Faculty Opinions recommendation of Prognostic significance of NPM1 mutations in the absence of FLT3-internal tandem duplication in older patients with acute myeloid leukemia: a SWOG and UK National Cancer Research Institute/Medical Research Council report.

2015 ◽  
Author(s):  
Arnon Nagler
Keyword(s):  
Older Patients ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Medical Research Council ◽  
Prognostic Significance ◽  
Internal Tandem Duplication ◽  
Cancer Research Institute ◽  
National Cancer Research Institute ◽  
Council Report ◽  
Flt3 Internal Tandem Duplication

The prognostic significance of IDH2 mutations in AML depends on the location of the mutation

Blood ◽  
2011 ◽  
Vol 118 (2) ◽  
pp. 409-412 ◽  
Author(s):  
Claire L. Green ◽  
Catherine M. Evans ◽  
Lu Zhao ◽  
Robert K. Hills ◽  
Alan K. Burnett ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Medical Research Council ◽  
Prognostic Significance ◽  
Patient Characteristics ◽  
Significant Heterogeneity ◽  
Internal Tandem Duplication ◽  
Isocitrate Dehydrogenase 2 ◽  
Favorable Prognostic Factor ◽  
Flt3 Internal Tandem Duplication

Abstract We have investigated the prognostic significance of isocitrate dehydrogenase 2 (IDH2) mutations in 1473 younger adult acute myeloid leukemia patients treated in 2 United Kingdom Medical Research Council trials. An IDH2 mutation was present in 148 cases (10%), 80% at R140 and 20% at R172. Patient characteristics and outcome differed markedly between the 2 mutations. IDH2R140 significantly correlated with nucleophosmin mutations (NPM1MUT), whereas IDH2R172 cases generally lacked other molecular mutations. An IDH2R140 mutation was an independent favorable prognostic factor for relapse (P = .004) and overall survival (P = .008), and there was no significant heterogeneity with regard to NPM1 or FLT3 internal tandem duplication (FLT3/ITD) genotype. Relapse in FLT3/ITDWTNPM1MUTIDH2R140 patients was lower than in favorable-risk cytogenetics patients in the same cohort (20% and 38% at 5 years, respectively). The presence of an IDH2R172 mutation was associated with a significantly worse outcome than IDH2R140, and relapse in FLT3/ITDWTNPM1WTIDH2R172 patients was comparable with adverse-risk cytogenetics patients (76% and 72%, respectively).

scholarly journals Prognostic Significance of NPM1 Mutations in the Absence of FLT3–Internal Tandem Duplication in Older Patients With Acute Myeloid Leukemia: A SWOG and UK National Cancer Research Institute/Medical Research Council Report

2015 ◽  
Vol 33 (10) ◽  
pp. 1157-1164 ◽  
Author(s):  
Fabiana Ostronoff ◽  
Megan Othus ◽  
Michelle Lazenby ◽  
Elihu Estey ◽  
Frederick R. Appelbaum ◽  
...  
Keyword(s):  
Cancer Research ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Research Council ◽  
Medical Research Council ◽  
Prognostic Significance ◽  
Cancer Research Institute ◽  
National Cancer Research Institute ◽  
The Impact ◽  
Acute Myeloid

Purpose Younger patients with acute myeloid leukemia (AML) harboring NPM1 mutations without FLT3–internal tandem duplications (ITDs; NPM1-positive/FLT3-ITD–negative genotype) are classified as better risk; however, it remains uncertain whether this favorable classification can be applied to older patients with AML with this genotype. Therefore, we examined the impact of age on the prognostic significance of NPM1-positive/FLT3-ITD–negative status in older patients with AML. Patients and Methods Patients with AML age ≥ 55 years treated with intensive chemotherapy as part of Southwest Oncology Gorup (SWOG) and UK National Cancer Research Institute/Medical Research Council (NCRI/MRC) trials were evaluated. A comprehensive analysis first examined 156 patients treated in SWOG trials. Validation analyses then examined 1,258 patients treated in MRC/NCRI trials. Univariable and multivariable analyses were used to determine the impact of age on the prognostic significance of NPM1 mutations, FLT3-ITDs, and the NPM1-positive/FLT3-ITD–negative genotype. Results Patients with AML age 55 to 65 years with NPM1-positive/FLT3-ITD–negative genotype treated in SWOG trials had a significantly improved 2-year overall survival (OS) as compared with those without this genotype (70% v 32%; P < .001). Moreover, patients age 55 to 65 years with NPM1-positive/FLT3-ITD–negative genotype had a significantly improved 2-year OS as compared with those age > 65 years with this genotype (70% v 27%; P < .001); any potential survival benefit of this genotype in patients age > 65 years was marginal (27% v 16%; P = .33). In multivariable analysis, NPM1-positive/FLT3-ITD–negative genotype remained independently associated with an improved OS in patients age 55 to 65 years (P = .002) but not in those age > 65 years (P = .82). These results were confirmed in validation analyses examining the NCRI/MRC patients. Conclusion NPM1-positive/FLT3-ITD–negative genotype remains a relatively favorable prognostic factor for patients with AML age 55 to 65 years but not in those age > 65 years.

Evolution of FLT3 Internal Tandem Duplication at the Diagnosis, Relapse, Remission or Induction Failure during the Treatment in Acute Myeloblastic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4485-4485
Author(s):  
Soo-Mee Bang ◽  
Jeong Yeal Ahn ◽  
Jiyoon Park ◽  
Se Hoon Park ◽  
Eun Mi Nam ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Remission Rate ◽  
Prognostic Significance ◽  
Chemotherapeutic Agents ◽  
Internal Tandem Duplication ◽  
Induction Failure ◽  
Flt3 Internal Tandem Duplication ◽  
Acute Myeloid

Abstract The FLT3 is class III fms-like tyrosine kinase. FLT3 mutations are one of the most frequent genetic changes at diagnosis and have been reported to be of prognostic significance in acute myeloid leukemia. FLT3 internal tandem duplication of the juxtamembrane domain (FLT3 ITD) was analyzed by PCR of genomic DNA at diagnosis or during the follow-up in patients with acute myeloid leukemia (AML). Total 223 patients were diagnosed as AML from Mar. 1996 till Aug. 2005. Their median age was 34 years-old (range: 0–86). The number of male or female patients was 116 or 107. Their FAB classifications were M0/1/2/3/4/5/6/7/RAEB/biphenotypic in 6/23/85/20/32/21/13/16/2/5 patients, respectively. Cytogenetic data at diagnosis were available in 182 patients; good/ intermediate/poor risk in 51/107/24 patients, respectively. Among the 190 patients receiving induction therapy, 147 patients achieved hematologic remission with a remission rate of 77%. Median event-free (EFS) and overall survival were 9 (95% confidence interval: 8–12) months and 14 (95% CI: 11–14) months, respectively. The incidence of FLT3 ITD at diagnosis was 13% (29/223). FLT3 ITD was more prevalent in M0~4 subtypes and older age. Among non-M3 population (N=203), patients with FLT3 ITD had a significantly short EFS when compared with those without ITD (p=0.0454). Among the 52 relapsed patients, 9 patients had a FLT3 ITD at diagnosis. Six patients showed reappearing of ITD and 3 patients remained negative at relapse. One patient acquired new ITD at relapse among 43 relapsed patients who had not baseline ITD. Tested 100 samples of 92 patients at remission were all negative for FLT3 ITD. Among the 28 patients at induction failure, one patient showed persistent ITD, one another re-appeared ITD after relapse, and the other one newly-developed ITD. Two others showed disappearance of ITD despite of persistent disease. Leukemic clones with FLT3 ITD may be susceptible to conventional chemotherapeutic agents and have no value for minimal residual disease. Therefore, effective induction and consolidation therapy could convert the poor prognosis of AML with FLT3 ITD.

Sign in / Sign up

Export Citation Format

Share Document