 23 genera isolated as pure cultures and identified by biochemical activity from mixed microbial biofilm derived from saliva of healthy and sick children. In microflora of children with hematologic malignancies a previously unknown type of streptococci with a large number of antibiotic resistance genes was revealed. Differences in oral microbiota composition of healthy children and children with hematological diseases in remission were revealed. The microbiota of children with hematologic malignancies contains more genes controlling antibiotic resistance. Also, it was observed previously unknown bacterium of the genus Streptococcus.

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

Science.gov (United States)

Mehta-Shah, Neha; Bartlett, Nancy L

2018-04-12

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

All in the family: Clueing into the link between metabolic syndrome and hematologic malignancies.

Science.gov (United States)

Karmali, Reem; Dalovisio, Andrew; Borgia, Jeffrey A; Venugopal, Parameswaran; Kim, Brian W; Grant-Szymanski, Kelly; Hari, Parameswaran; Lazarus, Hillard

2015-03-01

Metabolic syndrome constitutes a constellation of findings including central obesity, insulin resistance/type 2 diabetes mellitus (DM), dyslipidemia and hypertension. Metabolic syndrome affects 1 in 4 adults in the United States and is rapidly rising in prevalence, largely driven by the dramatic rise in obesity and insulin resistance/DM. Being central to the development of metabolic syndrome and its other related diseases, much focus has been placed on identifying the mitogenic effects of obesity and insulin resistance/DM as mechanistic clues of the link between metabolic syndrome and cancer. Pertinent mechanisms identified include altered lipid signaling, adipokine and inflammatory cytokine effects, and activation of PI3K/Akt/mTOR and RAS/RAF/MAPK/ERK pathways via dysregulated insulin/insulin-like growth factor-1 (IGF-1) signaling. Through variable activation of these multiple pathways, obesity and insulin resistance/DM pre-dispose to hematologic malignancies, imposing the aggressive and chemo-resistant phenotypes typically seen in cancer patients with underlying metabolic syndrome. Growing understanding of these pathways has identified druggable cancer targets, rationalizing the development and testing of agents like PI3K inhibitor idelalisib, mTOR inhibitors everolimus and temsirolimus, and IGF-1 receptor inhibitor linsitinib. It has also led to exploration of obesity and diabetes-directed therapies including statins and oral hypoglycemic for the management of metabolic syndrome-related hematologic neoplasms. Copyright © 2014 Elsevier Ltd. All rights reserved.

42 CFR 493.851 - Standard; Hematology.

Science.gov (United States)

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; Hematology. 493.851 Section 493.851 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.851 Standard; Hematology. (a) Failure to attain a score of at least 80 percent of...

Plasma spraying of refractory metals and refractory hard materials. State of the art

International Nuclear Information System (INIS)

Eschnauer, H.; Lugscheider, E.; Jaeger, D.

1989-01-01

Suitable spraying processes for manufacturing refractory metals, refractory hard materials as well as spray materials with refractory components are the VPS- and IPS-spraying techniques. The advantages of these special spraying process variations are described. The reactive spraying materials are systematically organized. The characteristical properties used in purpose of improving the substrate surfaces are explained. Finally some examples of the latest results of research concerning plasma spraying of reactive materials are shown. 16 refs., 10 figs. (Author)

Biological therapy of hematologic malignancies: toward a chemotherapy-free era.

Science.gov (United States)

Klener, Pavel; Etrych, Tomas; Klener, Pavel

2017-10-06

Less than 70 years ago, the vast majority of hematologic malignancies were untreatable diseases with fatal prognoses. The development of modern chemotherapy agents, which had begun after the Second World War, was markedly accelerated by the discovery of the structure of DNA and its role in cancer biology and tumor cell division. The path travelled from the first temporary remissions observed in children with acute lymphoblastic leukemia treated with single-agent antimetabolites until the first cures achieved by multi-agent chemotherapy regimens was incredibly short. Despite great successes, however, conventional genotoxic cytostatics suffered from an inherently narrow therapeutic index and extensive toxicity, which in many instances limited their clinical utilization. In the last decade of the 20th century, increasing knowledge on the biology of certain malignancies resulted in the conception and development of first molecularly targeted agents designed to inhibit specific druggable molecules involved in the survival of cancer cells. Advances in technology and genetic engineering enabled the production of structurally complex anticancer macromolecules called biologicals, including therapeutic monoclonal antibodies, antibody-drug conjugates and antibody fragments. The development of drug delivery systems (DDSs), in which conventional drugs were attached to various types of carriers including nanoparticles, liposomes or biodegradable polymers, represented an alternative approach to the development of new anticancer agents. Despite the fact that the antitumor activity of drugs attached to DDSs was not fundamentally different, the improved pharmacokinetic profiles, decreased toxic side effects and significantly increased therapeutic indexes resulted in their enhanced antitumor efficacy compared to conventional (unbound) drugs. Approval of the first immune checkpoint inhibitor for the treatment of cancer in 2011 initiated the era of cancer immunotherapy. Checkpoint

Understanding strength exercise intentions and behavior in hematologic cancer survivors: an analysis of the intention-behavior gap.

Science.gov (United States)

Vallerand, James R; Rhodes, Ryan E; Walker, Gordon J; Courneya, Kerry S

2016-12-01

Strength exercise improves many health outcomes in cancer survivors but the prevalence and correlates of strength exercise have not been well-described. Moreover, no study has examined the critical intention-behavior gap for exercise in cancer survivors. The aims of this study are to quantify the intention-behavior gap for strength exercise in hematologic cancer survivors (HCS) and examine correlates of both intention formation and translation using the multi-process action control framework (M-PAC). A random sample of 2100 HCS in Alberta, Canada, were mailed a survey assessing strength exercise behavior, the M-PAC, and demographic/medical variables. Separate logistic regressions were used to analyze the relationships between the correlates and intention formation and translation. Surveys were completed by 606 HCS with 58 % (n = 353) intending to do strength exercise. HCS who were not retired (OR = 1.56, p = 0.001), were highly educated (OR = 1.32, p = 0.001), and had a favorable attitude (OR = 1.56, p exercise intention. Of those with an exercise intention, 51 % (n = 181) reported regular strength exercise. HCS with a detailed plan (OR = 1.86, p attitude (OR = 1.68, p = 0.001), sense of obligation (OR = 1.38, p = 0.010), and self-regulated their affinity for competing activities (OR = 1.35, p = 0.012), were more likely to translate their intention into behavior. Just over half of HCS intended to do strength exercise and only half of intenders translated that intention into behavior. Interventions targeting both intention formation and translation may provide the best approach for increasing strength exercise in HCS.

Pandemic (H1N1) 2009 Outbreak at Camp for Children with Hematologic and Oncologic Conditions

Science.gov (United States)

Morrison, Cori; Maurtua-Neumann, Paola; Myint, Myo Thwin; Drury, Stacy S.

2011-01-01

An outbreak of influenza A pandemic (H1N1) 2009 occurred among campers and staff at a summer camp attended by children with hematologic and oncologic conditions. The overall attack rate was 36% and was highest among children and adolescents (43%), persons with cancer (48%), and persons with sickle cell disease (82%). PMID:21192861

Theoretical and practical aspects about corrosion of refractories used in steel metallurgy: part 3: characterization of commercial refractories

International Nuclear Information System (INIS)

Braganca, S.R.

2012-01-01

In this study, it was reviewed the main aspects found in the literature about refractories corrosion, evaluating the feasibility of certain tests and relating them with experimental results. The physical properties and microstructure of commercial refractories were analyzed, considering the differences between them and the quality implications and probable life of the refractory. Thus, it was studied the various types of refractories used as lining on steel ladle. Magnesia-carbon and doloma-carbon refractories were analyzed, highlighting the differences between them. The examined refractory showed characteristics favoring high resistance to corrosion process, presenting a series of properties to be selected in accordance with industry practice. (author)

Eosinophilic Dermatosis of Hematologic Malignancy.

Science.gov (United States)

Lucas-Truyols, S; Rodrigo-Nicolás, B; Lloret-Ruiz, C; Quecedo-Estébanez, E

Dermatosis characterized by tissue eosinophilia arising in the context of hematologic disease is known as eosinophilic dermatosis of hematologic malignancy. The most commonly associated malignancy is chronic lymphocytic leukemia. Eosinophilic dermatosis of hematologic malignancy is a rare condition with a wide variety of clinical presentations, ranging from papules, erythematous nodules, or blisters that simulate arthropod bites, to the formation of true plaques of differing sizes. Histology reveals the presence of abundant eosinophils. We present 4 new cases seen in Hospital Arnau de Vilanova, Valencia, during the past 7 years. Three of these cases were associated with chronic lymphocytic leukemia and 1 with mycosis fungoides. It is important to recognize this dermatosis as it can indicate progression of the underlying disease, as was the case in 3 of our patients. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Effect of socioeconomic position on survival after childhood cancer in Denmark

DEFF Research Database (Denmark)

Simony, Sofie B; Lund, Lasse W; Erdmann, Friederike

2016-01-01

(numbers. For hematological cancers, no significant associations were observed. For CNS tumors, better survival was seen with parents living together (HR 0.70, CI 0.51–0.97). For non-CNS solid tumors, survival...... were associated with survival after childhood cancer. Material and methods In a nationwide cohort of 3797 children diagnosed with cancer [hematological cancer, central nervous system (CNS) tumors, non-CNS solid tumors] before age 20 between 1990 and 2009 we identified parents and siblings and obtained...

Musculoskeletal Imaging Findings of Hematologic Malignancies.

Science.gov (United States)

Navarro, Shannon M; Matcuk, George R; Patel, Dakshesh B; Skalski, Matthew; White, Eric A; Tomasian, Anderanik; Schein, Aaron J

2017-01-01

Hematologic malignancies comprise a set of prevalent yet clinically diverse diseases that can affect every organ system. Because blood components originate in bone marrow, it is no surprise that bone marrow is a common location for both primary and metastatic hematologic neoplasms. Findings of hematologic malignancy can be seen with most imaging modalities including radiography, computed tomography (CT), technetium 99m ( 99m Tc) methylene diphosphonate (MDP) bone scanning, fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, and magnetic resonance (MR) imaging. Because of the diversity of imaging appearances and clinical behavior of this spectrum of disease, diagnosis can be challenging, and profound understanding of the underlying pathophysiologic changes and current treatment modalities can be daunting. The appearance of normal bone marrow at MR imaging and FDG PET/CT is also varied due to dynamic compositional changes with normal aging and in response to hematologic demand or treatment, which can lead to false-positive interpretation of imaging studies. In this article, the authors review the normal maturation and imaging appearance of bone marrow. Focusing on lymphoma, leukemia, and multiple myeloma, they present the spectrum of imaging findings of hematologic malignancy affecting the musculoskeletal system and the current imaging tools available to the radiologist. They discuss the imaging findings of posttreatment bone marrow and review commonly used staging systems and consensus recommendations for appropriate imaging for staging, management, and assessment of clinical remission. © RSNA, 2017.

Some hematological and biochemical parameters in smokeless ...

African Journals Online (AJOL)

AJB SERVER

2007-01-04

Jan 4, 2007 ... The effect of Jharda powder (smokeless tobacco) on some hematological and biochemical parameters in consumers was investigated. Hematological parameters including hemoglobin content and white blood cell and leukocyte counts were higher in jharda powder consumers, while monocytes and.

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

Science.gov (United States)

Novakovic, Barbara Jezersek

2015-01-01

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

A Feasibility Study of Virtual Reality Exercise in Elderly Patients with Hematologic Malignancies Receiving Chemotherapy.

Science.gov (United States)

Tsuda, Kenji; Sudo, Kazuaki; Goto, Goro; Takai, Makiko; Itokawa, Tatsuo; Isshiki, Takahiro; Takei, Naoko; Tanimoto, Tetsuya; Komatsu, Tsunehiko

2016-01-01

Adherence to rehabilitation exercise is much lower in patients with hematologic malignancies (22.5-45.8%) than in patients with solid tumors (60-85%) due to the administration of more intensive chemotherapeutic regimens in the former. Virtual reality exercise can be performed even in a biological clean room and it may improve the adherence rates in elderly patients with hematologic malignancies. Thus, in this pilot study, we aimed to investigate the feasibility and safety of virtual reality exercise intervention using Nintendo Wii Fit in patients with hematologic malignancies receiving chemotherapy. In this feasibility study, 16 hospitalized patients with hematologic malignancies aged ≥60 years performed virtual reality exercise for 20 minutes using the Nintendo Wii Fit once a day, five times a week, from the start of chemotherapy until hospital discharge. The adherence rate, safety, and physical and psychological performances were assessed. The adherence rate for all 16 patients was 66.5%. Nine patients completed the virtual reality exercise intervention with 88 sessions, and the adherence rate was 62.0%. No intervention-related adverse effects >Grade 2, according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0, were observed. We noted maintenance of the physical performance (e.g., Barthel index, handgrip strength, knee extension strength, one-leg standing time, and the scores of timed up and go test and Instrumental Activities of Daily Living) and psychosocial performance (e.g., score of hospital anxiety and depression scale). Virtual reality exercise using the Wii Fit may be feasible, safe and efficacious, as demonstrated in our preliminary results, for patients with hematologic malignancies receiving chemotherapy.

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

Salvage therapies in relapsed and/or refractory myeloma: what is current and what is the future?

Directory of Open Access Journals (Sweden)

Thumallapally N

2016-08-01

Full Text Available Nishitha Thumallapally,1 Hana Yu,1 Divya Asti,1 Adarsh Vennepureddy,1 Terenig Terjanian2 1Department of Internal Medicine, 2Division of Hematology and Oncology, Staten Island University Hospital, New York, NY, USA Abstract: The treatment landscape for multiple myeloma (MM is evolving with our understanding of its pathophysiology. However, given the inevitable cohort heterogeneity in salvage therapy, response to treatment and overall prognoses tend to vary widely, making meaningful conclusions about treatment efficacy difficult to derive. Despite the hurdles in current research, progress is underway toward more targeted therapeutic approaches. Several new drugs with novel mechanism of action and less toxic profile have been developed in the past decade, with the potential for use as single agents or in synergy with other treatment modalities in MM therapy. As our discovery of these emerging therapies progresses, so too does our need to reshape our knowledge on knowing how to apply them. This review highlights some of the recent landmark changes in MM management with specific emphasis on salvage drugs available for relapsed and refractory MM and also discusses some of the upcoming cutting-edge therapies that are currently in various stages of clinical development. Keywords: multiple myeloma, novel drugs, relapsed and refractory myeloma, salvage chemotherapy 

Some hematological and biochemical parameters in smokeless ...

African Journals Online (AJOL)

The effect of Jharda powder (smokeless tobacco) on some hematological and biochemical parameters in consumers was investigated. Hematological parameters including hemoglobin content and white blood cell and leukocyte counts were higher in jharda powder consumers, while monocytes and basophiles counts were ...

Irradiation of FDG-PET–Defined Active Bone Marrow Subregions and Acute Hematologic Toxicity in Anal Cancer Patients Undergoing Chemoradiation

International Nuclear Information System (INIS)

Rose, Brent S.; Jee, Kyung-Wook; Niemierko, Andrzej; Murphy, Janet E.; Blaszkowsky, Lawrence S.; Allen, Jill N.; Lee, Leslie K.; Wang, Yingbing; Drapek, Lorraine C.; Hong, Theodore S.; Wo, Jennifer Y.

2016-01-01

Purpose: Irradiation of pelvic bone marrow (BM) has been correlated with hematologic toxicity (HT) in patients undergoing chemoradiation for anal cancer. We hypothesized that irradiation of hematologically active bone marrow (ABM) subregions defined by fluorodeoxyglucose (FDG) positron emission tomography (PET) is a principal cause of radiation-associated HT. Methods and Materials: The cohort included 45 patients with nonmetastatic anal cancer who underwent FDG-PET imaging prior to definitive chemoradiation with mitomycin-C and 5-fluorouracil. Total bone marrow (TBM) was defined as the external contour of the pelvic bones from the top of lumbar 5 (L5) to the bottom of the ischial tuberosity. Standardized uptake values (SUV) for all voxels within the TBM were quantified and normalized by comparison to normal liver SUV. Subvolumes of the TBM that exhibited the highest and lowest 50% of the SUVs were designated ABM_5_0 and IBM_5_0, respectively. The primary endpoint was the absolute neutrophil count (ANC) nadir during or within 2 weeks of completion of treatment. Multivariate linear modeling was used to analyze the correlation between the equivalent uniform doses (EUD) with an a value of 0.5, 1 (equivalent to mean dose), 3, 7, and 12 to the BM structures and the ANC. Results: Mean ± SD ANC nadir was 0.77 × 10"9/L (±0.66 × 10"9/L). Grades 3 and 4 ANC toxicity occurred in 26.7% and 44.4% of patients, respectively. The EUD a parameter of 0.5 was optimal for all BM models indicating high radiation sensitivity. EUD of TBM and ABM_5_0 and IBM_5_0 were all significantly associated with ANC nadir. However, model performance for ABM_5_0 was not superior to that of the TBM and IBM_5_0 models. Conclusions: Irradiation of pelvic BM was associated with HT. However, FDG-PET–defined ABM models failed to improve model performance compared to the TBM model.

15th Congress of European Hematology Association

NARCIS (Netherlands)

Chomienne, Christine; Guenova, Margarita; Hagenbeek, Antony; Lacombe, Catherine; McCann, Shaun; Foa, Robin

2010-01-01

Each year the annual congress of the European Hematology Association gathers clinicians, biologists and scientists dedicated to all fields of hematology. This year's Congress was held in Barcelona, Spain, and presented an appealing program with experts presenting state-of-the-art sessions to more

Clinical Cancer Genetics and Prevention

Science.gov (United States)

Olufunmilayo F. Olopade MD, FACP, Professor of Medicine and Human Genetics and Director of the Cancer Risk Clinic Department of Medicine, BSD Section of Hematology/Oncology University of Chicago, presented "Clinical Cancer Genetics and Prevention".

Anti-infective Vaccination Strategies in Patients with Hematologic Malignancies or Solid Tumors - Guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO).

Science.gov (United States)

Rieger, C T; Liss, B; Mellinghoff, S; Buchheidt, D; Cornely, O A; Egerer, G; Heinz, W J; Hentrich, M; Maschmeyer, G; Mayer, K; Sandherr, M; Silling, G; Ullmann, A; Vehreschild, M J G T; von Lilienfeld-Toal, M; Wolf, H H; Lehners, N

2018-04-24

Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies. This guideline provides clinical recommendations on vaccine use in cancer patients including autologous stem cell transplant recipients, while allogeneic stem cell transplantation is subject of a separate guideline. The document was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) by reviewing currently available data and applying evidence-based medicine criteria.

Extracellular Vesicles in Hematological Disorders

Directory of Open Access Journals (Sweden)

Anat Aharon

2014-10-01

Full Text Available Extracellular vesicles (EVs, comprised of exosomes, microparticles, apoptotic bodies, and other microvesicles, are shed from a variety of cells upon cell activation or apoptosis. EVs promote clot formation, mediate pro-inflammatory processes, transfer proteins and miRNA to cells, and induce cell signaling that regulates cell differentiation, proliferation, migration, invasion, and apoptosis. This paper will review the contribution of EVs in hematological disorders, including hemoglobinopathies (sickle cell disease, thalassemia, paroxysmal nocturnal hemoglobinuria, and hematological malignancies (lymphomas, myelomas, and acute and chronic leukemias.

Utility of CRISPR/Cas9 systems in hematology research.

Science.gov (United States)

Lucas, Daniel; O'Leary, Heather A; Ebert, Benjamin L; Cowan, Chad A; Tremblay, Cedric S

2017-10-01

Since the end of the 20th century, novel approaches have emerged to manipulate experimental models of hematological disorders so that they more accurately mirror what is observed in the clinical setting. Despite these technological advances, the characterization of crucial genes for benign or malignant hematological disorders remains challenging, given the dynamic nature of the hematopoietic system and the genetic heterogeneity of these disorders. To overcome this limitation, genome-editing technologies have been developed to manipulate the genome specifically via deletion, insertion, or modification of targeted loci. These technologies have progressed swiftly, allowing their common use to investigate genetic function in experimental hematology. Among them, homologous-recombination-mediated targeting technologies have facilitated the manipulation of specific loci by generating knock-out and knock-in models. Despite promoting significant advances in our understanding of the molecular mechanisms involved in hematology, these inefficient, time-consuming, and labor-intensive approaches did not permit the development of cellular or animal models, recapitulating the complexity of hematological disorders. On October 26, 2016, Drs. Ben Ebert and Chad Cowan shared their knowledge of and experience with the utilization of CRISPR for models of myeloid malignancy, disease, and novel therapeutics in an International Society for Experimental Hematology webinar titled "Utility of CRISPR/Cas9 Systems in Hematology Research." Here, we provide an overview of the topics they covered, including their insights into the novel applications of the technique and its strengths and limitations. Copyright © 2017 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Evaluation of the reusing of MGO-C refractory brick in refractory mixes

International Nuclear Information System (INIS)

Silva, R.D.S. da; Braganca, S.R.

2012-01-01

The residue from the use of MgO-C refractories in electric arc furnace presents, mostly, magnesium oxide in its composition and some slag contamination and impurities from the process of electrofusion scrap iron/steel. In this study, it was studied the characteristics of this residue and reused through its introduction into a commercial refractory mix, employed as material of coating and repair. This refractory mix was tested by thermogravimetric analysis, compressive strength, evaluation of plasticity and porosity as well as aspects of its installation, such as adhesion in situ. Results showed that there potential for reuse with the introduction of the waste in commercial mix was 30%, with little loss of compressive strength and plasticity. (author)

Hematological abnormalities in adult patients with Down's syndrome.

LENUS (Irish Health Repository)

McLean, S

2012-02-01

BACKGROUND: There is a paucity of data regarding hematological abnormalities in adults with Down\\'s syndrome (DS). AIMS: We aimed to characterize hematological abnormalities in adult patients with DS and determine their long-term significance. METHODS: We retrospectively studied a cohort of nine DS patients referred to the adult hematology service in our institution between May 2001 and April 2008. Data collected were: full blood count (FBC), comorbidities, investigations performed, duration of follow-up and outcome to most recent follow-up. RESULTS: Median follow-up was 26 months (9-71). Of the nine patients, two had myelodysplastic syndrome (MDS) at presentation. Of these, one progressed, with increasing marrow failure, and requiring support with transfusions and gCSF. The remaining eight patients, with a variety of hematological abnormalities including leukopenia, macrocytosis, and thrombocytopenia, had persistently abnormal FBCs. However there was no evidence of progression, and no patient has evolved to acute myeloid leukemia (AML). CONCLUSIONS: MDS is a complication of DS and may require supportive therapy. However, minor hematological abnormalities are common in adult DS patients, and may not signify underlying marrow disease.

Cost-effectiveness of cetuximab and panitumumab for chemotherapy-refractory metastatic colorectal cancer.

Science.gov (United States)

Carvalho, Adriana Camargo; Leal, Frederico; Sasse, Andre Deeke

2017-01-01

Cetuximab and panitumumab are monoclonal antibodies targeting the epidermal growth factor receptor. Both drugs are active against RAS wild type metastatic colorectal cancer after chemotherapy failure, with similar efficacy and toxicity profiles. However, their cost and limited survival benefits may compromise incorporation in the Brazilian public healthcare system, the Unified Heath System (Sistema Único de Saúde) (SUS). A cost-effectiveness analysis was conducted using a Markov model from the Brazilian Public health perspective and a lifetime horizon in patients with RAS -wt mCRC. Transition probabilities and mortality rates were extracted from randomized studies. Treatment costs were obtained from price tables regulated by the Brazilian Health Ministry. The World Health Organization recommendation of three times GDP per capita was used to define the cost-effectiveness threshold. The use of cetuximab or panitumumab for chemotherapy-refractory mCRC patients resulted in 0.22 additional life-years relative to BSC, with incremental cost-effectiveness ratios (ICERs) of $58,240 and $52,772 per LY, respectively. That exceeds the pre-specified threshold for cost-effectiveness. Acquisition of biological agents was the major driver of increased costs. Our economic evaluation demonstrates that both cetuximab and panitumumab are not a cost-effective approach in RAS-wt mCRC patients. Discussion about drug price should be prioritized to enable incorporation of these monoclonal antibodies in the SUS.

Hormone-refractory prostate cancer and the skeleton

NARCIS (Netherlands)

Soerdjbalie-Maikoe, Vidija

2006-01-01

Prostate cancer is the second most common cancer in men in the UK. Androgen ablation with luteinising hormone-releasing hormone agonists (LHRH agonists) alone, or in combination with anti-androgens is the standard treatment for men with metastatic prostate cancer. Unfortunately, despite maximal

Radiation hematology

International Nuclear Information System (INIS)

Zherbin, E.A.; Chukhlovin, A.B.

1989-01-01

State-of-the-Art ofl radiation hematology and review of the problems now facing this brauch of radiobiology and nuclear medicine are presented. Distortion of division and maturation of hemopoiesis parent cells is considered as main factor of radiopathology for hematopoetic system. Problems of radiation injury and functional variation of hematopoetic microenvironment cell populations are discussed. 176 figs.; 23 figs.; 18 tabs

Telomere dynamics and cytogenetic changes in human hematologic neoplasias: a working hypothesis.

Science.gov (United States)

Ohyashiki, K; Ohyashiki, J H

1997-03-01

Chromosome termini, termed telomeres, provide important protection to avoid loss of master gene(s) that may exist at subtelomeric regions. Moreover, erosion of telomeres by cell division through end-replication problems resulted in telomeric-associated cytogenetic aberrations. To maintain a telomere length related to cell immortality, telomerase activity is upregulated in cancer cells, therefore, telomerase is considered to be a new marker of neoplasias. In this paper, we review and make suggestions regarding key aspects of telomere dynamics in both normal hematopoiesis and in malignant hematologic diseases.

Vorinostat in solid and hematologic malignancies

Directory of Open Access Journals (Sweden)

Richon Victoria M

2009-07-01

Full Text Available Abstract Vorinostat (Zolinza®, a histone deacetylase inhibitor, was approved by the US Food and Drug Administration in October 2006 for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies. This review summarizes evidence on the use of vorinostat in solid and hematologic malignancies and collated tolerability data from the vorinostat clinical trial program. Pooled vorinostat clinical trial data from 498 patients with solid or hematologic malignancies show that vorinostat was well tolerated as monotherapy or combination therapy. The most commonly reported drug-related adverse events (AEs associated with monotherapy (n = 341 were fatigue (61.9%, nausea (55.7%, diarrhea (49.3%, anorexia (48.1%, and vomiting (32.8%, and Grade 3/4 drug-related AEs included fatigue (12.0%, thrombocytopenia (10.6%, dehydration (7.3%, and decreased platelet count (5.3%. The most common drug-related AEs observed with vorinostat in combination therapy (n = 157, most of whom received vorinostat 400 mg qd for 14 days were nausea (48.4%, diarrhea (40.8%, fatigue (34.4%, vomiting (31.2%, and anorexia (20.4%, with the majority of AEs being Grade 2 or less. In Phase I trials, combinations with vorinostat were generally well tolerated and preliminary evidence of anticancer activity as monotherapy or in combination with other systemic therapies has been observed across a range of malignancies. Ongoing and planned studies will further evaluate the potential of vorinostat in combination therapy, including combinations with radiation, in patients with diverse malignancy types, including non-small-cell lung cancer, glioblastoma multiforme, multiple myeloma, and myelodysplastic syndrome.

Cost Effectiveness Analysis of Different Management Strategies between Best Supportive Care and Second-line Chemotherapy for Platinum-resistant or Refractory Ovarian Cancer.

Science.gov (United States)

Luealon, Phanida; Khempech, Nipon; Vasuratna, Apichai; Hanvoravongchai, Piya; Havanond, Piyalamporn

2016-01-01

There is no standard treatment for patients with platinum-resistant or refractory epithelial ovarian cancer. Single agent chemotherapies have evidence of more efficacy and less toxicity than combination therapy. Most are very expensive, with appreciable toxicity and minimal survival. Since it is difficult to make comparison between outcomes, economic analysis of single-agent chemotherapy regimens and best supportive care may help to make decisions about an appropriate management for the affected patients. To evaluate the cost effectiveness of second-line chemotherapy compared with best supportive care for patients with platinum-resistant or refractory epithelial ovarian cancer. A Markov model was used to estimate the effectiveness and total costs associated with treatments. The hypothetical patient population comprised women aged 55 with platinum-resistant or refractory epithelial ovarian cancer. Four types of alternative treatment options were evaluated: 1) gemcitabine followed by BSC; 2) pegylated liposomal doxorubicin (PLD) followed by BSC; 3) gemcitabine followed by topotecan; and 4) PLD followed by topotecan. Baseline comparator of alternative treatments was BSC. Time horizon of the analysis was 2 years. Health care provider perspective and 3% discount rate were used to determine the costs of medical treatment in this study. Quality-adjusted life-years (QALY) were used to measure the treatment effectiveness. Treatment effectiveness data were derived from the literature. Costs were calculated from unit cost treatment of epithelial ovarian cancer patients at various stages of disease in King Chulalongkorn Memorial Hospital (KCMH) in the year 2011. Parameter uncertainty was tested in probabilistic sensitivity analysis by using Monte Carlo simulation. One-way sensitivity analysis was used to explore each variable's impact on the uncertainty of the results. Approximated life expectancy of best supportive care was 0.182 years and its total cost was 26,862 Baht. All

Hematological parameters after acute radiation injury

International Nuclear Information System (INIS)

Hirashima, Kunitake

1989-01-01

According to clinical experiences of radiation accidents during the past two decades, utilization of measured hematologic changes as a direcrt indicator of the severity of radiation injury provides important information for diagnosis and prognostic evaluation in individual cases. Hematologic changes can be described in terms of prognostic categories based on the possible outcome of the acute radiation syndrome. The five categories suggested by Wald according to the grade of severity. By the actual application of this category to our experience of the 1971 Chiba accident of exposure to irridium 192, it was proved that the estimated dose was well correlated to the value by cytogenetic analysis and physical estimation used of thermo-luminescence phenomena. In hematological parameters, a decrease of lymphocytes occurs whithin 24 hours after the exposure. The level of this early lymphopenia is regarded as one of the best indicators of severity of radiation injury. For the decision of therapeutic procedures, however, the total granulocyte count and platelet count are more valuable to exclude severe infection and bleeding symptoms occurred one month after the exposure. The limitation of the approach by hematologic data must exist in the case exposed in a non-uniform fashion. To overwhelm this difficulty, the application of rapid marrow scanning by short-lived RI such as 52 Fe is expected and the bone marrow imaging by magnetic resonance studies is more exciting. For more sensitive and technically easy-drived methods detecting hematologic injury, our new method of detecting micro-nucleus in polychromatic erythroblasts from cultured erythroid colonies from peripheral blood is now developing. Preliminary data have shown the sensitivity of this method is comparable to the cytogenetic study of pheripheral lymphocytes. (author)

The management of metastatic radioiodine-refractory differentiated thyroid cancer requires an integrated approach including both directed and systemic therapies.

Science.gov (United States)

Cooray, Shamil D; Topliss, Duncan J

2017-01-01

A 58-year-old man with metastatic radioiodine-refractory differentiated thyroid cancer (DTC) presented with left thigh and right flank numbness. He had known progressive and widespread bony metastases, for which he received palliative radiotherapy, and multiple bilateral asymptomatic pulmonary metastases. CT scan and MRI of the spine revealed metastases at right T10-L1 vertebrae with extension into the central canal and epidural disease at T10 and T11 causing cord displacement and canal stenosis but retention of spinal cord signal. Spinal surgery was followed by palliative radiotherapy resulting in symptom resolution. Two months later, sorafenib received approval for use in Australia and was commenced and up-titrated with symptomatic management of mild adverse effects. Follow-up CT scan three months after commencement of sorafenib revealed regression of pulmonary metastases but no evident change in most bone metastases except for an advancing lesion eroding into the right acetabulum. The patient underwent a right total hip replacement, intra-lesional curettage and cementing. After six months of sorafenib therapy, CT scanning showed enlarging liver lesions with marked elevation of serum thyroglobulin. Lenvatinib was commenced and sorafenib was ceased. He now has stable disease with a falling thyroglobulin more than 5 years after metastatic radioiodine-refractory DTC was diagnosed. In DTC, 5% of distant metastases become radioiodine-refractory, resulting in a median overall survival of 2.5-3.5 years. Tyrosine kinase inhibitor (TKI) therapy has recently been demonstrated to increase progression-free survival in these patients but poses some unique management issues and is best used as part of an integrated approach with directed therapy. Directed therapies may have greater potential to control localised disease and related symptoms when compared to systemic therapies.Consider TKI therapy in progressive disease where benefits outweigh risks.Active surveillance and

Compatibility of refractory materials with boiling sodium

International Nuclear Information System (INIS)

Meacham, S.A.

1976-01-01

The program employed to determine the compatibility of commercially available refractories with boiling sodium is described. The effects of impurities contained within the refractory material, and their relations with the refractory's physical stability are discussed. Also, since consideration of refractories for use as an insulating material within Liquid Metal Fast Breeder Reactor Plants (LMFBR's) is currently under investigation; recommendations, based upon this program, are presented

REFRACTORY THROMBOCYTOPENIA AND NEUTROPENIA: A DIAGNOSTIC CHALLENGE

OpenAIRE

Emmanuel Gyan; François Dreyfus; Pierre Fenaux

2015-01-01

Background. The 2008 WHO classification identified refractory cytopenia with unilineage dysplasia (RCUD) as a composite entity encompassing refractory anemia, refractory thrombocytopenia (RT), and refractory neutropenia (RN), characterized by 10% or more dysplastic cells in the bone marrow respective lineage. The diagnosis of RT and RN is complicated by several factors.  Diagnosing RT first requires exclusion of familial thrombocytopenia, chronic auto-immune thrombocytopenia, concomitant medi...

Verification and quality control of routine hematology analyzers

NARCIS (Netherlands)

Vis, J Y; Huisman, A

2016-01-01

Verification of hematology analyzers (automated blood cell counters) is mandatory before new hematology analyzers may be used in routine clinical care. The verification process consists of several items which comprise among others: precision, accuracy, comparability, carryover, background and

Refractory bin for burning

Energy Technology Data Exchange (ETDEWEB)

McPherson, D.L.; McPherson, T.L.

1989-12-26

This patent describes a refractory bin. It has a generally rectangular horizontal cross sectional configuration. It has wall structures each comprising an upper and a lower pair of elongated horizontal vertically spaced generally parallel support beams each having a vertical flange defining a support edge along its upper surface, a first generally rectangular refractory panel arranged with its lower edge at the bottom of the bin and with its outer surface in flat face contacting relation with the vertical flanges of the lower pair of support beams, a plurality of brackets each having a horizontal part and a vertical part and being secured to the outer surface of the first refractory panel.

Report on the International Society for Laboratory Hematology Survey on guidelines to support clinical hematology laboratory practice.

Science.gov (United States)

Hayward, C P M; Moffat, K A; George, T I; Proytcheva, M; Iorio, A

2016-05-01

Given the importance of evidence-based guidelines in health care, we surveyed the laboratory hematology community to determine their opinions on guideline development and their experience and interest in developing clinical hematology laboratory practice guidelines. The study was conducted using an online survey, distributed to members of the International Society for Laboratory Hematology (ISLH) in 2015, with analysis of collected, anonymized responses. A total of 245 individuals participated. Most worked in clinical and/or research laboratories (83%) or industry (11%). 42% felt there were gaps in current guidelines. The majority (58%) recommended that ISLH engages its membership in guideline development. Participants differed in their familiarity with, and use of, different organizations' guidelines. Participants felt it was important to follow best practice recommendations on guideline development, including engagement of experts, statement about conflict of interests and how they were managed, systematic review and grading evidence for recommendations, identifying recommendations lacking evidence or consensus, and public input and peer review of the guideline. Moreover, it was considered important to provide guidelines free of charge. Industry involvement in guidelines was considered less important. The clinical laboratory hematology community has high expectations of laboratory practice guidelines that are consistent with recent recommendations on evidence-based guideline development. © 2016 John Wiley & Sons Ltd.

Regional approaches to the management of patients with advanced, radioactive iodine-refractory differentiated thyroid carcinoma.

Science.gov (United States)

Brose, Marcia S; Smit, Johannes; Capdevila, Jaume; Elisei, Rossella; Nutting, Christopher; Pitoia, Fabian; Robinson, Bruce; Schlumberger, Martin; Shong, Young Kee; Takami, Hiroshi

2012-09-01

For patients with advanced, radioactive iodine-refractory differentiated thyroid cancer, current treatment guidelines recommend clinical trial enrollment or small-molecule kinase inhibitor therapy. However, details of patient management vary between countries depending on trial availability and national regulatory policies. Insufficient clinical trial data and variable disease characteristics challenge the creation of universal guidelines, and treatment plans often reflect regional influences. A multidisciplinary, multiregional panel of experts met to discuss regional approaches to managing patients with advanced, radioactive iodine-refractory differentiated thyroid cancer and the potential impact of emerging therapies on current treatment strategies. Despite process-oriented regional differences, the decision-making strategies were similar. Multidisciplinary teams used to manage high-risk patients varied in composition across regions, particularly regarding the responsible physician's specialty. Cytotoxic chemotherapy was viewed as limited in clinical benefit, and targeted agents as attractive, based on promising data. Panel members support clinical trial enrollment as the preferred treatment strategy for managing these patients.

