Baylor College of Medicine, Houston, TX.
University of Alabama at Birmingham, Birmingham, AL.
J Clin Oncol. 2024 Nov;42(31):3739-3750. doi: 10.1200/JCO-24-01487. Epub 2024 Aug 2.
Therapy-related myeloid neoplasm (t-MN) is a life-threatening complication of autologous peripheral blood stem cell (PBSC) transplantation for non-Hodgkin lymphoma (NHL). Previous studies report an association between clonal hematopoiesis (CH) in PBSC and risk of t-MN, but small samples precluded examination of risk within specific subpopulations.
Targeted DNA sequencing was performed to identify CH mutations in PBSC from a retrospective cohort of 984 patients with NHL (median age at transplant, 57 years; 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 the association between CH and t-MN among males and females.
CH was identified in PBSC from 366 patients (37.2%). t-MN developed in 60 patients after a median follow-up of 5 years. Presence of ≥2 mutations conferred increased t-MN risk (adjusted hazard ratio [aHR], 2.10; 95% CI [1.08 to 4.11]; = .029). CH was associated with increased t-MN risk among males (aHR, 1.83 [95% CI, 1.01 to 3.31]) but not females (aHR, 0.56 [95% CI, 0.15 to 2.09]). Although the prevalence and type of CH mutations in PBSC were comparable, the 8-year cumulative incidence of t-MN was higher among males vs. females with CH (12.4% 3.6%) but was similar between males and females without CH (4.9% 3.9%). Expansion of CH clones from PBSC to t-MN was seen only among males.
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.
治疗相关的髓系肿瘤（t-MN）是自体外周血干细胞（PBSC）移植治疗非霍奇金淋巴瘤（NHL）的一种危及生命的并发症。先前的研究报告称，PBSC 中的克隆性造血（CH）与 t-MN 的风险之间存在关联，但由于样本量小，无法在特定亚群中检查风险。
对来自 NHL 患者回顾性队列（984 例患者，中位年龄 57 岁，范围 18-78 岁）的 PBSC 进行靶向 DNA 测序，以鉴定 CH 突变。Fine-Gray 比例亚分布风险回归模型估计了 CH 突变数量与 t-MN 之间的关联，调整了人口统计学、临床和治疗变量。次要分析评估了 CH 与男性和女性之间 t-MN 的关联。
在 366 例患者（37.2%）的 PBSC 中发现了 CH。在中位随访 5 年后，60 例患者发生 t-MN。存在≥2 个突变会增加 t-MN 的风险（调整后的危险比 [aHR]，2.10；95%CI[1.08 至 4.11]；P =.029）。CH 与男性 t-MN 风险增加相关（aHR，1.83 [95%CI，1.01 至 3.31]），但与女性无关（aHR，0.56 [95%CI，0.15 至 2.09]）。尽管 PBSC 中 CH 突变的患病率和类型相似，但患有 CH 的男性与女性相比，t-MN 的 8 年累积发生率更高（12.4% 3.6%），而无 CH 的男性与女性之间相似（4.9% 3.9%）。仅在男性中观察到从 PBSC 到 t-MN 的 CH 克隆扩张。
在 NHL 男性患者中，自体移植后 PBSC 中存在 CH 突变会增加 t-MN 的风险，但在女性患者中则不然。导致 CH 进展为 t-MN 的风险存在性别差异的因素值得进一步研究。
