4527 articles - 10.09.10
1: Transfusion. 2010 Aug 16; [Epub ahead of print]
Ostrowski SR, Bochsen L, Windelov NA, Salado-Jimena JA, Reynaerts I, Goodrich RP, Johansson PI.
From the Section for Transfusion Medicine, Capital Region Blood Bank, and the Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, and CaridianBCT Biotechnologies, Lakewood, Colorado.
BACKGROUND: Pathogen reduction technologies (PRTs) may influence the hemostatic potential of stored platelet (PLT) concentrates. To investigate this, buffy coat PLTs (BCPs) stored in PLT additive solution (SSP+) with or without Mirasol PRT treatment (CaridianBCT Biotechnologies) were compared by functional hemostatic assays. STUDY DESIGN AND METHODS: We performed in vitro comparison of PRT (PRT-BCP) and control pooled-and-split BCPs (CON-BCP) after 2, 3, 6, 7, and 8 days' storage. Hemostatic function was evaluated with thrombelastography (TEG) and impedance aggregometry (Multiplate), the latter also in a sample matrix (Day 2) with or without addition of red blood cells (RBCs), control plasma, and/or PRT-treated plasma. RESULTS: PRT treatment of 8-day-stored BCPs influenced clot formation (TEG) minimally, with reductions in maximum clot strength (maximum amplitude, p = 0.014) but unchanged initial fibrin formation (R), clot growth rate (alpha), and fibrinolysis resistance. In the absence of RBCs and plasma, PRT impaired aggregation (Multiplate) in stored BCPs, with reduced aggregation against thrombin receptor activating peptide-6 (p < 0.001), collagen (p = 0.014), adenosine 5'-diphosphate (p = 0.007), and arachidonic acid (p = 0.070). Addition of RBCs and PRT-treated or untreated plasma to PRT-BCP and CON-BCP, respectively, enhanced aggregation in both groups. CONCLUSIONS: Mirasol PRT treatment of BCPs had a minimal influence on clot formation, whereas aggregation in the absence of RBCs and plasma was significantly reduced. Addition of RBCs and plasma increased agonist-induced responses resulting in comparable aggregation between PRT-BCP and CON-BCP. The clinical relevance for PLT function in vivo of these findings will be investigated in a clinical trial.
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PMID: 20723169 [PubMed - as supplied by publisher]2: Transfusion. 2010 Jul 16; [Epub ahead of print]
So-Osman C, Nelissen R, Brand R, Brand A, Stiggelbout AM.
From the Department of Research and Development, Sanquin Blood Bank South West Region, Leiden; and the Department of Orthopaedic Surgery, the Department of Medical Statistics and BioInformatics, and the Department of Medical Decision Making, Leiden University Medical Centre (LUMC), Leiden, The Netherlands.
BACKGROUND: Lower limb joint replacement surgery provides a considerable improvement in quality of life (QoL), but is associated with peroperative blood loss and with anemia in the direct postoperative period. General acceptance of low transfusion thresholds and shorter postoperative hospital stays will result in patients leaving hospital with low hemoglobin (Hb) levels. To evaluate the role of QoL scores as a possible alternative for Hb values to serve as a further indicator for red blood cell transfusion, we performed a secondary analysis of a previously conducted randomized clinical trial to compare QoL and fatigue scores with simultaneously measured pre- and postoperative Hb levels, in total hip and knee arthroplasty patients. STUDY DESIGN AND METHODS: QoL measurement was measured preoperatively and twice up to 14 days postoperatively using the Functional Status Index (FSI), the Visual Analogue Score (VAS)-Fatigue score, and the Functional Assessment of Cancer Therapy Anemia (FACT-Anemia) subscale. Pearson correlation coefficients between (change in) FSI, VAS-Fatigue, and FACT-Anemia subscale scores and (change in) Hb levels were calculated. Additionally, partial correlations were calculated and linear regression analysis was performed, correcting for possible confounding variables. RESULTS: A total of 603 patients were evaluated. All patients scored worse postoperatively, but none of the scores correlated with Hb values, neither after correcting for confounding factors. Even more, the changes between preoperative and postoperative Hb levels were not correlated with changes in fatigue scores. CONCLUSION: In hip and knee prosthesis surgery no correlation existed between postoperative Hb levels or acute postoperative decline in Hb values and QoL scores (FSI, VAS-Fatigue, or FACT-Anemia).