Molecular Profiling of Refractory Adrenocortical Cancers and Predictive Biomarkers to Therapy

Directory of Open Access Journals (Sweden)

Sherri Z. Millis

2015-01-01

Full Text Available Purpose Current first-line chemotherapy for patients with metastatic adrenocortical cancer (ACC includes doxorubicin, etoposide, cisplatin, and mitotane with a reported response rate of only 23.2%. New therapeutic leads for patients with refractory tumors are needed; there is no standard second-line treatment. Methods Samples from 135 ACC tumors were analyzed by immunohistochemistry, in situ hybridization (FISH or CISH, and/or gene sequencing at a single commercial reference laboratory (Caris Life Sciences to identify markers associated with drug sensitivity and resistance. Results Overexpression of proteins related to demonstrated chemotherapy sensitivity or resistance included topoisomerase 1, progesterone receptor, and topoisomerase 2-alpha in 46%, 63%, and 42% of cases, respectively. Loss of excision repair cross-complementary group 1 (ERCC1, phosophatase and tensin homolog, O(6-methylguanine-methyltransferase, and ribonucleotide reductase M1 (RRM1 was identified in 56%, 59%, 71%, and 58% of cases, respectively. Other aberrations included overexpression of programmed death-ligand 1 or programmed cell death protein 1 tumor-infiltrating lymphocytes in >40% of cases. In all, 35% of cases had a mutation in the canonical Wnt signaling pathway (either CTNNB1 or APC and 48% had a mutation in TP53. No other genomic alterations were identified. Conclusion Biomarker alterations in ACC may be used to direct therapies, including recommendations for and potential resistance of some patients to traditional chemotherapies, which may explain the low response rate in the unselected population. Limited outcomes data support the use of mitotane and platinum therapies for patients with low levels of the proteins RRM1 and ERCC1.

Hematology laboratory standardization: a plan for harmonization in Asia.

Science.gov (United States)

Bunyaratvej, A; Tatsumi, N; Funahara, Y

1999-01-01

Hematology laboratory is generally required in the hospital. At the macroscale, hematology laboratories have served a large number of population. In Asia, more than 3,000 million people are potentially to use the hematology laboratory service, particularly the complete blood count. Since 1970s, automated technology has been introduced to Asia and as years passed by, technology diversity is increasing. However, there are considerable number of hematology laboratories that have no automated machine. They are still relied on manual technology which is still variable in spectrophotometer for hemoglobin determination, centrifuge for hematocrit and diluting pipet for cell counting. In particular, blood smear preparation and interpretation are very difficult to control for standardization from person to person and laboratory to laboratory. Different methodology and a large population in the huge geographical area in Asia, the agreement of standard criteria is greatly important. This report has shown strategy and action plan to reach the goal of hematology laboratory standardization in Asia.

Soluble endothelial protein C receptor (sEPCR) is likely a biomarker of cancer-associated hypercoagulability in human hematologic malignancies

International Nuclear Information System (INIS)

Ducros, Elodie; Mirshahi, Shah Soltan; Faussat, Anne-Marie; Mirshahi, Pezhman; Dimicoli, Sophie; Tang, Ruoping; Pardo, Julia; Ibrahim, Jdid; Marie, Jean-Pierre; Therwath, Amu; Soria, Jeannette; Mirshahi, Massoud

2012-01-01

Elevated plasma level of soluble endothelial protein C receptor (sEPCR) may be an indicator of thrombotic risk. The present study aims to correlate leukemia-associated hypercoagulability to high level plasma sEPCR and proposes its measurement in routine clinical practice. EPCR expressions in leukemic cell lines were determined by flow cytometry, immunocytochemistry, and reverse transcription polymerase chain reaction (RT-PCR). EPCR gene sequence of a candidate cell line HL-60 was also determined. Plasma samples (n = 76) and bone marrow aspirates (n = 72) from 148 patients with hematologic malignancies and 101 healthy volunteers were analyzed by enzyme-linked immunosorbent assay (ELISA) via a retrospective study for sEPCR and D-dimer. All leukemic cell lines were found to express EPCR. Also, HL-60 EPCR gene sequence showed extensive similarities with the endothelial reference gene. All single nucleotide polymorphisms (SNPs) originally described and some new SNPs were revealed in the promoter and intronic regions. Among these patients 67% had plasma sEPCR level higher than the controls (100 ± 28 ng/mL), wherein 16.3% patients had experienced a previous thrombotic event. These patients were divided into: group-1 (n = 45) with amount of plasmatic sEPCR below 100 ng/mL, group-2 (n = 45) where the concentration of sEPCR was between 100 and 200, and group-3 (n = 20) higher than 200 ng/mL. The numbers of thrombotic incidence recorded in each group were four, six, and eight, respectively. These results reveal that EPCR is expressed not only by a wide range of human malignant hematological cells but also the detection of plasma sEPCR levels provides a powerful insight into thrombotic risk assessment in cancer patients, especially when it surpasses 200 ng/mL

Value of innovation for hematologic malignancies.

Science.gov (United States)

Monia, Marchetti

2016-01-01

Several novel drugs are dramatically improving both lifespan and quality-of-life of patients with blood cancers. Prolonged disease duration and increased treatment costs for hematologic malignancies impose a relevant economic burden onto healthcare services, despite the low incidence of blood cancers. Therefore, an appropriate paradigm for valuing 'innovation' is urgently required in order to refine pricing and reimbursement decisions. Cost-per-QALY-gained is still the standard metric for assessing the 'incremental' value of new drugs; however, the high number of 'comparator' therapies and the huge variety of treatment sequences make plain two-treatment comparisons sub-optimal, while multiple-treatment and multiple-sequence comparisons require complex and less-transparent decision models. A repository of standard backbones for decision models might allow benchmarking and comparability among cost-effectiveness analyses; however, an international effort is required to build it up. Deontology recommends that hematologists act in optimizing healthcare resources while preserving patient-physician alliance, but clinical practice guidelines do not support doctors in balancing cost against clinical outcomes. Decision models of chronic blood cancers unexpectedly proved that cost might be an appropriate value for innovation if treatments avoided severe toxicity and further lines of treatments, despite the eventually long duration of treatment and the competing risk of death due to comorbidity and old age. The improved transparency of decision models allows sharing of relevant structural and analytic parameters (i.e., time horizon, comparator treatments, hierarchy of end-point, assumptions, source of data, sub-group analyses) by stakeholders, physicians and patients, making health economics a noble 'translator' of values for innovation.

Clinical and dosimetric predictors of acute hematologic toxicity in rectal cancer patients undergoing chemoradiotherapy

International Nuclear Information System (INIS)

Yang, T. Jonathan; Oh, Jung Hun; Apte, Aditya; Son, Christina H.; Deasy, Joseph O.; Goodman, Karyn A.

2014-01-01

Background and purpose: To identify clinical and dosimetric factors associated with hematologic toxicity (HT) during chemoradiotherapy for rectal cancer. Materials and methods: We analyzed 120 rectal cancer patients treated with neoadjuvant pelvic radiotherapy (PRT) with concurrent 5-fluorouracil-based chemotherapy. The coxal (ilium, ischium, and pubis) bone marrow (BM), sacral BM, and femoral BM were contoured and dose-volume parameters were extracted. Associations between cell count trend and clinical predictors were tested using repeated-measures analysis of variance (ANOVA) test. Associations between clinical variables, Vx (percentage volume receiving x Gy), and cell count ratio at nadir were tested using linear regression models. Results: Nadirs for white blood cell count (WBC), absolute neutrophil count (ANC), and platelets (PLT) occurred in the second week of PRT and the fifth week for hemoglobin and absolute lymphocyte count (ALC). Using cell count ratio, patients treated with 3DCRT had a lower WBC ratio trend during PRT compared to patients treated with IMRT (p = 0.04), and patients ⩾59 years of age had a lower hemoglobin ratio trend during PRT (p = 0.02). Using absolute cell count, patients treated with 3DCRT had lower ANC cell count trend (p = 0.03), and women had lower hemoglobin cell count trend compared to men (p = 0.03). On univariate analysis, use of 3DCRT was associated with a lower WBC ratio at nadir (p = 0.02). On multiple regression analysis using dosimetric variables, coxal BM V45 (p = 0.03) and sacral BM V45 (p = 0.03) were associated with a lower WBC and ANC ratio at nadir, respectively. Conclusions: HT trends during PRT revealed distinct patterns: WBC, ANC, and PLT cell counts reach nadirs early and recover, while hemoglobin and ALC decline steadily. Patients who were treated with 3DCRT and older patients experienced lower cell count ratio trend during PRT. Dosimetric constraints using coxal BM V45 and sacral BM V45 can be considered

Severe nivolumab-induced pneumonitis preceding durable clinical remission in a patient with refractory, metastatic lung squamous cell cancer: a case report

Directory of Open Access Journals (Sweden)

Hong Li

2017-02-01

Full Text Available Abstract Background Programmed cell death 1 (PD-1 and its ligand 1 (PD-L1 inhibitors have quickly become standard of care for patients with advanced non-small cell lung cancer and increasing numbers of other cancer types. In this report, we discuss the clinical history, pathological evaluation, and genomic findings in a patient with metastatic lung squamous cell cancer (SCC who developed severe nivolumab-induced pneumonitis preceding durable clinical remission after three doses of nivolumab. Case presentation A patient with chemotherapy-refractory, metastatic lung SCC developed symptomatic pneumonitis by week 4 after nivolumab treatment, concurrently with onset of a potent antitumor response. Despite discontinuation of nivolumab after three doses and the use of high dose oral corticosteroids for grade 3 pneumonitis, continued tumor response to a complete remission by 3 months was evident by radiographic assessment. At the time of this submission, the patient has remained in clinical remission for 14 months. High PD-L1 expression by immunohistochemistry staining was seen in intra-alveolar macrophages and viable tumor cells in the pneumonitis and recurrent tumor specimens, respectively. Tumor genomic profiling by FoundationOne targeted exome sequencing revealed a very high tumor mutation burden (TMB corresponding to 95–96 percentile in lung SCC, i.e., 87.4–91.0 and 82.9 mut/Mb, respectively, in pre- and post-nivolumab tumor specimens. Except for one, the 13 functional genomic alterations remained the same in the diagnostic, recurrent, and post-treatment, relapsed tumor specimens, suggesting that nivolumab reset the patient’s immune system against one or more preexisting tumor-associated antigens (TAAs. One potential TAA candidate is telomerase reverse transcriptase (TERT in which an oncogenic promoter -146C>T mutation was detected. Human leukocyte antigen (HLA typing revealed HLA-A*0201 homozygosity, which is the prevalent HLA class I

A Review on hematology and hemoglobin of fish

Directory of Open Access Journals (Sweden)

Ebru YILMAZ

2015-01-01

Full Text Available Determination of hematological parameters of fish living in natüre helps to recognize population and to determinate of pollutants in the aquatic environment. In this review, hematological parameters of fish, fish hemoglobin and the Bohr effect were given information.

131I-MIBG followed by consolidation with busulfan, melphalan and autologous stem cell transplantation for refractory neuroblastoma.

Science.gov (United States)

French, Sarah; DuBois, Steven G; Horn, Biljana; Granger, Meaghan; Hawkins, Randall; Pass, Amy; Plummer, Ellen; Matthay, Katherine

2013-05-01

(131) I-metaiodobenzylguanidine (MIBG) produces a 37% response rate in relapsed/refractory neuroblastoma, and could be used to improve remission status prior to myeloablative chemotherapy with autologous stem cell transplant (ASCT). The purpose of our report was to evaluate safety and response with MIBG therapy followed by myeloablative busulfan and melphalan (BuMel) with ASCT in patients with refractory neuroblastoma. Retrospective chart review was done on patients treated with MIBG (18 mCi/kg) on Day 1 and ASCT on day 14. Six to eight weeks after MIBG, patients without progressive disease received IV busulfan on days -6 to -2 (target Css 700-900), melphalan (140 mg/m2 IV) on day -1, and ASCT on Day 0. Response and toxicity were evaluated after MIBG and again after myeloablative therapy. Eight patients completed MIBG/ASCT followed by BuMel/ASCT. MIBG was well tolerated, with grade 3 or 4 non-hematologic toxicity limited to one patient with sepsis. Grade 3 mucositis occurred in six patients after BuMel/ASCT. One patient developed sinusoidal obstructive syndrome (SOS) and died 50 days post-ASCT following myeloablative conditioning. All patients engrafted neutrophils (median 16.5 days) and platelets (median 32 days) after BuMel, excluding the patient with SOS. After all therapy, there were three complete, two partial, and one minor response in seven evaluable patients. MIBG at doses up to 18 mCi/kg can be safely administered 6 weeks prior to a BuMel consolidative regimen for refractory neuroblastoma. Preceding MIBG did not impair engraftment following BuMel. This regimen is being further evaluated in a Children's Oncology Group (COG) trial. Copyright © 2012 Wiley Periodicals, Inc.

Refractory Depression, Fatigue, Irritable Bowel Syndrome, and Chronic Pain: A Functional Medicine Case Report.

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Plotnikoff, Gregory; Barber, Melissa

2016-01-01

Single-disorder or single-organ-system clinical practice guidelines are often of limited usefulness in guiding effective management of patients with chronic multidimensional signs and symptoms. The presence of multiple long-standing medical problems in a given patient despite intensive medical effort suggests that addressing systemic core imbalances could complement more narrowly focused approaches. A 72-year-old man experiencing longstanding depression, fatigue, irritable bowel syndrome, and chronic pain in the context of additional refractory illnesses was assessed and treated, guided by a system-oriented approach to underlying core imbalances termed functional medicine. This patient was referred from a team of clinicians representing primary care, cardiology, gastroenterology, hematology, and psychology. Prior treatment had been unsuccessful in managing multiple chronic comorbidities. Diagnostic assessment included comprehensive stool and nutritional/metabolic laboratory testing. The blood-, urine-, or stool-based measurements of relevant markers for multiple systemic issues, including digestion/absorption, inflammation, oxidative stress, and methylation, identified previously unrecognized root causes of his constellation of symptoms. These functional measurements guided rational recommendations for dietary choices and supplementation. The patient experienced steady and significant improvement in his mental health, fatigue, chronic pain, and irritable bowel syndrome-as well as the unexpected resolution of his chronic idiopathic pancytopenia. The success in this case suggests that other patients with chronic, complex, and treatment-refractory illness may benefit from a system-oriented assessment of core imbalances guided by specialized nutritional/metabolic and digestive laboratory testing.

Hematological profile of sickle cell disease from South Gujarat, India

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Sanjeev Shyam Rao

2012-05-01

Full Text Available The aim of this study was to determine hematological profile of sickle cell disease (SCD from Surat, South Gujarat, India. This prospective cross-sectional study was conducted in the Department of Pediatrics and Sickle Cell Anemia Laboratory, Faculty of Pathology, Government Medical College, Surat, India, between July 2009 and December 2010. Patients included in this study were in their steady state for a long period of time without any symptoms related to SCD or other diseases which could affect the hematological parameters. Venous blood of all patients was collected in ethylenediaminetetraacetic acid and hematological indices were measured. Thirty-three subjects homozygous in all were studied for their hematological parameters for sickle cell anemia. Moderate to severe anemia, low mean cell volume and high foetal hemoglobin dominate the hematological profile of SCD children.

INFLUENZA AND PNEUMOCOCCAL VACCINATION IN HEMATOLOGICAL MALIGNANCIES: A SYSTEMATIC REVIEW OF EFFICACY, EFFECTIVENESS AND SAFETY

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Giuseppe La Torre

2016-09-01

Full Text Available Background The risk of getting influenza and pneumococcal disease is higher in cancer patients and serum antibody levels tend to be lower in patients with hematological malignancy. Objective To asses flu and pneumococcal vaccinations efficacy, effectiveness and safety in onco-hematological patients. Methods Two systematic reviews and possible meta-analysis were conducted to summarize the results of all primary study in scientific literature about flu and pneumococcal vaccine in onco-hematological patients. Literature searches were performed using Pub-Med and Scopus databases. StatsDirect 2.8.0 was used for the analysis. Results 23 and 26 studies were collected respectively for flu and pneumococcal vaccinations. Protection rate of booster dose was 30% (95% CI = 6.2- 61% for H1N1. Pooled prevalence protection rate of H3N2 and B was available for meta-analysis only for first dose, 42.6% (95% CI = 23.2 – 63.3 % and 39.6 % (95% CI = 26%- 54.1% for H3N2 and B, respectively. Response rate of booster dose resulted 35% (95% CI = 19.7-51.2% for H1N1, 23% (95% CI = 16.6-31.5% for H3N2, 29% (95% CI = 21.3- 37% for B. Conclusion Despite low rate of response, flu and pneumococcal vaccines are worthwhile for patients with hematological malignancies. Patients undergoing chemotherapy in particular rituximab, splenectomy, transplant recipient had lower and impaired response. No serious adverse events were reported for both vaccines.

Emergency Surgery for Refractory Status Epilepticus.

Science.gov (United States)

Botre, Abhijeet; Udani, Vrajesh; Desai, Neelu; Jagadish, Spoorthy; Sankhe, Milind

2017-08-15

Management of refractory status epilepticus in children is extremely challenging. Two children with medically refractory status epilepticus, both of whom had lesional pathology on MRI and concordant data on EEG and PET scan. Emergency hemispherotomy performed in both patients. A complete, sustained seizure freedom obtained postoperatively. Emergency surgery is a treatment option in selected cases of drug refractory status epilepticus with lesional pathology and concordant data.

Current advances in T-cell-based cancer immunotherapy

Science.gov (United States)

Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

2015-01-01

Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy. PMID:25524383

BEST-TEST2: assessment of hematology trainee knowledge of transfusion medicine.

Science.gov (United States)

Lin, Yulia; Tinmouth, Alan; Mallick, Ranjeeta; Haspel, Richard L

2016-02-01

As transfusion is a common therapy and key component in every hematologist's practice, hematology training programs should dedicate significant time and effort to delivering high-quality transfusion medicine education to their trainees. The current state of hematology trainee knowledge of transfusion medicine is not known. A validated assessment tool developed by the Biomedical Excellence for Safer Transfusion (BEST) Collaborative was used to assess prior transfusion medicine education, attitudes, perceived ability, and transfusion medicine knowledge of hematology trainees. A total of 149 hematology trainees at 17 international sites were assessed. The overall mean exam score was 61.6% (standard deviation, 13.4%; range, 30%-100%) with no correlation in exam scores with postgraduate year or previous transfusion medicine education in medical school or internal medicine residency. However, better scores correlated with 3 or more hours of transfusion medicine education (p = 0.0003) and perceived higher-quality education during hematology training (p = 0.03). Hematology trainees at US sites, where hematology is often combined with oncology training, had statistically lower scores than trainees at non-US sites (56.2% vs. 67.4%; p hematology training programs to reevaluate the quality and quantity of transfusion medicine training and can assist in the development of targeted curricula. © 2015 AABB.

Breed-specific hematological phenotypes in the dog: a natural resource for the genetic dissection of hematological parameters in a mammalian species.

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Jennifer Lawrence

Full Text Available Remarkably little has been published on hematological phenotypes of the domestic dog, the most polymorphic species on the planet. Information on the signalment and complete blood cell count of all dogs with normal red and white blood cell parameters judged by existing reference intervals was extracted from a veterinary database. Normal hematological profiles were available for 6046 dogs, 5447 of which also had machine platelet concentrations within the reference interval. Seventy-five pure breeds plus a mixed breed control group were represented by 10 or more dogs. All measured parameters except mean corpuscular hemoglobin concentration (MCHC varied with age. Concentrations of white blood cells (WBCs, neutrophils, monocytes, lymphocytes, eosinophils and platelets, but not red blood cell parameters, all varied with sex. Neutering status had an impact on hemoglobin concentration, mean corpuscular hemoglobin (MCH, MCHC, and concentrations of WBCs, neutrophils, monocytes, lymphocytes and platelets. Principal component analysis of hematological data revealed 37 pure breeds with distinctive phenotypes. Furthermore, all hematological parameters except MCHC showed significant differences between specific individual breeds and the mixed breed group. Twenty-nine breeds had distinctive phenotypes when assessed in this way, of which 19 had already been identified by principal component analysis. Tentative breed-specific reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis. This study represents the first large-scale analysis of hematological phenotypes in the dog and underlines the important potential of this species in the elucidation of genetic determinants of hematological traits, triangulating phenotype, breed and genetic predisposition.

Updates in Refractory Status Epilepticus

Science.gov (United States)

Mahulikar, Advait; Suchdev, Kushak; Shah, Aashit

2018-01-01

Refractory status epilepticus is defined as persistent seizures despite appropriate use of two intravenous medications, one of which is a benzodiazepine. It can be seen in up to 40% of cases of status epilepticus with an acute symptomatic etiology as the most likely cause. New-onset refractory status epilepticus (NORSE) is a recently coined term for refractory status epilepticus where no apparent cause is found after initial testing. A large proportion of NORSE cases are eventually found to have an autoimmune etiology needing immunomodulatory treatment. Management of refractory status epilepticus involves treatment of an underlying etiology in addition to intravenous anesthetics and antiepileptic drugs. Alternative treatment options including diet therapies, electroconvulsive therapy, and surgical resection in case of a focal lesion should be considered. Short-term and long-term outcomes tend to be poor with significant morbidity and mortality with only one-third of patients reaching baseline neurological status. PMID:29854452

Refractory status epilepticus

Directory of Open Access Journals (Sweden)

Sanjay P Singh

2014-01-01

Full Text Available Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED, i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits.

Refractory status epilepticus

Science.gov (United States)

Singh, Sanjay P; Agarwal, Shubhi; Faulkner, M

2014-01-01

Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED), i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs) and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits. PMID:24791086

Association of the blood eosinophil count with hematological malignancies and mortality

DEFF Research Database (Denmark)

Andersen, Christen Bertel L; Siersma, Volkert Dirk; Hasselbalch, Hans K

2015-01-01

Blood eosinophilia (≥0.5 × 109/l) may be an early sign of hematological malignancy. We investigated associations between levels of blood eosinophils and risks of hematological malignancies and mortality in order to provide clinically derived cut-offs for referral to specialist hematology care. Fr...

The nuclear industry and the risk of cancer in the Manche district - Cancer epidemiology and nuclear industry in the Manche district

International Nuclear Information System (INIS)

Laurent, Michel; Collignon, Albert; Bara, Simona; Degre, Delphine; Mouchel, Dominique; Poncet, Jean-Marc; Troussard, Xavier

2013-12-01

This document proposed a summarized version and a full version of a study on cancer epidemiology in the Manche district in which are located four nuclear sites of different nature and with different potential risks: the Flamanville nuclear plant (with the EPR under construction), the La Hague Areva nuclear fuel processing plant, the Manche storage site, and the Cherbourg arsenal. It describes the missions of the two cancer registries regarding the Manche region population (the general cancer registry for the Manche district, and the specialized registry of hematologic malignancies for the Basse-Normandie region), discusses the post-accidental management of a nuclear accident, presents the levels of the various basic indicators of cancer epidemiology survey (share of cancers in global mortality and factors of risk cancer, radio-induced cancers), compares cancer occurrence in the Manche district and in France and outlines some peculiarities of cancer occurrence in the Manche district, comments the cartography of cancer occurrence in the Manche district over the 1999-2010 period (solid cancers, hematologic malignancies)

Development of refractory concrete for extreme conditions

International Nuclear Information System (INIS)

Pundiene, I; Antonovich, V; Stonys, R; Demidova-Buiziniene, I

2011-01-01

Comparative analysis is provided for the properties of medium-cement refractory concrete with microsilica based on mullite filler in relation to different type of deflocculant. The effect of different deflocculants on refractory concrete structure formation, hydration, rheology, strength and heat resistance is discussed. Corrosion resistance test, determined that samples with hybrid deflocculant showed better resistance for slag penetration than samples with only the sodium tripolyphosphate or polycarboxylate ether deflocculant. Moreover, a composition of hybrid deflocculant let to control the rate of the hydration process and to get features of refractory refractory concrete.

High-Density Infrared Surface Treatments of Refractories

Energy Technology Data Exchange (ETDEWEB)

Tiegs, T.N.

2005-03-31

Refractory materials play a crucial role in all energy-intensive industries and are truly a crosscutting technology for the Industries of the Future (IOF). One of the major mechanisms for the degradation of refractories and a general decrease in their performance has been the penetration and corrosion by molten metals or glass. Methods and materials that would reduce the penetration, wetting, and corrosive chemistry would significantly improve refractory performance and also maintain the quality of the processed liquid, be it metal or glass. This report presents the results of an R&D project aimed at investigating the use of high-density infrared (HDI) heating to surface treat refractories to improve their performance. The project was a joint effort between Oak Ridge National Laboratory (ORNL) and the University of Missouri-Rolla (UMR). HDI is capable of heating the near-surface region of materials to very high temperatures where sintering, diffusion, and melting can occur. The intended benefits of HDI processing of refractories were to (1) reduce surface porosity (by essentially sealing the surface to prevent liquid penetration), (2) allow surface chemistry changes to be performed by bonding an adherent coating onto the underlying refractory (in order to inhibit wetting and/or improve corrosion resistance), and (3) produce noncontact refractories with high-emissivity surface coatings.

Determination of the most appropriate method for extrapolating overall survival data from a placebo-controlled clinical trial of lenvatinib for progressive, radioiodine-refractory differentiated thyroid cancer.

Science.gov (United States)

Tremblay, Gabriel; Livings, Christopher; Crowe, Lydia; Kapetanakis, Venediktos; Briggs, Andrew

2016-01-01

Cost-effectiveness models for the treatment of long-term conditions often require information on survival beyond the period of available data. This paper aims to identify a robust and reliable method for the extrapolation of overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer receiving lenvatinib or placebo. Data from 392 patients (lenvatinib: 261, placebo: 131) from the SELECT trial are used over a 34-month period of follow-up. A previously published criterion-based approach is employed to ascertain credible estimates of OS beyond the trial data. Parametric models with and without a treatment covariate and piecewise models are used to extrapolate OS, and a holistic approach, where a series of statistical and visual tests are considered collectively, is taken in determining the most appropriate extrapolation model. A piecewise model, in which the Kaplan-Meier survivor function is used over the trial period and an extrapolated tail is based on the Exponential distribution, is identified as the optimal model. In the absence of long-term survival estimates from clinical trials, survival estimates often need to be extrapolated from the available data. The use of a systematic method based on a priori determined selection criteria provides a transparent approach and reduces the risk of bias. The extrapolated OS estimates will be used to investigate the potential long-term benefits of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer patients and populate future cost-effectiveness analyses.

Atrial Fibrillation in Hematologic Malignancies, Especially After Autologous Hematopoietic Stem Cell Transplantation: Review of Risk Factors, Current Management, and Future Directions.

Science.gov (United States)

Mathur, Pankaj; Paydak, Hakan; Thanendrarajan, Sharmilan; van Rhee, Frits

2016-02-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with significant morbidity and mortality worldwide. In addition to well-established risk factors, cancer has been increasingly associated with the development of AF. Its increased occurrence in those with hematologic malignancies has been attributed to chemotherapeutic agents and autologous hematopoietic stem cell transplantation (AHSCT). Recently, a few studies have attempted to define the etiopathogenesis of AF in hematologic malignancies. The management of AF in these patients is challenging because of the concurrent complicating factors, such as thrombocytopenia, orthostatic hypotension, and cardiac amyloidosis. More studies are needed to define the management of AF, especially rate versus rhythm control and anticoagulation. Arrhythmias, in particular, AF, have been associated with an increased length of stay, increased intensive care unit admissions, and greater cardiovascular mortality. In the present review, we describe AF in patients with hematologic malignancies, the risk factors, especially after AHSCT, and the current management of AF. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetics Home Reference: iron-refractory iron deficiency anemia

Science.gov (United States)

... refractory iron deficiency anemia Iron-refractory iron deficiency anemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Iron-refractory iron deficiency anemia is one of many types of anemia , which ...

Hematology - Open TG-GATEs | LSDB Archive [Life Science Database Archive metadata

Lifescience Database Archive (English)

Full Text Available ivo tests. Data file File name: open_tggates_hematology.zip File URL: ftp://ftp.biosciencedbc.jp/archive/ope...n-tggates/LATEST/open_tggates_hematology.zip File size: 636 KB Simple search URL ...http://togodb.biosciencedbc.jp/togodb/view/open_tggates_hematology#en Data acquisition method - Data analysi

Refractory hypertension: definition, prevalence, and patient characteristics.

Science.gov (United States)

Acelajado, Maria Czarina; Pisoni, Roberto; Dudenbostel, Tanja; Dell'Italia, Louis J; Cartmill, Falynn; Zhang, Bin; Cofield, Stacey S; Oparil, Suzanne; Calhoun, David A

2012-01-01

Among patients with resistant hypertension (RHTN), there are those whose blood pressure (BP) remains uncontrolled in spite of maximal medical therapy. This retrospective analysis aims to characterize these patients with refractory hypertension. Refractory hypertension was defined as BP that remained uncontrolled after ≥3 visits to a hypertension clinic within a minimum 6-month follow-up period. Of the 304 patients referred for RHTN, 29 (9.5%) remained refractory to treatment. Patients with refractory hypertension and those with controlled RHTN had similar aldosterone levels and plasma renin activity (PRA). Patients with refractory hypertension had higher baseline BP (175±23/97±15 mm Hg vs 158±25/89±15 mm Hg; P=.001/.005) and heart rate, and higher rates of prior stroke and congestive heart failure. During follow-up, the BP of patients with refractory hypertension remained uncontrolled (168.4±14.8/93.8±17.7 mm Hg) in spite of use of an average of 6 antihypertensive medications, while those of patients with controlled RHTN decreased to 129.3±11.2/77.6±10.8 mm Hg. Spironolactone reduced the BP by 12.9±17.8/6.6±13.7 mm Hg in patients with refractory hypertension and by 24.1±16.7/9.2±12.0 mm Hg in patients with controlled RHTN. In patients with RHTN, approximately 10% remain refractory to treatment. Similar aldosterone and PRA levels and a diminished response to spironolactone suggest that aldosterone excess does not explain the treatment failure. © 2011 Wiley Periodicals, Inc.

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial

Science.gov (United States)

Rizvi, Naiyer A; Mazières, Julien; Planchard, David; Stinchcombe, Thomas E; Dy, Grace K; Antonia, Scott J; Horn, Leora; Lena, Hervé; Minenza, Elisa; Mennecier, Bertrand; Otterson, Gregory A; Campos, Luis T; Gandara, David R; Levy, Benjamin P; Nair, Suresh G; Zalcman, Gérard; Wolf, Jürgen; Souquet, Pierre-Jean; Baldini, Editta; Cappuzzo, Federico; Chouaid, Christos; Dowlati, Afshin; Sanborn, Rachel; Lopez-Chavez, Ariel; Grohe, Christian; Huber, Rudolf M; Harbison, Christopher T; Baudelet, Christine; Lestini, Brian J; Ramalingam, Suresh S

2015-01-01

Summary Background Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. Methods We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov, number NCT01721759. Findings Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5%, 95% CI 8·7–22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2–4·8), and median duration of response was not reached (95% CI 8·31–not applicable); 13 (77%) of 17 of responses were ongoing at the time of analysis. 30 (26%) of 117 patients had stable disease (median duration 6·0 months, 95% CI 4·7–10·9). 20 (17%) of 117 patients reported grade 3–4 treatment-related adverse events, including: fatigue (five [4%] of 117 patients), pneumonitis (four [3%]), and diarrhoea (three [3%]). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease. Interpretation Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in

Rationale and design of decision: a double-blind, randomized, placebo-controlled phase III trial evaluating the efficacy and safety of sorafenib in patients with locally advanced or metastatic radioactive iodine (RAI)-refractory, differentiated thyroid cancer

International Nuclear Information System (INIS)

Brose, Marcia S; Schlumberger, Martin; Nutting, Christopher M; Sherman, Steven I; Shong, Young Kee; Smit, Johannes WA; Reike, Gerhard; Chung, John; Kalmus, Joachim; Kappeler, Christian

2011-01-01

The incidence of thyroid cancer and the number of patients who die from this disease are increasing globally. Differentiated thyroid cancer (DTC) is the histologic subtype present in most patients and is primarily responsible for the increased overall incidence of thyroid cancer. Sorafenib is a multikinase inhibitor that targets several molecular signals believed to be involved in the pathogenesis of thyroid cancer, including those implicated in DTC. In phase II studies of patients with DTC, sorafenib treatment has yielded a median progression-free survival (PFS) of 58 to 84 weeks and disease control rates of 59% to 100%. The DECISION trial was designed to assess the ability of sorafenib to improve PFS in patients with locally advanced or metastatic, radioactive iodine (RAI)-refractory DTC. DECISION is a multicenter, double-blind, randomized, placebo-controlled phase III study in patients with locally advanced/metastatic RAI-refractory DTC. Study treatment will continue until radiographically documented disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent. Efficacy will be evaluated every 56 days (2 cycles), whereas safety will be evaluated every 28 days (1 cycle) for the first 8 months and every 56 days thereafter. Following disease progression, patients may continue or start sorafenib, depending on whether they were randomized to receive sorafenib or placebo, at investigator discretion. Patients originally randomized to receive sorafenib will be followed up every 3 months for overall survival (OS); patients originally randomized to receive placebo will be followed up every month for 8 months after cross-over to sorafenib. The duration of the trial is expected to be 30 months from the time the first patient is randomized until the planned number of PFS events is attained. The primary endpoint is PFS; secondary endpoints include OS, time to disease progression, disease control rate, response rate, duration of response, safety, and

[68Ga]DOTATATE PET/MRI and [18F]FDG PET/CT are complementary and superior to diffusion-weighted MR imaging for radioactive-iodine-refractory differentiated thyroid cancer

International Nuclear Information System (INIS)

Vrachimis, Alexis; Stegger, Lars; Wenning, Christian; Noto, Benjamin; Konnert, Julia Renate; Riemann, Burkhard; Weckesser, Matthias; Burg, Matthias Christian; Allkemper, Thomas; Heindel, Walter; Schaefers, Michael

2016-01-01

The purpose of this study was to determine whether [ 68 Ga]DOTATATE PET/MRI with diffusion-weighted imaging (DWI) can replace or complement [ 18 F]FDG PET/CT in patients with radioactive-iodine (RAI)-refractory differentiated thyroid cancer (DTC). The study population comprised 12 patients with elevated thyroglobulin and a negative RAI scan after thyroidectomy and RAI remnant ablation who underwent both [ 18 F]FDG PET/CT and [ 68 Ga]DOTATATE PET/MRI within 8 weeks of each other. The presence of recurrent cancer was evaluated on a per-patient, per-organ and per-lesion basis. Histology, and prior and follow-up examinations served as the standard of reference. Recurrent or metastatic tumour was confirmed in 11 of the 12 patients. [ 68 Ga]DOTATATE PET(/MRI) correctly identified the tumour burden in all 11 patients, whereas in one patient local relapse was missed by [ 18 F]FDG PET/CT. In the lesion-based analysis, overall lesion detection rates were 79/85 (93 %), 69/85 (81 %) and 27/82 (33 %) for [ 18 F]FDG PET/CT, [ 68 Ga]DOTATATE PET/MRI and DWI, respectively. [ 18 F]FDG PET(/CT) was superior to [ 68 Ga]DOTATATE PET(/MRI) in the overall evaluation and in the detection of pulmonary metastases. In the detection of extrapulmonary metastases, [ 68 Ga]DOTATATE PET(/MRI) showed a higher sensitivity than [ 18 F]FDG PET(/CT), at the cost of lower specificity. DWI achieved only poor sensitivity and was significantly inferior to [ 18 F]FDG PET in the lesion-based evaluation in the detection of both extrapulmonary and pulmonary metastases. [ 18 F]FDG PET/CT was more sensitive than [ 68 Ga]DOTATATE PET/MRI in the evaluation of RAI-refractory DTC, mostly because of its excellent ability to detect lung metastases. In the evaluation of extrapulmonary lesions, [ 68 Ga]DOTATATE PET(/MRI) was more sensitive and [ 18 F]FDG PET(/CT) more specific. Furthermore, DWI did not provide additional information and cannot replace [ 18 F]FDG PET for postoperative monitoring of patients with

Canadian supportive care recommendations for the management of neutropenia in patients with cancer

OpenAIRE

Kouroukis, C.T.; Chia, S.; Verma, S.; Robson, D.; Desbiens, C.; Cripps, C.; Mikhael, J.

