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Review
. 2013 Mar;25(2):195-204.
doi: 10.1097/CCO.0b013e32835ec91f.

Hematopoietic transplantation for acute myeloid leukemia with internal tandem duplication of FLT3 gene (FLT3/ITD)

Salut Brunet  1 , Rodrigo Martino, Jorge Sierra
Affiliations
Review

Hematopoietic transplantation for acute myeloid leukemia with internal tandem duplication of FLT3 gene (FLT3/ITD)

Salut Brunet et al. Curr Opin Oncol. 2013 Mar.

Abstract

Purpose of review: Patients with acute myeloid leukemia (AML) traditionally classified as having an intermediate cytogenetic risk [mostly cytogenetically normal AML (CN-AML)] really include a significant proportion of cases with a poor outcome. This is based on the molecular findings at diagnosis, mainly the presence of internal tandem duplication in the FMS-like tyrosine kinase 3 gene(s) (FLT3/ITD). Optimal postremission therapy for these high-risk molecular cases is not well established; as the prognosis is adverse hematopoietic cell transplantation (HCT), mainly allogeneic HCT (allo-HCT), is the most widely accepted strategy.

Recent findings: As a rule, patients with FLT3/ITD have a poor outcome with conventional chemotherapy alone. Only patients with an associated nucleophosmin 1 (NPM1) mutation and those with a low mutated-to-wild-type allelic ratio of FLT3/ITD have less unfavorable outcome. Most studies show an advantage of allo-HCT in first complete remission (CR1), with higher 3-5 year disease-free survival and lower relapse risk than with chemotherapy or autologous transplantation (auto-HCT). Regarding allo-HCT proceeding early after reaching CR1 seems to improve survival, rather than after several courses of consolidation chemotherapy.

Summary: Patients with intermediate-risk cytogenetics AML and FLT3/ITD, especially NPM1-wild cases and those NPM1 mutated with a high allelic ratio, should proceed to allo-HCT if possible early after achieving CR1.

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