Annals of hematology
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Annals of hematology · Aug 2013
Randomized Controlled Trial Multicenter Study Comparative StudyHigh-dose imatinib versus high-dose imatinib in combination with intermediate-dose cytarabine in patients with first chronic phase myeloid leukemia: a randomized phase III trial of the Dutch-Belgian HOVON study group.
Despite the revolutionary change in the prognosis of chronic myeloid leukemia (CML) patients with the introduction of imatinib, patients with resistant disease still pose a considerable problem. In this multicenter, randomized phase III trial, we investigate whether the combination of high-dose imatinib and intermediate-dose cytarabine compared to high-dose imatinib alone, improves the rate of major molecular response (MMR) in newly diagnosed CML patients. This study was closed prematurely because of declining inclusion due to the introduction of second generation tyrosine kinase inhibitors and only one third of the initially required patients were accrued. ⋯ The addition of intermediate-dose of cytarabine to imatinib did not improve the MMR rate at 12 months. However, the underpowering of the study precludes any definitive conclusions. This trial is registered at www.trialregister.nl (NTR674).
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Annals of hematology · Jul 2013
Comparative StudyLow expression of glucocorticoid receptor alpha isoform in adult immune thrombocytopenia correlates with glucocorticoid resistance.
The expression of glucocorticoid receptor (GR) isoforms has been linked to glucocorticoid (GC) resistance in various diseases treated with GC. However, existing data are conflicting in these diseases, and little information is available regarding immune thrombocytopenia (ITP). To further investigate the role of GR isoforms in GC resistance in adult ITP patients, we measured the mRNA expression of GR isoforms (GRα, GRβ, GRγ, GRp) in peripheral blood mononuclear cells (PBMC) from 54 newly diagnosed ITP patients, including GC-sensitive (GCS) and GC-resistant (GCR) patients and 35 healthy volunteers. ⋯ Overall, we did not find differences in c-Jun/AP-1 protein expression between GCS and GCR patients. In summary, GC resistance in adult ITP patients is associated with a reduced expression of GRα, which may be related with increased NF-κB. GRβ was very low and may not be involved in GC resistance in adult ITP, warranting further exploration.
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Annals of hematology · Jul 2013
Low-dose alemtuzumab vs. standard policy for prevention of graft-versus-host disease in unrelated and related allogeneic stem cell transplantation-a matched pair analysis.
Antibody-mediated in vivo T cell depletion is common prior to unrelated (URD) or mismatched allogeneic stem cell transplantation (alloSCT) and optional in HLA-identical sibling (FAM) alloSCT. While anti-thymocyte globulin (ATG) is the current standard, alemtuzumab is an alternative. The optimal dose of alemtuzumab has not been defined. ⋯ A transplant-type stratified subanalysis consolidated equivalency of alemtuzumab and ATG in URD-SCT and indicates possible superiority of low-dose alemtuzumab compared to noAB in FAM-SCT. Low-dose alemtuzumab, as part of conditioning regimen prior to alloSCT, is safe and comparable to standard ATG. Prospective trials, particularly comparing alemtuzumab vs. noAB in FAM alloSCT, should be conducted.