2008-01-01

Hematologic toxicities of cancer chemotherapy are common and often limit the ability to provide treatment in a timely and dose-intensive manner. These limitations may be of utmost importance in the adjuvant and curative intent settings. Hematologic toxicities may result in febrile neutropenia, infections, fatigue, and bleeding, all of which may lead to additional complications and prolonged hospitalization. The older cancer patient and patients with significant comorbidities may be at highest...

Anticancer Role of PPARγ Agonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes

Directory of Open Access Journals (Sweden)

P. J. Simpson-Haidaris

2010-01-01

Full Text Available The use of targeted cancer therapies in combination with conventional chemotherapeutic agents and/or radiation treatment has increased overall survival of cancer patients. However, longer survival is accompanied by increased incidence of comorbidities due, in part, to drug side effects and toxicities. It is well accepted that inflammation and tumorigenesis are linked. Because peroxisome proliferator-activated receptor (PPAR-γ agonists are potent mediators of anti-inflammatory responses, it was a logical extension to examine the role of PPARγ agonists in the treatment and prevention of cancer. This paper has two objectives: first to highlight the potential uses for PPARγ agonists in anticancer therapy with special emphasis on their role when used as adjuvant or combined therapy in the treatment of hematological malignancies found in the vasculature, marrow, and eyes, and second, to review the potential role PPARγ and/or its ligands may have in modulating cancer-associated angiogenesis and tumor-stromal microenvironment crosstalk in bone marrow.

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

Science.gov (United States)

Ramos, Nestor R.; Mo, Clifton C.; Karp, Judith E.; Hourigan, Christopher S.

2015-01-01

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. PMID:25932335

Refractories for Industrial Processing. Opportunities for Improved Energy Efficiency

Energy Technology Data Exchange (ETDEWEB)

Hemrick, James G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hayden, H. Wayne [Metals Manufacture Process and Controls Technology, Inc., Oak Ridge, TN (United States); Angelini, Peter [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Moore, Robert E. [R.E. Moore Associates, Maricopa, AZ (United States); Headrick, William L. [R.E. Moore Associates, Maricopa, AZ (United States)

2005-01-01

Refractories are a class of materials of critical importance to manufacturing industries with high-temperature unit processes. This study describes industrial refractory applications and identifies refractory performance barriers to energy efficiency for processing. The report provides recommendations for R&D pathways leading to improved refractories for energy-efficient manufacturing and processing.

Evolution of regorafenib from bench to bedside in colorectal cancer: Is it an attractive option or merely a “me too” drug?

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Goel G

2018-03-01

Full Text Available Gaurav Goel Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Abstract: Colorectal cancer (CRC is a major public health problem in the United States with an estimated 50,260 deaths in 2017. Over the past two decades, several agents have been approved by the US Food and Drug Administration (FDA for the treatment of patients with metastatic CRC (mCRC. Regorafenib (BAY 73-4506 is a small-molecule multikinase inhibitor that was approved for the treatment of mCRC in 2012. This agent is a novel oral diphenylurea-based multikinase inhibitor that is active against several angiogenic receptor tyrosine kinases (RTKs; VEGFR-1, VEGFR-2, VEGFR-3, TIE-2, oncogenic RTKs (c-KIT, RET, stromal RTKs (PDGFR-B, FGFR-1, and intracellular signaling kinases (c-RAF/RAF-1, BRAF, BRAFV600E. Preclinical studies have documented its broad-spectrum activity against different solid tumor types including CRC. Phase I studies showed that it had an acceptable safety profile in advanced refractory mCRC. A subsequent Phase III trial (CORRECT demonstrated significant clinical efficacy of regorafenib in patients with refractory or advanced mCRC, which eventually led to its FDA approval for the treatment of mCRC in September 2012. However, the drug was associated with significant toxicity in clinical practice when administered at the approved doses, which necessitated a thorough reassessment of its dosing schedule and toxicity profile. This review summarizes the development of regorafenib from the initial preclinical studies to the Phase III trials and critically examines the current clinical space occupied by regorafenib in the treatment of mCRC, at 5 years after its initial FDA approval. Keywords: regorafenib, multikinase inhibitor, angiogenesis, colorectal cancer, colon cancer, stivarga, BAY 73-4506

Hematologic outcomes after total splenectomy and partial splenectomy for congenital hemolytic anemia.

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Englum, Brian R; Rothman, Jennifer; Leonard, Sarah; Reiter, Audra; Thornburg, Courtney; Brindle, Mary; Wright, Nicola; Heeney, Matthew M; Jason Smithers, C; Brown, Rebeccah L; Kalfa, Theodosia; Langer, Jacob C; Cada, Michaela; Oldham, Keith T; Scott, J Paul; St Peter, Shawn D; Sharma, Mukta; Davidoff, Andrew M; Nottage, Kerri; Bernabe, Kathryn; Wilson, David B; Dutta, Sanjeev; Glader, Bertil; Crary, Shelley E; Dassinger, Melvin S; Dunbar, Levette; Islam, Saleem; Kumar, Manjusha; Rescorla, Fred; Bruch, Steve; Campbell, Andrew; Austin, Mary; Sidonio, Robert; Blakely, Martin L; Rice, Henry E

2016-01-01

The purpose of this study was to define the hematologic response to total splenectomy (TS) or partial splenectomy (PS) in children with hereditary spherocytosis (HS) or sickle cell disease (SCD). The Splenectomy in Congenital Hemolytic Anemia (SICHA) consortium registry collected hematologic outcomes of children with CHA undergoing TS or PS to 1 year after surgery. Using random effects mixed modeling, we evaluated the association of operative type with change in hemoglobin, reticulocyte counts, and bilirubin. We also compared laparoscopic to open splenectomy. The analysis included 130 children, with 62.3% (n=81) undergoing TS. For children with HS, all hematologic measures improved after TS, including a 4.1g/dl increase in hemoglobin. Hematologic parameters also improved after PS, although the response was less robust (hemoglobin increase 2.4 g/dl, p<0.001). For children with SCD, there was no change in hemoglobin. Laparoscopy was not associated with differences in hematologic outcomes compared to open. TS and laparoscopy were associated with shorter length of stay. Children with HS have an excellent hematologic response after TS or PS, although the hematologic response is more robust following TS. Children with SCD have smaller changes in their hematologic parameters. These data offer guidance to families and clinicians considering TS or PS. Copyright © 2016 Elsevier Inc. All rights reserved.

B-Cell Hematologic Malignancy Vaccination Registry

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2017-12-29

Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Waldenstrom Macroglobulinemia; Lymphocytosis; Lymphoma, Non-Hodgkin; B-Cell Chronic Lymphocytic Leukemia; Hematological Malignancies

Endothelial and circulating progenitor cells in hematological diseases and allogeneic hematopoietic stem cell transplantation.

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Ruggeri, Annalisa; Paviglianiti, Annalisa; Volt, Fernanda; Kenzey, Chantal; Rafii, Hanadi; Rocha, Vanderson; Gluckman, Eliane

2017-10-12

Circulating endothelial cells (CECs), originated form endothelial progenitors (EPCs) are mature cells which are not associated with vessel walls, and that are detached from the endothelium. Normally, they are present in insignificant amounts in the peripheral blood of healthy individuals. On the other hand, elevated CECs and EPCs levels have been reported in the peripheral blood of patients with different types of cancers and some other diseases. Consequently, CECs and EPCs represent a potential biomarker in several clinical conditions involving endothelial turnover and remodeling, such as hematological diseases. These cells may be involved in disease progression and the neoplastic angiogenesis process. Moreover, CESs and EPCs are probably involved in endothelial damage that is a marker of several complications following allogeneic hematopoietic stem cell transplantation. This review aims to provide an overview on the characterization of CECs and EPCs, describe isolation methods and to identify the potential role of these cells in hematological diseases and hematopoietic stem cell transplantation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Plasmapheresis in immune hematology: review of clinical outcome data with respect to evidence-based medicine and clinical experience.

Science.gov (United States)

von Baeyer, Hans

2003-02-01

The objective of this paper is to assess the role of plasmapheresis in immune hematology by reviewing published clinical outcome data and narrative review articles. This information will be used to define evidence levels for appraisal of the efficacy and rank of plasmapheresis among other management options. This evidence-based strategy conforms to the concepts of the American Society of Hematology (ASH). as put forward in 1996 in the context of immune thrombocytopenia (ITP) treatment. The term 'experimental' is used to describe indications where the only scientific evidence of the efficacy of plasmapheresis consists of pathophysiological reasoning and empiric clinical findings. We reviewed the available literature on the use of plasmapheresis in autoimmune hemolytic anemia (AIHA), hemolytic disease of the newborn (HDN), autoimmune thrombocytopenic purpura (AITP), heparin-induced thrombocytopenia type II (HIT II), post-transfusion purpura (PTP), refractoriness to platelet transfusion (RPT), coagulation factor inhibitor (CFI) and catastrophic antiphospholipid syndrome (CAS). Plasmapheresis completes the spectrum of management options as it eliminates physically circulating free antibodies involved in the pathogenesis of these immune hematological syndromes. Because of the paucity of data, evidence levels had to be defined based on the findings of uncontrolled case series and the opinions of independent experts. In many cases, randomized clinical trials were not feasible because the syndromes are so rare. When defined as an 'experimental indication', plasmapheresis has a firm scientific basis, but larger scale clinical experience with the method is still lacking. In these cases, the detection and monitoring of symptomatic disease-related circulating free antibodies or immune complexes is a mandatory prerequisite for the use of plasmapheresis. The therapeutic benefit of plasmapheresis is substantiated by the level V of evidence of its efficacy in treatment of HDN, HIV

Single agent and synergistic combinatorial efficacy of first-in-class small molecule imipridone ONC201 in hematological malignancies.

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Prabhu, Varun V; Talekar, Mala K; Lulla, Amriti R; Kline, C Leah B; Zhou, Lanlan; Hall, Junior; Van den Heuvel, A Pieter J; Dicker, David T; Babar, Jawad; Grupp, Stephan A; Garnett, Mathew J; McDermott, Ultan; Benes, Cyril H; Pu, Jeffrey J; Claxton, David F; Khan, Nadia; Oster, Wolfgang; Allen, Joshua E; El-Deiry, Wafik S

2018-01-01

ONC201, founding member of the imipridone class of small molecules, is currently being evaluated in advancer cancer clinical trials. We explored single agent and combinatorial efficacy of ONC201 in preclinical models of hematological malignancies. ONC201 demonstrated (GI50 1-8 µM) dose- and time-dependent efficacy in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma, anaplastic large cell lymphoma (ALCL), cutaneous T-cell lymphoma (CTCL), Hodgkin's lymphoma (nodular sclerosis) and multiple myeloma (MM) cell lines including cells resistant to standard of care (dexamethasone in MM) and primary samples. ONC201 induced caspase-dependent apoptosis that involved activation of the integrated stress response (ATF4/CHOP) pathway, inhibition of Akt phosphorylation, Foxo3a activation, downregulation of cyclin D1, IAP and Bcl-2 family members. ONC201 synergistically reduced cell viability in combination with cytarabine and 5-azacytidine in AML cells. ONC201 combined with cytarabine in a Burkitt's lymphoma xenograft model induced tumor growth inhibition that was superior to either agent alone. ONC201 synergistically combined with bortezomib in MM, MCL and ALCL cells and with ixazomib or dexamethasone in MM cells. ONC201 combined with bortezomib in a Burkitt's lymphoma xenograft model reduced tumor cell density and improved CHOP induction compared to either agent alone. These results serve as a rationale for ONC201 single-agent trials in relapsed/refractory acute leukemia, non-Hodgkin's lymphoma, MM and combination trial with dexamethasone in MM, provide pharmacodynamic biomarkers and identify further synergistic combinatorial regimens that can be explored in the clinic.

Lansoprazole Exacerbates Pemetrexed-Mediated Hematologic Toxicity by Competitive Inhibition of Renal Basolateral Human Organic Anion Transporter 3.

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Ikemura, Kenji; Hamada, Yugo; Kaya, Chinatsu; Enokiya, Tomoyuki; Muraki, Yuichi; Nakahara, Hiroki; Fujimoto, Hajime; Kobayashi, Tetsu; Iwamoto, Takuya; Okuda, Masahiro

2016-10-01

Pemetrexed, a multitargeted antifolate, is eliminated by tubular secretion via human organic anion transporter 3 (hOAT3). Although proton pump inhibitors (PPIs) are frequently used in cancer patients, the drug interaction between PPIs and pemetrexed remains to be clarified. In this study, we examined the drug interaction between pemetrexed and PPIs in hOAT3-expressing cultured cells, and retrospectively analyzed the impact of PPIs on the development of hematologic toxicity in 108 patients who received pemetrexed and carboplatin treatment of nonsquamous non-small cell lung cancer for the first time between January 2011 and June 2015. We established that pemetrexed was transported via hOAT3 (Km = 68.3 ± 11.1 µM). Lansoprazole, rabeprazole, pantoprazole, esomeprazole, omeprazole, and vonoprazan inhibited hOAT3-mediated uptake of pemetrexed in a concentration-dependent manner. The inhibitory effect of lansoprazole was much greater than those of other PPIs and the apparent IC50 value of lansoprazole against pemetrexed transport via hOAT3 was 0.57 ± 0.17 µM. The inhibitory type of lansoprazole was competitive. In a retrospective study, multivariate analysis revealed that coadministration of lansoprazole, but not other PPIs, with pemetrexed and carboplatin was an independent risk factor significantly contributing to the development of hematologic toxicity (odds ratio: 10.004, P = 0.005). These findings demonstrated that coadministration of lansoprazole could exacerbate the hematologic toxicity associated with pemetrexed, at least in part, by competitive inhibition of hOAT3. Our results would aid clinicians to make decisions of coadministration drugs to avoid drug interaction-induced side effects for achievement of safe and appropriate chemotherapy with pemetrexed. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Tungsten and refractory metals 3, proceedings

International Nuclear Information System (INIS)

Bose, A.; Dowding, R.J.

1996-01-01

The Third International Conference on Tungsten and Refractory Metals was held in Greater Washington DC at the McLean Hilton, McLean Virginia, on November 15--16, 1995. This meeting was the third in a series of conferences held in the Washington DC area. The first meeting was in 1992 and was entitled ''International Conference on Tungsten and Tungsten Alloys.'' In 1994, the scope of the meeting was expanded to include other refractory metals such as molybdenum, iridium, rhenium, tantalum and niobium. The tremendous success of that meeting was the primary motivation for this Conference. The broader scope (the inclusion of other refractory metals and alloys) of the Conference was kept intact for this meeting. In fact, it was felt that the developments in the technology of these materials required a common forum for the interchange of current research information. The papers presented in this meeting examined the rapid advancements in the technology of refractory metals, with special emphasis on the processing, structure, and properties. Among the properties there was emphasis on both quasi-static and dynamic rates. Another topic that received considerable interest was the area of refractory carbides and tungsten-copper composites. One day of concurrent session was necessary to accommodate all of the presentations

Hematological Parameters in the Volatile Substance Sniffers

OpenAIRE

Dündaröz, Ruşen; Ceylan, Süleyman; Denli, Metin; Açıkel, Cengizhan; Balım, Elvan; Özışık, Tahir

2009-01-01

SüleymanDemirel Üniversitesi TIP FAKÜLTESİ DERGİSİ: 1999 Eylül; 6(3) Hematological Parameters in the Volatile Substance Sniffers Ruşen Dündaröz, Süleyman Ceylan, Metin Denli, Cengiz Han Açıkel, Elvan Balım, Tahir Özışık Abstract Glue sniffing is a frequent problem among teenagers. Various chemical substances, especially toluene and benzene, contained in the glues kave been reported to be hematotoxic. The hematological parameters of 44 healthy teenagers ~...

Potential refractory alloy requirements for space nuclear power applications

International Nuclear Information System (INIS)

Cooper, R.H. Jr.

1984-01-01

In reviewing design requirements for refractory alloys for space nuclear applications, several key points are identified. First, the successful utilization of refractory alloys is considered an enabling requirement for the successful deployment of high efficiency, lightweight, and small space nuclear systems. Second, the recapture of refractory alloy nuclear technology developed in the 1960s and early 1970s appears to be a pacing activity in the successful utilization of refractory alloys. Third, the successful application of refractory alloys for space nuclear applications will present a significant challenge to both the materials and the systems design communities

STATUS SEROLOGIS TIDAK MEMPENGARUHI PROFIL HEMATOLOGI ANAK TERINFEKSI VIRUS DENGUE

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Safari Wahyu Jatmiko

2017-06-01

Full Text Available Antibodi anti dengue bersifat autoantibodi yang bisa merusak self antigen. Respon imun humoral terhadap DENV adalah terbentuknya IgM dan IgG yang spesifik terhadap sub tipe DENV penyebab. Jika IgG dan IgM anti degue bersifat autoantibodi maka secara teoritis pasien dengan status serologis IgM (+ dan IgG + akan mempunyai profil hematologi yang lebih buruk dari pada pasien dengan IgG (+.Penelitian ini bertjuan untuk mengetahui perbedaan profil hematologi menurut status serologi pada anak terinfeksi virus dengue. Penelitian menggunakan desian analitik dengan pendekatan cross sectional. Data diambil dari pasien anak di RSUD Surakarta dari bulan September 2016 – Januari 2017. Kriteria pasien yang diikutkan dalam penelitian adalah semua pasien anak dengan usia kurang dari 14 tahun dan memenuhi kriteria infeksi virus dengue menurut WHO 2009. Pasien dengan riwayat kelainan hematologi dan pasien dengan riwayat immunocompremised dikeluarkan dari penelitian.Hasil penelitian ditemukan 65 pasien dengan IVD yang memenuhi kriteria.Tujuh belas pasien dengan IgM dan IgG positif sedangkan sisanya hanya IgG positif Hasil penelitian perbedaan profil hematologi jumlah leukosit, trombosit, hematokrit, dan hemoglobin berdasarkan status IgM (+ IgG (+ dengan IgG (+ didapatkan nilai p masing-masing 0.833, 0,865, 0,137, 0,086, dan 0,223. Dapat disimpilkan bahwa tidak terdapat perbedaan profil hematologi antara pasien dengan IgM (+ IgG (+ dengan pasien IgG (+.   Kata Kunci: infeksi virus dengue, antibodi anti dengue, autoantibodi, profil hematologi.

Refractories for steel-works

International Nuclear Information System (INIS)

Villanova, R.A.; Galant, C.L.; Haas, C.; Rosenbaum, V.

The routine procedures utilized for quality control of refractory materials used by PIRATINI's steel-works, are presented ' under an objetive and practical maner. The attention of the paper is concentrated upon the following' refractory types with higher consume: silicon-aluminous; aluminous; basic magnesia; basic chrom-magnesia. All steps of utilization are described, including specification, supplies programation, storage; sampling; physical tests, and also aplication procedures. Results from routine analysis during a six month period, by ' means of X-Ray Quantometry, using the fusion pearls procedure, are presented compared with Atomic Absorption [pt

Hematology reference intervals for neonatal Holstein calves.

Science.gov (United States)

Panousis, Nikolaos; Siachos, Nektarios; Kitkas, Georgios; Kalaitzakis, Emmanouil; Kritsepi-Konstantinou, Maria; Valergakis, Georgios E

2018-01-09

Data regarding hematologic reference intervals (RI) for neonatal calves have not been published yet. The aims of this study were: a) to establish hematology RIs for neonatal Holstein calves, b) to compare them with the RIs for lactating cows, and c) to investigate the relationship of age and gender with the hematologic profile of calves. Two-hundred and fifty-four clinically healthy Holstein calves (1-9days old, from 30 farms) and 82 healthy Holstein cows (between 30 and 150days in milk, from 10 farms) were blood sampled once for a complete blood count evaluation, using the ADVIA 120 hematology analyzer. An additional blood sample was collected from each calf for serum total protein concentration measurement. RIs and age-related RIs were calculated with the Reference Value Advisor freeware. Comparisons between calves and cows and between male and female calves were performed with t-test or Mann-Whitney test. Red blood cell count (RBC), white blood cell count (WBC), neutrophil, lymphocyte and platelet counts in calves were higher, while mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were lower than in cows. Lymphocyte and platelets showed a notable increase through age. Finally, female calves had higher RBC, hematocrit and hemoglobin concentration than males. Age-specific RIs should be used for the interpretation of the complete blood count in Holstein calves. Copyright © 2018 Elsevier Ltd. All rights reserved.

Development of AZS refractories for the glass industry

International Nuclear Information System (INIS)

Guzman, A.M.; Rodriguez, P.

2004-01-01

Refractory materials can support high temperatures, thermal strength and the contact with aggressive environments, for this reason they are widely used in the cement, glass and steel industry. Commercial AZS (alumina-zirconia-silica) refractories are a good alternative in refractory materials for the glass industry' because they can support the aggressive conditions during liquid processing of glass. However, another problem encountered in glass industry is contamination by refractory' material that fall into the molten glass, which can produce a series of defects in the final product. This research was conducted to develop new formulations of AZS refractories with different amounts of ZrO 2 with the purpose of improving the characteristics, properties and the work conditions in the glass melting furnaces and, at the same time, lower the costs this type of refractories. The results obtained indicate that the composition with low content of ZrO 2 can provide better properties than the commercial product, with some modifications in the particle size distribution. Copyright (2004) AD-TECH - International Foundation for the Advancement of Technology Ltd

Patterns in place of cancer death in the State of Qatar: a population-based study.

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Hassan Mohsen

Full Text Available BACKGROUND: International studies show that most people prefer to die at home; however, hospitals remain the most common place of death (PoD. This study aims to investigate the patterns in PoD and the associated factors, which are crucial for end-of-life cancer care enhancement. METHOD: This retrospective, population-based study analyzed all registered cancer deaths in Qatar between January 1, 2006 and December 31, 2012 (n = 1,224. The main outcome measures were patient characteristics: age, gender, nationality, cancer diagnosis, year of death, and PoD. Time trends for age-standardized proportions of death in individual PoDs were evaluated using chi-square analysis. Odds ratio (OR were determined for variables associated with the most preferred (acute palliative care unit [APCU] and hematology/oncology ward versus least preferred (ICU and general medicine ward PoDs in Qatar, stratified by nationality. RESULTS: The hematology/oncology ward was the most common PoD (32.4%; 95% CI 26.7-35.3% followed by ICU (31.4%; 95% CI 28.7-34.3%, APCU (26.9%; 95% CI 24.3-29.6%, and general medicine ward (9.2%; 95% CI 7.6-11.1%. APCU trended upward (+0.057/year; p<0.001, while the hematology/oncology ward trended downward (-0.055/year; p<0.001. No statistically significant changes occurred in the other PoDs; home deaths remained low (0.4%; 95% Cl 0.38-0.42. Qataris who died from liver cancer (OR 0.23 and aged 65 or older (OR 0.64 were less likely to die in the APCU or hematology/oncology ward (p<0.05. Non-Qataris who died from pancreatic cancer (OR 3.12 and female (OR 2.05 were more likely to die in the APCU or hematology/oncology ward (p<0.05. Both Qataris and non-Qataris who died from hematologic malignancy (OR 0.18 and 0.41, respectively were more likely to die in the ICU or general medicine ward (p<0.05. CONCLUSION: A high percentage of cancer deaths in Qatar occur in hospital. As home was the preferred PoD for most people, effective home care and hospice

Uridine diphosphate glucuronide transferase 1A1FNx0128 gene polymorphism and the toxicity of irinotecan in recurrent and refractory small cell lung cancer

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Fan Yun

2014-01-01

Full Text Available Objective: The aim was to investigate the association between uridine diphosphate glucuronide transferase 1A1 (UGT1A1 gene promoter region polymorphism and irinotecan-related adverse effects and efficacy on recurrent and refractory small cell lung cancer (SCLC. Materials and Methods: A total of 31 patients with recurrent and refractory SCLC were enrolled in this study from June 2012 to August 2013 and received at least two cycles of single-agent irinotecan chemotherapy. The efficacy and adverse effects of irinotecan were evaluated. DNA was extracted from peripheral blood and direct sequencing method was employed to test UGT1A1FNx0128 polymorphism, thus analyzing the correlation between UGT1A1FNx0128 polymorphism and irinotecan-related side-effects and efficacy. Results: A total of 25 cases (80.6% were UGT1A1FNx0128 wild-type (TA 6 /(TA 6 ; 6 cases (19.4% were heterozygous mutant (TA 6 /(TA 7 , no homozygous mutant genotype (TA 7 /(TA 7 was found. The incidences of grade 3/4 neutropenia, diarrhea and thrombocytopenia were 35.5%, 25.8% and 22.6% in all the patients, respectively. The incidence of 3/4 adverse effects in patients with genotype (TA 6 /(TA 6 and heterozygous (TA 6 /(TA 7 had no statistical difference (P > 0.05 for all. The overall response rate (ORR was 32.3%. Median progression free survival (PFS and overall survival (OS were 4 months and 7.5 months in all patients, respectively. There was no statistical difference in ORR, PFS and OS between genotype (TA 6 /(TA 6 patients and heterozygous (TA 6 /(TA 7 patients. Conclusion: Irinotecan showed efficacy in patients with recurrent and refractory SCLC; UGT1A1 FNx01 28 polymorphism failed to predict the incidence of serious adverse effects and efficacy of irinotecan.

A Phase I/II Trial of DCVac/IR Dendritic Cell Immunotherapy Combined with Irradiation in Cases of Refractory Colorectal Cancer with Multiple Liver Metastases

International Nuclear Information System (INIS)

Choi, Young-Min; Lee, Hyung-Sik; Kwon, Hyuk-Chan; Han, Sang-Young; Choi, Jong-Cheol; Chung, Ju-Seop; Kim, Chang-Won; Kim, Dong-Won; Kang, Chi-Duk

2008-01-01

To assess the toxicity and tumor response induced by DCVac/IR dendritic cell (DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of 6x10 6 DCs were packed into a vial (DCVac/IR, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses (3x10 6 to 12x10 6 DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Of the 24 registered patients, 22 received the DCs injections. Moreover

A Phase I/II Trial of DCVac/IR Dendritic Cell Immunotherapy Combined with Irradiation in Cases of Refractory Colorectal Cancer with Multiple Liver Metastases

Energy Technology Data Exchange (ETDEWEB)

Choi, Young-Min; Lee, Hyung-Sik; Kwon, Hyuk-Chan; Han, Sang-Young; Choi, Jong-Cheol [Donga Univ. School of Medicine, Busan (Korea, Republic of); Chung, Ju-Seop; Kim, Chang-Won; Kim, Dong-Won; Kang, Chi-Duk [Busan National University College of Medicine, Busan (Korea, Republic of)

2008-06-15

To assess the toxicity and tumor response induced by DCVac/IR dendritic cell (DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of 6x10{sup 6} DCs were packed into a vial (DCVac/IR, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses (3x10{sup 6} to 12x10{sup 6} DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Of the 24 registered patients, 22 received the DCs

PRELIMINARY STUDY OF HEMATOLOGICAL PARAMETERS IN HERZEGOVINIAN DONKEY

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Dunja Rukavina

2016-02-01

Full Text Available Herzegovinian donkey is a very important animal resource of Bosnia and Herzegovina. There have been no works attempted at determining the normal values of hematological parameters of Herzegovinian donkey. For this reason, the objective of the present study was to investigate some hematological parameters in Herzegovinian donkey. The research was performed on 30 apparently healthy donkeys (18 female and 12 male of ages from 1 to 20 years. Blood samples (3 ml were obtained by jugular vein puncture (vena jugularis externa in vacuum tubes with EDTA. The mean value of hematocrit was 29.19 %, hemoglobin concentration 10.6 g/dl, mean corpuscular hemoglobin concentration 36.33 g/dl, white blood cells 9.33 x109/L, granulocytes (109/L 5.45 x109/L, granulocytes (% 59.47%, lymphocyte/monocyte (109/L 3.89 x109/L, lymphocyte/monocyte (% 40.53% and platelet cells 148.97 x109/L. Parameters were determined using an automated analyzer IDEXX QBC VET AutoRead. Data were analyzed by SPSS V 15. All hematological parameters (except platelet cells were consistent with the recommended reference ranges for donkeys, and the values found in literature so far. Platelet cells values were much lower than in the literature for the other donkey breeds and the recommended reference ranges for donkeys. The slight differences found between our results and those reported in the previous works confirm the need for further studies to investigate the reference values of hematological parameters of Herzegovinian donkey. This work is a contribution to the study of hematological parameters of Herzegovinian donkey, and we expect these data to be applied to the further studies.

Refractory migraine in a headache clinic population

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Fernandez-Torron Roberto

2011-08-01

Full Text Available Abstract Background Many migraineurs who seek care in headache clinics are refractory to treatment, despite advances in headache therapies. Epidemiology is poorly characterized, because diagnostic criteria for refractory migraine were not available until recently. We aimed to determine the frequency of refractory migraine in patients attended in the Headache Unit in a tertiary care center, according to recently proposed criteria. Methods The study population consisted of a consecutive sample of 370 patients (60.8% females with a mean age of 43 years (range 14-86 evaluated for the first time in our headache unit over a one-year period (between October 2008 and October 2009. We recorded information on clinical features, previous treatments, Migraine Disability Assessment Score (MIDAS, and final diagnosis. Results Overall migraine and tension-type headache were found in 46.4% and 20.5% of patients, respectively. Refractory migraine was found in 5.1% of patients. In refractory migraineurs, the mean MIDAS score was 96, and 36.8% were medication-overusers. Conclusions Refractory migraine is a relatively common and very disabling condition between the patients attended in a headache unit. The proposed operational criteria may be useful in identifying those patients who require care in headache units, the selection of candidates for combinations of prophylactic drugs or invasive treatments such as neurostimulation, but also to facilitate clinical studies in this patient group.

NOvel Refractory Materials for High Alkali, High Temperature Environments

Energy Technology Data Exchange (ETDEWEB)

Hemrick, J.G.; Griffin, R. (MINTEQ International, Inc.)

2011-08-30

Refractory materials can be limited in their application by many factors including chemical reactions between the service environment and the refractory material, mechanical degradation of the refractory material by the service environment, temperature limitations on the use of a particular refractory material, and the inability to install or repair the refractory material in a cost effective manner or while the vessel was in service. The objective of this project was to address the need for new innovative refractory compositions by developing a family of novel MgO-Al2O3 spinel or other similar magnesia/alumina containing unshaped refractory composition (castables, gunnables, shotcretes, etc) utilizing new aggregate materials, bond systems, protective coatings, and phase formation techniques (in-situ phase formation, altered conversion temperatures, accelerated reactions, etc). This family of refractory compositions would then be tailored for use in high-temperature, highalkaline industrial environments like those found in the aluminum, chemical, forest products, glass, and steel industries. A research team was formed to carry out the proposed work led by Oak Ridge National Laboratory (ORNL) and was comprised of the academic institution Missouri University of Science and Technology (MS&T), and the industrial company MINTEQ International, Inc. (MINTEQ), along with representatives from the aluminum, chemical, glass, and forest products industries. The two goals of this project were to produce novel refractory compositions which will allow for improved energy efficiency and to develop new refractory application techniques which would improve the speed of installation. Also methods of hot installation were sought which would allow for hot repairs and on-line maintenance leading to reduced process downtimes and eliminating the need to cool and reheat process vessels.

SINTERED REFRACTORY TUNGSTEN ALLOYS. Gesinterte hochschmelzende wolframlegierungen

Energy Technology Data Exchange (ETDEWEB)

Kieffer, R.; Sedlatschek, K.; Braun, H.

1971-12-15

Dependence of the melting point of the refractory metals on their positions in the periodic system - alloys of tungsten with other refractory metals - sintering of the alloys - processing of the alloys - technological properties.

Laparoscopic Splenectomy for Benign Hematological Disorders in Adults: A Systematic Review.

Science.gov (United States)

Moris, Demetrios; Dimitriou, Nikoletta; Griniatsos, John

2017-01-01

Since its introduction in the early 1990s, laparoscopic splenectomy (LS) has gained worldwide acceptance for spleen removal, especially in hematological patients. The present review summarizes the current knowledge and results of LS for the treatment of benign hematological diseases in adults. A MEDLINE/PubMed database research was performed using the terms: "laparoscopic splenectomy" OR "laparoscopy" OR "splenectomy" AND "hematological disorders" OR "hematological disease" OR "hematology" AND "adults" as key words. We set our analysis starting date as January 1st 2010 and the end date as December 31st 2016. We identified 247 relative articles. All the references from the identified articles were searched for relevant information. Twenty-seven articles were deemed appropriate for our analysis. LS was found to be feasible and safe in the majority of patients with benign hematological disorders, with a mortality rate ranging from 0% to less than 4% and the postoperative complications rate from 0% to 35.7%. The conversion rate was also very low (4%) and response (complete or partial) was achieved in more than 80% of patients. Lateral approach with four trocars was the most commonly used approach with concommitant cholecystectomy being correlated with increased operative time and morbidity. Current literature holds that whenever splenectomy is required for the treatment of hematological disorders in adults, a laparoscopic approach should be offered as the gold standard. However, to strengthen the clinical evidence in favor of LS, more high-quality clinical trials on several issues of the procedure are necessary. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Challenges in cancer research and multifaceted approaches for cancer biomarker quest

Czech Academy of Sciences Publication Activity Database

Martinková, Jiřina; Gadher, S. J.; Hajduch, M.; Kovářová, Hana

2009-01-01

Roč. 583, - (2009), s. 1772-1784 ISSN 0014-5793 R&D Projects: GA MŠk LC07017 Institutional research plan: CEZ:AV0Z50450515 Keywords : cancer research * proteomics * genomics Subject RIV: FD - Oncology ; Hematology Impact factor: 3.541, year: 2009

The effects of Islamic fasting on blood hematological-biochemical parameters

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Mohamad Reza Sedaghat

2017-06-01

Conclusion:This study on healthy subjects suggests that fasting could affect some hematological-biochemical parameters but not all of them. Also, these changes in hematological-biochemical parameters were within the normal range and Ramadan fasting seems to be safe for healthy subjects.

Stochastic histories of refractory interstellar dust

International Nuclear Information System (INIS)

Liffman, K.; Chayton, D.D.

1988-01-01

The authors calculate histories for refractory dust particles in the interstellar medium. The double purposes are to learn something of the properties of interstellar dust as a system and to evaluate with specific assumptions the cosmic chemical memory interpretation of a specific class of isotopic anomalies. They assemble the profile of a particle population from a large number of stochastic, or Monte Carlo, histories of single particles, which are necessarily taken to be independent with this approach. They specify probabilities for each of the events that may befall a given particle and unfold its history by a sequence of random numbers. They assume that refractory particles are created only by thermal condensation within stellar material during its ejection from stars, and that these refractory particles can be destroyed only by being sputtered to a size too small for stability or by being incorporated into the formation of new stars. In order to record chemical detail, the authors take each new refractory particle to consist of a superrefractory core plus a more massive refractory mantle. They demonstrate that these superrefractory cores have effective lifetimes much longer than the turnover time of dust mass against sputtering. As examples of cosmic chemical memory they evaluate the 16 O-richness of interstellar aluminum and mechanisms for the 48 Ca/ 50 Ti correlation. Several related consequences of this approach are discussed

Hematological Toxicity After Robotic Stereotactic Body Radiosurgery for Treatment of Metastatic Gynecologic Malignancies

Energy Technology Data Exchange (ETDEWEB)

Kunos, Charles A., E-mail: charles.kunos@UHhospitals.org [Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Debernardo, Robert [Department of Obstetrics and Gynecology, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Radivoyevitch, Tomas [Department of Epidemiology and Biostatistics, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Fabien, Jeffrey; Dobbins, Donald C.; Zhang Yuxia; Brindle, James [Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio (United States)

2012-09-01

Purpose: To evaluate hematological toxicity after robotic stereotactic body radiosurgery (SBRT) for treatment of women with metastatic abdominopelvic gynecologic malignancies. Methods and Materials: A total of 61 women with stage IV gynecologic malignancies treated with abdominopelvic SBRT were analyzed after ablative radiation (2400 cGy/3 divided consecutive daily doses) delivered by a robotic-armed Cyberknife SBRT system. Abdominopelvic bone marrow was identified using computed tomography-guided contouring. Fatigue and hematologic toxicities were graded by retrospective assignment of common toxicity criteria for adverse events (version 4.0). Bone marrow volume receiving 1000 cGy (V10) was tested for association with post-therapy (median 32 days [25%-75% quartile, 28-45 days]) white- or red-cell counts, hemoglobin levels, and platelet counts as marrow toxicity surrogates. Results: In all, 61 women undergoing abdominopelvic SBRT had a median bone marrow V10 of 2% (25%-75% quartile: 0%-8%). Fifty-seven (93%) of 61 women had received at least 1 pre-SBRT marrow-taxing chemotherapy regimen for metastatic disease. Bone marrow V10 did not associate with hematological adverse events. In all, 15 grade 2 (25%) and 2 grade 3 (3%) fatigue symptoms were self-reported among the 61 women within the first 10 days post-therapy, with fatigue resolved spontaneously in all 17 women by 30 days post-therapy. Neutropenia was not observed. Three (5%) women had a grade 1 drop in hemoglobin level to <10.0 g/dL. Single grade 1, 2, and 3 thrombocytopenias were documented in 3 women. Conclusions: Abdominopelvic SBRT provided ablative radiation dose to cancer targets without increased bone marrow toxicity. Abdominopelvic SBRT for metastatic gynecologic malignancies warrants further study.

