Leukemia research
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The molecular response of chronic myeloid leukemia (CML) patients to tyrosine kinase inhibitor treatment can be evaluated either by BCR-ABL mRNA levels on international scale (IS) or by log reduction from the baseline level of the laboratory. Both methods were compared in 248 newly diagnosed chronic phase CML patients treated with imatinib. The major molecular responses (MMR) obtained by both methods predict progression-free survival (PFS, all P<0.0001). ⋯ The percentages of patients with BCR-ABL(IS) of ≤ 1%, >1-10%, and of >10% at 3 months and 6 months in the German CML Study IV were similar with those with corresponding BCR-ABL(IS) in our center, but was significantly different with those evaluated by the log reduction method. Therefore, the molecular response evaluated by BCR-ABL(IS) has similar trends in PFS and in response prediction, but can better differentiate patients than that by the log reduction method. Furthermore, the IS method allows comparison among molecular response results from different laboratories.
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Clinical evidence in chronic myeloid leukemia demonstrates a significant link between optimal response to tyrosine kinase inhibitor (TKI) therapy and favorable clinical outcome. For patients with suboptimal response to first-line TKI, clinical data show that a considerable proportion can be rescued by second-line TKI. Practice guidelines now recommend that clinicians consider a switch in TKI for patients with suboptimal response as early as 3 months after first-line TKI initiation, thus allowing clinicians to intervene in a timely manner and consider the potential benefit of a switch in TKI therapy.
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The acquired recurrent mutation, JAK2 V617F, is the most frequent mutation associated with myeloproliferative neoplasms (MPNs). JAK2 signaling is critical in normal hematopoiesis. Studies using genetically engineered mouse models demonstrated a central role of JAK2 V617F in the pathogenesis of MPNs. ⋯ Clinical trials demonstrated that JAK1/2 inhibitors ameliorate constitutional symptoms and reduce spleen size in patients with myelofibrosis. However, JAK2 inhibitors have limited ability to reduce JAK2 V617F allele burden or bone marrow fibrosis in humans. JAK2 inhibitor-based combination therapies are being explored.
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High-dose chemotherapy and autologous stem-cell transplantation (HDT-ASCT) is standard therapy for younger patients with multiple myeloma (MM) who are physically fit enough to undergo the treatment. Nevertheless, MM remains incurable and strategies to prevent or delay relapse after HDT-ASCT are needed. ⋯ Alternatively, extending treatment with novel induction regimens may delay the need for HDT-ASCT. Although there is some clinical evidence to support the use of these strategies, their efficacy has not been proven definitively in clinical trials; ongoing studies should help determine their merit in transplant-eligible patients with MM.
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We treated individuals for disseminated intravascular coagulation (DIC) caused by acute promyelocytic leukemia (APL) (n=9) using human soluble thrombomodulin (rTM) in combination with all-trans retinoic acid (ATRA) and chemotherapy, and compared the clinical outcomes with historical control patients (n=8) treated with ATRA and/or chemotherapy. Two control patients developed intracranial vascular incidents. ⋯ Notably, treatment with rTM rescued patients from DIC earlier than historical controls (log rank test, p=0.019). These results suggest that administration of rTM should be considered for the treatment of individuals with DIC associated with APL.