Faculty Collaboration Database

Impact of Conditioning Intensity of Allogeneic Transplantation for Acute Myeloid Leukemia With Genomic Evidence of Residual Disease. J Clin Oncol 2020 Apr 20;38(12):1273-1283

Date

12/21/2019

Pubmed ID

31860405

Pubmed Central ID

PMC7164487

DOI

10.1200/JCO.19.03011

Scopus ID

2-s2.0-85083545151 (requires institutional sign-in at Scopus site)   269 Citations

Abstract

PURPOSE: Patients with acute myeloid leukemia (AML) in remission remain at risk for relapse even after allogeneic hematopoietic cell transplantation (alloHCT). AML measurable residual disease (MRD) status before alloHCT has been shown to be prognostic. Whether modulation of the intensity of the alloHCT conditioning regimen in patients with AML who test positive for MRD can prevent relapse and improve survival is unknown.

METHODS: Ultra-deep, error-corrected sequencing for 13 commonly mutated genes in AML was performed on preconditioning blood from patients treated in a phase III clinical trial that randomly assigned adult patients with myeloid malignancy in morphologic complete remission to myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC).

RESULTS: No mutations were detected in 32% of MAC and 37% of RIC recipients; these groups had similar survival (3-year overall survival [OS], 56% v 63%; P = .96). In patients with a detectable mutation (next-generation sequencing [NGS] positive), relapse (3-year cumulative incidence, 19% v 67%; P < .001) and survival (3-year OS, 61% v 43%; P = .02) was significantly different between the MAC and RIC arms, respectively. In multivariable analysis for NGS-positive patients, adjusting for disease risk and donor group, RIC was significantly associated with increased relapse (hazard ratio [HR], 6.38; 95% CI, 3.37 to 12.10; P < .001), decreased relapse-free survival (HR, 2.94; 95% CI, 1.84 to 4.69; P < .001), and decreased OS (HR, 1.97; 95% CI, 1.17 to 3.30; P = .01) compared with MAC. Models of AML MRD also showed benefit for MAC over RIC for those who tested positive.

CONCLUSION: This study provides evidence that MAC rather than RIC in patients with AML with genomic evidence of MRD before alloHCT can result in improved survival.

Author List

Hourigan CS, Dillon LW, Gui G, Logan BR, Fei M, Ghannam J, Li Y, Licon A, Alyea EP, Bashey A, Deeg HJ, Devine SM, Fernandez HF, Giralt S, Hamadani M, Howard A, Maziarz RT, Porter DL, Scott BL, Warlick ED, Pasquini MC, Horwitz ME

Authors

Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Brent R. Logan PhD Director, Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Professor in the Medicine department at Medical College of Wisconsin

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

Adult
Aged
Circulating Tumor DNA
Clinical Trials, Phase III as Topic
Female
Hematopoietic Stem Cell Transplantation
High-Throughput Nucleotide Sequencing
Humans
Leukemia, Myeloid, Acute
Male
Middle Aged
Mutation
Neoplasm, Residual
Prognosis
Randomized Controlled Trials as Topic
Transplantation Conditioning
Transplantation, Homologous
Young Adult