Hematological Toxicity After Robotic Stereotactic Body Radiosurgery for Treatment of Metastatic Gynecologic Malignancies

International Nuclear Information System (INIS)

Kunos, Charles A.; Debernardo, Robert; Radivoyevitch, Tomas; Fabien, Jeffrey; Dobbins, Donald C.; Zhang Yuxia; Brindle, James

2012-01-01

Purpose: To evaluate hematological toxicity after robotic stereotactic body radiosurgery (SBRT) for treatment of women with metastatic abdominopelvic gynecologic malignancies. Methods and Materials: A total of 61 women with stage IV gynecologic malignancies treated with abdominopelvic SBRT were analyzed after ablative radiation (2400 cGy/3 divided consecutive daily doses) delivered by a robotic-armed Cyberknife SBRT system. Abdominopelvic bone marrow was identified using computed tomography-guided contouring. Fatigue and hematologic toxicities were graded by retrospective assignment of common toxicity criteria for adverse events (version 4.0). Bone marrow volume receiving 1000 cGy (V10) was tested for association with post-therapy (median 32 days [25%-75% quartile, 28-45 days]) white- or red-cell counts, hemoglobin levels, and platelet counts as marrow toxicity surrogates. Results: In all, 61 women undergoing abdominopelvic SBRT had a median bone marrow V10 of 2% (25%-75% quartile: 0%-8%). Fifty-seven (93%) of 61 women had received at least 1 pre-SBRT marrow-taxing chemotherapy regimen for metastatic disease. Bone marrow V10 did not associate with hematological adverse events. In all, 15 grade 2 (25%) and 2 grade 3 (3%) fatigue symptoms were self-reported among the 61 women within the first 10 days post-therapy, with fatigue resolved spontaneously in all 17 women by 30 days post-therapy. Neutropenia was not observed. Three (5%) women had a grade 1 drop in hemoglobin level to <10.0 g/dL. Single grade 1, 2, and 3 thrombocytopenias were documented in 3 women. Conclusions: Abdominopelvic SBRT provided ablative radiation dose to cancer targets without increased bone marrow toxicity. Abdominopelvic SBRT for metastatic gynecologic malignancies warrants further study.

Undergraduate hematology – a more integrated approach

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Di Carlofelice MA

2016-11-01

Full Text Available Matteo A Di Carlofelice,* Jack FT Cope*Faculty of Medicine, Imperial College London, London, UK*These authors contributed equally to this workAs fellow medical students we read with great interest the article by Mandan et al1 proposing a dedicated hematology rotation. The authors highlight a gap in clinical hematology teaching, particularly compared to “conventional rotations”.1 Their suggestion has merits and we agree with most of the points raised; however, propose instead for us to build on current teaching as opposed to establishing a new rotation.The integration of theoretical and practical learning was concluded to be beneficial to both teacher and student by Wrenn and Wrenn.2 In the original article it is mentioned that “clinical experience allows students to comprehend and apply this knowledge in practice, enabling the all-important integration of their learning”.1 As we agree that hematology overlaps with other specialties and therefore requires a thorough understanding, we value how a clinical attachment would be useful to solidify lecture-based teaching.View the original paper by Mandan et al.

Hematological findings in children with brucellosis.

Science.gov (United States)

Aypak, Adalet; Aypak, Cenk; Bayram, Yasemin

2015-12-01

Brucellosis produces a variety of non-specific hematological abnormalities. The aim of the present study was to evaluate the hematological findings in childhood brucellosis. Medical records of children with brucellosis admitted to a tertiary hospital in a 1 year period, were analyzed retrospectively. Sixty-nine patients (mean age, 14.5 ± 3.3 years) were diagnosed with brucellosis. The most common hematological finding was thrombocytopenia (n = 11, 15.9%). Thrombocytosis was detected in five patients (7.3%), leukopenia in four (5.8%), anemia in three (4.3%), and bicytopenia in three (4.3%). None of the patients had pancytopenia. Blood culture was positive for Brucella spp. in 41 patients (59.4%). Among those patients with positive blood culture, six (14.6%) had serum agglutination test titer ≤1/80. Platelet (PLT) count was significantly lower in the bacteremia-positive group. The OR (95%CI) of bacteremia for PLT cut-off 200,000/mm(3) was 0.148 (95%CI: 0.031-0.718) and relative risk was 1.718 (95%CI: 1.244-2.372; P = 0.010). Brucellosis should be kept in mind in the differential diagnosis of isolated thrombocytopenia in pediatric patients from endemic areas. © 2015 Japan Pediatric Society.

Response properties of the refractory auditory nerve fiber.

Science.gov (United States)

Miller, C A; Abbas, P J; Robinson, B K

2001-09-01

The refractory characteristics of auditory nerve fibers limit their ability to accurately encode temporal information. Therefore, they are relevant to the design of cochlear prostheses. It is also possible that the refractory property could be exploited by prosthetic devices to improve information transfer, as refractoriness may enhance the nerve's stochastic properties. Furthermore, refractory data are needed for the development of accurate computational models of auditory nerve fibers. We applied a two-pulse forward-masking paradigm to a feline model of the human auditory nerve to assess refractory properties of single fibers. Each fiber was driven to refractoriness by a single (masker) current pulse delivered intracochlearly. Properties of firing efficiency, latency, jitter, spike amplitude, and relative spread (a measure of dynamic range and stochasticity) were examined by exciting fibers with a second (probe) pulse and systematically varying the masker-probe interval (MPI). Responses to monophasic cathodic current pulses were analyzed. We estimated the mean absolute refractory period to be about 330 micros and the mean recovery time constant to be about 410 micros. A significant proportion of fibers (13 of 34) responded to the probe pulse with MPIs as short as 500 micros. Spike amplitude decreased with decreasing MPI, a finding relevant to the development of computational nerve-fiber models, interpretation of gross evoked potentials, and models of more central neural processing. A small mean decrement in spike jitter was noted at small MPI values. Some trends (such as spike latency-vs-MPI) varied across fibers, suggesting that sites of excitation varied across fibers. Relative spread was found to increase with decreasing MPI values, providing direct evidence that stochastic properties of fibers are altered under conditions of refractoriness.

Refractory alloy technology for space nuclear power applications

International Nuclear Information System (INIS)

Cooper, R.H. Jr.; Hoffman, E.E.

1984-01-01

Purpose of this symposium is twofold: (1) to review and document the status of refractory alloy technology for structural and fuel-cladding applications in space nuclear power systems, and (2) to identify and document the refractory alloy research and development needs for the SP-100 Program in both the short and the long term. In this symposium, an effort was made to recapture the space reactor refractory alloy technology that was cut off in midstream around 1973 when the national space nuclear reactor program began in the early 1960s, was terminated. The six technical areas covered in the program are compatibility, processing and production, welding and component fabrication, mechanical and physical properties, effects of irradiation, and machinability. The refractory alloys considered are niobium, molybdenum, tantalum, and tungsten. Thirteen of the 14 pages have been abstracted separately. The remaining paper summarizes key needs for further R and D on refractory alloys

Distribution and features of hematological malignancies in Eastern Morocco: a retrospective multicenter study over 5 years.

Science.gov (United States)

Elidrissi Errahhali, Mounia; Elidrissi Errahhali, Manal; Boulouiz, Redouane; Ouarzane, Meryem; Bellaoui, Mohammed

2016-02-25

Hematological malignancies (HM) are a public health problem. The pattern and distribution of diagnosed hematological cancers vary depending on age, sex, geography, and ethnicity suggesting the involvement of genetic and environmental factors for the development of these diseases. To our knowledge, there is no published report on HM in the case of Eastern Morocco. In this report we present for the first time the overall pattern of HM for this region. Retrospective descriptive study of patients diagnosed with HM between January 2008 and December 2012 in three centres in Eastern Morocco providing cancer diagnosis, treatment or palliative care services. The FAB (French-American-British) classification system has been taken into account in the analysis of myeloid and lymphoid neoplasms. In this study, a total of 660 cases of HM were registered between January 2008 and December 2012. Overall, 6075 cases of cancers all sites combined were registered during this study period, indicating that HM account for around 10.9 % (660/6075) of all cancers recorded. Among the 660 registered cases of HM, 53 % were males and 47 % were females, with a male to female ratio of 1.1. Thus, overall, men are slightly more affected with HM than women. By contrast, a female predominance was observed in the case of Hodgkin's lymphoma (HL), myeloproliferative neoplasms (MPN), acute myeloid leukemia (AML) and the myelodysplastic syndrome (MDS). HM occur at a relatively young age, with an overall median age at diagnosis of 54 years. Non-Hodgkin's lymphoma (NHL) was the most common HM accounting for 29.7 % of all HM, followed by HL, MPN, multiple myelomas (MM), chronic lymphocytic leukemia (CLL), AML, MDS, acute lymphoblastic leukemia (ALL), and Waldenström macroglobulinemia (WM). The majority of HM cases have been observed among patients aged 60 years and over (40.4 % of HM). Among this age group, NHL was the most common HM. In adolescents, HL was the most frequent HM. This study provided for the

Risk of severe hematologic toxicities in cancer patients treated with PARP inhibitors: results of monotherapy and combination therapy trials

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Alecu I

2018-02-01

Full Text Available Iulian Alecu, Tsveta Milenkova, Simon R Turner Research and Development, AstraZeneca UK Limited, Cambridge, UKThe tolerability profile of PARP inhibitors often includes hematologic toxicities, and the characterization of these adverse events is important to allow effective management by clinicians. Zhou et al1 recently carried out a meta-analysis of the incidence and relative risks of severe neutropenia, thrombocytopenia, and anemia events in 12 randomized controlled trials of PARP inhibitors, either as monotherapy or in combination with chemotherapy or radiotherapy. The authors concluded that olaparib resulted in a higher incidence of severe (common terminology criteria for adverse events [CTCAE] grade $3 neutropenia when compared with niraparib and veliparib; however, these conclusions are based on inappropriate and incomplete comparisons of hematologic toxicity with olaparib or veliparib in combination with myelotoxic chemotherapy versus niraparib monotherapy. While both monotherapy and combination therapy olaparib studies are discussed in the paper, the neutropenia analysis is based on olaparib data solely from studies in combination with paclitaxel or paclitaxel plus carboplatin. In order to inform the practicing clinician of the relative risk of hematologic toxicity associated with different PARP inhibitors, direct comparison needs to be conducted based on monotherapy, where applicable, as per the approved drug indication, otherwise the reader is given misleading information.View the original paper by Zhou et al.

Hematological parameters in children with Down syndrome

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Renato Nisihara

2015-04-01

Full Text Available Introduction: There are few studies that investigated whether Down syndrome (DS interferes with references values for complete blood counts (CBC test in children with the syndrome. Objective: This study aimed to analyze the results of CBC performed in children with DS. Patients and methods: Data from CBC of DS children were included; at the time of examination they were aged between 2 and 10 years and had no clinical signs and/or symptoms of infectious disease. The hematological parameters analyzed were: total number of erythrocytes (RBC, hemoglobin (Hb concentration, hematological indices, platelet count, and total number of leucocytes. Additionally, we compared the collected parameters according to gender and age of the children studied. Results: A total of 203 CBC (100 girls and 103 boys were evaluated. In general, no significant differences were observed in studied parameters between the values found in samples of DS children and the values described in the literature as a reference for children in this age group. No difference in the prevalence of anemia was observed in relation to gender (p = 0.33, 14/103 (13.6% boys, and 11/100 (11% girls had anemia. However, the Hb and hematological indices values found in boys was significantly lower than in girls (p < 0.001. Conclusion: This investigation is the first one in Brazil to present and analyze the CBC results of DS children, reporting that their hematological indices are within the expected range for children without DS. Additionally, it was found that 12.3% of them had anemia.

An investigation into mineral processing of north Semnan refractory earth

International Nuclear Information System (INIS)

Aslani, S.; Samin-Bani-Hashemi, H.R.; Taghi-Zadeh, O.

2002-01-01

This paper is dealing with refractory earth of North Semnan. Having an area of 2000 square kilometers, Semnan province is mainly formed by sedimentary rocks with a verity of refractory earth, red earth and kaolin containing heavy minerals. The refractory earth of this area contains a considerable rate of aluminum oxide in shape of dia spore minerals, behemoth and gybsite along with heavy minerals of iron and titanium. To improve the quality of refractory earth, in order to be used in related industries, these minerals have to be separated. To assess the quality of refractory earth of North Semnan as the raw materials of refractory industries, their genesis and mineralogy properties have been precisely studied. Based on the rate of aluminium oxide of the refractory earth of North Semnan mines, a suitable mineral deposit has been selected for more investigation. Using XRD and X RF methods along with electronic and photo microscopes, the refractory earth and heavy minerals of them have been assessed. The elementary laboratory experiments of fragmentation and magnetic separation have been performed. It has been proved that the iron minerals can be separated and, therefore, the quality of the refractory earth can be improved. The separation of titanium minerals has to be investigated with other methods

REFRACTORY THROMBOCYTOPENIA AND NEUTROPENIA: A DIAGNOSTIC CHALLENGE

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Emmanuel Gyan

2015-02-01

Full Text Available Background. The 2008 WHO classification identified refractory cytopenia with unilineage dysplasia (RCUD as a composite entity encompassing refractory anemia, refractory thrombocytopenia (RT, and refractory neutropenia (RN, characterized by 10% or more dysplastic cells in the bone marrow respective lineage. The diagnosis of RT and RN is complicated by several factors.  Diagnosing RT first requires exclusion of familial thrombocytopenia, chronic auto-immune thrombocytopenia, concomitant medications, viral infections, or hypersplenism. Diagnosis of RN should also be made after ruling out differential diagnoses such as ethnic or familial neutropenia, as well as acquired, drug-induced, infection-related or malignancy-related neutropenia. An accurate quantification of dysplasia should be performed in order to distinguish RT or RN from the provisional entity named idiopathic cytopenia of unknown significance (ICUS. Cytogenetic analysis, and possibly in the future somatic mutation analysis (of genes most frequently mutated in MDS, and flow cytometry analysis aberrant antigen expression on myeloid cells may help in this differential diagnosis. Importantly, we and others found that, while isolated neutropenia and thrombocytopenia are not rare in MDS, those patients can generally be classified (according to WHO 2008 classification as refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts, while RT and RN (according to WHO 2008 are quite rare.These results suggest in particular that identification of RT and RN as distinct entities could be reconsidered in future WHO classification updates.

Increased cancer risk in patients with periodontitis.

Science.gov (United States)

Dizdar, Omer; Hayran, Mutlu; Guven, Deniz Can; Yılmaz, Tolga Birtan; Taheri, Sahand; Akman, Abdullah C; Bilgin, Emre; Hüseyin, Beril; Berker, Ezel

2017-12-01

Previous studies have noted a possible association between periodontal diseases and the risk of various cancers. We assessed cancer risk in a cohort of patients with moderate to severe periodontitis. Patients diagnosed with moderate to severe periodontitis by a periodontist between 2001 and 2010 were identified from the hospital registry. Patients younger than 35 years of age or with a prior cancer diagnosis were excluded. The age- and gender-standardized incidence rates (SIR) were calculated by dividing the number of observed cases by the number of expected cases from Turkish National Cancer Registry 2013 data. A total of 280 patients were included (median age 49.6, 54% female). Median follow-up was 12 years. Twenty-five new cancer cases were observed. Patients with periodontitis had 77% increased risk of cancer (SIR 1.77, 95% CI 1.17-2.58, p = .004). Women with periodontitis had significantly higher risk of breast cancer (SIR 2.40, 95% CI 0.88-5.33) and men with periodontitis had significantly higher risk of prostate cancer (SIR 3.75, 95% CI 0.95-10.21) and hematological cancers (SIR 6.97, 95% CI 1.77-18.98). Although showing a causal association necessitates further investigation, our results support the idea that periodontitis might be associated with increased cancer risk, particularly with hematological, breast and prostate cancers.

Refractory alloy technology for space nuclear power applications

Energy Technology Data Exchange (ETDEWEB)

Cooper, R.H. Jr.; Hoffman, E.E. (eds.)

1984-01-01

Purpose of this symposium is twofold: (1) to review and document the status of refractory alloy technology for structural and fuel-cladding applications in space nuclear power systems, and (2) to identify and document the refractory alloy research and development needs for the SP-100 Program in both the short and the long term. In this symposium, an effort was made to recapture the space reactor refractory alloy technology that was cut off in midstream around 1973 when the national space nuclear reactor program began in the early 1960s, was terminated. The six technical areas covered in the program are compatibility, processing and production, welding and component fabrication, mechanical and physical properties, effects of irradiation, and machinability. The refractory alloys considered are niobium, molybdenum, tantalum, and tungsten. Thirteen of the 14 pages have been abstracted separately. The remaining paper summarizes key needs for further R and D on refractory alloys. (DLC)

Hope, quality of life, and benefit from treatment in women having chemotherapy for platinum-resistant/refractory recurrent ovarian cancer: the gynecologic cancer intergroup symptom benefit study.

Science.gov (United States)

Sjoquist, Katrin M; Friedlander, Michael L; O'Connell, Rachel L; Voysey, Merryn; King, Madeleine T; Stockler, Martin R; Oza, Amit M; Gillies, Kim; Martyn, Julie K; Butow, Phyllis N

2013-01-01

Chemotherapy for platinum-resistant/refractory ovarian cancer is motivated by the hope of benefit. We sought to determine the relationships between: (a) trait hope, expectation of symptom benefit from chemotherapy, and anxiety and depression; (b) hope and perceived efficacy of chemotherapy; and (c) unfulfilled hope (where expectations for benefit are not fulfilled) and depression. Methods. Adult patients enrolled within stage 1 of the Gynecologic Cancer Intergroup Symptom Benefit Study were included. Patient. Reported outcomes were collected from 126 women with predominantly platinum-resistant ovarian cancer at baseline, prior to the first four treatment cycles (12-16 weeks), and four weeks after completing chemotherapy or at disease progression, whichever came first. Associations were assessed with Spearman rank correlation coefficient (r) and odds ratio. Results. Trait hope and expectation of symptom benefit from chemotherapy were weakly correlated with each other (r = 0.25). Trait hope, but not expectation of symptom benefit, was negatively correlated with anxiety (r = -0.43) and depression (r = -0.50). The smaller the discrepancy between perceived and expected symptom benefit, the less likely the patient was to have scores indicative of depression (odds ratio: 0.68; 95% confidence interval: 0.49-0.96; p = .026). Conclusion. Trait hope and expectation of symptom benefit from chemotherapy appear to be distinct and independent of the aspects of quality of life and scores for depression. Hope did not appear to affect perceived efficacy of chemotherapy in alleviating symptoms, but women whose expectation of symptom benefit from chemotherapy was not fulfilled were more likely to have scores indicative of depression. It may be preferable to encourage hope toward achievable goals rather than toward benefits from chemotherapy.

Temperature and Thermal Stress Analysis of Refractory Products

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Shaoyang Shi

2013-05-01

Full Text Available Firstly current status of temperature and thermal stress research of refractory product at home and aboard are analyzed. Finite element model of two classical refractory products is building by using APDL language. Distribution law of temperature and thermal stress of two typical refractory products-ladles and tundish are analyzed and their structures are optimized. Stress of optimal structure is dropped obviously, and operation life is increased effectively.

Cancer cachexia

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Nada Rotovnik Kozjek

2013-02-01

Full Text Available The present article presents the Slovenian multidisciplinary agreement statement on the definition, staging, clinical classification and multimodal approach to the treatment of cachexia in cancer patients. The consensus was reached during a multidisciplinary plenary session, and is based on the international definition of cancer cachexia adopted in 2011. Cancer cachexia is a multifactorial metabolic syndrome defined by an ongoing loss of skeletal muscle with or without concomitant loss of fat, which cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterized by a negative energy and protein balance due to a variable combination of reduced food intake and metabolic changes. In cancer patients, the cachexia syndrome can develop progressively through various stages – from precachexia to cachexia and finally, to refractory cachexia–represent-ing a continuum of metabolic changes, clini-cal signs and symptoms. Patients can progress from precachexia to cachexia, and reverse from cachexia into precachectic stages, while (as the term itself implies, the condition of refractory or irreversible cachexia has poor therapeutic response. A clinical algorithm for recognition and treatment of cachexia in cancer patients is presented. All cancer patients should be screened for cachexia and precachexia on presentation. Patients who fulfil diagnostic criteria for cancer cachexia should have its clinical stage determined. According to phenotype / clinical stage, a multimodal approach should be adopted in the treatment of all cases of cancer cachexia. A typical multimodal management plan in cachectic patients consists of early dietary intervention, exercise, anti-inflammatory therapy and early cancer-related symptom relief. The cachexia treatment pathway should be adopted as a pathway parallel to conventional cancer treatment. Practical implementation of cancer cachexia

Hematologic outcomes after total splenectomy and partial splenectomy for congenital hemolytic anemia☆☆☆

Science.gov (United States)

Englum, Brian R.; Rothman, Jennifer; Leonard, Sarah; Reiter, Audra; Thornburg, Courtney; Brindle, Mary; Wright, Nicola; Heeney, Matthew M.; Smithers, C. Jason; Brown, Rebeccah L.; Kalfa, Theodosia; Langer, Jacob C.; Cada, Michaela; Oldham, Keith T.; Scott, J. Paul; St Peter, Shawn D; Sharma, Mukta; Davidoff, Andrew M.; Nottage, Kerri; Bernabe, Kathryn; Wilson, David B.; Dutta, Sanjeev; Glader, Bertil; Crary, Shelley E.; Dassinger, Melvin S.; Dunbar, Levette; Islam, Saleem; Kumar, Manjusha; Rescorla, Fred; Bruch, Steve; Campbell, Andrew; Austin, Mary; Sidonio, Robert; Blakely, Martin L.; Rice, Henry E.

2016-01-01

Purpose The purpose of this study was to define the hematologic response to total splenectomy (TS) or partial splenectomy (PS) in children with hereditary spherocytosis (HS) or sickle cell disease (SCD). Methods The Splenectomy in Congenital Hemolytic Anemia (SICHA) consortium registry collected hematologic outcomes of children with CHA undergoing TS or PS to 1 year after surgery. Using random effects mixed modeling, we evaluated the association of operative type with change in hemoglobin, reticulocyte counts, and bilirubin. We also compared laparoscopic to open splenectomy. Results The analysis included 130 children, with 62.3% (n = 81) undergoing TS. For children with HS, all hematologic measures improved after TS, including a 4.1 g/dl increase in hemoglobin. Hematologic parameters also improved after PS, although the response was less robust (hemoglobin increase 2.4 g/dl, p < 0.001). For children with SCD, there was no change in hemoglobin. Laparoscopy was not associated with differences in hematologic outcomes compared to open. TS and laparoscopy were associated with shorter length of stay. Conclusion Children with HS have an excellent hematologic response after TS or PS, although the hematologic response is more robust following TS. Children with SCD have smaller changes in their hematologic parameters. These data offer guidance to families and clinicians considering TS or PS. PMID:26613837

Hematological remission and long term hematological control of acute myeloblastic leukemia induced and maintained by granulocyte-colony stimulating factor (G-CSF) therapy.

Science.gov (United States)

Xavier, Luciana; Cunha, Manuel; Gonçalves, Cristina; Teixeira, Maria dos Anjos; Coutinho, Jorge; Ribeiro, António Carlos Pinto; Lima, Margarida

2003-12-01

We describe a case of a patient with CD34+, TdT+, CD13-, CD33-, MPO- undifferentiated acute leukemia who refused chemotherapy and who achieved complete hematological remission 14 months after the diagnosis, during a short course of granulocyte-colony stimulating factor (G-CSF) for neutropenia and life threatening infection. Relapse occurred approximately one year later and G-CSF was reintroduced, being maintained for 4 months, at a dose and frequency adapted to maintain normal blood counts, a complete hematological remission being achieved again. Five months after withdrawing the G-CSF therapy a second relapse was observed; G-CSF was tried again with success, resulting in a very good hematological response that was sustained by G-CSF maintenance therapy. One year latter there was the need of increasing the doses of G-CSF in order to obtain the same hematological effect, at same time blast cells acquired a more mature CD34+, TdT-, CD13+, CD33-, MPO+ myeloid phenotype. Finally, the patient developed progressive neutropenia, anemia, thrombocytopenia and acute leukemia in spite of G-CSF therapy, dying 64 months after initial diagnosis (50 months after starting G-CSF therapy) with overt G-CSF resistant acute myeloblastic leukemia (AML), after failure of conventional induction chemotherapy.

Subspeciality training in hematology and oncology, 2003: results of a survey of training program directors conducted by the American Society of Hematology.

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Todd, Robert F; Gitlin, Scott D; Burns, Linda J

2004-06-15

A survey of directors of adult and pediatric hematology/oncology subspecialty training programs in the United States and Canada was conducted to assess the environment in which recruitment and training is conducted in these medical disciplines. A total of 107 program directors responded to the survey, representing 66% of internal medicine and 47% of pediatric subspecialty programs in hematology or hematology/oncology. Specific areas covered in the web-based questionnaire included the type and demographics of the training program, profile of the training program director, characteristics of the applicant pool and existing trainee recruits, characteristics of the training program environment and curricula, research productivity of trainees, and the career pathways taken by recent training program graduates (including dominant areas of clinical interest). The results of this survey show considerable heterogeneity in the recruiting practices and the environment in which subspecialty training occurs, leading the authors to recommend improvements in or a heightened attention to issues, including recruitment of minority trainees, flexibility to recruit international medical school graduates, timing of trainee acceptance, maintaining the financial support of Medicare graduation medical education (GME), training of physician scientists, organization of the continuity clinic experience, visibility of nonmalignant hematology as a career path, and level of training program director support.

Complete androgen blockade safely allows for delay of cytotoxic chemotherapy in castration refractory prostate cancer

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Rafael A. Kaliks

2010-06-01

Full Text Available PURPOSE: Complete androgen blockade (CAB does not prolong overall survival (OS in patients with castration refractory prostate cancer (CRPC. Although there is variable clinical benefit with second-line hormone manipulation, we do not know which patients might benefit the most. OBJECTIVES: To identify clinical predictors of benefit of complete androgen blockade. MATERIALS AND METHODS: We reviewed the records for 54 patients who received treatment with CAB in the setting of disease progression despite castration. We evaluated progression-free survival (PFS and OS according to PSA at diagnosis, Gleason scores, age, testosterone level, and duration of prior disease control during castration in first line treatment. RESULTS: Among 54 patients who received CAB, the median PFS was 9 months (CI 4.3-13.7 and OS was 36 months (CI 24-48. We did not find an effect of PSA at diagnosis (p = 0.32, Gleason score (p = 0.91, age (p = 0.69 or disease control during castration (p = 0.87 on PFS or OS. Thirty-four patients subsequently received chemotherapy, with a mean OS of 21 months (CI 16.4-25.5, median not reached. CONCLUSION: Age, Gleason score, PSA at diagnosis and length of disease control with castration did not affect PFS or OS. In the absence of predictors of benefit, CAB should still be considered in CRPC.

A phase 2, open-label, multi-center study of amuvatinib in combination with platinum etoposide chemotherapy in platinum-refractory small cell lung cancer patients.

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Byers, Lauren Averett; Horn, Leora; Ghandi, Jitendra; Kloecker, Goetz; Owonikoko, Taofeek; Waqar, Saiama Naheed; Krzakowski, Maciej; Cardnell, Robert J; Fujimoto, Junya; Taverna, Pietro; Azab, Mohammad; Camidge, David Ross

2017-10-06

Amuvatinib (MP-470) is a multi-targeted kinase inhibitor with potent activity against c-Kit, synergistic with DNA-damaging agents. We evaluated amuvatinib in combination with platinum-etoposide (EP) chemotherapy by objective response rate, survival, and tolerability in platinum-refractory small cell lung cancer (SCLC) patients. This study used a Simon 2-stage design requiring ≥3 centrally confirmed responses in the first 21 subjects. Subjects received EP with 300 mg amuvatinib orally three times daily in cycles of 21 days. A three-day amuvatinib run-in period before EP occurred in Cycle 1. Subjects received the same EP chemotherapy regimen given prior to progression/relapse. Among 23 subjects treated, we observed four PRs (17.4%) per RECIST 1.1, only two of which were centrally confirmed (8.7%, response duration 119, 151 days). Three subjects (13%) had confirmed stable disease. c-Kit H-score was ≥100 in two subjects whose respective durations of disease control were 151 and 256 days. The addition of amuvatinib to EP chemotherapy in unselected, platinum-refractory SCLC did not meet the primary endpoint of ≥3 confirmed responses in stage 1. However, high c-Kit expression in two subjects with durable disease control suggests the potential for further study of amuvatinib in SCLC patients with high c-Kit expression.

Comparative evaluation of the locally manufactured low-alumina fireclay refractories

International Nuclear Information System (INIS)

Mohammad, D.; Ahmed, W.; Khan, M.I.

2007-01-01

Properties of domestically produced low-alumina refractories commonly known as medium duty fireclay refractories were studied and a comparative evaluation was performed. Refractory properties such as density, porosity, cold strength, reheat change and deformation at high-temperature were determined. Significant differences were discovered between these products sold as medium duty fireclay refractories. One brand marketed as medium duty refractory was found to be too inferior to be designated as medium duty firebrick. Absence of any standards and lack of awareness on the part of users of the various test methods appear to be the cause of this situation. (author)

Directed light fabrication of refractory metals and alloys

International Nuclear Information System (INIS)

Fonseca, J.C.; Lewis, G.K.; Dickerson, P.G.; Nemec, R.B.

1999-01-01

This report covers deposition of refractory pure metals and alloys using the Directed Light Fabrication (DLF) process and represents progress in depositing these materials through September 1998. In extending the DLF process technology to refractory metals for producing fully dense, structurally sound deposits, several problems have become evident. (1) Control of porosity in DLF-deposited refractory metal is difficult because of gases, apparently present in commercially purchased refractory metal powder starting materials. (2) The radiant heat from the molten pool during deposition melts the DLF powder feed nozzle. (3) The high reflectivity of molten refractory metals, at the Nd-YAG laser wavelength (1.06microm), produces damaging back reflections to the optical train and fiber optic delivery system that can terminate DLF processing. (4) The current limits on the maximum available laser power to prevent back reflection damage limit the parameter range available for densification of refractory metals. The work to date concentrated on niobium, W-25Re, and spherodized tungsten. Niobium samples, made from hydride-dehydride powder, had minimal gas porosity and the deposition parameters were optimized; however, test plates were not made at this time. W-25Re samples, containing sodium and potassium from a precipitation process, were made and porosity was a problem for all samples although minimized with some process parameters. Deposits made from potassium reduced tungsten that was plasma spherodized were made with minimized porosity. Results of this work indicate that further gas analysis of starting powders and de-gassing of starting powders and/or gas removal during deposition of refractory metals is required

Hematology of camelids.

Science.gov (United States)

Vap, Linda; Bohn, Andrea A

2015-01-01

Interpretation of camelid hematology results is similar to that of other mammals. Obtaining accurate results and using appropriate reference intervals can be a bit problematic, particularly when evaluating the erythron. Camelid erythrocytes vary from other mammals in that they are small, flat, and elliptical. This variation makes data obtained from samples collected from these species prone to error when using some automated instruments. Normal and abnormal findings in camelid blood are reviewed as well as how to ensure accurate results.

Hematological findings in Noonan syndrome

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Bertola Débora R.

2003-01-01

Full Text Available OBJECTIVE: Noonan syndrome is a multiple congenital anomaly syndrome, and bleeding diathesis is considered part of the clinical findings. The purpose of this study was to determine the frequency of hemostatic abnormalities in a group of Noonan syndrome patients. METHOD: We studied 30 patients with clinical diagnosis of Noonan syndrome regarding their hemostatic status consisting of bleeding time, prothrombin time, activated partial thromboplastin time and thrombin time tests, a platelet count, and a quantitative determination of factor XI. RESULTS: An abnormal laboratory result was observed in 9 patients (30%. Although coagulation-factor deficiencies, especially factor XI deficiency, were the most common hematological findings, we also observed abnormalities of platelet count and function in our screening. CONCLUSIONS: Hemostatic abnormalities are found with some frequency in Noonan syndrome patients (30% in our sample. Therefore, we emphasize the importance of a more extensive hematological investigation in these patients, especially prior to an invasive procedure, which is required with some frequency in this disorder.

Pancytopenia: A clinico-hematological study

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Fahim Manzoor

2014-01-01

Full Text Available Background: A review of both Western and Indian literature shows that there are few comprehensive studies on pancytopenia. In India, the causes of pancytopenia are not well defined. This data, if available, would help in planning the diagnostic and therapeutic approach in patients with pancytopenia. Aim: To evaluate the cases of pancytopenia by peripheral smear and/or bone marrow aspiration and/or bone marrow biopsy to find out the etiology, clinical, hematological, and histomorphologic features of pancytopenia. Materials and Methods: Detailed hematological investigations a complete hemogram, peripheral smear examination, bone marrow aspiration, and biopsy examination were done. Results: The most common cause of pancytopenia in our study was megaloblastic anemia (56%, followed by hypoplastic/aplastic anemia (14%, hypersplenism (8% and post viral illness (6%. Conclusion: Megaloblastic anemia due to vitamin B12/folate deficiency seems to reflect the higher prevalence of pancytopenia in Indian subjects, putting hypoplastic/aplastic anemia in the second position, which is the leading cause for pancytopenia in the Western countries.

Machining refractory alloys: an overview

International Nuclear Information System (INIS)

Christopher, J.D.

1984-01-01

Nontraditional machining is a generic term for those material removal processes that differ drastically from the historic operations such as turning, milling, drilling, tapping, and grinding. The use of primary energy modes other than mechanical, such as thermal, electrical, and chemical, sets these operations apart and reinforces their nontraditional label. Several of these newer processes have been very successful in machining close tolerance parts from refractory materials. This paper provides a general overview of both traditional and nontraditional aspects of machining refractory materials. 11 figures, 7 tables

Pretreatment long interspersed element (LINE-1 methylation levels, not early hypomethylation under treatment, predict hematological response to azacitidine in elderly patients with acute myeloid leukemia

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Cross M

2013-06-01

Full Text Available Michael Cross,1 Enrica Bach,1 Thao Tran,1 Rainer Krahl,1 Nadja Jaekel,1 Dietger Niederwieser,1 Christian Junghanss,2 Georg Maschmeyer,3 Haifa Kathrin Al-Ali11Division of Hematology and Oncology, University of Leipzig, Leipzig, Germany; 2Clinic for Hematology, Oncology and Palliative Medicine, University of Rostock, Rostock, Germany; 3Clinic for Hematology, Oncology and Palliative Medicine, Ernst-von-Bergmann Clinic, Potsdam, GermanyBackground: Epigenetic modulations, including changes in DNA cytosine methylation, are implicated in the pathogenesis and progression of acute myeloid leukemia (AML. Azacitidine is a hypomethylating agent that is incorporated into RNA as well as DNA. Thus, there is a rationale to its use in patients with AML. We determined whether baseline and/or early changes in the methylation of long interspersed element (LINE-1 or CDH13 correlate with bone marrow blast clearance, hematological response, or survival in patients with AML treated with azacitidine.Methods: An open label, phase I/II trial was performed in 40 AML patients (median bone marrow blast count was 42% unfit for intensive chemotherapy treated with azacitidine 75 mg/m2/day subcutaneously for 5 days every 4 weeks. Bone marrow mononuclear cell samples were taken on day 0 (pretreatment and day 15 during the first treatment cycle; LINE-1 and CDH13 methylation levels were quantified by methylation-specific, semiquantitative, real-time polymerase chain reaction.Results: Treatment with azacitidine significantly reduced LINE-1 but not CDH13 methylation levels over the first cycle (P < 0.0001. Absolute LINE-1 methylation levels tended to be lower on day 0 (P = 0.06 and day 15 of cycle 1 (P = 0.03 in patients who went on to achieve subsequent complete remission, partial remission or hematological improvement versus patients with stable disease. However, the decrease in LINE-1 methylation over the first treatment cycle did not correlate with subsequent response (P = 0

Intraoperative radiotherapy for locally advanced refractory cancer

Energy Technology Data Exchange (ETDEWEB)

Abe, Mitsuyuki; Takahashi, Masaji; Ono, Koji; Dodo, Yoshihiro; Hiraoka, Masahiro [Kyoto Univ. (Japan). Faculty of Medicine

1983-05-01

Clinical results of intraoperative radiotherapy (IOR) in carcinoma of the stomach and prostate, and malignant soft tissue tumors are reported. The 5-year survival rate was found to be increased by IOR in stages II-IV gastric cancer. From the analysis of the clinical results of prostatic cancer, a single dose of 3,500 rad was considered to be a potential curative dose for the tumor less than 3 cm in diameter. The local recurrence rate of patients with malignant soft tissue tumors who received a single dose ranging from 3,000 to 4,500 rad was 5.9 and the 5-year survival rate was 64.6 %.

