Outcomes and Genetic Dynamics of Acute Myeloid Leukemia at First Relapse

Authors

Alex Bataller
Hagop Kantarjian
Alexandre Bazinet
Tapan Kadia
Naval Daver
Courtney D DiNardo
Gautam Borthakur
Sanam Loghavi
Keyur Patel
Guilin Tang
Koji Sasaki
Nicholas J Short
Musa Yilmaz
Ghayas C Issa
Yesid Alvarado
Guillermo Montalban-Bravo
Abhishek Maiti
Hussein A Abbas
Koichi Takahashi
Sherry Pierce
Elias Jabbour
Guillermo Garcia-Manero
Farhad Ravandi

Publication Date

11-1-2024

Journal

Haematologica

Abstract

Patients with relapsed acute myeloid leukemia (AML) experience dismal outcomes. We performed a comprehensive analysis of patients with relapsed AML to determine the genetic dynamics and factors predicting survival. We analyzed 875 patients with newly diagnosed AML who received intensive treatment or low-intensity treatment. Of these patients, 197 subsequently relapsed. Data were available for 164 of these patients, with a median time from complete remission/complete remission with incomplete blood count recovery to relapse of 6.5 months. Thirty-five of the 164 patients (21%) experienced relapse after allogeneic hematopoietic stem cell transplantation. At relapse, mutations in genes involved in pathway signaling tended to disappear, whereas clonal hematopoiesis-related mutations or TP53 tended to persist. Patients with normal karyotypes tended to acquire cytogenetic abnormalities at relapse. Patients treated intensively had a higher rate of emergence of TP53 mutations (16%), compared to patients given low-intensity treatment (1%, P=0.009). The overall response rates were 38% and 35% for patients treated with salvage intensive treatment or low-intensity treatment, respectively. Seventeen patients (10%) underwent allogeneic stem cell transplantation after salvage therapy. The median overall survival duration after relapse was 5.3 months, with a 1-year overall survival rate of 17.6%. Complex karyotype (hazard ratio [HR]=2.14, P<0.001), a KMT2A rearrangement (HR=3.52, P=0.011), time in remission <12 months (HR=1.71, P=0.011), and an elevated white blood cell count at relapse (HR=2.38, P=0.005) were independent risk factors for overall survival duration. More effective frontline and maintenance therapies are warranted to prevent relapsed AML.

Keywords

Humans, Leukemia, Myeloid, Acute, Female, Male, Middle Aged, Adult, Aged, Hematopoietic Stem Cell Transplantation, Mutation, Recurrence, Young Adult, Adolescent, Prognosis, Treatment Outcome, Transplantation, Homologous

DOI

10.3324/haematol.2024.285057

PMID

38695144

PMCID

PMC11532689

PubMedCentral® Posted Date

5-2-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes