Cytogenetic risk classification maintains its prognostic significance in transplanted FLT3-ITD mutated acute myeloid leukemia patients: On behalf of the acute leukemia working party/European society of blood and marrow transplantation

Arnon Nagler*, Myriam Labopin, Charles Craddock, Gerard Socié, Ibrahim Yakoub-Agha, Tobias Gedde-Dahl, Riitta Niittyvuopio, Jennifer Louise Byrne, Jan J. Cornelissen, Hélène Labussière-Wallet, William Arcese, Noel Milpied, Jordi Esteve, Jonathan Canaani, Mohamad Mohty

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutational status is a pivotal prognosticator in acute myeloid leukemia (AML) patients and significantly increases the risk of disease relapse. However, it remains unclear whether in FLT3-ITD patients referred for allogeneic stem cell transplantation (allo-SCT), baseline cytogenetics significantly impacts clinical outcome. Using the European Society of Blood and Marrow Transplantation registry, we performed a retrospective analysis of 1631 FLT3-ITD AML patients who underwent allo-SCT with the aim of determining the influence of cytogenetic risk category on patient outcomes. Median patient age was 49 years and median follow-up duration was 36 months. Two-year leukemia-free survival (LFS) and incidence of relapse were 54% and 31.6%, respectively. Non-relapse mortality was experienced by 14.4% with a 2-year overall survival (OS) of 60.1%. On multivariate analysis, LFS was significantly lower in patients with intermediate and adverse risk cytogenetics compared with those with favorable risk cytogenetics, (hazard ratio [HR] = 1.48, 95% confidence interval [CI], 1.06–2.06; p =.02), and (HR = 01.65, 95% CI, 1.13–2.40; p =.009), respectively. OS was significantly lower in patients with adverse risk cytogenetics compared with patients with favorable risk cytogenetics (HR = 1.74, 95% CI, 1.16–2.61; p =.008) with a trend toward lower OS in patients with intermediate risk cytogenetics compared to those with favorable risk cytogenetics (HR = 1.43, 95% CI, 1.00–2.05; p =.052). In addition, adverse risk patients and intermediate risk patients experienced higher relapse rates compared with favorable risk patients (HR = 1.83, 95% CI, 1.13–2.94; p =.013 and HR = 1.82, 95% CI, 1.19–2.77; p =.005). Overall, cytogenetic studies aid in refinement of risk stratification in transplanted FLT3-ITD AML patients.

Original languageEnglish
Pages (from-to)274-282
Number of pages9
JournalAmerican Journal of Hematology
Volume97
Issue number3
DOIs
Publication statusE-pub ahead of print - 3 Jan 2022

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