Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University, Durham, North Carolina.
Duke University School of Medicine, Durham, North Carolina.
Transplant Cell Ther. 2021 Aug;27(8):669.e1-669.e8. doi: 10.1016/j.jtct.2021.05.002. Epub 2021 May 12.
Allogeneic hematopoietic stem cell transplantation (HCT) has the potential to cure hematologic malignancies but is associated with significant morbidity and mortality. Although deaths during the first year after transplantation are often attributable to treatment toxicities and complications, death after the first year may be due to sequelae of accelerated aging caused by cellular senescence. Cytotoxic therapies and radiation used in cancer treatments and conditioning regimens for HCT can induce aging at the molecular level; HCT patients experience time-dependent effects, such as frailty and aging-associated diseases, more rapidly than people who have not been exposed to these treatments. Consistent with this, recipients of younger cells tend to have decreased markers of aging and improved survival, decreased graft-versus-host disease, and lower relapse rates. Given that umbilical cord blood (UCB) is the youngest donor source available, we studied the outcomes after the first year of UCB transplantation versus matched related donor (MRD) and matched unrelated donor (MUD) transplantation in patients with hematologic malignancies over a 20-year period. In this single-center, retrospective study, we examined the outcomes of all adult patients who underwent their first allogeneic HCT through the Duke Adult Bone Marrow Transplant program from January 1, 1996, to December 31, 2015, to allow for at least 3 years of follow-up. Patients were excluded if they died or were lost to follow-up before day 365 after HCT, received an allogeneic HCT for a disease other than a hematologic malignancy, or received cells from a haploidentical or mismatched adult donor. UCB recipients experienced a better unadjusted overall survival than MRD/MUD recipients (log rank P = .03, median overall survival: UCB not reached, MRD/MUD 7.4 years). After adjusting for selected covariates, UCB recipients who survived at least 1 year after HCT had a hazard of death that was 31% lower than that of MRD/MUD recipients (hazard ratio, 0.69; 95% confidence interval, 0.47-0.99; P = .049). This trend held true in a subset analysis of subjects with acute leukemia. UCB recipients also experienced lower rates of moderate or severe chronic graft-versus-host disease (GVHD) and nonrelapse mortality, and slower time to relapse. UCB and MRD/MUD recipients experienced similar rates of grade 2-4 acute GVHD, chronic GHVD, secondary malignancy, and subsequent allogeneic HCT. UCB is already widely used as a donor source in pediatric HCT; however, adult outcomes and adoption have historically lagged behind in comparison. Recent advancements in UCB transplantation such as the implementation of lower-intensity conditioning regimens, double unit transplants, and ex vivo expansion have improved early mortality, making UCB an increasingly attractive donor source for adults; furthermore, our findings suggest that UCB may actually be a preferred donor source for mitigating late effects of HCT.
异基因造血干细胞移植(HCT)有治愈血液系统恶性肿瘤的潜力,但也与显著的发病率和死亡率相关。尽管移植后第一年的死亡通常归因于治疗毒性和并发症,但第一年之后的死亡可能是由于细胞衰老引起的加速衰老的后遗症。癌症治疗和 HCT 预处理方案中使用的细胞毒性疗法和辐射可在分子水平上诱导衰老;HCT 患者比未接受这些治疗的患者更快地经历脆弱和与衰老相关的疾病等时间依赖性效应。与此一致的是,接受年轻细胞的受体往往具有降低的衰老标志物和改善的存活率、降低的移植物抗宿主病和更低的复发率。鉴于脐带血(UCB)是可用的最年轻供体来源,我们在 20 年的时间内研究了血液系统恶性肿瘤患者 UCB 移植后第一年与匹配的亲缘供体(MRD)和匹配的无关供体(MUD)移植后的结果。在这项单中心回顾性研究中,我们检查了 1996 年 1 月 1 日至 2015 年 12 月 31 日期间通过杜克成人骨髓移植计划接受首次异基因 HCT 的所有成年患者的结果,以确保至少 3 年的随访。如果患者在 HCT 后第 365 天之前死亡或失访、接受除血液系统恶性肿瘤以外的疾病的异基因 HCT 或接受半相合或不匹配的成人供体的细胞,则将其排除在外。UCB 受体的未调整总体生存率优于 MRD/MUD 受体(对数秩 P=0.03,中位总体生存率:UCB 未达到,MRD/MUD 7.4 年)。在调整了选定的协变量后,HCT 后至少存活 1 年的 UCB 受体的死亡风险比 MRD/MUD 受体低 31%(风险比,0.69;95%置信区间,0.47-0.99;P=0.049)。这一趋势在急性白血病患者的亚组分析中成立。UCB 受体还经历了较低的中度或重度慢性移植物抗宿主病(GVHD)和非复发死亡率,以及较慢的复发时间。UCB 和 MRD/MUD 受体经历了相似的 2-4 级急性 GVHD、慢性 GVHD、继发性恶性肿瘤和随后的异基因 HCT 发生率。UCB 已广泛用作儿科 HCT 的供体来源;然而,与儿科相比,成人的结果和采用情况一直滞后。UCB 移植的最新进展,如实施低强度预处理方案、双单位移植和体外扩增,降低了早期死亡率,使 UCB 成为成人越来越有吸引力的供体来源;此外,我们的研究结果表明,UCB 实际上可能是减轻 HCT 晚期影响的首选供体来源。
Biol Blood Marrow Transplant. 2017-8-15
Biol Blood Marrow Transplant. 2014-10
J Nutr Health Aging. 2020
Bone Marrow Transplant. 2020-1
Obstet Gynecol. 2019-3
Hematology Am Soc Hematol Educ Program. 2018-11-30
Hematol Transfus Cell Ther. 2018
Biol Blood Marrow Transplant. 2018-2-14
ESMO Open. 2017-12-18