Main hematological parameters of sturgeon species (Acipenseridae (review

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M. Simon

2017-03-01

Full Text Available Purpose. To analyze scientific sources on the physiological, biochemical, ecological and genetic features of the main hematological paremeters and patterns of their variability in sturgeon species (Acipenseridae. To examine the fundamental aspects of lipid and protein metabolism in blood serum and the effect of biotic and abiotic factors on them. To highlight the common features of serum enzymes. Findings. A review of scientific papers revealed that although hematological parameters of sturgeons are generally similar to those of teleosts and mammals, there are a number of significant differences. In addition, many hematological parameters are characterized by species specificity, even within a family. Special attention is given to the variability of hematological parameters under the effect of factors of both internal and external environment. The paper describes the effects of sex and age, as well as the seasons of the year on the compositio of sturgeon blood. The fundamentals of the use of serum proteins in genetic and population studies are outlined. The features of the functioning of hemoglobin in sturgeon’s red blood cells are examined. The main hematological parameters involved in the formation and maturation of sexual products, and their effect on fertility are reviewed. For example, the spawners, which hadn’t put reproductive product, are characterized by a low rate of hemoglobin, increase in erythrocyte sedimentation speed and also a rise of the level of crude protein in blood and β-lipoproteid serum.The biochemical parameters (total protein and fractions, glucose, creatinine, cholesterol, the activity of some enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine kinase in serum are examined. Practical value. The systematized data on the main hematological parameters and patterns of their variability in sturgeon species will be useful for both scientits and fish farmers. This is due to the

Invasive fungal sinusitis in patients with hematological malignancy: 15 years experience in a single university hospital in Taiwan

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Huang Shang-Yi

2011-09-01

Full Text Available Abstract Background Risk factors and outcomes in hematological patients who acquire invasive fungal sinusitis (IFS are infrequently reported in the modern medical era. Method A retrospective study of hospitalized patients with hematological disease was conducted at National Taiwan University Hospital between January 1995 and December 2009. Results Clinical characteristics and outcomes with their associated radiographic and microbiological findings were analyzed. Forty-six patients with IFS and 64 patients with chronic non-invasive sinusitis were enrolled as comparsion. IFS developed more commonly in patients with acute myeloid leukemia (AML and with prolonged neutropenia (absolute neutrophil count less than 500/mm3 for more than 10 days (p Aspergillus flavus was the most common pathogen isolated (44%. Serum Aspergillus galactomannan antigen was elevated in seven of eleven patients (64% with IFS caused by aspergillosis but negative for all three patients with mucormycosis. Bony erosion and extra-sinus infiltration was found in 15 of 46 (33% patients on imaging. Overall, 19 of 46 patients (41.3% died within 6 weeks. Patients with disease subtype of AML (p = 0.044; Odds Ratio [OR], 5.84; 95% confidence interval [95% CI], 1.02-30.56 and refractory leukemia status (p = 0.05; OR, 4.27; 95% CI, 1.003-18.15 had worse prognosis. Multivariate analysis identified surgical debridement as an independent good prognostic factor (p = 0.047 in patients with IFS. Conclusions Patients of AML with prolonged neutropenia (> 10 days had significantly higher risk of IFS. Early introduction of anti-fungal agent and aggressive surgical debridement potentially decrease morbidity and mortality in high risk patients with IFS.

The Importance of Hematological Parameters in Acute Respiratory Viral Infections in Children

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L. A. Alekseeva

2013-01-01

Full Text Available Hematological studies are basic and mandatory in diagnostics and laboratory monitoring of infectious diseases, which led to their inclusion in the modern standards of laboratory examinations of children. Assessment of hematological parameters used for the provisional differential diagnosis of viral or bacterial nature of the disease. For research currently being used increasingly Hematology analyzers, which allows to facilitate and standardize the results. In this paper a comparison and differences hematological parameters practically healthy children and children with respiratory infections. Identified some changes in indicators of haemogram depending on the etiology and character of the clinical course of the disease. On the basis of the leukocyte formula defined leukocyte indices of intoxication and illustrates their importance in assessing the severity of the infection process.

Production of lightweight refractory material by hydrothermal process

International Nuclear Information System (INIS)

Sulejmani, Ramiz B.

2002-01-01

Many different processes of production of lightweight refractories are well known over the World. Traditional production of lightweight refractories is by addition of combustibles or by a special frothing process. This work is concerned with hydrothermal of lightweight refractories from rice husk ash. The rice husk ash, used in present investigations were from Kocani region, R. Macedonia. The chemical analysis of the rice husk ash shows that it contains 91,8 - 93,7% SiO 2 and some alkaline and alkaline earth oxides. Microscopic and X - ray diffraction examinations of the rice husk ash have shown that it is composed of cristobalite, tridimite and amorphous silica. The composition of the mixture for lightweight refractory brick production is 93,4% rice husk ash and 6,6% Ca(OH) 2 . The mixtures were well mixed, moistened and pressed at 5 - 10 MPa. The hydrothermal reactions between calcium hydroxide and rice husk ash over the temperature range 80 - 160 o C were investigated. The period of autoclave treatment was from 2 to 72 h. After the hydrothermal treatment of the samples, the mineralogical composition, bulk density, density, cold crushing strength, porosity, refractoriness and thermal expansion were examined. Analysing the properties of the obtained samples it can be concluded that from rice husk ash and calcium hydroxide under hydrothermal condition it is possible to obtain lightweight acid refractory material with high quality.(Author)

Quality of life in children with cancer and their normal siblings

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Hilda Hilda

2015-10-01

Full Text Available Background Cancer treatment in children influences the quality of life of patients and their families. The Pediatric Quality of Life (PedsQL inventory is a questionnaire to assess quality of life of the healthy and ill children. Objective To compare quality of life in children with cancer and their normal siblings, and to compare quality of life in those with hematologic malignancies to those with solid tumors. Methods A cross-sectional study was conducted among 5-to-18- year-olds at the Hematology-Oncology Division at Haji Adam Malik Hospital, Medan, North Sumatera, from May to July 2012. The case group (subjects with cancer filled the PedsQL 3.0 and 4.0 questionnaires, while the control group (normal siblings filled only the PedsQL 4.0 questionnaire. Independent T-test was used to compare the quality of life between children with cancer and their normal siblings. Results There were 46 children in each group. The PedsQL 4.0 results in children with cancer and their normal siblings, and PedsQL 3.0 between hematology malignant and solid cancer were as follows: physical function 36.9 vs. 80.7, respectively (95%CI of differences -52.639 to -34.990; P= 0.0001, emotional function 40.4 vs. 69.3, respectively (95%CI of differences -35.912 to -21.914; P=0.0001, social function 71.5 vs. 93.9, respectively (95%CI of differences - 29.238 to -15.587; P=0.0001, school function 20.7 vs. 74.2, respectively (95%CI of differences - 62.124 to -44.832; P=0.0001, and total score 42.1 vs. 79.3, respectively (95%CI of differences - 43.066 to -31.344; P=0.0001. School function was the most affected parameter in children with cancer compared to their normal siblings. Conclusion There is a significant difference in quality of life between children with cancer and their normal siblings, for all four parameters examined by the PedsQL inventory. However, there are no significant differences in quality of life between children with hematologic malignancy and those with

Symptomatic splenic hamartoma with renal, cutaneous, and hematological abnormalities

International Nuclear Information System (INIS)

Kassarjian, A.; Patenaude, Y.G.; Bernard, C.; Bell, L.

2001-01-01

Background. There is a rare association between splenic hamartomas and hematological abnormalities with, to our knowledge, only 24 reported cases in the English literature. Patients and methods. We report a case of a splenic hamartoma in a 14-year-old boy associated with membranoproliferative glomerulonephritis, multiple lobular capillary hemangiomas of the skin, hypertension, and anemia. Following imaging with ultrasonography, MRI, and nuclear scans, a hamartoma was suspected, but malignancy could not be excluded. The lesion was removed by partial splenectomy, and pathological examination confirmed the presence of a red pulp splenic hamartoma. Results. The renal, hematological, and dermatological abnormalities resolved following removal of the splenic hamartoma. This is the first reported case of a splenic hamartoma associated with renal, cutaneous, and hematological abnormalities and only the second reported case of a symptomatic splenic hamartoma treated by partial splenectomy. (orig.)

Symptomatic splenic hamartoma with renal, cutaneous, and hematological abnormalities

Energy Technology Data Exchange (ETDEWEB)

Kassarjian, A.; Patenaude, Y.G. [Dept. of Medical Imaging, Montreal Children' s Hospital, PQ (Canada); Bernard, C. [Dept. of Pathology, Montreal Children' s Hospital, PQ (Canada); Bell, L. [Dept. of Nephrology, Montreal Children' s Hospital, PQ (Canada)

2001-02-01

Background. There is a rare association between splenic hamartomas and hematological abnormalities with, to our knowledge, only 24 reported cases in the English literature. Patients and methods. We report a case of a splenic hamartoma in a 14-year-old boy associated with membranoproliferative glomerulonephritis, multiple lobular capillary hemangiomas of the skin, hypertension, and anemia. Following imaging with ultrasonography, MRI, and nuclear scans, a hamartoma was suspected, but malignancy could not be excluded. The lesion was removed by partial splenectomy, and pathological examination confirmed the presence of a red pulp splenic hamartoma. Results. The renal, hematological, and dermatological abnormalities resolved following removal of the splenic hamartoma. This is the first reported case of a splenic hamartoma associated with renal, cutaneous, and hematological abnormalities and only the second reported case of a symptomatic splenic hamartoma treated by partial splenectomy. (orig.)

Directed light fabrication of refractory metals and alloys

International Nuclear Information System (INIS)

Fonseca, J.C.; Lewis, G.K.; Dickerson, P.G.; Nemec, R.B.

1999-01-01

This report covers work performed under Order No. FA0000020 AN Contract DE-AC12-76SN00052 for deposition of refractory pure metals and alloys using the Directed Light Fabrication (DLF) process and represents the progress in depositing these materials through September 1998. In extending the DLF process technology to refractory metals for producing fully dense, structurally sound deposits, several problems have become evident. 1. Control of porosity in DLF-deposited refractory metal is difficult because of gases, apparently present in commercially purchased refractory metal powder starting materials. 2. The radiant heat from the molten pool during deposition melts the DLF powder feed nozzle. 3. The high reflectivity of molten refractory metals, at the Nd-YAG laser wavelength (1.06microm), produces damaging back reflections to the optical train and fiber optic delivery system that can terminate DLF processing. 4. The current limits on the maximum available laser power to prevent back reflection damage limit the parameter range available for densification of refractory metals. The work to date concentrated on niobium, W-25Re, and spherodized tungsten. Niobium samples, made from hydride-dehydride powder, had minimal gas porosity and the deposition parameters were optimized; however, test plates were not made at this time. W-25Re samples, containing sodium and potassium from a precipitation process, were made and porosity was a problem for all samples although minimized with some process parameters. Deposits made from potassium reduced tungsten that was plasma spherodized were made with minimized porosity. Results of this work indicate that further gas analysis of starting powders and de-gassing of starting powders and/or gas removal during deposition of refractory metals is required

Technical considerations for the use of CRISPR/Cas9 in hematology research.

Science.gov (United States)

Gundry, Michael C; Dever, Daniel P; Yudovich, David; Bauer, Daniel E; Haas, Simon; Wilkinson, Adam C; Singbrant, Sofie

2017-10-01

The hematopoietic system is responsible for transporting oxygen and nutrients, fighting infections, and repairing tissue damage. Hematopoietic system dysfunction therefore causes a range of serious health consequences. Lifelong hematopoiesis is maintained by repopulating multipotent hematopoietic stem cells (HSCs) that replenish shorter-lived, mature blood cell types. A prokaryotic mechanism of immunity, the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 nuclease system, has been recently "repurposed" to mutate mammalian genomes efficiently and in a sequence-specific manner. The application of this genome-editing technology to hematology has afforded new approaches for functional genomics and even the prospect of "correcting" dysfunctional HSCs in the treatment of serious genetic hematological diseases. In this Perspective, we provide an overview of three recent CRISPR/Cas9 methods in hematology: gene disruption, gene targeting, and saturating mutagenesis. We also summarize the technical considerations and advice provided during the May 2017 International Society of Experimental Hematology New Investigator Committee webinar on the same topic. Copyright © 2017 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Spinning of refractory metals

International Nuclear Information System (INIS)

Chang Wenkua; Zheng Han

1989-01-01

The effects of spinning process parameters including max. pass percentage reduction, spinning temperature, feed rate, lubricant and annealing technology on the quality of shaped components are summarized and discussed in the present paper. The above mentioned parameters are adopted in the process of spinning of barrel-shaped and specially shaped components of refractory metals and their alloys W, Mo, Nb, Zr, TZM molybdenum alloy, C-103, C-752 niobium alloy etc. The cause of leading to usual defects of spun products of refractory metals such as lamellar as 'scaling', crack, swelling, wrinkle, etc. have been analysed and the ways to eliminate the defects have been put forward. 8 figs., 5 tabs. (Author)

Triploidy in the hematology of jundia juveniles (Siluriformes: Heptapteridae)

OpenAIRE

Fukushima, H; Bailone, RL; Weiss, LA; Martins, ML; Zaniboni-Filho, E

2012-01-01

This study compared the hematological characteristics of diploid and triploid of jundia, Rhamdia quelen juveniles, an important freshwater fish cultured in south Brazil. Hematological morphometry of erythrocytes were determined in blood smears under a light microscope. The blood was used to measure the number of red blood cells (RBC) with a hemocytometer Neubauer chamber, and the numbers of white blood cells (WBC) and thrombocytes that were obtained using an indirect method. The results showe...

Migration of TRU-containing slag into candidate refractories for waste management

International Nuclear Information System (INIS)

Seymour, W.C.

1978-11-01

Results of initial tests on transuranic migration into commercial refractories are reported. Five castable refractories and a plastic-bonded refractory were tested using the cup test method. Initial results indicate that castable materials will not survive conditions expected in the slagging pyrolysis unit; plastic refractories appear to have better performance. The major mechanism of migration into the tested refractories is pore penetration. Al 2 O 3 and Al 2 O 3 -Cr 2 O 3 phases appear resistant to chemical diffusion of transuranics. 2 figures, 16 tables

Refractory of Furnaces to Reduce Environmental Impact

International Nuclear Information System (INIS)

Hanzawa, Shigeru

2011-01-01

The energy load of furnaces used in the manufacturing process of ceramics is quite large. Most of the environmental impact of ceramics manufacturing is due to the CO 2 produced from this high energy load. To improve this situation, R and D has focused on furnace systems and techniques of control in order to reduce energy load. Since furnaces are comprised of refractory, consideration of their mechanical and thermal characteristics is important. Herein are described several refractory types which were chosen through comparison of the characteristics which contribute to heat capacity reduction, heat insulating reinforcement and high emissivity, thereby improving thermal radiation heat transfer efficiency to the ceramic articles. One selected refractory material which will reduce the environmental impact of a furnace, chosen considering low heat capacity and high emissivity characteristics, is SiC. In this study, thermal radiation heat transfer efficiency improvement and its effect on ceramic articles in the furnace and oxidation behaviour were investigated at 1700K. A high density SiC refractory, built into the furnace at construction, has relatively high oxidation durability and has the ability to reduce environmental impact-CO 2 by 10 percent by decreasing the furnace's energy load. However, new oxidation prevention techniques for SiC will be necessary for long-term use in industrial furnaces, because passive to active oxidation transition behaviour of commercial SiC refractory is coming to close ideal.

Refractory of Furnaces to Reduce Environmental Impact

Science.gov (United States)

Hanzawa, Shigeru

2011-10-01

The energy load of furnaces used in the manufacturing process of ceramics is quite large. Most of the environmental impact of ceramics manufacturing is due to the CO2 produced from this high energy load. To improve this situation, R&D has focused on furnace systems and techniques of control in order to reduce energy load. Since furnaces are comprised of refractory, consideration of their mechanical and thermal characteristics is important. Herein are described several refractory types which were chosen through comparison of the characteristics which contribute to heat capacity reduction, heat insulating reinforcement and high emissivity, thereby improving thermal radiation heat transfer efficiency to the ceramic articles. One selected refractory material which will reduce the environmental impact of a furnace, chosen considering low heat capacity and high emissivity characteristics, is SiC. In this study, thermal radiation heat transfer efficiency improvement and its effect on ceramic articles in the furnace and oxidation behaviour were investigated at 1700K. A high density SiC refractory, built into the furnace at construction, has relatively high oxidation durability and has the ability to reduce environmental impact-CO2 by 10 percent by decreasing the furnace's energy load. However, new oxidation prevention techniques for SiC will be necessary for long-term use in industrial furnaces, because passive to active oxidation transition behaviour of commercial SiC refractory is coming to close ideal.

Development of alumino-silicate refractories in Ghana

International Nuclear Information System (INIS)

Kisiedu, A. K.; Tetteh, D.M.B.; Obiri, H. A.; Brenya, E. F.; Ayensu, A.

2008-01-01

Alumino-silicate (bauxite), andalusite, kaolin and clay were investigated for suitability in production of alumina, mullite and fireclay brick refractories. The raw materials were characterized by X-ray diffraction, differential thermal and silicate analyses. The x-ray diffraction analysis of alumina and mullite refractories fired at 1450 0 C, and fireclay bricks fired at 1350 0 C, indicated presence of corundum and alpha-alumina crystals. The values of thermal (fired) shrinkage, crushing, strength, porosity, water absorption and bulk density determined were 31.1%, 2.3 x 10 3 kg/m 3 , 4.86 x 10 6 N/m 2 and 13.2 % for mullite; 30.2%, 2.4 x 10 3 kg/m 3 , 3.20 x 10 6 N/m 2 and W = 12.8 % for alumina; and 25.2 %, 2.1 x 10 3 kg/m 3 , 2.61 x 10 6 N/m 2 and W = 11.8% for fireclay, respectively. Bauxite, andalusite and special kaolin were identified as potential raw materials for developing alumina and mullite refractories for construction of high temperature kilns and furnaces operating at 1350 0 C. The clay and kaolin minerals could be used to produce fireclay refractories for construction of incinerators operating at maximum temperatures of about 1000 0 C. The performance of the refractories was demonstrated by producing bricks to construct kilns and incinerators for the ceramic industry and hospitals. (au)

Hematology, cytochemistry and ultrastructure of blood cells in fishing cat (Felis viverrina).

Science.gov (United States)

Prihirunkit, Kreangsak; Salakij, Chaleow; Apibal, Suntaree; Narkkong, Nual Anong

2007-06-01

Hematological, cytochemical and ultrastructural features of blood cells in fishing cat (Felis viverrina) were evaluated using complete blood cell counts with routine and cytochemical blood stains, and scanning and transmission electron microscopy. No statistically significant difference was found in different genders of this animal. Unique features of blood cells in this animal were identified in hematological, cytochemical and ultrastructural studies. This study contributes to broaden hematological resources in wildlife animals and provides a guideline for identification of blood cells in the fishing cat.

Hope, Quality of Life, and Benefit From Treatment in Women Having Chemotherapy for Platinum-Resistant/Refractory Recurrent Ovarian Cancer: The Gynecologic Cancer Intergroup Symptom Benefit Study

Science.gov (United States)

Sjoquist, Katrin M.; Friedlander, Michael L.; O'Connell, Rachel L.; Voysey, Merryn; King, Madeleine T.; Stockler, Martin R.; Oza, Amit M.; Gillies, Kim; Martyn, Julie K.

2013-01-01

Purpose. Chemotherapy for platinum-resistant/refractory ovarian cancer is motivated by the hope of benefit. We sought to determine the relationships between: (a) trait hope, expectation of symptom benefit from chemotherapy, and anxiety and depression; (b) hope and perceived efficacy of chemotherapy; and (c) unfulfilled hope (where expectations for benefit are not fulfilled) and depression. Methods. Adult patients enrolled within stage 1 of the Gynecologic Cancer Intergroup Symptom Benefit Study were included. Patient. Reported outcomes were collected from 126 women with predominantly platinum-resistant ovarian cancer at baseline, prior to the first four treatment cycles (12–16 weeks), and four weeks after completing chemotherapy or at disease progression, whichever came first. Associations were assessed with Spearman rank correlation coefficient (r) and odds ratio. Results. Trait hope and expectation of symptom benefit from chemotherapy were weakly correlated with each other (r = 0.25). Trait hope, but not expectation of symptom benefit, was negatively correlated with anxiety (r = −0.43) and depression (r = −0.50). The smaller the discrepancy between perceived and expected symptom benefit, the less likely the patient was to have scores indicative of depression (odds ratio: 0.68; 95% confidence interval: 0.49–0.96; p = .026). Conclusion. Trait hope and expectation of symptom benefit from chemotherapy appear to be distinct and independent of the aspects of quality of life and scores for depression. Hope did not appear to affect perceived efficacy of chemotherapy in alleviating symptoms, but women whose expectation of symptom benefit from chemotherapy was not fulfilled were more likely to have scores indicative of depression. It may be preferable to encourage hope toward achievable goals rather than toward benefits from chemotherapy. PMID:24107972

Refractory disease in antineutrophil cytoplasmic antibodies associated vasculitis

NARCIS (Netherlands)

Rutgers, Abraham; Kallenberg, Cornelis

Purpose of review Induction treatment of antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) is not always successful and nonresponding patients are considered refractory. Recent findings Refractory disease should be subdefined to the treatment that was received.

Diagnosis and management of refractory celiac disease: a systematic review.

Science.gov (United States)

Labidi, Asma; Serghini, Meriem; Karoui, Sami; Boubaker, Jalel; Filali, Azza

2013-01-01

Refractory celiac disease is defined by persisting malabsorptive symptoms in spite of a strict gluten free diet for at least 6 to 12 months. Alternatives to gluten free diet seem to be still controversial. To describe the clinical and epidemiologic aspects of refractory celiac disease, and to identify therapeutic options in this condition. Systematic review and critical analysis of observational studies, clinical trials and case reports that focused on diagnosis and management of refractory celiac disease. Refractory celiac disease can be classified as type 1 or type 2 according to the phenotype of intraepithelial lymphocytes. Great complications such as enteropathy-associated T-cell lymphoma may occur in a subgroup of these patients mainly in refractory celiac disease type 2. Curative therapies are still lacking. Refractory celiac disease remains a diagnosis of exclusion. Its prognosis remains still dismal by the absence yet of curative therapies. However, some new treatments seem to hold promise during few cohort-studies.

Modern materials based on refractory compounds

International Nuclear Information System (INIS)

Kosolapova, T.Ya.

1979-01-01

Discussed are the existing methods for synthesizing powders of binary refractory compounds and high-productivity techniques which hold promise as regards the manufacture of highly disperse and pure powders. Plasmochemical synthesis is shown to be an effective method for obtaining practically all carbides, nitrides and borides. A description is given of three main methods for obtaining single crystals of refractory compounds (TiN, TiC, ZrC, ZrB 2 , NbC) fairly perfect in structure and composition. These processes include deposition from vapour-gas phase, melting in arc plasma and crystallization from solutions in metallic melts. The advantages have been shown of the self-propagating high-temperature synthesis of refractory compounds, ensuring the manufacture of products, close in composition to stoichiometric ones simultaneously with forming of items. Mechanical, thermal, abrasive, and resistive characteristics of the above materials are presented

Efficacy and tolerability of gemtuzumab ozogamicin (anti-CD33 monoclonal antibody, CMA-676, Mylotarg® in children with relapsed/refractory myeloid leukemia

Directory of Open Access Journals (Sweden)

Bertrand Yves

2006-06-01

Full Text Available Abstract Background Gemtuzumab ozogamicin (GO is a cytotoxic anti-CD33 monoclonal antibody that has given promising preliminary results in adult myeloid CD33+ AML. We conducted a retrospective multicenter study of 12 children treated with GO on a compassionate basis (median age 5.5 y. Three patients (2 MDS/AML, 1 JMML were refractory to first-line treatment, 8 patients with de novo AML were in refractory first relapse, and one patient with de novo AML was in 2nd relapse after stem cell transplantation (SCT. CD33 expression exceeded 20% in all cases. Methods GO was administered alone, at a unit dose of 3–9 mg/m2, once (3 patients, twice (3 patients, three (5 patients or five times (1 patient. Mean follow-up was 128 days (8–585 d. Results There were three complete responses (25% leading to further curative treatment (SCT. Treatment failed in the other nine patients, and only one patient was alive at the end of follow-up. NCI-CTC grade III/IV adverse events comprised hematological toxicity (n = 12, hypertransaminasemia (n = 2, allergy and hyperbilirubinemia (1 case each. There was only one major adverse event (grade IV allergy. No case of sinusoidal obstruction syndrome occurred. Conclusion These results warrant a prospective trial of GO in a larger population of children with AML.

21 CFR 864.9285 - Automated cell-washing centrifuge for immuno-hematology.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated cell-washing centrifuge for immuno... Establishments That Manufacture Blood and Blood Products § 864.9285 Automated cell-washing centrifuge for immuno-hematology. (a) Identification. An automated cell-washing centrifuge for immuno-hematology is a device used...

Structure, preparation and properties of refractory compounds and systems

International Nuclear Information System (INIS)

Holleck, H.; Thuemmler, F.

1977-01-01

At the beginning of this report the possibilities of hardness optimization of refractory carbides are generally discussed. Three papers deal with TaC-basis refractories and hard metals. In particular, carbides with very low nonmetal/metal ratios and composites with hard phases formed by decomposition of tantalum carbonitrides are discussed. Another contribution reports investigations concerning the influence of the microstructure on the hardness of polycristaline mixed carbides. In a series of four papers, results are presented on the work of optimization conventional WC hard metals by introduction of a Fe,Co,Ni-binder: The influence of composition, carbon content and sintering conditions, as well as the wetting behaviour between carbides and binder metals are discussed. Phase relations in the refractory nitride and refractory nitride-binder metal systems as well as phase stabilities of ordered transition metal phases are reported in three papers, fundamental in character. Finally, the work concerning chemical analysis of refractory systems is described. (orig.) [de

Possibilities and tasks of ray hematology in the radiation treatment of mamma carcinomas

International Nuclear Information System (INIS)

Mozsa, Sz.

1980-01-01

The hematologic implications the ray treatment of mamma carcinomas are outlined. The main lines of the evolution of the problem, the causes of the increasing interest in radiation hematology as well as the pathophysiological bases of clinical phenomena are discussed. Also, the more detailed hematological clinical characteristics, the critical peripheric values, the problem of the local inactivation bone marrow dose, and finally, the problems of the cell reserves and the provocative methods are dealt with. Because of its theoretical importance the kinetic problems of the T/B-lymphocytes are discussed. The most important factors of the chemo and hormone therapy and the laboratory examinations and the principles of general radiation hematology are also reviewed. (N.I.)

Performance, immunity, serum biochemical and hematological ...

African Journals Online (AJOL)

... results suggest that supplementing broilers' diet with 5 g/kg thyme can indicate favorable influences of antibiotic growth promoter on performance without any detrimental impacts on immune responses and blood parameters. Key words: Broiler, thyme, growth performance, immunity, serum biochemistry, hematology.

Association between PER3 length polymorphism and onco-hematological diseases and its influences on patients' functionality

Directory of Open Access Journals (Sweden)

María Belén Cerliani

2015-12-01

Full Text Available Circadian clock gene PER3 and its length polymorphism may have a role in oncogenesis as clock genes act as key regulators of cell cycle and DNA repair pathways. The polymorphism may affect the condition of patients who show disrupted circadian rhythm due to tumor development. The aim was to assess the association between PER3 polymorphism and onco-hematological diseases, and analyze whether this variant has an impact on patient’s functionality. We conducted a case-control study on 125 patients with onco-hematological diseases and 310 control patients. PER3 allelic variants were detected by using polymerase chain reaction. Sociodemographic data and information on patient’s habits and functionality were obtained through questionnaire. Genotypes 4/5 + 5/5 showed an odd ratio (OR = 1.39, with no statistical significance. However, those genotypes were associated with a two-fold increase in the risk of acute/chronic lymphoblastic/myeloblastic leukemia, taken all together. The occurrence of “changes in humor during last two months” was significantly associated with onco-hematological diseases. “Fatigue on awakening” and “self-reported snore” were associated with cases carrying the 4/5 or 5/5 genotypes. The results suggested that PER3 polymorphism may have a role in the risk of leukemia, and might be a possible marker for individual differences in susceptibility to sleep disruption. This work provides insights for the identification of individuals at high risk of cancer, and those who are more susceptible to circadian disruption, which may decrease the physiological defenses against the tumor.

Refractory versus resistant hypertension: Novel distinctive phenotypes

Science.gov (United States)

Dudenbostel, Tanja; Siddiqui, Mohammed; Gharpure, Nitin; Calhoun, David A.

2017-01-01

Resistant hypertension (RHTN) is relatively common with an estimated prevalence of 10-20% of treated hypertensive patients. It is defined as blood pressure (BP) >140/90 mmHg treated with ≥3 antihypertensive medications, including a diuretic, if tolerated. Refractory hypertension is a novel phenotype of severe antihypertensive treatment failure. The proposed definition for refractory hypertension, i.e. BP >140/90 mmHg with use of ≥5 different antihypertensive medications, including a diuretic and a mineralocorticoid receptor antagonist (MRA) has been applied inconsistently. In comparison to RHTN, refractory hypertension seems to be less prevalent than RHTN. This review focuses on current knowledge about this novel phenotype compared with RHTN including definition, prevalence, mechanisms, characteristics and comorbidities, including cardiovascular risk. In patients with RHTN excess fluid retention is thought to be a common mechanism for the development of RHTN. Recently, evidence has emerged suggesting that refractory hypertension may be more of neurogenic etiology due to increased sympathetic activity as opposed to excess fluid retention. Treatment recommendations for RHTN are generally based on use and intensification of diuretic therapy, especially with the combination of a long-acting thiazide-like diuretic and an MRA. Based on findings from available studies, such an approach does not seem to be a successful strategy to control BP in patients with refractory hypertension and effective sympathetic inhibition in such patients, either with medications and/or device based approaches may be needed. PMID:29034321

Eosinophilic pustular folliculitis associated with hematological disorders: A report of two cases and review of Japanese literature.

Science.gov (United States)

Takamura, Saori; Teraki, Yuichi

2016-04-01

Eosinophilic pustular folliculitis (EPF) occurs in patients with hematological disorders. However, clinical information about hematological disorder-associated EPF is scarce. We report two cases of EPF associated with mantle cell lymphoma and reviewed the available published work on Japanese cases. We identified a total of 23 Japanese cases, including the two cases reported here, who had hematological disorder-associated EPF. Fourteen cases were associated with treatment for hematological malignancies (transplantation-related EPF) and nine cases were associated with hematological malignancies themselves (hematological malignancy-related EPF). Although the skin eruption was clinically indistinguishable between the two subtypes, transplantation-related EPF occurred on the face and trunk of young and middle-aged men and women, whereas hematological malignancy-related EPF occurred mostly on the face of older men. Peripheral blood eosinophilia was more frequently observed in transplantation-related EPF. These observations suggest variations among patients with EPF associated with hematological disorders. © 2015 Japanese Dermatological Association.

Forming Refractory Insulation On Copper Wire

Science.gov (United States)

Setlock, J.; Roberts, G.

1995-01-01

Alternative insulating process forms flexible coat of uncured refractory insulating material on copper wire. Coated wire formed into coil or other complex shape. Wire-coating apparatus forms "green" coat on copper wire. After wire coiled, heating converts "green" coat to refractory electrical insulator. When cured to final brittle form, insulating material withstands temperatures above melting temperature of wire. Process used to make coils for motors, solenoids, and other electrical devices to be operated at high temperatures.

High-dose chemotherapy and auto-SCT for relapsed and refractory Hodgkin's lymphoma patients refractory to first-line salvage chemotherapy but responsive to second-line salvage chemotherapy.

Science.gov (United States)

Rauf, Muhammad Shahzad; Maghfoor, Irfan; Elhassan, Tusneem Ahmed M; Akhtar, Saad

2015-01-01

Relapsed or primary refractory Hodgkin's lymphoma (HL) patients refractory to first-line salvage chemotherapy (first salvage) and unable to undergo high-dose chemotherapy (HDC) and autologous stem cell transplant (auto-SCT) have very poor outcome. Some patients are offered second-line salvage chemotherapy (second salvage), if they are responsive and may receive HDC auto-SCT. We identified 31 patients (18 males, 13 females) from 1996-2012 who received second salvage prior to auto-SCT. Median age at auto-SCT is 22 years. Patients were grouped as (1) relapsed-refractory (Rel:Ref): patients with prior complete response (CR) and on relapse found refractory to first salvage and received second salvage and (2) refractory-refractory (Ref:Ref): patients refractory to both primary treatment and first salvage and received second salvage. Median follow-up is 63 months (18-170). Disease status after second salvage prior to HDC was CR 16 %, partial response (PR) 71 % and stable disease 13 %. After HDC auto-SCT, CR:PR: progressive disease was observed in 18 (58 %): four (12 %): nine (29 %) patients, respectively. Five-year overall survival (OS) for whole group is 57 % (Rel:Ref vs. Ref:Ref, 73 % vs. 48 %, p = 0.48). Progression-free survival (PFS) for whole group is 52 % (Rel:Ref vs. Ref:Ref, 73 % vs. 40 % respectively, p = 0.11). Second-line salvage is a valid approach with no long-term side effects for those HL patients who do not respond to first-line salvage chemotherapy and they can be candidate of HDC and stem cell transplant with a high ORR, the PFS and OS in relapse-refractory and refractory-refractory group of patients.

Refractory myasthenia gravis - clinical profile, comorbidities and response to rituximab.

Science.gov (United States)

Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

2016-01-01

Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27-53 years. In our study 25 patients (32.89%) belonged to the age group of 21-30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA 1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% ( p =3.3x10 -8 ) to 94.6% ( p =2.2x10 -14 ) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA 1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low.

RESULTS OF OUTPATIENT PROGRAM ON EFFECTIVE THERAPY OF REFRACTORY ARTERIAL HYPERTENSION

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M. M. Batyushin

2015-12-01

Full Text Available Aim. To increase in efficacy of antihypertensive therapy in patients with refractory arterial hypertension (HT.Material and methods. Patients with refractory HT were revealed during first month of program. The causes of refractory HT were analyzed. Combined antihypertensive therapy was prescribed to reach target level of blood pressure (BP. This therapy lasted 24 weeks and included angiotensin converting enzyme (ACE inhibitor, thiazid diuretic (indapamide and dihydropyridine calcium antagonist (nifedipine XL.Results. 200 patients with refractory HT were revealed. True refractory HT took place in 59,9% of patients and pseudo refractory HT – in 40,1% of patients. Lack of diuretics or combined antihypertensive therapy were the main reason of insufficient BP control. Proposed 3-drugs therapy resulted in reduction of systolic BP from 190 to 132 Hg mm and diastolic BP from 104 to 81 Hg mm. Target level of BP was reached in 94% patients. There were no side effects which demanded to stop therapy.Conclusion. High incidence of pseudorefractory HT (40,1% is revealed. Significant prevalence of renal disturbances especially chronic interstitial inflammatory could be responsible for refractory HT development. Use of 3-drugs therapy (ACE inhibitor, indapamide and nifedipine XL provides effective control of BP in refractory and pseudorefractory HT.

RESULTS OF OUTPATIENT PROGRAM ON EFFECTIVE THERAPY OF REFRACTORY ARTERIAL HYPERTENSION

Directory of Open Access Journals (Sweden)

M. M. Batyushin

2007-01-01

Full Text Available Aim. To increase in efficacy of antihypertensive therapy in patients with refractory arterial hypertension (HT.Material and methods. Patients with refractory HT were revealed during first month of program. The causes of refractory HT were analyzed. Combined antihypertensive therapy was prescribed to reach target level of blood pressure (BP. This therapy lasted 24 weeks and included angiotensin converting enzyme (ACE inhibitor, thiazid diuretic (indapamide and dihydropyridine calcium antagonist (nifedipine XL.Results. 200 patients with refractory HT were revealed. True refractory HT took place in 59,9% of patients and pseudo refractory HT – in 40,1% of patients. Lack of diuretics or combined antihypertensive therapy were the main reason of insufficient BP control. Proposed 3-drugs therapy resulted in reduction of systolic BP from 190 to 132 Hg mm and diastolic BP from 104 to 81 Hg mm. Target level of BP was reached in 94% patients. There were no side effects which demanded to stop therapy.Conclusion. High incidence of pseudorefractory HT (40,1% is revealed. Significant prevalence of renal disturbances especially chronic interstitial inflammatory could be responsible for refractory HT development. Use of 3-drugs therapy (ACE inhibitor, indapamide and nifedipine XL provides effective control of BP in refractory and pseudorefractory HT.

