Therapy-Related Chronic Myelomonocytic Leukemia Does Not Have the High-Risk Features of a Therapy-Related Neoplasm

Authors

Alex Bataller
Georgina Gener-Ricos
Emmanuel Almanza-Huante
Kelly S Chien
Samuel Urrutia
Alexandre Bazinet
Juan Jose Rodriguez-Sevilla
Danielle Hammond
Koji Sasaki
Koichi Takahashi
Courtney D DiNardo
Farhad Ravandi
Gautam Borthakur
Tapan M Kadia
Rashmi Kanagal-Shamanna
Hagop M Kantarjian
Guillermo Garcia-Manero
Guillermo Montalban-Bravo

Publication Date

6-11-2024

Journal

Blood Advances

Abstract

Therapy-related myeloid neoplasms (t-MNs) arise after exposure to cytotoxic therapies and are associated with high-risk genetic features and poor outcomes. We analyzed a cohort of patients with therapy-related chronic myelomonocytic leukemia (tCMML; n = 71) and compared its features to that of de novo CMML (dnCMML; n = 461). Median time from cytotoxic therapy to tCMML diagnosis was 6.5 years. Compared with dnCMML, chromosome-7 abnormalities (4% vs 13%; P = .005) but not complex karyotype (3% vs 7%; P = .15), were more frequent in tCMML. tCMML was characterized by higher TP53 mutation frequency (4% vs 12%; P = .04) and lower NRAS (6% vs 22%, P = .007) and CBL (4% vs 12%, P = .04) mutation frequency. Prior therapy with antimetabolites (odd ratio [OR], 1.22; 95% confidence interval [CI], 1.05-1.42; P = .01) and mitotic inhibitors (OR, 1.24; 95% CI, 1.06-1.44; P = .009) was associated with NF1 and SETBP1 mutations whereas prior mitotic inhibitor therapy was associated with lower TET2 mutation frequency (OR, 0.71; 95% CI, 0.55-0.92; P = .01). Although no differences in median overall survival (OS) were observed among tCMML and dnCMML (34.7 months vs 35.9 months, P = .26), multivariate analysis for OS revealed that prior chemotherapy was associated with increased risk of death (hazard ratio, 1.76; 95% CI, 1.07-2.89; P = .026). Compared with a cohort of therapy-related myelodysplastic syndrome, tCMML had lower TP53 mutation frequency (12% vs 44.4%, P < .001) and less unfavorable outcomes. In summary, tCMML does not exhibit the high-risk features and poor outcomes of t-MNs.

Keywords

Humans, Leukemia, Myelomonocytic, Chronic, Male, Female, Aged, Middle Aged, Neoplasms, Second Primary, Mutation, Aged, 80 and over, Adult, Risk Factors

Comments

Associated Data

PMID: 38513082

DOI

10.1182/bloodadvances.2024012565

PMID

38513082

PMCID

PMC11170163

PubMedCentral® Posted Date

May 2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes