0000000000164343
AUTHOR
Insa Gathmann
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-…
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 …
Ratify (Alliance 10603): Prognostic Impact of FLT3 tyrosine Kinase Domain (TKD) and NPM1 Mutation Status in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Treated with Midostaurin or Placebo Plus Standard Chemotherapy
Abstract Introduction: Mutations localized in the tyrosine kinase domain activation loop of FLT3 (FLT3-TKD), representing point mutations in codon D835/I836 and rarely deletions of codon I836, induce constitutive tyrosine phosphorylation and activation of the receptor tyrosine kinase similarly to FLT3 internal tandem duplication (ITD) mutations. However, the prognostic role of FLT3-TKD in AML, particularly in the presence of NPM1 mutations, is not well established. The phase 3 RATIFY trial [NCT00651261; Stone et al. N Engl J Med. 2017] showed that in combination with standard chemotherapy, midostaurin (PKC412) improved survival outcomes across all 3 FLT3 stratification subgroups (ITD high a…
Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia
Contains fulltext : 218279.pdf (Publisher’s version ) (Open Access) Patients with acute myeloid leukemia (AML) harboring FLT3 internal tandem duplications (ITDs) have poor outcomes, in particular AML with a high (>/=0.5) mutant/wild-type allelic ratio (AR). The 2017 European LeukemiaNet (ELN) recommendations defined 4 distinct FLT3-ITD genotypes based on the ITD AR and the NPM1 mutational status. In this retrospective exploratory study, we investigated the prognostic and predictive impact of the NPM1/FLT3-ITD genotypes categorized according to the 2017 ELN risk groups in patients randomized within the RATIFY trial, which evaluated the addition of midostaurin to standard chemotherapy. The 4 …
Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia.
Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML.We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression.Afte…