Current status of sperm banking for young cancer patients in Japanese nationwide survey.

Science.gov (United States)

Yumura, Yasushi; Tsujimura, Akira; Okada, Hiroshi; Ota, Kuniaki; Kitazawa, Masahumi; Suzuki, Tatsuya; Kakinuma, Tosiyuki; Takae, Seido; Suzuki, Nao; Iwamoto, Teruaki

2018-02-02

This study aimed to ascertain the current status of Japanese sperm banking for young cancer patients. During 2015, we mailed the directors of 695 institutes where sperm cryopreservation might be performed with questionnaires requesting information on the number of patients, age, precryopreservation chemotherapy, semen analyses results and diagnoses, cryopreservation success rate, and causes of unsuccessful cryopreservation. Of these 695 institutes, 92 had cryopreserved sperm before chemotherapy within the study period. In all, 820 cancer patients (237 testicular, 383 hematological, 46 bone and soft tissue, 20 brain, and 134 other malignancy) consulted the responding institutes for sperm cryopreservation. Except for testicular tumor, the number of patients whose sperm was preserved before cancer treatment was low compared to that of young cancer patients. Approximately 20% of patients with malignancies other than testicular tumor underwent chemotherapy before cryopreservation. The success rate of cryopreservation in hematological malignancy was 82.5%, significantly lower than that of both the testicular cancer (93.6%) and other malignancy groups (95.6%) (P < 0.05). The primary reasons for preservation failure were azoospermia and poor semen quality. Patients with hematological malignancies had a higher rate of unsuccessful cryopreservation compared to those in other groups, possibly due to the large number of patients requesting sperm cryopreservation after chemotherapy induction. In Japan, information regarding sperm banking prior to cancer treatment appears to be lacking. Information regarding sperm preservation before chemotherapy should be provided to all Japanese oncologists.

Cancer in ANCA-Associated Glomerulonephritis: A Registry-Based Cohort Study

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Sanjeevan Sriskandarajah

2017-01-01

Full Text Available Background. Immunosuppressive therapy for antineutrophil cytoplasmic antibody-associated vasculitis has been associated with increased malignancy risk. Objectives. To quantify the cancer risk associated with contemporary cyclophosphamide-sparing protocols. Methods. Patients from the Norwegian Kidney Biopsy Registry between 1988 and 2012 who had biopsy-verified pauci-immune glomerulonephritis and positive antineutrophil cytoplasmic antibody (ANCA serology were included. Standardised incidence ratios (SIRs were calculated to compare the study cohort with the general population. Results. The study cohort included 419 patients. During 3010 person-years, cancer developed in 41 patients (9.79%; the expected number of cancer cases was 37.5 (8.95%. The cohort had SIRs as follows: 1.09, all cancer types (95% CI, 0.81 to 1.49; 0.96, all types except nonmelanoma skin cancer (95% CI, 0.69 to 1.34; 3.40, nonmelanoma skin cancer (95% CI, 1.62 to 7.14; 3.52, hematologic cancer (95% CI, 1.32 to 9.37; 2.12, posttransplant cancer (95% CI, 1.01 to 4.44; and 1.53, during the 1–5-year follow-up after diagnosis (95% CI, 1.01 to 2.32. Conclusions. Cancer risk did not increase significantly in this cohort with ANCA-associated glomerulonephritis. However, increased risk of nonmelanoma skin cancer, posttransplant cancer, and hematologic cancer indicates an association between immunosuppression and malignancy.

Long term survival with whole abdominopelvic irradiation (WAI) in platinum-refractory ovarian cancer

International Nuclear Information System (INIS)

Cmelak, Anthony J.; Cox, Richard S.; Kapp, Daniel S.

1996-01-01

Purpose: To evaluate the efficacy and toxicity of WAI in persistent or recurrent epithelial ovarian carcinoma after initial chemotherapy. Methods and Materials: Between 1970 and 1995, 41 women with persistent or recurrent ovarian carcinoma after initial surgical debulking and chemotherapy were treated with WAI. Median age was 57 years (range 27-75). Initial FIGO stages were I and II - 5 patients (12%), III - 26 (64%), and IV - 10 (24%). Tumor grade was 1 - 4 (10%), II - 16 (39%), and III - 20 (49%). Four to eighteen (median eight) cycles of chemotherapy had been given prior to WAI. Thirty-one patients had received platinum-based regimens, and 22 of these had failed within six months after completion of chemotherapy (platinum-refractory). Prior to WAI, 11 (27%) patients had microscopic residual disease, 21 (51%) had gross residual disease up to 1.5 cm, and 9 (22%) had tumors greater than 1.5 cm in maximal diameter. Median doses of 28 Gy to the abdomen and 48 Gy to the pelvis were delivered using an open-field technique with appropriate liver and kidney shielding. Results: With follow-up of 1 month to 16.5 years, the 5-year actuarial disease specific survival was 47% in all 41 patients, and 49% in 22 platinum-refractory patients. Both disease bulk at WAI (p -4 ) and initial stage (p=0.005) were of prognostic value. Five-year disease specific survivals were stage I and II - 100%, stage III - 55%, and stage IV - 27%. Five-year disease specific survival of all nonbulky (less than 1.5 cm) patients was 40%; 0% for patients with disease greater than 1.5 cm. Five-year disease specific survival for grade I - 66%, II - 59%, and III - 33%. Stage I, II, or III patients with residual disease bulk of 1.5 cm or less before WAI had a 10-year actuarial disease specific survival of 50%. Twelve patients (29%) failed to complete the planned course of WAI due to acute toxicity (most often due to prolonged thrombocytopenia). Late bowel toxicity included obstruction in one patient and

Bronchoscopic examinations for evaluating chest abnormal shadows associated with hematological disease

International Nuclear Information System (INIS)

Nakayama, Masayuki; Bando, Masashi; Kobayashi, Akira; Yamasawa, Hideaki; Ohno, Shoji; Sugiyama, Yukihiko

2006-01-01

Hematological diseases cause various respiratory complications, but their differentiation only by blood tests and chest radiology is often difficult. To clarify the characteristics of respiratory complications associated with hematological diseases and the diagnostic usefulness of bronchoscopic examinations for these complications, we clinically evaluated mainly underlying diseases, chest radiological findings, and bronchoscopic findings in 31 patients in whom we performed bronchoscopy for chest abnormal shadows associated with hematological disease during the past 13-year period. Among hematological disease, leukemia was most frequently observed, followed by malignant lymphoma and myelodysplastic syndrome. The most frequently observed chest CT findings were localized consolidation and diffuse Ground-glass opacity. Bronchoscopic examinations provided a definitive diagnosis in 20 patients (64.5%), and the most frequent diagnosis was pulmonary invasion by neoplastic cells (7 patients). Pulmonary invasion by neoplastic cells showed various images, and transbronchial lung biopsy : TBLB was useful for definitive diagnosis. After consideration of the general condition of patients and the risk of complications, bronchoscopy including TBLB should be performed when possible. (author)

Selective Androgen Receptor Down-Regulators (SARDs): A New Prostate Cancer Therapy

National Research Council Canada - National Science Library

Bhattacharyya, Rumi S

2007-01-01

The androgen receptor (AR) plays a key role in the development and progression of prostate cancer Targeting the AR for down-regulation would be a useful strategy for treating prostate cancer, especially hormone-refractory...

Bone marrow immunophenotyping by flow cytometry in refractory cytopenia of childhood

NARCIS (Netherlands)

A.M. Aalbers (Anna Maartje); M.M. van den Heuvel-Eibrink (Marry); I. Baumann (Irith); M.N. Dworzak (Michael); H. Hasle (Henrik); F. Locatelli (Franco); B. de Moerloose (Barbara); M. Schmugge; E. Mejstříková (Ester); M. Nováková (Michaela); M. Zecca (Marco); C.M. Zwaan (Christian Michel); J.G. te Marvelde (Jeroen); A.W. Langerak (Anton); J.J.M. van Dongen (Jacques); R. Pieters (Rob); C.M. Niemeyer (Charlotte); V.H.J. van der Velden (Vincent)

2015-01-01

textabstractRefractory cytopenia of childhood is the most common type of childhood myelodysplastic syndrome. Because the majority of children with refractory cytopenia have a normal karyotype and a hypocellular bone marrow, differentiating refractory cytopenia from the immune-mediated bone marrow

New Molecular Targeted Therapy and Redifferentiation Therapy for Radioiodine-Refractory Advanced Papillary Thyroid Carcinoma: Literature Review

Directory of Open Access Journals (Sweden)

Kai-Pun Wong

2012-01-01

Full Text Available Although the majority of papillary thyroid carcinoma could be successfully managed by complete surgical resection alone or resection followed by radioiodine ablation, a small proportion of patients may develop radioiodine-refractory progressive disease which is not amenable to surgery, local ablative treatment or other treatment modalities. The use of FDG-PET/CT scan for persistent/recurrent disease has improved the accuracy of restaging as well as cancer prognostication. Given that patients with RAI-refractory disease tend to do significantly worse than those with radioiodine-avid or non-progressive disease, an increasing number of phase I and II studies have been conducted to evaluate the efficacy of new molecular targeted drugs such as the tyrosine kinase inhibitors and redifferentiation drugs. The overall response rate of these drugs ranged between 0–53%, depending on whether the patients had been previously treated with these drugs, performance status and extent of disease. However, drug toxicity remains a major concern in administration of target therapies. Nevertheless, there are also ongoing phase III studies evaluating the efficacy of these new drugs. The aim of the review was to summarize and discuss the results of these targeted drugs and redifferentiation agents for patients with progressive, radioiodine-refractory papillary thyroid carcinoma.

Targeting Cancer Stem Cells and Their Niche: Current Therapeutic Implications and Challenges in Pancreatic Cancer

Directory of Open Access Journals (Sweden)

Jiangang Zhao

2017-01-01

Full Text Available Cancer stem cells (CSCs have been identified as a subpopulation of stem-like cancer cells with the ability of self-renewal and differentiation in hematological malignancies and solid tumors. Pancreatic cancer is one of the most lethal cancers worldwide. CSCs are thought to be responsible for cancer initiation, progression, metastasis, chemoresistance, and recurrence in pancreatic cancer. In this review, we summarize the characteristics of pancreatic CSCs and discuss the mechanisms involved in resistance to chemotherapy, the interactions with the niche, and the potential role in cancer immunoediting. We propose that immunotherapy targeting pancreatic CSCs, in combination with targeting the niche components, may provide a novel treatment strategy to eradicate pancreatic CSCs and hence improve outcomes in pancreatic cancer.

Bacteremia and candidemia in hematological malignancies

DEFF Research Database (Denmark)

Hovgaard, D; Skinhøj, P; Bangsborg, Jette Marie

1988-01-01

171 episodes of bacteremia and candidemia in 142 patients were recorded during the period 1981-1985 in patients with hematological malignancies. Overall mortality, within 1 week of onset of bacteremia, was 20%. Increased mortality was found in patients with poor disease-prognosis (39%), with gran...

Extracorporeal photopheresis for graft-versus-host disease: the role of patient, transplant, and classification criteria and hematologic values on outcome-results from a large single-center study.

Science.gov (United States)

Berger, Massimo; Albiani, Roberto; Sini, Bruno; Fagioli, Franca

2015-04-01

Extracorporeal photopheresis (ECP) has been shown as active therapy for graft-versus-host disease (GVHD). The aim was to ascertain the role of ECP in 71 patients with steroid-refractory or -dependent acute and chronic GVHD (aGVHD and cGVHD) with special focus on hematologic variables and GVHD staging classification. A total of 34 patients were treated for aGVHD and 37 for cGVHD. The overall response rate (ORR) for aGVHD was 65% and the complete aGVHD-free survival was 50% (95% confidence interval [CI], 36%-70%). The ORR for cGVHD response was 81% while the complete cGVHD-free survival was 50% (95% CI, 34%-73%). The aGVHD-free survival was associated with aGVHD grading (Grade II 81%, Grade III 33%, and Grade IV 0%, p ≤ 0.00) and the absence of visceral involvement (77% vs. 33%, p = 0.03). The cGVHD-free survival was associated with the female sex (67% vs. 25%, p = 0.01) and with the limited form according to the Seattle classification (67% vs. 20%, p = 0.003). No role for hematologic values or apheresis cell count was found, except for the cGVHD ORR (p = 0.037). Transplant-related mortality and overall survival were associated with ECP response 0% versus 54% (p = 0.0001) and 77% versus 45% (p = 0.03) for aGVHD patients and 7% versus 14% (p = 0.02) and 73% versus 20% (p = 0.0003) for cGVHD patients, respectively. While confirming a higher probability of GVHD responses for early GVHD, our study shows no role of hematologic values or apheresis cell count on GVHD response. © 2014 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

Prospective trial of an herbal formula BYSH and Saw palmetto in patients with hormonal refractory prostate cancer: a pilot study.

Science.gov (United States)

Ng, Anthony C-F; Cheng, K-F; Leung, P-C

2014-01-01

BYSH, a herbal formula, was evaluated for efficacy and safety in a pilot study for patients with advanced hormone refractory prostate cancer (HRPC). The pilot study was designed as a single-center open-label trial. Patients with HRPC were treated with BYSH for 24 weeks. The primary end point was the changes in serum prostate-specific antigen (PSA) level. Safety parameters such as liver and renal functions were monitored during the study period. Ten patients were eligible for the study. Most of them had stable PSA levels while taking BYSH. However, at the end of the BYSH treatment, the level of PSA increased. The median survival from diagnosis of HRPC was 16.4 months. Liver and renal functions remained normal. BYSH was well tolerated and no patient reported adverse events during the study period. Although it is inappropriate to make a conclusion based on the pilot study results, the trend of improvement is obvious. Further investigations should be conducted to demonstrate its clinical benefits. We have also briefly reviewed some plant products which are patented and also available in market.

Integrating molecular mechanisms and clinical evidence in the management of trastuzumab resistant or refractory HER-2⁺ metastatic breast cancer.

Science.gov (United States)

Wong, Hilda; Leung, Roland; Kwong, Ava; Chiu, Joanne; Liang, Raymond; Swanton, Charles; Yau, Thomas

2011-01-01

Human epidermal growth factor receptor (HER)-2(+) breast cancer is a distinct molecular and clinical entity, the prognosis of which is improved by trastuzumab. However, primary resistance to trastuzumab is observed in >50% of patients with HER-2(+) advanced breast cancer, and the majority of patients who initially respond to treatment eventually develop disease progression. To facilitate crosstrial comparisons and the understanding of resistance mechanisms, we propose a unifying definition of trastuzumab resistance as progression at first radiological reassessment at 8-12 weeks or within 3 months after first-line trastuzumab in the metastatic setting or new recurrences diagnosed during or within 12 months after adjuvant trastuzumab. In contrast, we define trastuzumab-refractory breast cancer as disease progression after two or more lines of trastuzumab-containing regimens that initially achieved disease response or stabilization at first radiological assessment. We review mechanisms of trastuzumab resistance mediated by p95HER-2 overexpression, phosphoinositide 3-kinase pathway activation, and signaling pathway activation driven by HER-3, epidermal growth factor receptor, and insulin-like growth factor 1 receptor. We distinguish in vitro from in vivo evidence, highlighting that most data describing trastuzumab resistance are derived from preclinical studies or small retrospective patient cohorts, and discuss targeted therapeutic approaches to overcome resistance. Prospective analysis through clinical trials with robust tissue collection procedures, prior to and following acquisition of resistance, integrated with next-generation tumor genome sequencing technologies, is identified as a priority area for development. The identification of predictive biomarkers is of paramount importance to optimize health economic costs and enhance stratification of anti-HER-2 targeted therapies.

Resources for Hematology On and Off the Web.

Science.gov (United States)

Sebald-Kinder, Shirley; Petty, Janet L

2017-09-01

Searching the literature can be challenging because of the large volume of information. It can be time consuming to locate and determine what evidence will provide the best health outcomes for patients. In addition, locating hematology information for patients and family members is one of the most challenging of all health care topics. Hematology can be technical and difficult for most people to understand, especially for those with little or no science background and poor reading skills. This article provides guidance on how and where to locate information to address the needs of both clinicians and patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Should a clinical rotation in hematology be mandatory for undergraduate medical students?

Directory of Open Access Journals (Sweden)

Mandan J

2016-09-01

Full Text Available Jay Mandan,1 Harmeet Singh Sidhu,1 Adil Mahmood2 1Faculty of Medicine, Imperial College London, London, UK; 2Faculty of Life Sciences and Medicine, King’s College London, London, UK Abstract: Clinical rotations form the foundation of medical education. Medical students in the UK are offered conventional rotations such as cardiology, surgery, and psychiatry as part of their undergraduate curriculum, but a rotation in hematology is not currently mandatory. This paper explores the benefits of a compulsory hematology rotation, and suggests recommendations for its implementation in UK medical school curricula. Keywords: medical education, clinical rotations, hematology

Colectomy for refractory constipation

DEFF Research Database (Denmark)

Raahave, Dennis; Loud, Franck Bjørn; Christensen, Elsebeth

2010-01-01

OBJECTIVE: This study evaluated the type of colectomy, postoperative complications, functional results, and satisfaction in patients with constipation refractory to conservative therapy. Further, colonic transit time (CTT), faecal load (coprostasis), and colon length (redundancies) were compared ...

[Cancer and Malnutrition].

Science.gov (United States)

Tsuzuki, Norimasa; Higashiguchi, Takashi; Ito, Akihiro; Ohara, Hiroshi; Futamura, Akihiko

2015-07-01

A Japanese proverb says that a balanced diet leads to a healthy body. However, the relation between healthy life and nutrition has not been established precisely and quantitatively. Cancer cachexia, which is malnutrition in cancer patients, has been studied extensively. Appropriate nutrition support can prevent the progression of malnutrition in cancer patients and advance the tolerance for anticancer therapy. In refractory cachexia (terminally cancer patients), we will judge the necessity of reduction of nutrition support, what it is called "gear-change", because the support is burden for the body. It is important to restrict the quantity of nutrition and to give medical treatment to retain bodily function in these patients.

Statistical experimental design for refractory coatings

International Nuclear Information System (INIS)

McKinnon, J.A.; Standard, O.C.

2000-01-01

The production of refractory coatings on metal casting moulds is critically dependent on the development of suitable rheological characteristics, such as viscosity and thixotropy, in the initial coating slurry. In this paper, the basic concepts of mixture design and analysis are applied to the formulation of a refractory coating, with illustration by a worked example. Experimental data of coating viscosity versus composition are fitted to a statistical model to obtain a reliable method of predicting the optimal formulation of the coating. Copyright (2000) The Australian Ceramic Society

Typical corrosion of alumina refractory in aluminum reflow oven

International Nuclear Information System (INIS)

Baldo, Jaoa B.

2014-01-01

The refractory linings of furnaces for secondary melting of aluminum, are exposed to intense attack by the molten metal. This occurs, because molten aluminum has a strong reducing power over the refractory oxide components, particularly Fe 2 O 3 , SiO 2 and TiO 2 . In this work, based on X-ray diffraction and scanning electron microscopy, it is presented a post mortem study of the mechanisms that lead to a premature wear of a 80% Al2O3 chemically bonded refractory bricks, used in the metal line of an aluminum re-melting furnace. The SEM analysis demonstrated that the oxides SiO 2 and TiO 2 contained in the refractory were reduced and transformed into their metallic elements causing an intense structural spalling. (author)

Beta-blockers in cirrhosis and refractory ascites

DEFF Research Database (Denmark)

Kimer, Nina; Feineis, Martin; Møller, Søren

2015-01-01

OBJECTIVE: It is currently discussed if beta-blockers exert harmful effects and increase mortality in patients with cirrhosis and refractory ascites. In this study, we provide an overview of the available literature in this field in combination with a retrospective analysis of 61 patients...... trials (9 trials on propranolol, 1 case-control study and 4 retrospective analyses) were identified. One trial suggested an increased mortality in patients treated with beta-blockers and refractory ascites. The results of the remaining trials were inconclusive. No increase in mortality among beta-blocker......-treated patients was found in the present retrospective analysis. CONCLUSIONS: Treatment with beta-blockers may increase mortality in patients with cirrhosis and refractory ascites. However, the current evidence is sparse and high-quality studies are warranted to clarify the matter....

Elucidation of the Molecular Mechanisms Underlying Lymph Node Metastasis in Prostate Cancer

National Research Council Canada - National Science Library

Datta, Kaustubh

2007-01-01

.... Again, the cancer will often progress to an androgen refractory (independent), metastatic stage. Recent reports have suggested that the expression of VEGF-C is directly correlated with lymph node dissemination in prostate cancer...

Efficacy of Progressive Muscle Relaxation Training on Anxiety, Depression and Quality of Life in Cancer Patients Undergoing Chemotherapy at Tabriz Hematology and Oncology Research Center, Iran in 2010

Directory of Open Access Journals (Sweden)

Reza Shabanlui

2012-01-01

Full Text Available Background: Chemotherapy is an important treatment for cancer, yet some of its side effects are serious and painful. Many patients with cancer suffer from psychiatric disorders that most likely result from therapeutic drugs or mental strategies to cope with their illness. Progressive muscle relaxation is one of the cost effective, self-help methods that promotes mental health in healthy participants. Thisstudy aims to determine the effect of progressive muscle relaxation training on anxiety and depression in cancer patients undergoing chemotherapy.Methods: This was a randomized, clinical study that enrolled 60 patients who received inpatient chemotherapy in the Tabriz Hematology and Oncology Research Center in 2010. We divided patients into two groups, intervention and control. All participants signed written formal consents and completed the Hospital Anxiety & Depression Scale questionnaires. Intervention group participants were trained inprogressive muscle relaxation in groups of 3-6 to enable participants to perform this technique when they were alone in the hospital and after discharge, two to three times each day. After one and three months, questionnaires were completed again by both groups and the results compared. 17th version of SPSS software was used fordata analysis.Results: After data analysis, most participants were satisfied with learning and experiencing this technique. There was no significant difference between scales in the case and control groups after one month (P>0.05. However after three months, anxiety and depression considerably improved in patients who underwent progressive muscle relaxation training (P<0.05.Conclusion: Progressive muscle relaxation training can improve anxietyand depression in cancer patients.

Fire and explosion hazards of refractory compound powders

International Nuclear Information System (INIS)

Krivtsov, V.A.; Kostina, E.S.

1978-01-01

Data on fire and explosion hazards of refractory compound powders (HfC, ZrC,LaB 6 , ZrN, etc.) are presented. It is shown that refractory compounds can be fire- and exposion hazardous in various degrees. Qualitative and quantitative estimations of one of fire-hazard characteristics - smoldering temperature - are presented

Cognitive compensatory processes of older, clinically fit patients with hematologic malignancies undergoing chemotherapy: A longitudinal cohort study.

Science.gov (United States)

Libert, Yves; Borghgraef, Cindy; Beguin, Yves; Delvaux, Nicole; Devos, Martine; Doyen, Chantal; Dubruille, Stéphanie; Etienne, Anne-Marie; Liénard, Aurore; Merckaert, Isabelle; Reynaert, Christine; Slachmuylder, Jean-Louis; Straetmans, Nicole; Van Den Neste, Eric; Bron, Dominique; Razavi, Darius

2017-12-01

Despite the well-known negative impacts of cancer and anticancer therapies on cognitive performance, little is known about the cognitive compensatory processes of older patients with cancer. This study was designed to investigate the cognitive compensatory processes of older, clinically fit patients with hematologic malignancies undergoing chemotherapy. We assessed 89 consecutive patients (age ≥ 65 y) without severe cognitive impairment and 89 age-, sex-, and education level-matched healthy controls. Cognitive compensatory processes were investigated by (1) comparing cognitive performance of patients and healthy controls in novel (first exposure to cognitive tasks) and non-novel (second exposure to the same cognitive tasks) contexts, and (2) assessing psychological factors that may facilitate or inhibit cognitive performance, such as motivation, psychological distress, and perceived cognitive performance. We assessed cognitive performance with the Trail-Making, Digit Span and FCSR-IR tests, psychological distress with the Hospital Anxiety and Depression Scale, and perceived cognitive performance with the FACT-Cog questionnaire. In novel and non-novel contexts, average cognitive performances of healthy controls were higher than those of patients and were associated with motivation. Cognitive performance of patients was not associated with investigated psychological factors in the novel context but was associated with motivation and psychological distress in the non-novel context. Older, clinically fit patients with hematologic malignancies undergoing chemotherapy demonstrated lower cognitive compensatory processes compared to healthy controls. Reducing distress and increasing motivation may improve cognitive compensatory processes of patients in non-novel contexts. Copyright © 2017 John Wiley & Sons, Ltd.

Effect of Resveratrol on Hematological and Biochemical Alterations in Rats Exposed to Fluoride

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Nurgül Atmaca

2014-01-01

Full Text Available We investigated the protective effects of resveratrol on hematological and biochemical changes induced by fluoride in rats. A total of 28 rats were divided into 4 groups: control, resveratrol, fluoride, and fluoride/resveratrol (n=7 each, for a total of 21 days of treatment. Blood samples were taken and hematological and biochemical parameters were measured. Compared to the control group, the fluoride-treated group showed significant differences in several hematological parameters, including decreases in WBC, RBC, and PLT counts and neutrophil ratio. The group that received resveratrol alone showed a decrease in WBC count compared to the control group. Furthermore, in comparison to the control group, the fluoride group showed significantly increased ALT enzyme activity and decreased inorganic phosphorus level. The hematological and biochemical parameters in the fluoride + resveratrol treated group were similar to control group. In the fluoride + resveratrol group, resveratrol restored the changes observed following fluoride treatment, including decreased counts of WBC, RBC, and PLT, decreased neutrophil ratio and inorganic phosphorus levels, and elevated ALT enzyme activity. The present study showed that fluoride caused adverse effects in rats and that resveratrol reduced hematological and biochemical alterations produced by fluoride exposure.

Association between the ABO locus and hematological traits in Korean

Directory of Open Access Journals (Sweden)

Hong Kyung-Won

2012-09-01

Full Text Available Abstract Background Recently, genome-wide association studies identified a pleiotropic gene locus, ABO, as being significantly associated with hematological traits. To confirm the effects of ABO on hematological traits, we examined the link between the ABO locus and hematological traits in Korean population-based cohorts. Results Six tagging SNPs for ABO were analyzed with regard to their effects on hematological traits [white blood cell count (WBC, red blood cell count (RBC, platelet (Plat, mean corpuscular volume (MCV, and mean corpuscular haemoglobin concentration (MCHC]. Linear regression analyses were performed, controlling for recruitment center, sex, and age as covariates. Of the 6 tagging SNPs, 3 (rs2073823, rs8176720, and rs495828 and 3 (rs2073823, rs8176717, and rs687289 were significantly associated with RBC and MCV, respectively (Bonferroni correction p-value criteria r2s = 0.99. Of the remaining 3 SNPs (rs8176720, rs8176717 and rs687289, rs8176717 generated an independent signal with moderate p-value (= 0.045 when it was adjusted for by rs2073823 (the most significant SNP. We also identified a copy number variation (CNV that was tagged by the SNP rs8176717, the minor allele of which correlated with the deletion allele of CNV. Our haplotype analysis indicated that the haplotype that contained the CNV deletion was significantly associated with MCV (β ± se = 0.363 ± 0.118, p =2.09 × 10-3. Conclusions Our findings confirm that ABO is one of the genetic factors that are associated with hematological traits in the Korean population. This result is notable, because GWASs fail to evaluate the link between a CNV and phenotype traits.

Bacterial Infections Following Splenectomy for Malignant and Nonmalignant Hematologic Diseases

Science.gov (United States)

Leone, Giuseppe; Pizzigallo, Eligio

2015-01-01

Splenectomy, while often necessary in otherwise healthy patients after major trauma, finds its primary indication for patients with underlying malignant or nonmalignant hematologic diseases. Indications of splenectomy for hematologic diseases have been reducing in the last few years, due to improved diagnostic and therapeutic tools. In high-income countries, there is a clear decrease over calendar time in the incidence of all indication splenectomy except nonmalignant hematologic diseases. However, splenectomy, even if with different modalities including laparoscopic splenectomy and partial splenectomy, continue to be a current surgical practice both in nonmalignant hematologic diseases, such as Immune Thrombocytopenic Purpura (ITP), Autoimmune Hemolytic Anemia (AIHA), Congenital Hemolytic Anemia such as Spherocytosis, Sickle Cell Anemia and Thalassemia and Malignant Hematological Disease, such as lymphoma. Today millions of people in the world are splenectomized. Splenectomy, independently of its cause, induces an early and late increase in the incidence of venous thromboembolism and infections. Infections remain the most dangerous complication of splenectomy. After splenectomy, the levels of antibody are preserved but there is a loss of memory B cells against pneumococcus and tetanus, and the loss of marginal zone monocytes deputed to immunological defense from capsulated bacteria. Commonly, the infections strictly correlated to the absence of the spleen or a decreased or absent splenic function are due to encapsulated bacteria that are the most virulent pathogens in this set of patients. Vaccination with polysaccharide and conjugate vaccines again Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis should be performed before the splenectomy. This practice reduces but does not eliminate the occurrence of overwhelming infections due to capsulated bacteria. At present, most of infections found in splenectomized patients are due to Gram

Immunoglobulin therapy in hematologic neoplasms and after hematopoietic cell transplantation.

Science.gov (United States)

Ueda, Masumi; Berger, Melvin; Gale, Robert Peter; Lazarus, Hillard M

2018-03-01

Immunoglobulins are used to prevent or reduce infection risk in primary immune deficiencies and in settings which exploit its anti-inflammatory and immune-modulatory effects. Rigorous proof of immunoglobulin efficacy in persons with lympho-proliferative neoplasms, plasma cell myeloma, and persons receiving hematopoietic cell transplants is lacking despite many clinical trials. Further, there are few consensus guidelines or algorithms for use in these conditions. Rapid development of new therapies targeting B-cell signaling and survival pathways and increased use of chimeric antigen receptor T-cell (CAR-T) therapy will likely result in more acquired deficiencies of humoral immunity and infections in persons with cancer. We review immunoglobulin formulations and discuss efficacy and potential adverse effects in the context of preventing infections and in graft-versus-host disease. We suggest an algorithm for evaluating acquired deficiencies of humoral immunity in persons with hematologic neoplasms and recommend appropriate use of immunoglobulin therapy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Ketamine for cancer pain: what is the evidence?

Science.gov (United States)

Jonkman, Kelly; van de Donk, Tine; Dahan, Albert

2017-06-01

In this review, we assess the benefit of ketamine in the treatment of terminal cancer pain that is refractory to opioid treatment and/or complicated by neuropathy. While randomized controlled trials consistently show lack of clinical efficacy of ketamine in treating cancer pain, a large number of open-label studies and case series show benefit. Ketamine is an N-methyl-D-aspartate receptor antagonist that at low-dose has effective analgesic properties. In cancer pain, ketamine is usually prescribed as adjuvant to opioid therapy when pain becomes opioid resistant or when neuropathic pain symptoms dominate the clinical picture. A literature search revealed four randomized controlled trials that examined the benefit of oral, subcutaneous or intravenous ketamine in opioid refractory cancer pain. None showed clinically relevant benefit in relieving pain or reducing opioid consumption. This suggests absence of evidence of benefit for ketamine as adjuvant analgesic in cancer pain. These findings contrast the benefit from ketamine observed in a large number of open-label studies and (retrospective) case series. We relate the opposite outcomes to methodological issues. The complete picture is such that there is still insufficient evidence to state with certainty that ketamine is not effective in cancer pain.

Molecular Determinants of Hormone-Refractory Prostate Cancer

Science.gov (United States)

2015-07-01

Suzuki Y, Honda G, et al. Large-scale identification and characterization of human genes that activate NF- kappaB and MAPK signaling pathways. Oncogene...2003 May 22;22(21):3307-18. Mendiratta P, et al. Genomic strategy for targeting therapy in castration-resistant prostate cancer. J Clin Oncol. 2009 Apr

Evaluation of performance of veterinary in-clinic hematology analyzers.

Science.gov (United States)

Rishniw, Mark; Pion, Paul D

2016-12-01

A previous study provided information regarding the quality of in-clinic veterinary biochemistry testing. However, no similar studies for in-clinic veterinary hematology testing have been conducted. The objective of this study was to assess the quality of hematology testing in veterinary in-clinic laboratories using results obtained from testing 3 levels of canine EDTA blood samples. Clinicians prepared blood samples to achieve measurand concentrations within, below, and above their RIs and evaluated the samples in triplicate using their in-clinic analyzers. Quality was assessed by comparison of calculated total error with quality requirements, determination of sigma metrics, use of a quality goal index, and agreement between in-clinic and reference laboratory instruments. Suitability for statistical quality control was determined using adaptations from the computerized program, EZRules3. Evaluation of 10 veterinary in-clinic hematology analyzers showed that these instruments often fail to meet quality requirements. At least 60% of analyzers reasonably determined RBC, WBC, HCT, and HGB, when assessed by most quality goal criteria; platelets were less reliably measured, with 80% deemed suitable for low platelet counts, but only 30% for high platelet counts, and automated differential leukocyte counts were generally considered unsuitable for clinical use with fewer than 40% of analyzers meeting the least stringent quality goal requirements. Fewer than 50% of analyzers were able to meet requirements for statistical quality control for any measurand. These findings reflect the current status of in-clinic hematology analyzer performance and provide a basis for future evaluations of the quality of veterinary laboratory testing. © 2016 American Society for Veterinary Clinical Pathology.

Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines

DEFF Research Database (Denmark)

Jandu, Haatisha; Aluzaite, Kristina; Fogh, Louise

2016-01-01

Background: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30 % response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this ......Background: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30 % response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim...... or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer...... of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan....

[Therapy-resistant and therapy-refractory arterial hypertension].

Science.gov (United States)

Wallbach, M; Koziolek, M J

2018-05-02

Therapy-resistant and therapy-refractory arterial hypertension differ in prevalence, pathogenesis, prognosis and therapy. In both cases, a structured approach is required, with the exclusion of pseudoresistance and, subsequently, secondary hypertension. Resistant hypertension has been reported to be more responsive to intensified diuretic therapy, whereas refractory hypertension is presumed to require sympathoinhibitory therapy. Once the general measures and the drug-based step-up therapy have been exhausted, interventional procedures are available.

Refractory myasthenia gravis – clinical profile, comorbidities and response to rituximab

Science.gov (United States)

Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

2016-01-01

Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27–53 years. In our study 25 patients (32.89%) belonged to the age group of 21–30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% (p=3.3x10–8) to 94.6% (p=2.2x10–14) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low. PMID:27790079

IMPROVED CORROSION RESISTANCE OF ALUMINA REFRACTORIES

Energy Technology Data Exchange (ETDEWEB)

John P. Hurley; Patty L. Kleven

2001-09-30

The initial objective of this project was to do a literature search to define the problems of refractory selection in the metals and glass industries. The problems fall into three categories: Economic--What do the major problems cost the industries financially? Operational--How do the major problems affect production efficiency and impact the environment? and Scientific--What are the chemical and physical mechanisms that cause the problems to occur? This report presents a summary of these problems. It was used to determine the areas in which the EERC can provide the most assistance through bench-scale and laboratory testing. The final objective of this project was to design and build a bench-scale high-temperature controlled atmosphere dynamic corrosion application furnace (CADCAF). The furnace will be used to evaluate refractory test samples in the presence of flowing corrodents for extended periods, to temperatures of 1600 C under controlled atmospheres. Corrodents will include molten slag, steel, and glass. This test should prove useful for the glass and steel industries when faced with the decision of choosing the best refractory for flowing corrodent conditions.

Clinical and microbiological features of refractory periodontitis subjects.

Science.gov (United States)

Colombo, A P; Haffajee, A D; Dewhirst, F E; Paster, B J; Smith, C M; Cugini, M A; Socransky, S S

1998-02-01

The purpose of this investigation was to compare the clinical parameters and the site prevalence and levels of 40 subgingival species in successfully treated and refractory periodontitis subjects. 94 subjects received scaling and root planing and if needed, periodontal surgery and systemically administered tetracycline. 28 refractory subjects showed mean full mouth attachment loss and/or > 3 sites showing attachment loss > 2.5 mm within 1 year post-therapy. 66 successfully treated subjects showed mean attachment level gain and no sites with attachment loss > 2.5 mm. Baseline subgingival plaque samples were taken from the mesial aspect of each tooth and the presence and levels of 40 subgingival taxa were determined using whole genomic DNA probes and checkerboard DNA-DNA hybridization. The mean levels and % of sites colonized by each species (prevalence) was computed for each subject and differences between groups sought using the Mann-Whitney test. Most of the 40 species tested, including Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola and Bacteroides forsythus, were equally or less prevalent in the refractory group. Prevotella nigrescens was significantly more prevalent in successfully treated subjects, while refractory subjects harbored a larger proportion of Streptococcus species, particularly Streptococcus constellatus. The odds of a subject being refractory was 8.6 (p or = 3.5% of the total DNA probe count. Since few microbiological differences existed between treatment outcome groups using DNA probes to known species, the predominant cultivable microbiota of 33 subgingival samples from 14 refractory subjects was examined. 85% of the 1649 isolates were identified using probes to 69 recognized subgingival species. The remaining unidentified strains were classified by analyzing 16S rRNA gene sequences. Many sequenced isolates were of taxa not considered a common part of the oral microbiota such as Acinetobacter baumanni

Fibrinogen measurements in plasma and whole blood: a performance evaluation study of the dry-hematology system.

