0000000000164337

AUTHOR

Michael W. Deininger

The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in philadelphia chromosome-negative cells.

BACKGROUND. Clonal cytogenetic abnormalities (CCA) were detected in Philadelphia chromosome (Ph)-negative cells in some patients with chronic myeloid leukemia (CML) who attained a cytogenetic response to imatinib mesylate. In some patients, CCA/Ph-negative status was associated with myelodysplasia or acute myeloid leukemia. The objective of the current study was to determine the prognostic impact of CCA/Ph-negative cells. METHODS. The authors compared the pretherapeutic risk factors (Kruskall-Wallis test), exposure to cytotoxic drugs (chi-square test), and overall and progression-free survival (Kaplan-Meyer and logistic regression analysis, respectively) of 515 patients with mostly chronic-…

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Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia

The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy.We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events.The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best …

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Response to imatinib in patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia

We studied 128 patients with chronic myeloid leukemia (CML) relapsing after allogeneic stem cell transplantation (SCT). Disease at the time of treatment with Imatinib was in chronic phase (CP) in 51 patients, accelerated phase (AP) in 31 and blastic crisis (BC) in 46. Of the 51 patients in CP, 14 were in cytogenetic and two in molecular relapses. The median interval between relapse and Imatinib therapy was 5 months (0–65). A total of 50 patients had failed treatment with donor lymphocyte infusions prior to Imatinib. The overall hemato-logical response rate was 84% (98% for patients relapsing in CP). The complete cytogenetic response (CCR) was 58% for patients in CP, 48% for AP and 22% for p…

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Pioneer: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of Avapritinib in Patients with Indolent or Smoldering Systemic Mastocytosis with Symptoms Inadequately Controlled with Standard Therapy

Background: The gain-of function mutation KIT D816V plays a central role in the pathogenesis of systemic mastocytosis (SM). Among subtypes of SM, indolent SM (ISM) is the most frequent and is associated with normal/near-normal life expectancy; smoldering SM (SSM) is a subtype with a relatively higher burden of mast cells and may be associated with an increased risk of progression to advanced mastocytosis. However, both ISM and SSM patients may experience severe symptoms associated with mast cell mediator release, such as pruritus, diarrhea, anaphylaxis, and bone pain, which can be severely debilitating and have a profoundly negative impact on quality of life. Symptomatic treatments (eg, ant…

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Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon alpha/ara-C.

We sought to determine dynamics of BCR-ABL mRNA expression levels in 139 patients with chronic myelogenous leukemia (CML) in early chronic phase, randomized to receive imatinib (n=69) or interferon (IFN)/Ara-C (n=70). The response was sequentially monitored by cytogenetics from bone marrow metaphases (n=803) and qualitative and quantitative RT-PCR from peripheral blood samples (n=1117). Complete cytogenetic response (CCR) was achieved in 60 (imatinib, 87%) vs 10 patients (IFN/Ara-C, 14%) after a median observation time of 24 months. Within the first year after CCR, best median ratio BCR-ABL/ABL was 0.087%, (imatinib, n=48) vs 0.27% (IFN/Ara-C, n=9, P=0.025). BCR-ABL was undetectable in 25 c…

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Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts

Summary The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global public health crisis. Multiple observations indicate poorer post-infection outcomes for patients with cancer than for the general population. Herein, we highlight the challenges in caring for patients with acute leukaemias and myeloid neoplasms amid the COVID-19 pandemic. We summarise key changes related to service allocation, clinical and supportive care, clinical trial participation, and ethical considerations regarding the use of lifesaving measures for these patients. We recognise that these recommendations might be more applicable to high-income countries and might not be general…

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