scholarly journals Minor BCR-ABL1-Positive Acute Myeloid Leukemia Associated With the NPM1 Mutation and FLT3 Internal Tandem Duplication

2016 ◽  
Vol 36 (3) ◽  
pp. 263-265 ◽  
Author(s):  
Moon Jung Kim ◽  
Sunhyun Ahn ◽  
Seong-hyun Jeong ◽  
Ja-Hyun Jang ◽  
Jae Ho Han ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Internal Tandem Duplication ◽  
Npm1 Mutation ◽  
Flt3 Internal Tandem Duplication ◽  
Acute Myeloid

The Role of Cytogenetic Abnormalities in Acute Myeloid Leukemia with NPM1 mutations and No FLT3 Internal Tandem Duplication.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1594-1594
Author(s):  
Jean-Baptiste Micol ◽  
Nicolas Boissel ◽  
Aline Renneville ◽  
Sylvie Castaigne ◽  
Claude Gardin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Favorable Outcome ◽  
Internal Tandem Duplication ◽  
Npm1 Mutation ◽  
Molecular Abnormalities ◽  
Flt3 Internal Tandem Duplication ◽  
Acute Myeloid

Abstract Abstract 1594 Poster Board I-620 Background Nucleophosmin (NPM1) gene mutations are observed in almost one-third of adult acute myeloid leukemia (AML). If the favorable genotype defined by the presence of NPM1 mutations without fms-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is known to be associated with favorable outcome in patients with cytogenetically normal (CN) acute myeloid leukemia (AML), impact of these molecular abnormalities are still debated in those with cytogenetically abnormal (CA) AML. Patients and Methods We analyzed the role of these factors in newly diagnosed AML patients homogeneously treated in the Acute Leukemia French Association (ALFA) trials between 1990 and 2006 (ALFA 9000, 9801, 9802). Among 1529 patients (15-70 years of age), 554 patients were screened for NPM1 mutation, FLT3-ITD and have informative karyotype. Mutations screening were centrally performed according to previously described procedures. Karyotype was considered as normal if at least 20 normal marrow metaphases were present without any abnormal marrow metaphases. Favorable core binding factor (CBF) AML (74 patients) were excluded from this analysis. Results Among the 480 remaining patients, 137 (29%; median age 48 years, range 17-68) were NPM1 mutated, 22 of them (16%) having CA-AML. We found no difference between NPM1 mutated CN-AML patients (n=115) and NPM1 mutated non-CBF CA-AML patients (n=22) in term of complete remission rate (88% vs 83%; P= .49), overall survival (OS) (39% vs 38 % at 5 years, P= .85), event-free survival (EFS) (33% vs 25% at 5 years, P= .39). However, in the context of the favorable genotype, EFS was significantly longer in the 79 CN- than in the 16 CA-AML patients (41% vs 19% at 5 years ; P= .04) with a trend to better OS (51% vs 31% at 5 years ; P= .12). No significant differences were observed in patients with NPM1 mutated AML but FLT3-ITD (5-year EFS, 12% vs 40%; 5-year OS, 20% vs 60%; P= .47 and .27, respectively), even if the numbers of patients were here very low (35 CN- vs 5 CA-AML). More importantly, the favorable genotype was predictive of a longer EFS and OS in the 267 patients with CN-AML (5-year EFS, 41% vs 19%; 5-year OS, 51% vs 30%; P= .0001 and .001, respectively), while no differences were observed in the 213 patients with non-CBF CA-AML (5-year EFS, 19% vs 16%; 5-year OS, 31% vs 27%; P= .38 and .36, respectively). Conclusion As shown, patients with the favorable genotype but CA-AML had an outcome relatively similar to those with a non favorable genotype and either CA- or CN-AML. The favorable outcome associated with NPM1 mutation in the absence of FLT3-ITD might thus depend on the presence of a normal karyotype. We thus think that larger studies or overviews are needed to definitely answer this question. Disclosures Dombret: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

FLT3 Internal Tandem Duplication in Acute Myeloid Leukemia with Normal Karyotype

2007 ◽  
Vol 42 (3) ◽  
pp. 250 ◽  
Author(s):  
Sang-Ho Kim ◽  
Yeo-Kyeoung Kim ◽  
Il-Kwon Lee ◽  
Deog-Yeon Jo ◽  
Jong-Ho Won ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Normal Karyotype ◽  
Internal Tandem Duplication ◽  
Flt3 Internal Tandem Duplication ◽  
Acute Myeloid

scholarly journals Idarubicin Dose Escalation During Consolidation Therapy for Adult Acute Myeloid Leukemia

2017 ◽  
Vol 35 (15) ◽  
pp. 1678-1685 ◽  
Author(s):  
Kenneth F. Bradstock ◽  
Emma Link ◽  
Juliana Di Iulio ◽  
Jeff Szer ◽  
Paula Marlton ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Gene Mutations ◽  
Severe Neutropenia ◽  
Consolidation Therapy ◽  
Internal Tandem Duplication ◽  
Flt3 Internal Tandem Duplication ◽  
Acute Myeloid

Purpose Higher doses of the anthracycline daunorubicin during induction therapy for acute myeloid leukemia (AML) have been shown to improve remission rates and survival. We hypothesized that improvements in outcomes in adult AML may be further achieved by increased anthracycline dose during consolidation therapy. Patients and Methods Patients with AML in complete remission after induction therapy were randomly assigned to receive two cycles of consolidation therapy with cytarabine 100 mg/m2 daily for 5 days, etoposide 75 mg/m2 daily for 5 days, and idarubicin 9 mg/m2 daily for either 2 or 3 days (standard and intensive arms, respectively). The primary end point was leukemia-free survival (LFS). Results Two hundred ninety-three patients 16 to 60 years of age, excluding those with core binding factor AML and acute promyelocytic leukemia, were randomly assigned to treatment groups (146 to the standard arm and 147 to the intensive arm). Both groups were balanced for age, karyotypic risk, and FLT3–internal tandem duplication and NPM1 gene mutations. One hundred twenty patients in the standard arm (82%) and 95 patients in the intensive arm (65%) completed planned consolidation ( P < .001). Durations of severe neutropenia and thrombocytopenia were prolonged in the intensive arm, but there were no differences in serious nonhematological toxicities. With a median follow-up of 5.3 years (range, 0.6 to 9.9 years), there was a statistically significant improvement in LFS in the intensive arm compared with the standard arm (3-year LFS, 47% [95% CI, 40% to 56%] v 35% [95% CI, 28% to 44%]; P = .045). At 5 years, the overall survival rate was 57% in the intensive arm and 47% in the standard arm ( P = .092). There was no evidence of selective benefit of intensive consolidation within the cytogenetic or FLT3–internal tandem duplication and NPM1 gene mutation subgroups. Conclusion An increased cumulative dose of idarubicin during consolidation therapy for adult AML resulted in improved LFS, without increased nonhematologic toxicity.

Flt3 Internal Tandem Duplication and P-Glycoprotein Functionality in 171 Patients with Acute Myeloid Leukemia

2006 ◽  
Vol 12 (23) ◽  
pp. 7018-7024 ◽  
Author(s):  
Christophe Marzac ◽  
I. Teyssandier ◽  
Ors'Anton Calendini ◽  
Jean-Yves Perrot ◽  
Anne-Marie Faussat ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Internal Tandem Duplication ◽  
P Glycoprotein ◽  
Flt3 Internal Tandem Duplication ◽  
Acute Myeloid
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