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20663113&dopt=ExternalLink
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PMID: 20663113 [PubMed - as supplied by publisher]3: Blood. 2010 Jul 23; [Epub ahead of print]
Crowther M, Lim W, Crowther MA.
Department of Haematology, Worcestershire Royal Hospital, Worcestershire, United Kingdom;
Systematic reviews and meta-analyses are being increasingly used to summarize medical literature and identify areas where research is needed. Systematic reviews limit bias by using a reproducible scientific process to search the literature and evaluate the quality of the individual studies. If possible the results are statistically combined into a meta-analysis where the data are weighted and pooled to produce an estimate of effect. This article aims to provide the reader with a practical overview of systematic review and meta-analysis methodology, with a focus on the process of performing a review and the related issues at each step.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20656933&dopt=ExternalLink
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PMID: 20656933 [PubMed - as supplied by publisher]4: Blood. 2010 Jul 19; [Epub ahead of print]
Sharmeen S, Skrtic M, Sukhai MA, Hurren R, Gronda M, Wang X, Fonseca SB, Sun H, Wood TE, Ward R, Minden MD, Batey RA, Datti A, Wrana J, Kelley SO, Schimmer AD.
Princess Margaret Hospital, Ontario Cancer Institute, Toronto, ON, Canada;
To identify known drugs with previously unrecognized anti-cancer activity, we compiled and screened a library of such compounds to identify agents cytotoxic to leukemia cells. From these screens, we identified ivermectin, a derivative of avermectin B1 that is licensed for the treatment of the parasitic infections strongyloidiasis and onchocerciasis, but is also effective against other worm infestations. As a potential anti-leukemic agent, ivermectin induced cell death at low micromolar concentrations in acute myeloid leukemia cell lines and primary patient samples preferentially over normal hematopoietic cells. Ivermectin also delayed tumor growth in three independent mouse models of leukemia at concentrations that appear pharmacologically achievable. As an anti-parasitic, ivermectin binds and activates chloride ion channels in nematodes, so we tested the effects of ivermectin on chloride flux in leukemia cells. Ivermectin increased intracellular chloride ion concentrations and cell size in leukemia cells. Chloride influx was accompanied by plasma membrane hyperpolarization, but did not change mitochondrial membrane potential. Ivermectin also increased reactive oxygen species (ROS) generation that was functionally important for ivermectin-induced cell death. Finally, ivermectin synergized with cytarabine and daunorubicin that also increase ROS production. Thus, given its known toxicology and pharmacology, ivermectin could be rapidly advanced into clinical trial for leukemia.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20644115&dopt=ExternalLink
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PMID: 20644115 [PubMed - as supplied by publisher]5: Blood. 2010 Jul 12; [Epub ahead of print]
Castillo JJ, Dalia S, Pascual S.
The Warren Alpert Medical School of Brown University, Division of Hematology and Oncology, The Miriam Hospital, Providence, RI, United States;
The incidence of non-Hodgkin lymphoma (NHL) has increased steadily for the last few decades. Previous studies have suggested an association between blood transfusions and NHL. The main objective of this study was to evaluate this relationship using a meta-analysis of observational studies. A literature search was undertaken, looking for case-control and cohort studies evaluating the risk of developing NHL in individuals who have received allogeneic blood transfusions; fourteen studies were included. Outcome was calculated and reported as relative risk (RR). Heterogeneity was assessed using Cochrane Q and I(2) statistics. Dissemination bias was evaluated by funnel plot visualization and trim-and-fill analysis. Quality assessment was performed using the Newcastle-Ottawa scale. Our analysis showed a RR of developing NHL of 1.05 (95% CI 0.89-1.25; p=0.42) and 1.34 (95% CI 1.15-1.55; p<0.01) in case-control and cohort studies, respectively. When pooling all studies, the RR was 1.2 (95% CI 1.07-1.35; p<0.01). In the subset analysis, the RR of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was 1.66 (95% CI 1.08-2.56; p=0.02). The RR of NHL was elevated in both men and women, and in individuals transfused either before or after 1992. Blood transfusions appear to increase the risk of developing NHL; however, the risk of CLL/SLL appears higher than for other NHL subtypes.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20625008&dopt=ExternalLink
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PMID: 20625008 [PubMed - as supplied by publisher]6: Semin Hematol. 2010 Jul;47(3):289-98.
