Measurable residual disease, FLT3-ITD mutation, and disease status have independent prognostic influence on outcome of allogeneic stem cell transplantation in NPM1-mutated acute myeloid leukemia

Rama Al Hamed, Myriam Labopin, Etienne Daguindau, Riitta Niittyvuopio, Anne Huynh, Gerard Socie, Micha Srour, Jean Henri Bourhis, Nicolaus Kroeger, Eleni Tholouli, Goda Choi, Xavier Poire, Hans Martin, Marie-Therese Rubio, Pavel Jindra, Didier Blaise, Dietrich Beelen, Helene Labussiere-Wallet, Arnon Nagler, Ali BazarbachiMohamad Mohty*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

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    Abstract

    Nucleophosmin-1 (NPM1) mutations in acute myeloid leukemia (AML) confer a survival advantage in the absence of FLT3-internal tandem duplication (FLT3-ITD). Here, we investigated the main predictors of outcome after allogeneic hematopoietic stem cell transplantation (allo-HCT). We identified 1572 adult (age >= 18 year) patients with NPM1-mutated AML in first complete remission (CR1:78%) or second complete remission (CR2:22%) who were transplanted from matched sibling donors (30.8%) or unrelated donors (57.4%) between 2007 and 2019 at EBMT participating centers. Median follow-up for survivors was 23.7 months. FLT3-ITD was present in 69.3% of patients and 39.2% had detectable minimal/measurable residual disease (MRD) at transplant. In multivariate analysis, relapse incidence (RI) and leukemia-free survival (LFS) were negatively affected by concomitant FLT3-ITD mutation (HR 1.66 p = 0.0001, and HR 1.53, p < 0.0001, respectively), MRD positivity at transplant (HR 2.18, p < 10(-5) and HR 1.71, p < 10(-5), respectively), and transplant in CR2 (HR 1.36, p = 0.026, and HR 1.26, p = 0.033, respectively), but positively affected by Karnofsky score >= 90 (HR 0.74, p = 0.012, and HR 0.7, p = 0.0002, respectively). Overall survival (OS) was also negatively influenced by concomitant FLT3-ITD (HR 1.6, p = 0.0001), MRD positivity at transplant (HR 1.61, p < 10(-5)), and older age (HR 1.22 per 10 years, p < 0.0001), but positively affected by matched sibling donor (unrelated donor: HR 1.35, p = 0.012; haploidentical donor: HR 1.45, p = 0.037) and Karnofsky score >= 90 (HR 0.73, p = 0.004). These results highlight the independent and significant role of FLT3-ITD, MRD status, and disease status on posttransplant outcomes in patients with NPM1-mutated AML allowing physicians to identify patients at risk of relapse who may benefit from posttransplant prophylactic interventions.

    Original languageEnglish
    Pages (from-to)1068-1080
    Number of pages13
    JournalCancer medicine
    Volume11
    Issue number4
    DOIs
    Publication statusPublished - Feb-2022

    Keywords

    • acute myeloid leukemia
    • FLT3-ITD
    • minimal residual disease
    • NPM-1 mutation
    • ACUTE MYELOGENOUS LEUKEMIA
    • VERSUS-HOST-DISEASE
    • NUCLEOPHOSMIN NPM1
    • AML
    • SORAFENIB
    • DEFINITION
    • SURVIVAL
    • RELAPSE
    • ADULTS

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