Science.gov (United States)

Ogawa, Satoru; Tanaka, Kenichi A; Nakajima, Yasufumi; Nakayama, Yoshinobu; Takeshita, Jun; Arai, Masatoshi; Mizobe, Toshiki

2015-01-01

An accurate and rapid determination of fibrinogen level is important during hemorrhage to establish a timely hemostatic intervention. The accuracy of fibrinogen measurements may be affected by the specific methodology for its determination, fluid therapies, and anticoagulant agents. The dry-hematology method (DRIHEMATO®) is a novel approach to determine fibrinogen levels in plasma and whole blood based on thrombin-activated coagulation time. We hypothesized that plasma or whole blood fibrinogen level using the dry-hematology method would be similar to those measured with conventional plasma fibrinogen assays. Acquired hypofibrinogenemia was modeled by serial dilutions of blood samples obtained from 12 healthy volunteers. Citrated whole blood samples were diluted with either normal saline, 5% human albumin, or 6% hydroxyethyl starch to achieve 25%, 50%, and 75% volume replacement. The dry-hematology method, the Clauss method, the prothrombin time (PT)-derived method, determination of antigen levels, and thromboelastometric fibrin formation were compared in plasma or whole blood samples. The effect of heparin on each assay was examined (0 to 6 IU/mL). Comparisons of dry-hematology and other methods were also conducted using ex vivo samples obtained from cardiac surgical patients (n = 60). In plasma samples, there were no significant differences between dry-hematology and the Clauss method, while dry-hematology showed lower fibrinogen levels compared with PT-derived and antigen level methods. The dry-hematology method yielded acceptable concordance correlation coefficients (Pc) with the Clauss method, the PT-derived method, and fibrinogen antigen levels (Pc = 0.91-0.99). The type of diluents and heparin affected the results of the PT-derived method and thromboelastometric assay, but not the dry-hematology method. In cardiac surgical patients, the overall correlation in fibrinogen levels between dry-hematology and the other methods was comparable to the results from

Baseline hematology and serum biochemistry results for Indian leopards (Panthera pardus fusca

Directory of Open Access Journals (Sweden)

Arun Attur Shanmugam

2017-07-01

Full Text Available Aim: The aim of the study was to establish the baseline hematology and serum biochemistry values for Indian leopards (Panthera pardus fusca, and to assess the possible variations in these parameters based on age and gender. Materials and Methods: Hemato-biochemical test reports from a total of 83 healthy leopards, carried out as part of routine health evaluation in Bannerghatta Biological Park and Manikdoh Leopard Rescue Center, were used to establish baseline hematology and serum biochemistry parameters for the subspecies. The hematological parameters considered for the analysis included hemoglobin (Hb, packed cell volume, total erythrocyte count (TEC, total leukocyte count (TLC, mean corpuscular volume (MCV, mean corpuscular Hb (MCH, and MCH concentration. The serum biochemistry parameters considered included total protein (TP, albumin, globulin, aspartate aminotransferase, alanine aminotransferase (ALT, blood urea nitrogen, creatinine, triglycerides, calcium, and phosphorus. Results: Even though few differences were observed in hematologic and biochemistry values between male and female Indian leopards, the differences were statistically not significant. Effects of age, however, were evident in relation to many hematologic and biochemical parameters. Sub-adults had significantly greater values for Hb, TEC, and TLC compared to adults and geriatric group, whereas they had significantly lower MCV and MCH compared to adults and geriatric group. Among, serum biochemistry parameters the sub-adult age group was observed to have significantly lower values for TP and ALT than adult and geriatric leopards. Conclusion: The study provides a comprehensive analysis of hematologic and biochemical parameters for Indian leopards. Baselines established here will permit better captive management of the subspecies, serve as a guide to assess the health and physiological status of the free ranging leopards, and may contribute valuable information for making

Baseline hematology and serum biochemistry results for Indian leopards (Panthera pardus fusca)

Science.gov (United States)

Shanmugam, Arun Attur; Muliya, Sanath Krishna; Deshmukh, Ajay; Suresh, Sujay; Nath, Anukul; Kalaignan, Pa; Venkataravanappa, Manjunath; Jose, Lyju

2017-01-01

Aim: The aim of the study was to establish the baseline hematology and serum biochemistry values for Indian leopards (Panthera pardus fusca), and to assess the possible variations in these parameters based on age and gender. Materials and Methods: Hemato-biochemical test reports from a total of 83 healthy leopards, carried out as part of routine health evaluation in Bannerghatta Biological Park and Manikdoh Leopard Rescue Center, were used to establish baseline hematology and serum biochemistry parameters for the subspecies. The hematological parameters considered for the analysis included hemoglobin (Hb), packed cell volume, total erythrocyte count (TEC), total leukocyte count (TLC), mean corpuscular volume (MCV), mean corpuscular Hb (MCH), and MCH concentration. The serum biochemistry parameters considered included total protein (TP), albumin, globulin, aspartate aminotransferase, alanine aminotransferase (ALT), blood urea nitrogen, creatinine, triglycerides, calcium, and phosphorus. Results: Even though few differences were observed in hematologic and biochemistry values between male and female Indian leopards, the differences were statistically not significant. Effects of age, however, were evident in relation to many hematologic and biochemical parameters. Sub-adults had significantly greater values for Hb, TEC, and TLC compared to adults and geriatric group, whereas they had significantly lower MCV and MCH compared to adults and geriatric group. Among, serum biochemistry parameters the sub-adult age group was observed to have significantly lower values for TP and ALT than adult and geriatric leopards. Conclusion: The study provides a comprehensive analysis of hematologic and biochemical parameters for Indian leopards. Baselines established here will permit better captive management of the subspecies, serve as a guide to assess the health and physiological status of the free ranging leopards, and may contribute valuable information for making effective

Asia-Pacific consensus on the management of gastro-oesophageal reflux disease: an update focusing on refractory reflux disease and Barrett's oesophagus.

Science.gov (United States)

Fock, Kwong Ming; Talley, Nicholas; Goh, Khean Lee; Sugano, Kentaro; Katelaris, Peter; Holtmann, Gerald; Pandolfino, John E; Sharma, Prateek; Ang, Tiing Leong; Hongo, Michio; Wu, Justin; Chen, Minhu; Choi, Myung-Gyu; Law, Ngai Moh; Sheu, Bor-Shyang; Zhang, Jun; Ho, Khek Yu; Sollano, Jose; Rani, Abdul Aziz; Kositchaiwat, Chomsri; Bhatia, Shobna

2016-09-01

Since the publication of the Asia-Pacific consensus on gastro-oesophageal reflux disease in 2008, there has been further scientific advancement in this field. This updated consensus focuses on proton pump inhibitor-refractory reflux disease and Barrett's oesophagus. A steering committee identified three areas to address: (1) burden of disease and diagnosis of reflux disease; (2) proton pump inhibitor-refractory reflux disease; (3) Barrett's oesophagus. Three working groups formulated draft statements with supporting evidence. Discussions were done via email before a final face-to-face discussion. We used a Delphi consensus process, with a 70% agreement threshold, using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to categorise the quality of evidence and strength of recommendations. A total of 32 statements were proposed and 31 were accepted by consensus. A rise in the prevalence rates of gastro-oesophageal reflux disease in Asia was noted, with the majority being non-erosive reflux disease. Overweight and obesity contributed to the rise. Proton pump inhibitor-refractory reflux disease was recognised to be common. A distinction was made between refractory symptoms and refractory reflux disease, with clarification of the roles of endoscopy and functional testing summarised in two algorithms. The definition of Barrett's oesophagus was revised such that a minimum length of 1 cm was required and the presence of intestinal metaplasia no longer necessary. We recommended the use of standardised endoscopic reporting and advocated endoscopic therapy for confirmed dysplasia and early cancer. These guidelines standardise the management of patients with refractory gastro-oesophageal reflux disease and Barrett's oesophagus in the Asia-Pacific region. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Human primary erythroid cells as a more sensitive alternative in vitro hematological model for nanotoxicity studies: Toxicological effects of silver nanoparticles.

Science.gov (United States)

Rujanapun, Narawadee; Aueviriyavit, Sasitorn; Boonrungsiman, Suwimon; Rosena, Apiwan; Phummiratch, Duangkamol; Riolueang, Suchada; Chalaow, Nipon; Viprakasit, Vip; Maniratanachote, Rawiwan

2015-12-01

Although immortalized cells established from cancerous cells have been widely used for studies in nanotoxicology studies, the reliability of the results derived from immortalized cells has been questioned because of their different characteristics from normal cells. In the present study, human primary erythroid cells in liquid culture were used as an in vitro hematological cell model for investigation of the nanotoxicity of silver nanoparticles (AgNPs) and comparing the results to the immortalized hematological cell lines HL60 and K562. The AgNPs caused significant cytotoxic effects in the primary erythroid cells, as shown by the decreased cell viability and induction of intracellular ROS generation and apoptosis, whereas they showed much lower cytotoxic and apoptotic effects in HL60 and K562 cells and did not induced ROS generation in these cell lines. Scanning electron microcopy revealed an interaction of AgNPs to the cell membrane in both primary erythroid and immortalized cells. In addition, AgNPs induced hemolysis in the primary erythroid cells in a dose-dependent manner, and transmission electron microcopy analysis revealed that AgNPs damaged the erythroid cell membrane. Taken together, these results suggest that human primary erythroid cells in liquid culture are a more sensitive alternative in vitro hematological model for nanotoxicology studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Feasibility of Cancer Immunotherapy with WT1 Peptide Vaccination for Solid and Hematological Malignancies in Children.

Science.gov (United States)

Sawada, Akihisa; Inoue, Masami; Kondo, Osamu; Yamada-Nakata, Kayo; Ishihara, Takashi; Kuwae, Yuko; Nishikawa, Masanori; Ammori, Yasuhiro; Tsuboi, Akihiro; Oji, Yusuke; Koyama-Sato, Maho; Oka, Yoshihiro; Yasui, Masahiro; Sugiyama, Haruo; Kawa, Keisei

2016-02-01

Advances in cancer immunotherapy in the pediatric field are needed in order to improve the prognosis of children with malignancies. We conducted a prospective phase I/II study of WT1 peptide vaccination for children with relapsed or refractory malignancies. The main eligibility criteria were affected tissues or leukemic cells expressing the WT1 gene, and patients (and donors for allogeneic hematopoietic stem cell transplantation) having HLA-A*24:02. Vaccination using the WT1 peptide (CYTWNQMNL), which was modified for higher affinity to this HLA-type molecule with the adjuvant Montanide ISA51, was performed weekly 12 times. Twenty-six patients were enrolled and 13 (50.0%) completed the vaccination 12 times. Evidence for the induction of WT1-specific cytotoxic T-lymphocyte (CTL) responses without severe systemic side effects was obtained. Two out of 12 patients with bulky disease exhibited a transient clinical effect (one mixed response and one stable disease), three out of six patients with minimal residual disease achieved transient molecular remission, and five out of eight patients without a detectable level of the molecular marker, but with a high risk of relapse, had the best outcome of long-term continuous complete remission. WT1 vaccination is a safe immunotherapy and induced WT1-specific CTL responses in children; however, as a single agent, vaccination only provided patients in remission, but with a high risk of relapse, with "long-term benefits" in the context of its use for relapse prevention. WT1 peptide-based treatments in combination with other modalities, such as anti-tumor drugs or immunomodulating agents, need to be planned. © 2015 Wiley Periodicals, Inc.

Use of Electronic Consultation System to Improve Access to Care in Pediatric Hematology/Oncology.

Science.gov (United States)

Johnston, Donna L; Murto, Kimmo; Kurzawa, Julia; Liddy, Clare; Keely, Erin; Lai, Lillian

2017-10-01

Electronic consultations (eConsult) allow for communication between primary care providers and specialists in an asynchronous manner. This study examined provider satisfaction, topics of interest, and efficiency of eConsult in pediatric hematology/oncology in Ottawa, Canada. We conducted a cross-sectional assessment of all eConsult cases directed to pediatric hematology/oncology specialists using the Champlain BASE (Building Access to Specialists through eConsultation) eConsult service from June 1, 2014 to May 31, 2016. There were 1064 eConsults to pediatrics during the study timeperiod and pediatric hematology/oncology consults accounted for 8% (85). During the same study timeperiod, 524 consults were seen in the pediatric hematology/oncology clinic. The majority of the eConsults were for hematology (90.5%) in contrast to oncology topics (9.5%). The most common topics were anemia, hemoglobinopathy, bleeding disorder, and thrombotic state. Primary care providers rated the eConsult service very highly, and their comments were very positive. The eConsult service resulted in deferral of 40% of consults originally contemplated to require a face-to-face specialist visit. This study showed successful implementation and use of the eConsult service for pediatric hematology/oncology and resulted in avoidance of a large number of face-to-face consultation. The common topics identified areas for continuing medical education.

Vitamin D in colorectal, breast, prostate and lung cancer: A pilot study

Czech Academy of Sciences Publication Activity Database

Padziora, P.; Svobodová, Š.; Fuchsová, R.; Kučera, R.; Pražáková, M.; Vrzalová, J.; Ňaršanská, A.; Straková, M.; Třešková, I.; Pecen, Ladislav; Třeška, V.; Holubec jr., L.; Pešek, M.; Finek, J.; Topolčan, O.

2011-01-01

Roč. 31, č. 10 (2011), s. 3619-3621 ISSN 0250-7005 Grant - others:GA MZd(CZ) NS9727; GA MZd(CZ) NS10258; GA MZd(CZ) NT11017; GA MZd(CZ) NS10230; GA MZd(CZ) NS10253 Institutional research plan: CEZ:AV0Z10300504 Keywords : vitamin D * colorectal cancer * breast cancer * prostate cancer * lung cancer Subject RIV: FD - Oncology ; Hematology Impact factor: 1.725, year: 2011

Defining refractory migraine: results of the RHSIS Survey of American Headache Society members.

Science.gov (United States)

Schulman, Elliott A; Peterlin, B Lee; Lake, Alvin E; Lipton, Richard B; Hanlon, Alexandra; Siegel, Sherry; Levin, Morris; Goadsby, Peter J; Markley, Herbert G

2009-04-01

To gauge consensus regarding a proposed definition for refractory migraine proposed by Refractory Headache Special Interest Section, and where its use would be most appropriate. Headache experts have long recognized that a subgroup of headache sufferers remains refractory to treatment. Although different groups have proposed criteria to define refractory migraine, the definition remains controversial. The Refractory Headache Special Interest Section of the American Headache Society developed a definition through a consensus process, assisted by a literature review and initial membership survey. A 12-item questionnaire was distributed at the American Headache Society meeting in 2007 during a platform session and at the Refractory Headache Special Interest Section symposium. The same questionnaire was subsequently sent to all American Headache Society members via e-mail. A total of 151 responses from AHS members form the basis of this report. The survey instrument was designed using Survey Monkey. Frequencies and percentages of the survey were used to describe survey responses. American Headache Society members agreed that a definition for refractory migraine is needed (91%) that it should be added to the International Classification of Headache Disorders-2 (86%), and that refractory forms of non-migraine headache disorders should be defined (87%). Responders believed a refractory migraine definition would be of greatest value in selecting patients for clinical drug trials. The current refractory migraine definition requires a diagnosis of migraine, interference with function or quality of life despite modification of lifestyle factors, and adequate trials of acute and preventive medicines with established efficacy. The proposed criteria for the refractory migraine definition require failing 2 preventive medications to meet the threshold for failure. Although 42% of respondents agreed with the working definition of refractory migraine, 43% favored increasing the

The Role of Refractory Dissolved Organic Matter in Ocean Carbon Sequestration

DEFF Research Database (Denmark)

Jørgensen, Linda

The ocean assimilates a large amount of atmospheric CO2 and is potentially a buffer for climate change. A fraction of the assimilated CO2 is incorporated into algal biomass and further converted into refractory dissolved organic matter (DOM). Carbon bound in refractory DOM has the potential...... studies the prokaryotic production and degradation of oceanic refractory DOM and discusses the reasons for the persistent nature of this large DOM fraction. The first two papers investigate the microbial carbon pump, i.e. prokaryotic transfor-mation of organic carbon into refractory DOM. The results show...... DOM compounds in the ocean are rare—possibly too rare to sustain viable uptake and assimilation. Hence, the dilute concentration of individual compounds is a possible explanation for the apparent refractory nature of most DOM in the ocean. Understanding the mechanisms that control the quality...

Intraepithelial lymphocytes in refractory celiac disease : lost in transition

NARCIS (Netherlands)

Schmitz, Frederike

2014-01-01

Refractory coeliac disease type II (RCDII) is a severe complication of coeliac disease. Whereas celiac disease can successfully be treated by the strict avoidance of gluten, refractory celiac patients show no remission despite a gluten-free diet. The pathology of RCDII is only partially understood,

Hematology evaluation in workers exposed to ionizing radiation of a radiotherapy service

International Nuclear Information System (INIS)

Lopez P, G.; Frometa S, I.

1996-01-01

The verification of hematology indicators is performed as a routine at the initial and periodic evaluation of the health of workers which are exposed to ionizing radiation. In order to analyze the behavior of such indicators in connection with the exposure time and the received dose, a sample (n=74) of workers of the Radiotherapy Service in the Cancer Hospital in La Habana has been studied during 8 years. It was observed that the mean number of leucocytes, blood platelet and hemoglobin did not show meaningful variations and oscillated into normal limits; however an increase in the number of leukopenia cases was detected when the exposure time and the accumulated dose increased. This increase was two, three times higher in the last year of pursuit in connection with the initial value. (authors). 8 refs., 2 figs., 3 tabs

Clinical Features of Refractory Ascites in Outpatients

Directory of Open Access Journals (Sweden)

Wanda Regina Caly

Full Text Available OBJECTIVES: To present the clinical features and outcomes of outpatients who suffer from refractory ascites. METHODS: This prospective observational study consecutively enrolled patients with cirrhotic ascites who submitted to a clinical evaluation, a sodium restriction diet, biochemical blood tests, 24 hour urine tests and an ascitic fluid analysis. All patients received a multidisciplinary evaluation and diuretic treatment. Patients who did not respond to the diuretic treatment were controlled by therapeutic serial paracentesis, and a transjugular intrahepatic portosystemic shunt was indicated for patients who required therapeutic serial paracentesis up to twice a month. RESULTS: The most common etiology of cirrhosis in both groups was alcoholism [49 refractory (R and 11 non-refractory ascites (NR]. The majority of patients in the refractory group had Child-Pugh class B cirrhosis (p=0.034. The nutritional assessment showed protein-energy malnutrition in 81.6% of the patients in the R group and 35.5% of the patients in the NR group, while hepatic encephalopathy, hernia, spontaneous bacterial peritonitis, upper digestive hemorrhage and type 2 hepatorenal syndrome were present in 51%, 44.9%, 38.8%, 38.8% and 26.5% of the patients in the R group and 9.1%, 18.2%, 0%, 0% and 0% of the patients in the NR group, respectively (p=0.016, p=0.173, p=0.012, p=0.012, and p=0.100, respectively. Mortality occurred in 28.6% of the patients in the R group and in 9.1% of the patients in the NR group (p=0.262. CONCLUSION: Patients with refractory ascites were malnourished, suffered from hernias, had a high prevalence of complications and had a high postoperative death frequency, which was mostly due to infectious processes.

Reference values of clinical chemistry and hematology parameters in rhesus monkeys (Macaca mulatta).

Science.gov (United States)

Chen, Younan; Qin, Shengfang; Ding, Yang; Wei, Lingling; Zhang, Jie; Li, Hongxia; Bu, Hong; Lu, Yanrong; Cheng, Jingqiu

2009-01-01

Rhesus monkey models are valuable to the studies of human biology. Reference values for clinical chemistry and hematology parameters of rhesus monkeys are required for proper data interpretation. Whole blood was collected from 36 healthy Chinese rhesus monkeys (Macaca mulatta) of either sex, 3 to 5 yr old. Routine chemistry and hematology parameters, and some special coagulation parameters including thromboelastograph and activities of coagulation factors were tested. We presented here the baseline values of clinical chemistry and hematology parameters in normal Chinese rhesus monkeys. These data may provide valuable information for veterinarians and investigators using rhesus monkeys in experimental studies.

Blood at 70: its roots in the history of hematology and its birth.

Science.gov (United States)

Coller, Barry S

2015-12-10

This year we celebrate Blood's 70th year of publication. Created from the partnership of the book publisher Henry M. Stratton and the prominent hematologist Dr William Dameshek of Tufts School of Medicine, Blood has published many papers describing major advances in the science and clinical practice of hematology. Blood's founding antedated that of the American Society of Hematology (ASH) by more than 11 years and Stratton and Dameshek helped galvanize support for the creation of ASH. In this review, I place the birth of Blood in the context of the history of hematology before 1946, emphasizing the American experience from which it emerged, and focusing on research conducted during World War II. I also provide a few milestones along Blood's 70 years of publication, including: the growth in Blood's publications, the evolution of its appearance, the countries of submission of Blood papers, current subscriptions to Blood, and the evolution of topics reported in Blood's papers. The latter provides a snapshot of the evolution of hematology as a scientific and clinical discipline and the introduction of new technology to study blood and bone marrow. Detailed descriptions of the landmark discoveries reported in Blood will appear in later papers celebrating Blood's birthday authored by past Editors-in-Chief. © 2015 by The American Society of Hematology.

Hematological Manifestation in HIV Infected Children

International Nuclear Information System (INIS)

Bhowmik, A.; Banerjee, P.

2015-01-01

Objective: To determine the common hematological abnormalities in HIV infected children and any association of these abnormalities with HIV disease severity. Study Design: Cross-sectional study. Place and Duration of Study: Regional Pediatric ART centre, Medical College and Hospital, Kolkata, West Bengal, India, from November 2011 to November 2012. Methodology: Children up to 12 years with confirmed diagnosis of HIV infection were clinically examined and tested for complete hemogram and CD4 count. Bone marrow study was done in selected patient depending on hemogram report. Children were divided in different stages according to WHO clinical staging. Each of the hematological parameters was assessed for any association with progression of disease. Fisher's Exact Test was used for determining the association between WHO clinical staging and abnormal blood parameters. P-value < 0.05 was taken as significant. Results: Sixty nine percent of the study population was anemic; 47.37% (18/38), 66.67% (8/12), 71.43% (15/21) and 93.10% (27/29) of stage 1, 2, 3 and 4 respectively were anemic in the study population (p=0.001). Leucopenia was present in 34% (34/100) children. Neutropenia and lymphopenia was present in 19% (19/100) and 22% (22/100) children. Lymphopenia was present in 7.89% (3/38), 16.67% (2/12), 19.05% (4/21) and 44.83% (13/29) of patient with stage 1, 2, 3 and 4 respectively (p=0.020). Eosinophilia was present in 17% (17/100) and thrombocytopenia in 11% (11/100) children. 2 patients with stage 4 disease were with hypoplastic bone marrow. Conclusion: Anemia was the most common hematological abnormality in HIV infected children. Anemia and lymphopenia had a significant association with the stage of the disease. (author)

Resistant and Refractory Hypertension: Antihypertensive Treatment Resistance vs Treatment Failure

Science.gov (United States)

Siddiqui, Mohammed; Dudenbostel, Tanja; Calhoun, David A.

2017-01-01

Resistant or difficult to treat hypertension is defined as high blood pressure that remains uncontrolled with 3 or more different antihypertensive medications, including a diuretic. Recent definitions also include controlled blood pressure with use of 4 or more medications as also being resistant to treatment. Recently, refractory hypertension, an extreme phenotype of antihypertensive treatment failure has been defined as hypertension uncontrolled with use of 5 or more antihypertensive agents, including a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Patients with resistant vs refractory hypertension share similar characteristics and comorbidities, including obesity, African American race, female sex, diabetes, coronary heart disease, chronic kidney disease, and obstructive sleep apnea. Patients with refractory vs resistant hypertension tend to be younger and are more likely to have been diagnosed with congestive heart failure. Refractory hypertension might also differ from resistant hypertension in terms of underlying cause. Preliminary evidence suggests that refractory hypertension is more likely to be neurogenic in etiology (ie, heightened sympathetic tone), vs a volume-dependent hypertension that is more characteristic of resistant hypertension in general. PMID:26514749

Performance assessment of refractory samples in the Los Alamos Controlled Air Incinerator

International Nuclear Information System (INIS)

Hutchins, D.A.; Borduin, L.C.; Koenig, R.A.; Vavruska, J.S.; Warner, C.L.

1986-01-01

A refractory evaluation project was initiated in 1979 to study the performance of six selected refractory materials within the Los Alamos Controlled Air Incinerator (CAI). Determining refractory resistance to thermal shock, chemical attack, and plutonium uptake was of particular interest. The experimental refractories were subjected to a variety of waste materials, including transuranic (TRU) contaminated wastes, highly chlorinated compounds and alkaline metal salts of perchlorate, chlorate, nitrate and oxylate, over the six year period of this study. Results of this study to date indicate that the use of high alumina, and possibly specialty plastic refractories, is advisable for the lining of incinerators used for the thermal destruction of diverse chemical compounds. 12 refs., 4 tabs

HTLV-I and HTLV-II infections in hematologic disorder patients, cancer patients, and healthy individuals from Rio de Janeiro, Brazil.

Science.gov (United States)

Farias de Carvalho, S M; Pombo de Oliveira, M S; Thuler, L C; Rios, M; Coelho, R C; Rubim, L C; Silva, E M; Reis, A M; Catovsky, D

1997-07-01

To clarify the seroprevalence of human T-cell lymphotropic virus type I (HTLV-I) among hematologic and cancer patients in the State of Rio de Janeiro, Brazil, we investigated sera from 2430 individuals from the following groups: 152 patients with T-cell diseases, 250 with B-cell disorders, 67 with myeloid leukemia, 41 with Hodgkin's disease, 351 with a history of multiple blood transfusions, 235 patients with solid tumors of different types, and 109 family members of HTLV-I-infected patients. Antibodies to HTLV-I were screened by enzyme-linked immunosorbent assay or particle agglutination assays (or both). Repeatedly reactive samples were tested by Western blot and polymerase chain reaction assay to differentiate HTLV-I from HTLV-II. We found an increased seroprevalence rate of HTLV-I among those with lymphoid malignancies, mainly in T-cell diseases (28.9%), and these results were important in characterizing 44 cases of adult T-cell leukemia/lymphoma. We confirmed the presence of HTLV-I and HTLV-II infections in blood donors (0.4% and 0.1%, respectively), in patients exposed to multiple blood transfusions (10.2% and 0.8%, respectively), and in 30 (27.5%) of 109 family members of HTLV-I- or HTLV-II-infected patients. We also confirmed the high rate occurrence of adult T-cell leukemia/lymphoma among lymphoproliferative disorders in Rio de Janeiro, Brazil.

Hematological outcome in neonatal alloimmune hemolytic disease

NARCIS (Netherlands)

Rath, Mirjam Eva Aafke

2013-01-01

This thesis focuses on several aspects related to the hematological outcome of infants with hemolytic disease of the fetus and newborn (HDFN) due to red blood cell alloimmunization, including pathogenesis and management of the disease. The presence of leukocytopenie and thrombocytopenia support the

[North-South cooperation on transfusion and hematology teaching: A Benin experience].

Science.gov (United States)

Lafia, E; Anani, L; Glitho, S; Bankole, C; Fachinan, H; Py, J-Y; Domenech, J; Martenot, B; Colombat, P; Chobli, M; Zohoun, I

2015-06-01

Hematologic diseases are a significant part of health disorders in Benin. As an example, anemia is the second cause of hospitalization, measuring up to 7.9% all over the country (National Plan of Sanitary Development, 2009-2018). By contrast, there is only one active hematologist in the country. Thanks to two partnerships, on one hand between the health sciences faculty in Cotonou (Benin) and the medicine one in Tours (France), and on the other hand between the Beninese Blood Transfusion National Agency and the French Blood Establishment, a first blood transfusion and hematology formation was held in Cotonou on December 2014. Among other benefits, was created an hematology-transfusion network in order to facilitate relations between Beninese hospital doctors, with the support of the two French partner institutions. The article describes this progress. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

White-Coat Effect Is Uncommon in Patients With Refractory Hypertension.

Science.gov (United States)

Siddiqui, Mohammed; Judd, Eric K; Oparil, Suzanne; Calhoun, David A

2017-09-01

Refractory hypertension is a recently described phenotype of antihypertensive treatment failure defined as uncontrolled blood pressure (BP) despite the use of ≥5 different antihypertensive agents, including chlorthalidone and spironolactone. Recent studies indicate that refractory hypertension is uncommon, with a prevalence of ≈5% to 10% of patients referred to a hypertension specialty clinic for uncontrolled hypertension. The prevalence of white-coat effect, that is, uncontrolled automated office BP ≥135/85 mm Hg and controlled out-of-office BP hypertensive patients overall is ≈30% to 40%. The prevalence of white-coat effect among patients with refractory hypertension has not been previously reported. In this prospective evaluation, consecutive patients referred to the University of Alabama at Birmingham Hypertension Clinic for uncontrolled hypertension were enrolled. Refractory hypertension was defined as uncontrolled automated office BP ≥135/85 mm Hg with the use of ≥5 antihypertensive agents, including chlorthalidone and spironolactone. Automated office BP measurements were based on 6 serial readings, done automatically with the use of a BpTRU device unobserved in the clinic. Out-of-office BP measurements were done by 24-hour ambulatory BP monitor. Thirty-four patients were diagnosed with refractory hypertension, of whom 31 had adequate ambulatory BP monitor readings. White-coat effect was present in only 2 patients, or 6.5% of the 31 patients with refractory hypertension, suggesting that white-coat effect is largely absent in patients with refractory hypertension. These findings suggest that white-coat effect is not a common cause of apparent lack of BP control in patients failing maximal antihypertensive treatment. © 2017 American Heart Association, Inc.

Dose-volume effects for pelvic bone marrow in predicting hematological toxicity in prostate cancer radiotherapy with pelvic node irradiation.

Science.gov (United States)

Sini, Carla; Fiorino, Claudio; Perna, Lucia; Noris Chiorda, Barbara; Deantoni, Chiara Lucrezia; Bianchi, Marco; Sacco, Vincenzo; Briganti, Alberto; Montorsi, Francesco; Calandrino, Riccardo; Di Muzio, Nadia; Cozzarini, Cesare

2016-01-01

To prospectively identify clinical/dosimetric predictors of acute/late hematologic toxicity (HT) in chemo-naÏve patients treated with whole-pelvis radiotherapy (WPRT) for prostate cancer. Data of 121 patients treated with adjuvant/salvage WPRT were analyzed (static-field IMRT n=19; VMAT/Rapidarc n=57; Tomotherapy n=45). Pelvic bone marrow (BM) was delineated as ilium (IL), lumbosacral, lower and whole pelvis (WP), and the relative DVHs were calculated. HT was graded both according to CTCAE v4.03 and as variation in percentage relative to baseline. Logistic regression was used to analyze association between HT and clinical/DVHs factors. Significant differences (p<0.005) in the DVH of BM volumes between different techniques were found: Tomotherapy was associated with larger volumes receiving low doses (3-20 Gy) and smaller receiving 40-50 Gy. Lower baseline absolute values of WBC, neutrophils and lymphocytes (ALC) predicted acute/late HT (p ⩽ 0.001). Higher BM V40 was associated with higher risk of acute Grade3 (OR=1.018) or late Grade2 lymphopenia (OR=1.005). Two models predicting lymphopenia were developed, both including baseline ALC, and BM WP-V40 (AUC=0.73) and IL-V40+smoking (AUC=0.904) for acute/late respectively. Specific regions of pelvic BM predicting acute/late lymphopenia, a risk factor for viral infections, were identified. The 2-variable models including specific constraints to BM may help reduce HT. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comparison of hematological toxicities between innovator and generic cisplatin formulations in cervical cancer patients treated with concurrent chemoradiotherapy

International Nuclear Information System (INIS)

Oike, Takahiro; Ohno, Tatsuya; Noda, Shin-ei; Sato, Hiro; Tamaki, Tomoaki; Kiyohara, Hiroki; Ando, Ken; Nakano, Takashi

2013-01-01

To compare the incidence and degree of hematological toxicity between innovator and generic cisplatin formulations, decreases in white blood cell (WBC) count (leukopenia) and platelet counts (thrombocytopenia) were retrospectively examined, using the Common Toxicity Criteria for Adverse Events ver. 4.0, in patients with uterine cervical cancer treated with concurrent chemoradiotherapy using innovator (innovator group, n = 22) or generic (generic group, n = 22) cisplatin formulations. There were no significant differences in patient characteristics except in the technique of external irradiation; larger numbers of patients in the innovator and generic groups were irradiated using the parallel-opposed two-field technique and the four-field box technique, respectively (P = 0.00012), which is in line with the historical progress of external beam radiation therapy. The numbers of patients showing Grade 1, 2, 3 and 4 leukopenia were 1 (4.5%), 14 (64%), 7 (32%) and 0 (0.0%) in the innovator group, and 1 (4.5%), 6 (27%), 13 (59%) and 2 (9.0%) in the generic group, respectively. The number of patients showing Grade 3–4 leukopenia was significantly greater in the generic group than in the innovator group (P = 0.034). There was no significant relationship between the incidence of Grade 3–4 leukopenia and the technique of external irradiation. There were no significant differences in the incidence and degree of thrombocytopenia between the two groups. These results indicate the possibility that the generic cisplatin formulation may have a different toxicity profile compared to the innovator formulation in terms of the incidence of leukopenia

Parameters of biological activity in colorectal cancer

Czech Academy of Sciences Publication Activity Database

Svobodová, Š.; Topolčan, O.; Holubec jr., L.; Levý, M.; Pecen, Ladislav; Svačina, Š.

2011-01-01

Roč. 31, č. 1 (2011), s. 373-378 ISSN 0250-7005 Institutional research plan: CEZ:AV0Z10300504 Keywords : colorectal cancer * biological activity * prognosis * tumor markers * angiogenetic factors * metalloproteinases * adhesion molecules Subject RIV: FD - Oncology ; Hematology Impact factor: 1.725, year: 2011

Friction measurements of steel on refractory bricks

International Nuclear Information System (INIS)

Eiselstein, L.E.

1981-08-01

During startup or shutdown of a pool-type LMFBR, substantial shear stresses may arise between the base of the steel reactor vessel and the refractory brick support base. The magnitude of these stresses, which result from differences in thermal expansion, can be estimated if the friction coefficient is known. This report describes experiments to determine friction coefficients between 2 1/4 Cr-1Mo steel and several refractory materials and to examine effects to contact pressure, temperature, sliding velocity, lubricants, and surface condition

Characterization of refractory brick based on local raw material from Lampung Province - Indonesia

Science.gov (United States)

Amin, Muhammad; Suryana, Yayat I.; Isnugroho, Kusno; Aji, Bramantyo B.; Birawidha, David C.; Hendronursito, Yusup

2018-04-01

Refractories are non-metallic inorganic materials that are difficult to melt at high temperatures and used in high-temperature casting industries. Refractories are classified into their constituent mineral feed stocks, refractories having typical plot properties commonly called fire bricks. In the manufacture of refractory bricks that exist in the market during the use of mangrove materials derived from abroad that is from China. In this research the refractory brick materials used are quartz sand, feldspart, kaolin, bentonite, and ball clay. All materials come from local Lampung Province - Indonesia. The experiment, there are 7 kinds of experimental composition, made of plot shape with size 230 mm, 65 mm in thickness, 114 mm height mould using manual press machine with 10 tons power and burning at 1400°C for 5 hours. Refractory brick product is done by physical test in the form of porosity, specific gravity, compressive strength and XRF and SEM characteristics. The result of XRF characteristic of refractory brick composition of 1 to 5 compared to the refractory brick type SK 34 in the market and the result of composition 1 is a composition close to refractory brick composition type SK 34 namely SiO2 is 54.21 %, Al2O3 is 25.38 % and test Physical of Bulk density is 2.25 g/cm3, porosity is 18.98 % and compressive strength is 325 kg/cm2.

Neutropenia in pediatric hematology/oncology practice

Directory of Open Access Journals (Sweden)

E. A. Deordieva

2015-06-01

Full Text Available Acquired neutropenia is one of the most common conditions in pediatric hematology practice. These conditions usually are benign. In contrast, congenital neutropenia are rare conditions, but in the absence of pathogenic therapy can cause fatal complications. Approach to the differential diagnosis and management of these patients are discussed in this review.

