Melissa A Richard, Chengcheng Yan, Yanjun Chen, Christopher J Gibson, Rashi Kalra, Alysia Bosworth, David K Crossman, Purnima Singh, Lindsey Hageman, Jianbo He, Saro H Armenian, Julie Vose, Daniel J Weisdorf, Benjamin L Ebert, Yutaka Yasui, Changde Cheng, Stephen J Forman, Smita Bhatia, Ravi Bhatia
{"title":"Sex-Based Differences in Risk of Therapy-Related Myeloid Neoplasms.","authors":"Melissa A Richard, Chengcheng Yan, Yanjun Chen, Christopher J Gibson, Rashi Kalra, Alysia Bosworth, David K Crossman, Purnima Singh, Lindsey Hageman, Jianbo He, Saro H Armenian, Julie Vose, Daniel J Weisdorf, Benjamin L Ebert, Yutaka Yasui, Changde Cheng, Stephen J Forman, Smita Bhatia, Ravi Bhatia","doi":"10.1200/JCO-24-01487","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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]; <i>P</i> = .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% <i>v</i> 3.6%) but was similar between males and females without CH (4.9% <i>v</i> 3.9%). Expansion of CH clones from PBSC to t-MN was seen only among males.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521772/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/JCO-24-01487","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/2 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: 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.
Methods: 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.
Results: 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]; P = .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% v 3.6%) but was similar between males and females without CH (4.9% v 3.9%). Expansion of CH clones from PBSC to t-MN was seen only among males.
Conclusion: 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.
背景:治疗相关髓样肿瘤(t-MN)是自体外周血干细胞(PBSC)移植治疗非霍奇金淋巴瘤(NHL)的一种威胁生命的并发症。先前的研究报告称,PBSC中的克隆造血(CH)与t-MN风险之间存在关联,但由于样本较少,无法对特定亚人群的风险进行检测:方法:对984名NHL患者(移植时中位年龄为57岁;范围:18-78岁)的PBSC进行靶向DNA测序,以确定CH突变。细灰比例亚分布危险回归模型估计了CH突变数量与t-MN之间的关系,并对人口统计学、临床和治疗变量进行了调整。二次分析评估了CH与男性和女性t-MN之间的关系:中位随访5年后,60名患者出现了t-MN。出现≥2个突变会增加t-MN风险(调整后危险比[aHR]=2.10,95%置信区间[CI]=1.08-4.11,P=0.029)。CH与男性(aHR=1.83,95%CI=1.01-3.31)而非女性(aHR=0.56,95%CI=0.15-2.09)的t-MN风险增加有关。虽然PBSC中CH突变的发生率和类型相当,但男性与女性CH患者8年的t-MN累积发生率更高(12.4% vs. 3.6%),但男性与女性无CH患者的t-MN累积发生率相似(4.9% vs. 3.9%)。PBSC中的CH克隆扩增到t-MN仅见于男性:结论:PBSC中存在CH突变会增加男性NHL患者自体移植后出现t-MN的风险,但不会增加女性NHL患者自体移植后出现t-MN的风险。CH进展为t-MN风险的性别差异因素值得进一步研究。
期刊介绍:
The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.