Gillis Nancy, Ebied Amr, Thompson Zachary J, Pidala Joseph A
Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL, United States; Department of Malignant Hematology, Moffitt Cancer Center and Research Institute, Tampa, FL.
Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL.
Haematologica. 2024 Dec 1;109(12):3952-3964. doi: 10.3324/haematol.2024.285392.
Hematopoietic cell transplantation (HCT) is the only potentially curative treatment option for many patients with hematologic malignancies. While HCT outcomes have improved drastically over the years, patients and clinicians continue to face numerous survivorship challenges, such as relapse, graft-versus-host disease, and secondary malignancies. Recent literature suggests that clonal hematopoiesis (CH), the presence of a recurrent somatic mutation in hematopoietic cells, in HCT patients or donors may be associated with outcomes in autologous and allogeneic HCT. Herein, we perform a review of the literature and summarize reported associations between CH and clinical outcomes in HCT. For commonly reported outcomes, we used meta-analysis methods to provide estimates of effect sizes when combining results. A total of 32 articles with relevant and independent contributions were included, covering both autologous (N=19) and allogeneic (N=13) HCT. The articles report variable risk for developing outcomes according to CH characteristics, patient disease status, and method of HCT. Using meta-analysis of available results, HCT outcomes with statistically significant effects by CH status include therapy-related myeloid neoplasms (odds ratio =3.65; 95% confidence interval [CI]: 2.18-6.10) and overall survival (hazard ratio [HR]=1.38; 95% CI: 1.20-1.58) in autologous HCT and relapse (HR=0.80; 95% CI: 0.68-0.94) in allogeneic HCT. However, heterogeneity, biases, and limitations in the literature provide challenges for informing the translation of CH to clinical decision- making. We conclude with a call to action and discussion of next steps to build upon the current literature and provide granularity to the true clinical impact of CH in the setting of HCT.
造血细胞移植（HCT）是许多血液系统恶性肿瘤患者唯一可能治愈的治疗选择。尽管多年来HCT的疗效有了显著改善，但患者和临床医生仍面临诸多生存挑战，如复发、移植物抗宿主病和继发性恶性肿瘤。最近的文献表明，HCT患者或供体中造血细胞存在复发性体细胞突变的克隆性造血（CH）可能与自体和异基因HCT的预后相关。在此，我们对文献进行综述，总结CH与HCT临床结局之间已报道的关联。对于常见的报道结局，我们在合并结果时使用荟萃分析方法来提供效应大小的估计值。共纳入32篇有相关独立贡献的文章，涵盖自体（N = 19）和异基因（N = 13）HCT。这些文章报道了根据CH特征、患者疾病状态和HCT方法发生结局的风险各不相同。通过对现有结果进行荟萃分析，CH状态具有统计学显著影响的HCT结局包括自体HCT中的治疗相关髓系肿瘤（优势比 = 3.65；95%置信区间[CI]：2.18 - 6.10）和总生存期（风险比[HR] = 1.38；95% CI：1.20 - 1.58），以及异基因HCT中的复发（HR = 0.80；95% CI：0.68 - 0.94）。然而，文献中的异质性、偏差和局限性为将CH转化为临床决策带来了挑战。我们最后呼吁采取行动，并讨论下一步措施，以在当前文献的基础上进一步深入研究，明确CH在HCT背景下的真实临床影响。