Cuker A.
Department of Medicine and Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. adam.cuker@uphs.upenn.edu
The thrombopoietic growth factors (TGFs) are a novel class of compounds for the treatment of chronic immune thrombocytopenia (ITP). The first of these agents to receive regulatory approval, romiplostim and eltrombopag, have demonstrated impressive efficacy and tolerability in randomized controlled trials and open-label extension studies of several years duration and stand poised to revolutionize the management of ITP. Nonetheless, critical questions regarding the safety of these agents, particularly after long-term administration, remain partially unanswered. The objective of this review is to describe the reported and potential toxicities of the TGFs, including bone marrow fibrosis, thrombosis, rebound thrombocytopenia, hematologic malignancy, neutralizing antibody formation, hepatotoxicity, cataract formation, and common adverse events. The incidence and clinical implications of these toxicities as well as strategies for patient safety monitoring are examined.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20620441&dopt=ExternalLink
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PMID: 20620441 [PubMed - in process]7: Blood. 2010 Jul 8; [Epub ahead of print]
Cao Z, Sun X, Icli B, Wara AK, Feinberg MW.
Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
The Kruppel-like transcription factor (KLF) family participates in diverse aspects of cellular growth, development, differentiation, and activation. Recently, several groups have identified new connections between the function of these factors and leukocyte responses in health and disease. Gene targeting of individual KLFs in mice has uncovered novel and unexpected physiologic roles among myeloid and lymphocyte cell lineage maturation, particularly in the bone marrow niche and blood. In addition, several KLF family members are downstream targets of stimuli and signaling pathways critical to T cell trafficking, T regulatory cell differentiation or suppressor function, monocyte/macrophage activation or renewal, and B memory cell maturation or activation. Indeed, KLFs have been implicated in subtypes of leukemia, lymphoma, autoimmunity, and in acute and chronic inflammatory disease states, such as atherosclerosis, diabetes, and airway inflammation, raising the possibility that KLFs and their upstream signals are of therapeutic interest. This review focuses on the relevant literature of Kruppel-like factors in leukocyte biology and their implications in clinical settings.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20616217&dopt=ExternalLink
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PMID: 20616217 [PubMed - as supplied by publisher]8: Transfusion. 2010 Jun 23; [Epub ahead of print]
Arnold DM, Crowther MA, Meyer RM, Carruthers J, Ditomasso J, Heddle NM, McLeod A, Kelton JG.
From the Department of Medicine, Michael DeGroote School of Medicine, McMaster University, Hamilton, Ontario; Canadian Blood Services, Hamilton, Ontario; St Joseph's Healthcare, Hamilton, Ontario; the Departments of Oncology, Medicine, and Community Health and Epidemiology, NCIC Clinical Trials Group, Queen's University, Kingston, Ontario; Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences, Hamilton, Ontario; and Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
BACKGROUND: Rituximab may cause reactivation of hepatitis B virus (HBV) even in patients with remote HBV infection. Thus, the presence of hepatitis B core antibodies (anti-HBc) was an exclusion criterion for a randomized trial of rituximab for patients with immune thrombocytopenia. A high seroprevalence of anti-HBc observed among patients screened for the trial prompted this substudy to investigate for an association between anti-HBc seropositivity and exposure to intravenous immunoglobulin (IVIG). STUDY DESIGN AND METHODS: This was a retrospective case-control study that was a substudy of a randomized controlled trial. RESULTS: Of 24 trial participants screened at one center, 11 (45.8%) were anti-HBc positive and of those, 10 (90.0%) had received IVIG in the preceding 4 weeks. Of 13 seronegative patients screened, five (38.5%) had received IVIG (odds ratio, 16; 95% confidence interval, 1.5-166.1). Seven (70%) of 10 seropositive participants subsequently reverted to negative upon repeat testing. Serial testing before and after IVIG (n = 2) demonstrated transient anti-HBc that lasted for up to 11 weeks after the last dose of IVIG. Samples from three of five different IVIG products were found to contain anti-HBc. CONCLUSIONS: Passive transfer of anti-HBc from certain IVIG products may lead to misinterpretation of hepatitis test results with implications for treatment and clinical trial eligibility. To avoid misleading test results, anti-HBc should be measured before or 3 months after IVIG administration; alternatively an IVIG product known to be free of anti-HBc should be used.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20576011&dopt=ExternalLink
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PMID: 20576011 [PubMed - as supplied by publisher]9: Br J Haematol. 2010 Aug;150(3):303-12. Epub 2010 Jun 10.
Santos FP, Kantarjian H, Fava C, O'Brien S, Garcia-Manero G, Ravandi F, Wierda W, Thomas D, Shan J, Cortes J.
Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
Second (2nd)-generation tyrosine kinase inhibitors (TKI) (dasatinib, nilotinib) are effective in patients with all phases of chronic myeloid leukaemia (CML). Dose reductions and treatment interruptions are frequently required due to toxicity, but their significance is unknown. We analysed the impact of dose reductions/interruptions and dose intensity of 2nd-generation TKI on response and survival. A total of 280 patients with CML (all phases) were analysed. Dose reductions were considered when the daily dose was below the standard dose. Dose intensity was determined based on the percentage of the ideal dose intensity. Overall, 176 patients (63%) required treatment interruptions and/or dose reduction at least once during therapy. Dose reductions/interruptions, analysed as a time-dependent covariate, were associated with worse failure-free survival only in patients with untreated CML. Dose intensity analysis did not reveal a worse response or survival in patients who received a lower dose intensity (<100%) during therapy or during the first 6 months. In conclusion, dose reductions and treatment interruptions of 2nd generation TKI in patients with CML have a minimal impact in the response rate and survival of these patients. Further studies are required to determine whether there might be a minimum adequate dose of these agents.
Publication Types: Meta-Analysis Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20553275&dopt=ExternalLink
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PMID: 20553275 [PubMed - indexed for MEDLINE]10: Br J Haematol. 2010 Aug;150(3):326-33. Epub 2010 Jun 10.
Schey SA, Morgan GJ, Ramasamy K, Hazel B, Ladon D, Corderoy S, Jenner M, Phekoo K, Boyd K, Davies FE.
Department of Haematological Medicine, King's College Hospital, London, UK. sschey@nhs.net
We report the results of a Phase I/II dose escalation study to determine the maximum tolerated dose (MTD) of cyclophosphamide when combined with lenalidomide and dexamethasone in relapsed/refractory myeloma. Thirty-one patients were enrolled in cohorts of 3, at five dose levels of cyclophosphamide to a maximum of 700 mg on days 1 and 8 of a 28-d cycle. Patients received lenalidomide 25 mg days 1-21 and dexamethasone 20 mg orally days 1-4 and 8-11. The MTD was 600 mg cyclophosphamide, days 1 and 8. Grade 3/4 haematological complications occurred in 26% of patients, grade 3/4 infection in 3% (both at 700 mg cyclophosphamide), with thromboembolic complications in 6% of patients. Overall complete response (CR) rate was 29%, very good partial response rate 7% and partial response rate 45% giving an overall response rate of 81%. After 21 months median follow-up, projected 2-year progression-free survival was 56%, with 80% overall survival at 30 months. Ten further patients were treated at MTD with a 40% CR rate. No dose reductions for any study drugs or deaths occurred during cycles 1-9. Lenalidomide, cyclophosphamide and dexamethasone is a safe, effective combination in relapsed myeloma inducing a high response rate, warranting further investigation in phase III trials.
Publication Types: Clinical Trial, Phase I Clinical Trial, Phase II Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20553268&dopt=ExternalLink
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PMID: 20553268 [PubMed - indexed for MEDLINE]11: Thromb Haemost. 2010 Jul 5;104(1):49-60. Epub 2010 Jun 10.
Ahrens I, Lip GY, Peter K.
