Morton Lindsay M, Saber Wael, Baker K Scott, Barrett A John, Bhatia Smita, Engels Eric A, Gadalla Shahinaz M, Kleiner David E, Pavletic Steven, Burns Linda J
Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Center for International Blood and Marrow Transplant Research, Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Biol Blood Marrow Transplant. 2017 Mar;23(3):367-378. doi: 10.1016/j.bbmt.2016.09.005. Epub 2016 Sep 12.
Subsequent neoplasms (SN) after hematopoietic cell transplantation (HCT) cause significant patient morbidity and mortality. Risks for specific SN types vary substantially, with particularly elevated risks for post-transplantation lymphoproliferative disorders, myelodysplastic syndrome/acute myeloid leukemia, and squamous cell malignancies. This document provides an overview of the current state of knowledge regarding SN after HCT and recommends priorities and approaches to overcome challenges and gaps in understanding. Numerous factors have been suggested to affect risk, including patient-related (eg, age), primary disease-related (eg, disease type, pre-HCT therapies), and HCT-related characteristics (eg, type and intensity of conditioning regimen, stem cell source, development of graft-versus-host disease). However, gaps in understanding remain for each of these risk factors, particularly for patients receiving HCT in the current era because of substantial advances in clinical transplantation practices. Additionally, the influence of nontransplantation-related risk factors (eg, germline genetic susceptibility, oncogenic viruses, lifestyle factors) is poorly understood. Clarification of the magnitude of SN risks and identification of etiologic factors will require large-scale, long-term, systematic follow-up of HCT survivors with detailed clinical data. Most investigations of the mechanisms of SN pathogenesis after HCT have focused on immune drivers. Expansion of our understanding in this area will require interdisciplinary laboratory collaborations utilizing measures of immune function and availability of archival tissue from SN diagnoses. Consensus-based recommendations for optimal preventive, screening, and therapeutic approaches have been developed for certain SN after HCT, whereas for other SN, general population guidelines are recommended. Further evidence is needed to specifically tailor preventive, screening, and therapeutic guidelines for SN after HCT, particularly for unique patient populations. Accomplishment of this broad research agenda will require increased investment in systematic data collection with engagement from patients, clinicians, and interdisciplinary scientists to reduce the burden of SN in the rapidly growing population of HCT survivors.
造血细胞移植（HCT）后的继发性肿瘤（SN）会导致患者出现严重的发病和死亡情况。特定类型SN的风险差异很大，其中移植后淋巴细胞增殖性疾病、骨髓增生异常综合征/急性髓系白血病和鳞状细胞恶性肿瘤的风险尤其升高。本文概述了目前关于HCT后SN的知识现状，并提出了优先事项以及克服理解方面的挑战和差距的方法。许多因素被认为会影响风险，包括患者相关因素（如年龄）、原发性疾病相关因素（如疾病类型、HCT前治疗）以及HCT相关特征（如预处理方案的类型和强度、干细胞来源、移植物抗宿主病的发生）。然而，对于这些风险因素中的每一个，仍存在理解上的差距，特别是对于当前时代接受HCT的患者，因为临床移植实践有了重大进展。此外还不清楚非移植相关风险因素（如种系遗传易感性、致癌病毒、生活方式因素）的影响。要明确SN风险的程度并确定病因，需要对HCT幸存者进行大规模、长期、系统的随访，并提供详细的临床数据。大多数关于HCT后SN发病机制的研究都集中在免疫驱动因素上。要扩大我们在这一领域的理解，需要跨学科实验室合作，利用免疫功能测量方法和SN诊断时存档组织的可用性。对于HCT后的某些SN，已经制定了基于共识的最佳预防、筛查和治疗方法建议，而对于其他SN，则建议遵循一般人群指南。需要更多证据来专门为HCT后的SN制定预防、筛查和治疗指南，特别是针对独特的患者群体。要完成这一广泛的研究议程，需要增加对系统数据收集的投入，患者、临床医生和跨学科科学家都要参与进来，以减轻HCT幸存者快速增长群体中SN的负担。