Refractory benign esophageal strictures

Directory of Open Access Journals (Sweden)

Gopal Goyal

2016-01-01

Full Text Available Refractory benign esophageal stricture (RBES is a frequently encountered problem worldwide. These strictures arise from various causes such as corrosive injury, radiation therapy, peptic origin, ablative therapy, and after surgery. Most strictures can be treated successfully with endoscopic dilatation using bougies or balloons, with only a few complications. Those patients who fail after serial dilatation with bougies or balloons will come to the category of refractory strictures. Dilatation combined with intralesional steroid injections can be considered for peptic strictures, whereas incisional therapy has been demonstrated to be effective for short anastomotic strictures. When these therapeutic options do not resolve the stenosis, stent placement should be considered. Self-bougienage can be proposed to a selected group of patients with a proximal stenosis. Most of the patients of RBES respond to above-mentioned treatment and occasional patient may require surgery as the final treatment option. This review aims to provide a comprehensive approach toward endoscopic management of RBESs based on current literature and personal experience.

Illness identity in young adults with refractory epilepsy.

Science.gov (United States)

Luyckx, Koen; Oris, Leen; Raymaekers, Koen; Rassart, Jessica; Moons, Philip; Verdyck, Ludo; Mijnster, Teus; Mark, Ruth E

2018-03-01

Refractory epilepsy is an intrusive condition with important implications for daily functioning in emerging and young adulthood. The present study examined the degree to which refractory epilepsy is integrated in one's identity, and examined how such a sense of illness identity was related to health-related quality of life (HRQOL). A total of 121 18- to 40-year-old patients with refractory epilepsy (56.2% women) completed self-report questionnaires assessing the four illness identity states of acceptance, enrichment, engulfment, and rejection (Illness Identity Questionnaire (IIQ)); HRQOL (Quality of Life in Epilepsy Inventory - 31); and seizure frequency and severity (Liverpool Seizure Severity Scale (LSSS)). Illness identity scores were compared with a sample of 191 patients with a nonneurological chronic disease (congenital heart disease). Hierarchical regression analyses were conducted to assess the predictive value of illness identity for HRQOL when simultaneously controlling for demographic and clinical features. Patients with refractory epilepsy scored higher on rejection and engulfment and lower on acceptance when compared with patients with congenital heart disease. Further, seizure severity and number of medication side-effects were positively related to engulfment and negatively to acceptance. Finally, when simultaneously controlling for various demographic and clinical variables, illness identity significantly predicted HRQOL (with engulfment being the strongest and most consistent predictor). The extent to which patients with refractory epilepsy succeed in integrating their illness into their identity may have important implications for HRQOL. Clinicians should be especially attentive for signs that patients feel engulfed by their epilepsy. Copyright © 2018 Elsevier Inc. All rights reserved.

Hematologic patients' clinical and psychosocial experiences with implanted long-term central venous catheter

DEFF Research Database (Denmark)

Møller, Tom; Adamsen, Lis

2010-01-01

A significant decrease in catheter-related infections was demonstrated in our earlier randomized controlled trial of central venous catheter (CVC) care in hematologic patients.......A significant decrease in catheter-related infections was demonstrated in our earlier randomized controlled trial of central venous catheter (CVC) care in hematologic patients....

Ketogenic diet treatment for pediatric super-refractory status epilepticus.

Science.gov (United States)

Appavu, Brian; Vanatta, Lisa; Condie, John; Kerrigan, John F; Jarrar, Randa

2016-10-01

We aimed to study whether ketogenic diet (KD) therapy leads to resolution of super-refractory status epilepticus in pediatric patients without significant harm. A retrospective review was performed at Phoenix Children's Hospital on patients with super-refractory status epilepticus undergoing ketogenic diet therapy from 2011 to 2015. Ten children with super-refractory status epilepticus, ages 2-16 years, were identified. 4/10 patients had immune mediated encephalitis, including Rasmussen encephalitis, anti-N-methyl-d-aspartate receptor encephalitis, and post-infectious mycoplasma encephalitis. Other etiologies included Lennox Gastaut Syndrome, non-ketotic hyperglycinemia, PCDH19 and GABRG2 genetic epilepsy, New Onset Refractory Status Epilepticus, and Febrile Infection-Related Epilepsy Syndrome. 4/10 patients' EEG features suggested focal with status epilepticus, and 6/10 suggested generalized with status epilepticus. Median hospital length was 61days and median ICU length was 27days. The median number of antiepileptic medications prior to diet initiation was 3.0 drugs, and the median after ketogenic diet treatment was 3.5 drugs. Median duration of status epilepticus prior to KD was 18days. 9/10 patients had resolution of super-refractory status epilepticus in a median of 7days after diet initiation. 8/9 patients were weaned off anesthesia within 15days of diet initiation, and within 1day of achieving ketonuria. 1/10 patients experienced side effects on the diet requiring supplementation. Most patients achieved resolution of status epilepticus on KD therapy, suggesting it could be an effective therapy that can be utilized early in the treatment of children with super refractory status epilepticus. Copyright © 2016. Published by Elsevier Ltd.

Growth performance, carcass and hematological characteristics of ...

African Journals Online (AJOL)

Growth performance, carcass and hematological characteristics of rabbits fed graded levels of tiger nuts ( Cyperus esculentus ) ... (p>0.05) difference between treatments. Results demonstrated that (Cyperus esculentus) could be used up to 5% in rabbit's diets without adverse effect on the animals' performance and health.

78 FR 54487 - Abbott Laboratories; Diagnostic-Hematology; Including On-Site Leased Workers From Manpower...

Science.gov (United States)

2013-09-04

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-82,379] Abbott Laboratories... February 22, 2013, applicable to workers of Abbott Laboratories, Diagnostic--Hematology division, including... Clara, California location of Abbott Laboratories, Diagnostic--Hematology Division. The Department has...

ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to Chemotherapy

NARCIS (Netherlands)

Wielenga, Mattheus C. B.; Colak, Selcuk; Heijmans, Jarom; van Lidth de Jeude, Jooske F.; Rodermond, Hans M.; Paton, James C.; Paton, Adrienne W.; Vermeulen, Louis; Medema, Jan Paul; van den Brink, Gijs R.

2015-01-01

Colon cancer stem cells (colon-CSCs) are more resistant to conventional chemotherapy than differentiated cancer cells. This subset of therapy refractory cells is therefore believed to play an important role in post-therapeutic tumor relapse. In order to improve the rate of sustained response to

Multicenter study in monitoring central venous catheters complications in hematologic patiennts

Directory of Open Access Journals (Sweden)

Carmen García Gabás

2013-05-01

Full Text Available Most hematological patients suffer a significant venous damage related to different administrated intravenous therapy, being necessary to place central venous catheters (CVC. CVC is associated with various complications. The most common catheter-related complications are occlusion and infection. To avoid such of them, the development of protocols for insertion and care are needed, as well as recording and following up complications. To this end, we propose a cross-sectional carried out during 13 months whose main goal is to know the incidence of CVC- related complications (mainly occlusion and infection in hematological patients.Population included all the =14 ages patients admitted to different hematological units at Ramon y Cajal and Gregorio Marañón hospitals in Madrid and who signed informed consent. Socio-demographic, clinical characteristics and complications were entered into a log which included a pursuit of care protocol.

Evidence of selective reporting bias in hematology journals: A systematic review.

Science.gov (United States)

Wayant, Cole; Scheckel, Caleb; Hicks, Chandler; Nissen, Timothy; Leduc, Linda; Som, Mousumi; Vassar, Matt

2017-01-01

Selective reporting bias occurs when chance or selective outcome reporting rather than the intervention contributes to group differences. The prevailing concern about selective reporting bias is the possibility of results being modified towards specific conclusions. In this study, we evaluate randomized controlled trials (RCTs) published in hematology journals, a group in which selective outcome reporting has not yet been explored. Our primary goal was to examine discrepancies between the reported primary and secondary outcomes in registered and published RCTs concerning hematological malignancies reported in hematology journals with a high impact factor. The secondary goals were to address whether outcome reporting discrepancies favored statistically significant outcomes, whether a pattern existed between the funding source and likelihood of outcome reporting bias, and whether temporal trends were present in outcome reporting bias. For trials with major outcome discrepancies, we contacted trialists to determine reasons for these discrepancies. Trials published between January 1, 2010 and December 31, 2015 in Blood; British Journal of Haematology; American Journal of Hematology; Leukemia; and Haematologica were included. Of 499 RCTs screened, 109 RCTs were included. Our analysis revealed 118 major discrepancies and 629 total discrepancies. Among the 118 discrepancies, 30 (25.4%) primary outcomes were demoted, 47 (39.8%) primary outcomes were omitted, and 30 (25.4%) primary outcomes were added. Three (2.5%) secondary outcomes were upgraded to a primary outcome. The timing of assessment for a primary outcome changed eight (6.8%) times. Thirty-one major discrepancies were published with a P-value and twenty-five (80.6%) favored statistical significance. A majority of authors whom we contacted cited a pre-planned subgroup analysis as a reason for outcome changes. Our results suggest that outcome changes occur frequently in hematology trials. Because RCTs ultimately

Hematology, cytochemistry and ultrastructure of blood cells in fishing cat (Felis viverrina)

OpenAIRE

Prihirunkit, Kreangsak; Salakij, Chaleow; Apibal, Suntaree; Narkkong, Nual-Anong

2007-01-01

Hematological, cytochemical and ultrastructural features of blood cells in fishing cat (Felis viverrina) were evaluated using complete blood cell counts with routine and cytochemical blood stains, and scanning and transmission electron microscopy. No statistically significant difference was found in different genders of this animal. Unique features of blood cells in this animal were identified in hematological, cytochemical and ultrastructural studies. This study contributes to broaden hemato...

Central Diabetes Insipidus in Refractory Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

Science.gov (United States)

Ohashi, Keiji; Morishita, Michiko; Watanabe, Haruki; Sada, Ken-Ei; Katsuyama, Takayuki; Miyawaki, Yoshia; Katsuyama, Eri; Narazaki, Mariko; Tatebe, Noriko; Watanabe, Katsue; Kawabata, Tomoko; Wada, Jun

2017-11-01

We herein describe two cases of refractory antineutrophil cytoplasmic antibody-associated vasculitis (AAV) complicated with diabetes insipidus (DI) possibly related to hypertrophic pachymeningitis (HP). One patient had microscopic polyangiitis and HP, which were refractory to cyclophosphamide, azathioprine, rituximab, mycophenolate mofetil (MMF), and mizoribine. Remission was finally achieved with the use of etanercept, but DI occurred 5 years later. The other patient had granulomatosis with polyangiitis, which that was refractory to cyclophosphamide, methotrexate, MMF, and rituximab. DI subsequently developed, but was successfully treated with etanercept. Dura mater hypertrophy was macroscopically observed in the latter case.

Expression profiling of circulating tumor cells in metastatic breast cancer

Czech Academy of Sciences Publication Activity Database

Lang, J.; Scott, J.H.; Wolf, D.M.; Novák, Petr; Punj, V.; Magbanua, M.J.M.; Zhu, W.Z.; Mineyev, N.; Haqq, CH.; Crothers, J.

2015-01-01

Roč. 149, č. 1 (2015), s. 121-131 ISSN 0167-6806 Institutional support: RVO:60077344 Keywords : Circulating tumor cells * Micrometastases * Breast cancer * EpCAM Subject RIV: FD - Oncology ; Hematology Impact factor: 4.085, year: 2015

A Review on Recent Advances on Magnesia-Doloma Refractories by Nano-Technology.

Directory of Open Access Journals (Sweden)

Salman Ghasemi-Kahrizsangi

2017-07-01

Full Text Available Due to exhibiting an excellent chemical resistance against basic environments at high temperature, good thermal shock resistance, thermodynamic stability in the presence of carbon, and a suitable abrasion resistance, MgO-CaO refractories are widely used in argon-oxygen decarburization furnaces in the metallurgy industry and cement rotary kilns. Furthermore, MgO-CaO refractories are beneficial to removing inclusions from molten steels; thus, they have been considered to be one of the effective refractory types for processing clean steel products. Also, MgO-CaO materials have become one of the attractive steelmaking refractories because of their low cost and high ore reserves.  However, in spite of these primary advantages, the application of MgO-CaO refractories has not been popular due to its tendency to hydration when exposed to the atmosphere.  In world most of MgO-CaO bricks producers used of organic components such as tar, pitch, and peck for produce MgO-CaO refractories. But during the application of these bricks in steel and cement and industrials, they released CO and CO2 gases to air and pollute the atmosphere. For this reason, recently some researcher investigate the effect of additive nanoparticles on MgO-CaO refractories performance. They reported the used of Nano-additive have acceptable results and additive nanoparticles can replace by aforementioned environment contaminating organic compounds. In this study, we reviewed all effort that done for improving the hydration resistance of MgO-CaO refractories by application of Nano-additives with an emphasis on the beneficial the use of additives nanoparticle for reduction of environmental pollution by various industries which used of MgO-CaO refractory bricks.

Refractory Research Group - U.S. DOE, Albany Research Center [Institution Profile

Energy Technology Data Exchange (ETDEWEB)

Bennett, James P.

2004-09-01

The refractory research group at the Albany Research Center (ARC) has a long history of conducting materials research within the U.S. Bureau of Mines, and more recently, within the U.S. Dept. of Energy. When under the U.S. Bureau of Mines, research was driven by national needs to develop substitute materials and to conserve raw materials. This mission was accomplished by improving refractory material properties and/or by recycling refractories using critical and strategic materials. Currently, as a U.S. Dept of Energy Fossil Energy field site, research is driven primarily by the need to assist DOE in meeting its vision to develop economically and environmentally viable technologies for the production of electricity from fossil fuels. Research at ARC impacts this vision by: • Providing information on the performance characteristics of materials being specified for the current generation of power systems; • Developing cost-effective, high performance materials for inclusion in the next generation of fossil power systems; and • Solving environmental emission and waste problems related to fossil energy systems. A brief history of past refractory research within the U.S. Bureau of Mines, the current refractory research at ARC, and the equipment and capabilities used to conduct refractory research at ARC will be discussed.

Profile of hematological abnormalities of Indian HIV infected individuals

Directory of Open Access Journals (Sweden)

Sharma Aman

2009-08-01

Full Text Available Abstract Background Hematological abnormalities are a common complication of HIV infection. These abnormalities increase as the disease advances. Bone marrow abnormalities occur in all stages of HIV infection. Methods Two hundred HIV infected individual were screened for hematological abnormalities from March 2007–March 2008. Absolute CD4 cell count analysis was carried out by flowcytometry. Depending on the results of the primary screening further investigations were performed, like iron studies, hemolytic work up, PNH work up and bone marrow evaluation. Other investigations included coagulation profile, urine analysis, blood culture (bacterial, fungal, mycobacterial, serology for Epstein Barr virus (EBV, Cytomegalovirus (CMV, Hepatitis B and C, and Parvo B19 infection. Results The most common hematological abnormality was anemia, seen in 65.5% (131/200 patients. Iron deficiency anemia was seen in 49.2% (/200 cases while anemia of chronic disease occurred in 50.7% (/200 cases. Bone marrow evaluation was carried out in 14 patients out of which staging marrow was performed in 2 cases of non-Hodgkin's lymphoma (NHL and did not show any bone marrow infiltration. In remaining12 cases bone marrow was done for evaluation of pancytopenia. Among patients with pancytopenia 50% (6/12 showed granulomas (4 were positive for AFB, 2 were positive for fungal cryptococci, 25% (3/12 showed hemophagocytosis. There was a strong negative correlation between anemia and CD4 counts in this study. Thrombocytopenia was seen in 7% (14/200 cases and had no significant correlation with CD4 counts. No patient had absolute neutrophil count (ANC Conclusion Anemia in HIV patients can be a good clinical indicator to predict and access the underlying immune status. Patients should be investigated for hematological manifestations and appropriate steps should be taken to identify and treat the reversible factors.

Assembly and evaluation of an inventory of guidelines that are available to support clinical hematology laboratory practice.

Science.gov (United States)

Hayward, C P M; Moffat, K A; George, T I; Proytcheva, M

2015-05-01

Practice guidelines provide helpful support for clinical laboratories. Our goal was to assemble an inventory of publically listed guidelines on hematology laboratory topics, to create a resource for laboratories and for assessing gaps in practice-focused guidelines. PubMed and website searches were conducted to assemble an inventory of hematology laboratory-focused guidelines. Exclusions included annual, technical, or collaborative study reports, clinically focused guidelines, position papers, nomenclature, and calibration documents. Sixty-eight guidelines were identified on hematology laboratory practice topics from 12 organizations, some as joint guidelines. The median year of publication was 2010 and 15% were >10 years old. Coagulation topics had the largest numbers of guidelines, whereas some areas of practice had few guidelines. A minority of guidelines showed evidence of periodic updates, as some organizations did not remove or identify outdated guidelines. This inventory of current practice guidelines will encourage awareness and uptake of guideline recommendations by the worldwide hematology laboratory community, with the International Society for Laboratory Hematology facilitating ongoing updates. There is a need to encourage best guideline development practices, to ensure that hematology laboratory community has current, high-quality, and evidence-based practice guidelines that cover the full scope of hematology laboratory practice. © 2015 John Wiley & Sons Ltd.

Diurnal variation of hematology parameters in healthy young males: the Bispebjerg study of diurnal variations

DEFF Research Database (Denmark)

Sennels, Henriette P; Jørgensen, Henrik L; Hansen, Anne-Louise S

2011-01-01

To evaluate the influence of time of day on the circulating concentrations of 21 hematology parameters.......To evaluate the influence of time of day on the circulating concentrations of 21 hematology parameters....

Patterns of Cancer in Kurdistan - Results of Eight Years Cancer Registration in Sulaymaniyah Province-Kurdistan-Iraq.

Science.gov (United States)

Khoshnaw, Najmaddin; Mohammed, Hazha A; Abdullah, Dana A

2015-01-01

Cancer has become a major health problem associated with high mortality worldwide, especially in developing countries. The aim of our study was to evaluate the incidence rates of different types of cancer in Sulaymaniyah from January-2006 to January-2014. The data were compared with those reported for other middle east countries. This retrospective study depended on data collected from Hiwa hospital cancer registry unit, death records and histopathology reports in all Sulaymaniyah teaching hospitals, using international classification of diseases. A total of 8,031 cases were registered during the eight year period, the annual incidence rate in all age groups rose from 38 to 61.7 cases/100,000 population/year, with averages over 50 in males and 50.7 in females. The male to female ratio in all age groups were 0.98, while in the pediatric age group it was 1.33. The hematological malignancies in all age groups accounted for 20% but in the pediatric group around half of all cancer cases. Pediatric cancers were occluding 7% of total cancers with rates of 10.3 in boys and 8.7 in girls. The commonest malignancies by primary site were leukemia, lymphoma, brain, kidney and bone. In males in all age groups they were lung, leukaemia, lymphoma, colorectal, prostate, bladder, brain, stomach, carcinoma of unknown primary (CUP) and skin, while in females they were breast, leukaemia, lymphoma, colorectal, ovary, lung, brain, CUP, and stomach. Most cancers were increased with increasing age except breast cancer where decrease was noted in older ages. High mortality rates were found with leukemia, lung, lymphoma, colorectal, breast and stomach cancers. We here found an increase in annual cancer incidence rates across the period of study, because of increase of cancer with age and higher rates of hematological malignancies. Our study is valuable for Kurdistan and Iraq because it provides more accurate data about the exact patterns of cancer and mortality in our region.

Eosinophilia in routine blood samples and the subsequent risk of hematological malignancies and death

DEFF Research Database (Denmark)

Andersen, Christen Bertel L; Siersma, Volkert Dirk; Hasselbalch, HC

2013-01-01

Eosinophilia may represent an early paraclinical sign of hematological malignant disease, but no reports exist on its predictive value for hematological malignancies. From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356,196 individuals with at least one differ...

Proteomics of anti-cancer drugs

Czech Academy of Sciences Publication Activity Database

Kovářová, Hana; Martinková, Jiřina; Hrabáková, Rita; Skalníková, Helena; Novák, Petr; Hajdůch, M.; Gadher, S. J.

2009-01-01

Roč. 276, Supplement 1 (2009), s. 84-84 E-ISSN 1742-4658. [34th FEBS Congress. 04.07.2009-09.07.2009, Praha] R&D Projects: GA MŠk LC07017 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510 Keywords : proteomics * anti-cancer drugs * biomarkers Subject RIV: FD - Oncology ; Hematology

Female Representation in the Academic Oncology Physician Workforce: Radiation Oncology Losing Ground to Hematology Oncology

Energy Technology Data Exchange (ETDEWEB)

Ahmed, Awad A. [Sylvester Comprehensive Cancer Center University of Miami Health System, Miami, Florida (United States); Hwang, Wei-Ting [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Holliday, Emma B. [Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chapman, Christina H.; Jagsi, Reshma [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Thomas, Charles R. [Department of Radiation Medicine, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon (United States); Deville, Curtiland, E-mail: cdeville@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland (United States)

2017-05-01

Purpose: Our purpose was to assess comparative female representation trends for trainees and full-time faculty in the academic radiation oncology and hematology oncology workforce of the United States over 3 decades. Methods and Materials: Simple linear regression models with year as the independent variable were used to determine changes in female percentage representation per year and associated 95% confidence intervals for trainees and full-time faculty in each specialty. Results: Peak representation was 48.4% (801/1654) in 2013 for hematology oncology trainees, 39.0% (585/1499) in 2014 for hematology oncology full-time faculty, 34.8% (202/581) in 2007 for radiation oncology trainees, and 27.7% (439/1584) in 2015 for radiation oncology full-time faculty. Representation significantly increased for trainees and full-time faculty in both specialties at approximately 1% per year for hematology oncology trainees and full-time faculty and 0.3% per year for radiation oncology trainees and full-time faculty. Compared with radiation oncology, the rates were 3.84 and 2.94 times greater for hematology oncology trainees and full-time faculty, respectively. Conclusion: Despite increased female trainee and full-time faculty representation over time in the academic oncology physician workforce, radiation oncology is lagging behind hematology oncology, with trainees declining in recent years in radiation oncology; this suggests a de facto ceiling in female representation. Whether such issues as delayed or insufficient exposure, inadequate mentorship, or specialty competitiveness disparately affect female representation in radiation oncology compared to hematology oncology are underexplored and require continued investigation to ensure that the future oncologic physician workforce reflects the diversity of the population it serves.

Female Representation in the Academic Oncology Physician Workforce: Radiation Oncology Losing Ground to Hematology Oncology

International Nuclear Information System (INIS)

Ahmed, Awad A.; Hwang, Wei-Ting; Holliday, Emma B.; Chapman, Christina H.; Jagsi, Reshma; Thomas, Charles R.; Deville, Curtiland

2017-01-01

Purpose: Our purpose was to assess comparative female representation trends for trainees and full-time faculty in the academic radiation oncology and hematology oncology workforce of the United States over 3 decades. Methods and Materials: Simple linear regression models with year as the independent variable were used to determine changes in female percentage representation per year and associated 95% confidence intervals for trainees and full-time faculty in each specialty. Results: Peak representation was 48.4% (801/1654) in 2013 for hematology oncology trainees, 39.0% (585/1499) in 2014 for hematology oncology full-time faculty, 34.8% (202/581) in 2007 for radiation oncology trainees, and 27.7% (439/1584) in 2015 for radiation oncology full-time faculty. Representation significantly increased for trainees and full-time faculty in both specialties at approximately 1% per year for hematology oncology trainees and full-time faculty and 0.3% per year for radiation oncology trainees and full-time faculty. Compared with radiation oncology, the rates were 3.84 and 2.94 times greater for hematology oncology trainees and full-time faculty, respectively. Conclusion: Despite increased female trainee and full-time faculty representation over time in the academic oncology physician workforce, radiation oncology is lagging behind hematology oncology, with trainees declining in recent years in radiation oncology; this suggests a de facto ceiling in female representation. Whether such issues as delayed or insufficient exposure, inadequate mentorship, or specialty competitiveness disparately affect female representation in radiation oncology compared to hematology oncology are underexplored and require continued investigation to ensure that the future oncologic physician workforce reflects the diversity of the population it serves.

Female Representation in the Academic Oncology Physician Workforce: Radiation Oncology Losing Ground to Hematology Oncology.

Science.gov (United States)

Ahmed, Awad A; Hwang, Wei-Ting; Holliday, Emma B; Chapman, Christina H; Jagsi, Reshma; Thomas, Charles R; Deville, Curtiland

2017-05-01

Our purpose was to assess comparative female representation trends for trainees and full-time faculty in the academic radiation oncology and hematology oncology workforce of the United States over 3 decades. Simple linear regression models with year as the independent variable were used to determine changes in female percentage representation per year and associated 95% confidence intervals for trainees and full-time faculty in each specialty. Peak representation was 48.4% (801/1654) in 2013 for hematology oncology trainees, 39.0% (585/1499) in 2014 for hematology oncology full-time faculty, 34.8% (202/581) in 2007 for radiation oncology trainees, and 27.7% (439/1584) in 2015 for radiation oncology full-time faculty. Representation significantly increased for trainees and full-time faculty in both specialties at approximately 1% per year for hematology oncology trainees and full-time faculty and 0.3% per year for radiation oncology trainees and full-time faculty. Compared with radiation oncology, the rates were 3.84 and 2.94 times greater for hematology oncology trainees and full-time faculty, respectively. Despite increased female trainee and full-time faculty representation over time in the academic oncology physician workforce, radiation oncology is lagging behind hematology oncology, with trainees declining in recent years in radiation oncology; this suggests a de facto ceiling in female representation. Whether such issues as delayed or insufficient exposure, inadequate mentorship, or specialty competitiveness disparately affect female representation in radiation oncology compared to hematology oncology are underexplored and require continued investigation to ensure that the future oncologic physician workforce reflects the diversity of the population it serves. Copyright © 2017 Elsevier Inc. All rights reserved.

Brentuximab Vedotin Treatment for Primary Refractory Hodgkin Lymphoma

Directory of Open Access Journals (Sweden)

Hung-Bo Wu

2013-01-01

Full Text Available Up to 40% of patients with advanced Hodgkin lymphoma (HL become refractory or relapsed after current standard chemotherapy, among which primary refractory HL confers a particularly poor outcome. With intensive salvage chemotherapy and autologous stem cell transplantation, the long-term remission rate for these patients was only 30%, but more selective treatments with higher therapeutic index are needed. We report the experience of using a new anti-CD30 immunotoxin, brentuximab vedotin, in salvage treatment of a 30-year-old woman with primary refractory Hodgkin lymphoma. The patient presented with SVC syndrome due to the bulky mediastinal tumor and was confirmed to have classical Hodgkin lymphoma, nodular sclerosis type, stage IIIA. The tumor responded to induction chemotherapy transiently, but local progression was noted during subsequent cycles of treatment. Salvage radiotherapy to the mediastinal tumor, obtained no remission but was followed by rapid in-field progression and then lung metastasis. She declined stem cell transplantation and received salvage brentuximab vedotin (BV therapy, which induced dramatic shrinkage of tumor without significant side effects. Serial followup of PET/CT imaging confirmed a rapid and continuous complete remission for 12 months. Although durability of the remission needs further observation, this case illustrates the excellent efficacy of brentuximab vedotin in primary refractory Hodgkin lymphoma.

Prognostic Significance of TMPRSS2-ERG Fusion Gene in Prostate Cancer

Czech Academy of Sciences Publication Activity Database

Kulda, V.; Topolčan, O.; Kučera, R.; Kripnerová, M.; Srbecká, K.; Hora, M.; Hes, O.; Klečka, J.; Babuška, V.; Rousárová, M.; Benson, Veronika; Pesta, M.

2016-01-01

Roč. 36, č. 7 (2016), s. 4787-4793 ISSN 0250-7005 Institutional support: RVO:61388971 Keywords : Prostate cancer * TMPRSS2-ERG * PSA Subject RIV: FD - Oncology ; Hematology Impact factor: 1.937, year: 2016

Effects of maternal dexamethasone exposure on hematological ...

African Journals Online (AJOL)

Exposure to dexamethasone at LD 1-14 and 1-21 significantly (P<0.05) reduced RBC and platelet counts but it raised MCV and MCH relative to control. This study suggests that prenatal and lactational dexamethasone administration may affect the hematological indices in the male offspring. Keywords: Dexamethasone ...

Testing of the melter lid refractory for the West Valley Demonstration Project (WVDP)

International Nuclear Information System (INIS)

Gupta, A.; Jain, V.; Mahoney, J.L.; Holman, T.M.

1991-01-01

Monofrax H and Mulfrax 202 refractory were tested for potential application as the melter lid refractory for the WVDP. Resistance to spalling and corrosion by the slurry and offgas salts were primary criteria for selection. Test specimens were subjected to thermal cycling between 450 and 1,100C for five weeks. Visual examination indicated some corrosion but no spalling. SEM/EDS analysis was performed to determine the glass/refractory interface corrosion mechanism. The refractory selection basis will be discussed

Clinical factors related to the efficacy of tyrosine kinase inhibitor therapy in radioactive iodine refractory recurrent differentiated thyroid cancer patients.

Science.gov (United States)

Sugino, Kiminori; Nagahama, Mitsuji; Kitagawa, Wataru; Ohkuwa, Keiko; Uruno, Takashi; Matsuzu, Kenichi; Suzuki, Akifumi; Masaki, Chie; Akaishi, Junko; Hames, Kiyomi Y; Tomoda, Chisato; Ogimi, Yuna; Ito, Koichi

2018-03-28

New insights in thyroid cancer biology propelled the development of targeted therapies as salvage treatment for radioiodine-refractory differentiated thyroid cancer (RR-DTC), and the tyrosine kinase inhibitor (TKI) lenvatinib has recently become available as a new line of therapy for RR-DTC. The aim of this study is to investigate clinical factors related to the efficacy of TKI therapy in recurrent RR-DTC patients and identify the optimal timing for the start of TKI therapy. The subjects consisted of 29 patients with progressive RR-DTC, 9 males and 20 females, median age 66 years. A univariate analysis was conducted in relation to progression free survival (PFS) and overall survival (OS) by the Kaplan-Meier method for the following variables: age, sex, histology of the primary tumor, thyroglobulin doubling time before the start of lenvatinib therapy, site of the target lesions, presence of a tumor-mediated symptom at the start of lenvatinib therapy, and baseline tumor size of the target lesions. Median duration of lenvatinib therapy was 14.7 months and median drug intensity was 9.5 mg. At the time of the data cut-off for the analysis, 9 patients (31.0%) have died of their disease (DOD), and a PR (partial response), SD (stable disease), and PD (progressive disease) were observed in 20 patients (69%), 6 patients (20.7%), 3 patients (10.3%), respectively. Univariate analyses showed that the presence of a symptom was the only factor significantly related to poorer PFS and OS. Clinical benefit of TKI therapy will be possibly limited when the therapy starts after tumor-mediated symptoms appear.

Computerized tomography in the study of intracranial complications in hematology

International Nuclear Information System (INIS)

Gastaut, J.L.; Gastaut, J.A.

1979-01-01

CT was used to examine 100 patients with various hematologic disorders. It was generally in patients with clinical signs of encephalic alteration (68% of the cases) that we demonstrated lesions. In several cases, the lesions were detected by CT, whereas common neurological investigational methods remained negative. The most interesting findings were in acute leukemias (leucoblastic infiltrations, cerebral hemorrhages and infarctions, and iatrogenic morphologic modifications) and in Hodgkin diseases (intracranial localizations). CT permits a more complete neurologic work-up for patients with hematologic disorders and provides a better knowledge of the frequency and varieties of intracranial complications. (orig.) 891 MG/orig. 892 MB [de

Hematology of healthy Florida manatees (Trichechus manatus)

Science.gov (United States)

Harvey, J.W.; Harr, K.E.; Murphy, D.; Walsh, M.T.; Nolan, E.C.; Bonde, R.K.; Pate, M.G.; Deutsch, C.J.; Edwards, H.H.; Clapp, W.L.

2009-01-01

Background: Hematologic analysis is an important tool in evaluating the general health status of free-ranging manatees and in the diagnosis and monitoring of rehabilitating animals. Objectives: The purpose of this study was to evaluate diagnostically important hematologic analytes in healthy manatees (Trichechus manatus) and to assess variations with respect to location (free ranging vs captive), age class (small calves, large calves, subadults, and adults), and gender. Methods: Blood was collected from 55 free-ranging and 63 captive healthy manatees. Most analytes were measured using a CELL-DYN 3500R; automated reticulocytes were measured with an ADVIA 120. Standard manual methods were used for differential leukocyte counts, reticulocyte and Heinz body counts, and plasma protein and fibrinogen concentrations. Results: Rouleaux, slight polychromasia, stomatocytosis, and low numbers of schistocytes and nucleated RBCs (NRBCs) were seen often in stained blood films. Manual reticulocyte counts were higher than automated reticulocyte counts. Heinz bodies were present in erythrocytes of most manatees. Compared with free-ranging manatees, captive animals had slightly lower MCV, MCH, and eosinophil counts and slightly higher heterophil and NRBC counts, and fibrinogen concentration. Total leukocyte, heterophil, and monocyte counts tended to be lower in adults than in younger animals. Small calves tended to have higher reticulocyte counts and NRBC counts than older animals. Conclusions: Hematologic findings were generally similar between captive and free-ranging manatees. Higher manual reticulocyte counts suggest the ADVIA detects only reticulocytes containing large amounts of RNA. Higher reticulocyte and NRBC counts in young calves probably reflect an increased rate of erythropoiesis compared with older animals. ?? 2009 American Society for Veterinary Clinical Pathology.

Integration of microarray analysis into the clinical diagnosis of hematological malignancies: How much can we improve cytogenetic testing?

Science.gov (United States)

Peterson, Jess F.; Aggarwal, Nidhi; Smith, Clayton A.; Gollin, Susanne M.; Surti, Urvashi; Rajkovic, Aleksandar; Swerdlow, Steven H.; Yatsenko, Svetlana A.

2015-01-01

Purpose To evaluate the clinical utility, diagnostic yield and rationale of integrating microarray analysis in the clinical diagnosis of hematological malignancies in comparison with classical chromosome karyotyping/fluorescence in situ hybridization (FISH). Methods G-banded chromosome analysis, FISH and microarray studies using customized CGH and CGH+SNP designs were performed on 27 samples from patients with hematological malignancies. A comprehensive comparison of the results obtained by three methods was conducted to evaluate benefits and limitations of these techniques for clinical diagnosis. Results Overall, 89.7% of chromosomal abnormalities identified by karyotyping/FISH studies were also detectable by microarray. Among 183 acquired copy number alterations (CNAs) identified by microarray, 94 were additional findings revealed in 14 cases (52%), and at least 30% of CNAs were in genomic regions of diagnostic/prognostic significance. Approximately 30% of novel alterations detected by microarray were >20 Mb in size. Balanced abnormalities were not detected by microarray; however, of the 19 apparently “balanced” rearrangements, 55% (6/11) of recurrent and 13% (1/8) of non-recurrent translocations had alterations at the breakpoints discovered by microarray. Conclusion Microarray technology enables accurate, cost-effective and time-efficient whole-genome analysis at a resolution significantly higher than that of conventional karyotyping and FISH. Array-CGH showed advantage in identification of cryptic imbalances and detection of clonal aberrations in population of non-dividing cancer cells and samples with poor chromosome morphology. The integration of microarray analysis into the cytogenetic diagnosis of hematologic malignancies has the potential to improve patient management by providing clinicians with additional disease specific and potentially clinically actionable genomic alterations. PMID:26299921

Effectiveness of botulinum toxin A in treatment of refractory erythromelalgia

Directory of Open Access Journals (Sweden)

Kuan-Hsiang Lin

2013-05-01

Full Text Available Erythromelalgia is characterized by intense burning pain, erythema, and heat in affected areas after precipitating factors such as warm temperature or stress. It is refractory to treatment in some situations. We describe a woman with adenosquamous cell carcinoma of the lung and medically refractory erythromelalgia. The symptoms of erythromelalgia presented as refractory to any medical treatment. Due to the unresponsive nature of her condition, botulinum toxin type A (onabotulinumtoxin A was injected over both of her cheeks, periodically for six cycles. Her symptoms responded dramatically to subcutaneous and intradermal injection of botulinum toxin type A. Repetitive injection demonstrated consistent and reproducible responses, and the efficacy was maintained for approximately 1 month. No adverse effects or complications were noted. Botulinum toxin type A might be safe and effective as an alternative treatment for refractory erythromelalgia, but further large-scale studies are required.

Theoretical and practical aspects about corrosion of refractories used in steel metallurgy: part 3: characterization of commercial refractories; Aspectos teoricos e praticos sobre a corrosao de refratarios utilizados na metalurgia: caracterizacao de refratarios comerciais

Energy Technology Data Exchange (ETDEWEB)

Braganca, S.R., E-mail: saulorb@ufrgs.br [Universidade Federal do Rio Grande Sul (DEMAT/UFRGS), RS (Brazil)

2012-07-01