Innere Medizin III, Kardiologie und Angiologie, Universitatsklinik, Hugstetter Strasse 55, Freiburg, Germany. ingo.ahrens@uniklinik-freiburg.de
Oral anticoagulation has been limited to vitamin K antagonists (VKAs) for over 60 years. VKAs are effective and recommended for the prevention of venous and arterial thromboembolism in cardiovascular disease, but their pharmacodynamics are difficult to predict and the highly variable interindividual and intraindividual response to treatment accounts for the need of continuous monitoring. This prompted the intensive exploration of numerous substances within the last decade in an attempt to meet the shortcomings of current oral anticoagulation with VKAs. The development and clinical investigation of two novel groups of oral anticoagulants targeting central factors of the coagulation system either factor Xa or thrombin (factor IIa) has now reached the daily clinical practice with the approval of the oral direct thrombin inhibitor dabigatran etexilate and the oral direct factor Xa inhibitor rivaroxaban. Ongoing clinical trials are investigating these substances and other novel oral anticoagulants with similar mechanisms of action in patients with atrial fibrillation and acute coronary syndromes. This review article discusses the clinical evaluation and pharmacological properties of novel oral anticoagulants in late and earlier stages of clinical development, thereby providing a critical analysis and an outlook on the future of oral anticoagulation in cardiovascular disease.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20539909&dopt=ExternalLink
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PMID: 20539909 [PubMed - in process]12: Transfusion. 2010 May 28; [Epub ahead of print]
Spinella PC, Dressler A, Tucci M, Carroll CL, Rosen RS, Hume H, Sloan SR, Lacroix J; for the Pediatric Acute Lung Injury and Sepsis Investigators Network.
From the Department of Pediatrics and the Department of Surgery, Connecticut Children's Hospital, Hartford, Connecticut; the Department of Pediatrics and the Department of Hematology-Oncology, Sainte-Justine Hospital and Universite de Montreal, Montreal, Quebec, Canada; Blood Systems Research Institute, San Francisco, California; and the Joint Program of Transfusion Medicine and Department of Laboratory Medicine, Children's Hospital Boston, Boston, Massachusetts.
BACKGROUND: Previous surveys have reported variation in transfusion practice or policies in specific pediatric populations. Our objective was to determine the current transfusion policies in US and Canadian children's hospitals for both neonatal and pediatric general populations. STUDY DESIGN AND METHODS: US and Canadian blood bank (BB) personnel at children's hospitals that provide blood products between the dates of October 2008 and January 2009 were surveyed. RESULTS: Of the 90 US and Canadian children's hospitals identified, 51 (56.7%) blood bankers or their designees responded. There were 42 of 51 (82.4%) respondents from the United States and 9 of 51 (17.6%) from Canada. There was wide variation in beliefs regarding the effect of red blood cell (RBC) storage age on outcomes with 66.6% of respondents interested in a prospective randomized trial in critically ill children. There was also wide variation in policies restricting the storage age of RBCs according to patient age and clinical condition. In the United States 28 of 33 (84.8%) respondents provide universal leukoreduction of RBCs whereas it is 9 of 9 (100%) in Canada. Variation of policies existed for RBC irradiation and washing. The majority of respondents indicated that RBC transfusions were audited if the pretransfusion hemoglobin level was more than 8 to 10 mg/dL. Fresh whole blood is available at 6 of 40 (15%) responding children's hospitals. CONCLUSIONS: There is a wide variation in BB policies regarding RBC transfusions at children's hospitals in the United States and Canada. Prospective randomized controlled trials are needed to allow for evidence-based standards of care regarding RBC transfusions.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20529008&dopt=ExternalLink
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PMID: 20529008 [PubMed - as supplied by publisher]13: Transfusion. 2010 May 28; [Epub ahead of print]
Marschner S, Fast LD, Baldwin Iii WM, Slichter SJ, Goodrich RP.
From CaridianBCT Biotechnologies, LLC, Lakewood, Colorado; the Department of Medicine, Rhode Island Hospital and Warren Alpert Medical School of Brown University, Providence, Rhode Island; the Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; and the Puget Sound Blood Center, Seattle, Washington.
