%0 Journal Article
%T Sex-based Differences in Risk for Therapy-related Myeloid Neoplasms.
%A Richard MA
%A Yan C
%A Chen Y
%A Gibson CJ
%A Kalra R
%A Bosworth A
%A Crossman DK
%A Singh P
%A Hageman L
%A He J
%A Armenian SH
%A Vose J
%A Weisdorf DJ
%A Ebert BL
%A Yasui Y
%A Cheng C
%A Forman SJ
%A Bhatia S
%A Bhatia R
%J J Clin Oncol
%V 0
%N 0
%D 2024 Aug 2
%M 39094067
%F 50.717
%R 10.1200/JCO-24-01487
%X UNASSIGNED: Therapy-related myeloid neoplasm (t-MN) is a life-threatening complication of autologous peripheral blood stem cell (PBSC) transplantation for non-Hodgkin lymphoma (NHL). Prior studies report an association between clonal hematopoiesis (CH) in PBSC and risk of t-MN, but small samples precluded examination of risk within specific sub-populations.
UNASSIGNED: Targeted DNA sequencing was performed to identify CH mutations in PBSC from a retrospective cohort of 984 NHL patients (median age at transplant 57y; range: 18-78). Fine-Gray proportional subdistribution hazard regression models estimated association between number of CH mutations and t-MN, adjusting for demographic, clinical, and therapeutic variables. Secondary analyses evaluated association between CH and t-MN among males and females.
UNASSIGNED: CH was identified in PBSC from 366 patients (37.2%). t-MN developed in 60 patients after median follow-up of 5y. Presence of ≥2 mutations conferred increased t-MN risk (adjusted hazard ratio [aHR]=2.10, 95% confidence interval [CI]=1.08-4.11, p=0.029). CH was associated with increased t-MN risk among males (aHR=1.83, 95%CI=1.01-3.31) but not females (aHR=0.56, 95%CI=0.15-2.09). Although prevalence and type of CH mutations in PBSC was comparable, the 8y cumulative incidence of t-MN was higher among males vs. females with CH (12.4% vs. 3.6%) but was similar between males and females without CH (4.9% vs. 3.9%). Expansion of CH clones from PBSC to t-MN was seen only among males.
UNASSIGNED: Presence of CH mutations in PBSC confers increased risk of t-MN after autologous transplantation in male but not female patients with NHL. Factors underlying sex-based differences in risk of CH progression to t-MN merit further investigation.