Faculty Collaboration Database

Impact of transplant conditioning, NPM1 mutations, and measurable residual disease in FLT3-ITD acute myeloid leukemia. Blood Adv 2025 Oct 28;9(20):5123-5133

Date

07/01/2025

Pubmed ID

40590852

Pubmed Central ID

PMC12550156

DOI

10.1182/bloodadvances.2025016306

Scopus ID

2-s2.0-105022727141 (requires institutional sign-in at Scopus site)   5 Citations

Abstract

We conducted a post hoc analysis of data from Blood and Marrow Transplant Clinical Trials Network 1506 (MORPHO), a randomized trial of gilteritinib vs placebo as posttransplantation maintenance for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), focusing the interactions between conditioning regimen intensity, measurable residual disease (MRD), and NPM1 comutation status reported from diagnosis. Comparing FLT3-ITD MRD before and after conditioning, there was no difference between myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) in eradication or reduction of FLT3-ITD MRD. For participants who were FLT3-ITD MRD negative before HCT, there was no difference in the cumulative incidence of relapse during follow-up between those receiving MAC vs RIC. NPM1 comutation was associated with the largest magnitude of relapse-free survival benefit from post-HCT gilteritinib, and in these participants, post-HCT gilteritinib in the setting of RIC appeared to be as effective as MAC at preventing relapse. MAC appeared superior to RIC in preventing relapse only in participants who were NPM1 wild type at diagnosis and FLT3-ITD MRD positive before HCT. Our findings suggest that only a subset of patients with FLT3-ITD AML undergoing HCT may benefit from MAC and that, similar to AML therapy before HCT, the intensity of the HCT regimen should be adapted according to the molecular features of the disease. This trial was registered at www.clinicaltrials.gov as #NCT02997202.

Author List

Levis MJ, Hamadani M, Logan BR, Jones RJ, Singh AK, Litzow MR, Wingard JR, Papadopoulos EB, Perl AE, Soiffer RJ, Ustun C, Oshima MU, Uy GL, Waller EK, Vasu S, Solh M, Mishra A, Muffly LS, Kim HJ, Stelljes M, Najima Y, Onozawa M, Thomson K, Chen C, Hasabou N, Rosales M, Hill JE, Gill SC, Nuthethi R, King D, Mendizabal A, Devine SM, Horowitz MM, Chen YB

Authors

Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
Brent R. Logan PhD Director, Professor in the Data Science Institute department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aniline Compounds
Female
Hematopoietic Stem Cell Transplantation
Humans
Leukemia, Myeloid, Acute
Male
Middle Aged
Mutation
Neoplasm, Residual
Nuclear Proteins
Pyrazines
Transplantation Conditioning
Transplantation, Homologous
fms-Like Tyrosine Kinase 3