Functional white blood cells (WBCs) in blood components may be responsible for a number of adverse transfusion effects, including transfusion-associated graft-versus-host disease (TA-GVHD), alloimmunization, and alloimmune platelet (PLT) refractoriness. TA-GVHD occurs when functional lymphocytes are transfused into a patient who is unable to mount an immune response to the human leukocyte antigen (HLA) due to HLA compatibility or immunosuppression. Alloantibodies against HLA antigens on donor WBCs and PLTs are the major cause of refractoriness to PLT transfusions in patients receiving repeated blood transfusions. Attempts to reduce these undesirable effects have included leukoreduction filters and gamma irradiation. Studies have shown that exposure of PLT concentrates to riboflavin and light (Mirasol pathogen reduction technology [PRT], CaridianBCT Biotechnologies) causes irreparable modifications of nucleic acids that result in inactivation of a wide range of pathogens as well as inhibition of the immunologic responses mediated by WBCs present in PLT concentrates. This article summarizes these studies and also reports on additional findings from the Trial to Reduce Alloimmunization to Platelets (TRAP) and Mirasol Clinical Evaluation (MIRACLE) trials. Data from in vitro studies and this clinical trial suggest that PRT treatment may be as effective as gamma irradiation in preventing TA-GVHD and more effective than leukoreduction in preventing alloimmunization.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20529002&dopt=ExternalLink
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PMID: 20529002 [PubMed - as supplied by publisher]14: Br J Haematol. 2010 Jul;150(2):200-8. Epub 2010 May 26.
Romaguera JE, Fayad LE, Feng L, Hartig K, Weaver P, Rodriguez MA, Hagemeister FB, Pro B, McLaughlin P, Younes A, Samaniego F, Goy A, Cabanillas F, Kantarjian H, Kwak L, Wang M.
Department of Lymphoma/Myeloma, University of Texas M D Anderson Cancer Center, Houston, TX, USA. jromague@mdanderson.org
Mantle cell lymphoma (MCL) has a poor overall survival after treatment with conventional chemotherapy. Intense chemoimmunotherapy without consolidation stem cell transplantation is a potential therapeutic option. We report on a prospective Phase II study with rituximab in combination with fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (R-Hyper-CVAD) alternating with rituximab in combination with high-dose methotrexate-cytarabine (R-MA) in untreated patients with diffuse and nodular MCL and their blastoid variants. Ninety-seven patients were treated, of whom 97% responded and 87% achieved a complete remission. At 10 years of follow up (median 8 years), the median overall survival (OS) for all patients had not been reached and the median time to failure (TTF) for all patients was 4.6 years, without a plateau in the curves. For the group of patients aged 65 years or younger, the median OS had not been reached and the median TTF was 5.9 years. Multivariate analysis revealed pre-treatment serum levels of beta(2) microglobulin, International Prognostic Index (IPI) score and mantle cell IPI (MIPI) score, as predictive of both OS and TTF. We conclude that intense chemoimmunotherapy without stem cell transplantation is effective for untreated aggressive MCL.
Publication Types: Clinical Trial, Phase II Research Support, Non-U.S. Gov't Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20528872&dopt=ExternalLink
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PMID: 20528872 [PubMed - indexed for MEDLINE]15: Br J Haematol. 2010 Aug;150(3):345-51. Epub 2010 May 26.
Commander LA, Seif AE, Insogna IG, Rheingold SR.
Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
A combination of 5 d of nelarabine (AraG) with 5 d of etoposide (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T-cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensory and motor neuropathy and musculoskeletal pain. Haematological toxicity was greater for the combination than AraG alone, although median time to neutrophil and platelet recovery was consistent with other salvage therapies. All patients had some response to the combined therapy and five of the seven went into complete remission after one or two courses of AraG/VP/CPM. Our experience supports the safety of giving AraG as salvage therapy in synchrony with etoposide and cyclophosphamide, although neurological toxicity must be closely monitored.
Publication Types: Clinical Trial
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PMID: 20528871 [PubMed - indexed for MEDLINE]16: Eur J Haematol. 2010 May;84(5):421-9.
Royer DJ, George JN, Terrell DR.
Department of Biostatistics & Epidemiology, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
BACKGROUND: Thrombocytopenia is a well-recognized adverse effect of many drugs. However, the association of thrombocytopenia with complementary/alternative medicines, herbal remedies, nutritional supplements, foods, and beverages has been rarely described, except for reports of thrombocytopenia caused by quinine-containing beverages. OBJECTIVES: To systematically identify all published reports of thrombocytopenia associated with these substances and to assess the evidence supporting their causal association with thrombocytopenia. METHODS: Eleven databases were searched to identify relevant published reports. A priori criteria were defined for article selection and assessment. Each selected article was independently assessed by the three authors to document the presence of the criteria and determine the level of evidence for a causal association of the reported substance with thrombocytopenia. RESULTS: Twenty-seven articles were identified that reported the occurrence of thrombocytopenia with 25 substances (other than quinine). However, only six articles describing five substances (cow's milk, cranberry juice, Jui [Chinese herbal tea], Lupinus termis bean, and tahini [pulped sesame seeds]) reported clinical data supporting definite evidence of a causal association with thrombocytopenia. Four articles provided probable evidence for four additional substances, and five articles provided possible evidence for five additional substances. In the remaining articles, the association with thrombocytopenia was unlikely or the articles were excluded from review. CONCLUSIONS: Reports of thrombocytopenia describing definite or probable evidence for an association of a complementary/alternative medicines, herbal remedies, nutritional supplements, foods, and beverages are rare. Whether the occurrence of thrombocytopenia with these substances is uncommon or unrecognized is unknown.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20525061&dopt=ExternalLink
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PMID: 20525061 [PubMed - indexed for MEDLINE]17: Thromb Haemost. 2010 Jul 5;104(1):86-91. Epub 2010 May 27.
van Doormaal FF, Cohen AT, Davidson BL, Decousus H, Gallus AS, Gent M, Piovella F, Prins MH, Raskob GE, Buller HR.
Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, Amsterdam, The Netherlands. F.F.vanDoormaal@amc.uva.nl
Standard treatment with heparin followed by vitamin K antagonists is frequently complicated by bleeding and recurrent venous thromboembolism (VTE) in cancer patients with VTE. To compare the efficacy, safety and overall survival of long-term idraparinux treatment to standard therapy in cancer patients we conducted a post-hoc analysis in the subgroup of non-active and active cancer patients included in the Van Gogh DVT clinical trial. The cancer patients with deep venous thrombosis (DVT) and without pulmonary embolism (PE) were randomised to standard treatment or a once-weekly subcutaneous injection of idraparinux (2.5 mg), a synthetic pentasaccharide. 421 cancer patients were included. A total of 220 patients received idraparinux and 201 were allocated to standard therapy for three months (8%) or six months (92%). A recurrent VTE was observed during the first six months in 2.5% (n=5) of the idraparinux recipients compared to 6.4% (n=12) in the standard therapy group (hazard ratio 0.39, 95% confidence interval [CI]; 0.14-1.11). The rate of bleeding was comparable (odds ratio 0.89, 95% CI; 0.50-1.59). The outcomes were similar at three months after randomisation in all patients. Of the idraparinux recipients, 22.7% (n=50) died during the study period compared to 48 patients (23.9%) in the standard treatment group (hazard ratio 0.99, 95% CI; 0.66-1.48). In conclusion, no significant safety or survival differences were observed between cancer patients with DVT treated with idraparinux for six months compared to standard therapy. Fewer recurrent VTEs were observed in the idraparinux group; however, this was not statistically significant and also because of study limitations this should be interpreted with caution.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20508907&dopt=ExternalLink
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PMID: 20508907 [PubMed - in process]18: Blood. 2010 May 27; [Epub ahead of print]
Chang J, Patton JT, Sarkar A, Ernst B, Magnani JL, Frenette PS.
