Sex-Based Differences in Risk of Therapy-Related Myeloid Neoplasms

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Therapy-related myeloid neoplasm (t-MN) is a serious complication following autologous stem cell transplantation for non-Hodgkin lymphoma (NHL).
• Previous research suggests a link between clonal hematopoiesis (CH) in peripheral blood stem cells (PBSC) and t-MN risk, but lacked sufficient power to analyze specific patient groups.

Purpose of the Study:

• To investigate the association between CH mutations in PBSC and the risk of developing t-MN after autologous transplantation in NHL patients.
• To examine potential sex-based differences in the risk of t-MN associated with CH.

Main Methods:

• Retrospective cohort study of 984 NHL patients undergoing autologous PBSC transplantation.
• Targeted DNA sequencing to detect CH mutations in PBSC.
• Fine-Gray regression models to assess the association between CH mutation burden and t-MN risk, adjusting for covariates.

Main Results:

• CH was detected in 37.2% of patients; 60 developed t-MN.
• The presence of two or more CH mutations significantly increased t-MN risk (aHR, 2.10; P=.029).
• CH was associated with higher t-MN risk in males (aHR, 1.83) but not females (aHR, 0.56); 8-year t-MN incidence was higher in males with CH (12.4%) vs. females with CH (3.6%).

Conclusions:

• CH mutations in PBSC are a risk factor for t-MN post-transplant in male NHL patients.
• The association between CH and t-MN risk was not significant in female patients.
• Further investigation into the biological mechanisms underlying sex differences in CH progression to t-MN is warranted.