About this item:

155 Views | 135 Downloads

Author Notes:

Matthew A. Kutny, MD University of Alabama at Birmingham Department of Pediatrics, Division of Hematology/Oncology ACC 512, 1600 7th Ave S Birmingham, AL 35233-1711, Phone: 205-939-9285, Fax: 205-975-1941, Email: mkutny@peds.uab.edu.

We would like to thank the patients and their families who consented to use of the specimens used in the conduct of this research and the COG AML Reference Laboratory for providing these specimens.

The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

A complete listing of grant support for research conducted by CCG and POG before initiation of the COG grant in 2003 is available online at: http://www.childrensoncologygroup.org/admin/grantinfo.html

Conflict of Interest Statement: The authors report no pertinent conflicts of interest.

Subjects:

Research Funding:

This work was supported by the National Institutes of Health grants including the Ruth L. Kirschstein National Research Service Award T32CA009351 (M.A.K.) and R01-CA114563 (S.M.).

Supported by Grants No. U10-CA98543 (Chair's Grant), U10-CA98413 (Statistics and Data Center Grant), U24-CA114766 (Children's Oncology Group), NCI R01-CA114563 (S.M.), and NCI R21 CA 104964-02 (SM).

Dr. Matthew Kutny was supported in part by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award T32CA009351.

The research for CALGB 9710 was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, MD, Chairman) and to the CALGB Statistical Center (Stephen George, PhD, CA33601).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Hematology
  • Pediatrics
  • acute promyelocytic leukemia
  • APL
  • FLT3 mutation
  • pediatric
  • ACUTE MYELOID-LEUKEMIA
  • INTERNAL TANDEM DUPLICATION
  • PML/RAR-ALPHA
  • GENE
  • SUBTYPES
  • IMPACT
  • ASSOCIATION
  • PROGNOSIS
  • PATHWAYS
  • SURVIVAL

FLT3 Mutation Status is a Predictor of Early Death in Pediatric Acute Promyelocytic Leukemia: A Report From The Children's Oncology Group

Show all authors Show less authors

Tools:

Journal Title:

Pediatric Blood and Cancer

Volume:

Volume 59, Number 4

Publisher:

, Pages 662-667

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Background: FLT3 mutations (FLT3/Mut) are prevalent in de novo AML and are associated with early relapse. The prevalence and prognostic significance of FLT3/Mut have not been well defined in childhood acute promyelocytic leukemia (APL). Procedure: Diagnostic specimens from 104 pediatric APL patients were screened for FLT3/Mut (FLT3/ITD or FLT3/ALM). FLT3/Mut status was correlated with disease characteristics and clinical outcome for patients treated on CALGB C9710 (n=50). Results: Forty-two of the 104 patients (40%) had either FLT3/ITD (n=28, 27%) or FLT3/ALM (n=15, 14%). Median diagnostic WBC count was 23,400cells/μl vs. 3,600cells/μl for those with and without FLT3/Mut (P<0.001), and similar results for the cohort of 50 patients treated on C9710 (P<0.001). In patients treated on C9710, presence of a FLT3 mutation was highly correlated with diagnostic WBC count >10,000 (P=0.004), microgranular variant histology (P=0.035), and a lower remission rate (P=0.009). In patients who received ATRA (C9710 or CCG-2911, n=58), those with FLT3/Mut had an induction death rate of 30% (7/23) compared to 3% (1/35) in FLT3/WT patients (P=0.005). In patients with high WBC counts (>10,000), those with FLT3/Mut had a significantly higher risk of induction death versus FLT3/WT patients (47% vs. 0%, P=0.05). FLT3/Mut was not associated with adverse outcome in those who survived induction therapy. Conclusions: FLT3/Mut are prevalent in pediatric APL and are associated with high WBC count and increased induction death. This study provides further evidence for testing APL patients for FLT3/Mut and the potential role for FLT3 inhibitors in this disease.

Copyright information:

© 2012 Wiley Periodicals, Inc.

Export to EndNote