Mount Sinai School of Medicine, Departments of Medicine, and Gene and Cell Medicine, New York, NY, United States;
Leukocyte adhesion in the microvasculature influences blood rheology and plays a key role in vaso-occlusive (VOC) manifestations of sickle cell disease (SCD). Notably, polymorphonuclear neutrophils (PMNs) can capture circulating sickle red blood cells (sRBCs) in inflamed venules leading to critical reduction in blood flow and VOC. Recent studies have suggested that E-selectin expression by endothelial cells plays a key role by sending activating signals leading to the activation of Mac-1 at the leading edge of PMNs thereby allowing RBC capture. Thus, the inhibition of E-selectin may represent a valuable target in this disease. Here, we have tested the biological properties of a novel synthetic pan-selectin inhibitor, GMI-1070, using in vitro assays and in a humanized model of sickle cell vaso-occlusion analyzed by intravital microcopy. We have found that GMI-1070 predominantly inhibited E-selectin-mediated adhesion, and dramatically inhibited sRBC-leukocyte interactions, leading to improved microcirculatory blood flow and improved survival. These results suggest that GMI-1070 may represent a valuable novel therapeutic intervention for acute sickle cell crises that should be further evaluated in a clinical trial.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20508165&dopt=ExternalLink
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PMID: 20508165 [PubMed - as supplied by publisher]19: Blood. 2010 May 27; [Epub ahead of print]
Gratama JW, Boeckh M, Nakamura R, Cornelissen JJ, Brooimans RA, Zaia JA, Forman SJ, Gaal K, Bray KR, Gasior GH, Boyce CS, Sullivan LA, Southwick PC.
Departments of Clinical and Tumor Immunology, Hematology, Erasmus Medical Center / Daniel den Hoed Cancer Center, Rotterdam, Netherlands;
CMV infection is an important cause of morbidity and mortality in HCT recipients despite the introduction of post-transplant viral monitoring and preemptive antiviral therapy. We evaluated the use of HLA Class I tetramers in monitoring CMV-specific T-cell recovery to predict patients at risk for CMV-related complications. This prospective multicenter clinical trial obtained nearly 1,400 tetramer/allele results in >800 biweekly blood samples from 83 patients monitored for up to 1 year following transplantation. Major HLA types were included (A*0101,A*0201,B*0702,B*0801,B*3501). iTAg MHC Tetramers (Beckman Coulter) were used to enumerate CMV-specific CD8+ T-cells by flow cytometry using a single-platform absolute counting method. Assay variability was </=8%, and results were available within 3 hours. Delayed recovery of CMV-specific T-cells (<7 cells/microL in all blood samples during the first 65 days post-transplant) was found to be a significant risk factor for CMV-related complications; these patients were more likely to develop recurrent or persistent CMV infection (relative risk 2.6, CI 1.2-5.8, p=0.01) than patients showing rapid recovery, which was associated with protection from CMV-related complications (p=0.004). CMV tetramer-based immune monitoring, in conjunction with virologic monitoring, can be an important new tool that permits clinicians to assess risk of CMV-related complications and to guide preemptive therapeutic choices.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20508161&dopt=ExternalLink
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PMID: 20508161 [PubMed - as supplied by publisher]20: Br J Haematol. 2010 Jul;150(1):28-38. Epub 2010 May 9.
Berenson JR, Anderson KC, Audell RA, Boccia RV, Coleman M, Dimopoulos MA, Drake MT, Fonseca R, Harousseau JL, Joshua D, Lonial S, Niesvizky R, Palumbo A, Roodman GD, San-Miguel JF, Singhal S, Weber DM, Zangari M, Wirtschafter E, Yellin O, Kyle RA.
Institute for Myeloma & Bone Cancer Research, West Hollywood, CA 90069, USA. jberenson@imbcr.org
On February 25, 2009, a panel of international experts on plasma cell dyscrasia and skeletal disease met to discuss monoclonal gammopathy of undetermined significance (MGUS). This non-malignant B-cell disorder is the most common plasma cell dyscrasia and is associated with an increased risk of developing serious B-cell disorders. Individuals with MGUS also have an increased risk of osteoporosis and osteopenia associated with an increased likelihood of developing fractures especially in the vertebral column, peripheral neuropathy and thromboembolic events. The goal of the meeting was to develop a consensus statement regarding the appropriate tests to screen, evaluate and follow-up patients with MGUS. The panel also addressed the identification and treatment of MGUS-related skeletal problems, thromboembolic events and neurological complications. The following consensus statement outlines the conclusions and marks the first time that a consensus statement for the screening and treatment of MGUS has been clearly stated.
Publication Types: Consensus Development Conference
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20507313&dopt=ExternalLink
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PMID: 20507313 [PubMed - indexed for MEDLINE]