年轻的半相合供者与年长的匹配无关供者在AML/MDS患者中的比较

Younger haploidentical donor versus older matched unrelated donor for patients with AML/MDS

AMERICAN JOURNAL OF HEMATOLOGY

影响因子:9.9

分区:医学1区 Top / 血液学2区

发表日期:2023 May

作者: Curtis Marcoux, David Marin, Jeremy Ramdial, Gheath AlAtrash, Amin M Alousi, Betul Oran, Partow Kebriaei, Uday R Popat, Katayoun Rezvani, Richard E Champlin, Elizabeth J Shpall, Rohtesh S Mehta

DOI: 10.1002/ajh.26870

摘要

最佳供者选择是成功异基因造血干细胞移植（HCT）的基础，而供者年龄影响匹配无关供者（MUD）和半相合供者HCT后的存活率。尽管最新研究显示MUD与半相合HCT的结果相似，但尚不清楚年轻半相合供者与年长MUD供者HCT后的结果是否存在差异。因此，我们进行了一项回顾性分析，比较接受年轻（≤35岁）半相合供者（n=494）或年长（>35岁）MUD（n=1005）HCT的骨髓发育异常综合征（MDS）和急性髓性白血病（AML）患者的结局。两组患者均接受了移植后环磷酰胺（PTCy）和常规移植物抗宿主病（GVHD）预防措施。在多变量分析中，使用年轻半相合供者与改善的整体生存率（风险比[HR] 0.81，95%置信区间[CI] 0.69-0.95，p=0.01）以及较低的II-IV级急性GVHD（HR 0.64，95%CI 0.53-0.77，p<0.001）、III-IV级急性GVHD（HR 0.37，95%CI 0.25-0.53，p<0.001）和慢性GVHD（HR 0.49，95%CI 0.40-0.60，p<0.001）发生率相关。在接受高强度预处理的患者中，复发率相似，但在年轻半相合供者接受减强度预处理的患者中更高（HR 1.49，95%CI 1.18-1.88，p=0.001）。年轻半相合组在移植后≥3个月的非复发死亡率明显较低（HR 0.59，95%CI 0.38-0.90，p=0.02）。我们的数据支持在MDS或AML患者中，采用PTCy的年轻半相合供者优于使用常规预防措施的年长MUD供者。未来还需进一步研究供者年龄在采用PTCy预防的半相合与MUD HCT中的作用。

Abstract

Optimal donor selection is fundamental to successful allogeneic hematopoietic cell transplantation (HCT), and donor age influences survival after both matched unrelated donor (MUD) and haploidentical donor HCT. Though recent studies have shown similar outcomes between MUD and haploidentical HCT, it is unknown if outcomes differ following HCT with younger haploidentical donors compared to HCT with older MUDs. Therefore, we performed a retrospective analysis comparing outcomes of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients who underwent HCT with younger (≤35 years) haploidentical donors (n = 494) or older (>35 years) MUDs (n = 1005). Patients in the haploidentical and MUD groups received post-transplant cyclophosphamide (PTCy) and conventional graft-versus-host-disease (GVHD) prophylaxis, respectively. In multivariate analysis, use of younger haploidentical donors was associated with improved overall survival (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.69-0.95, p = .01) and lower rates of grade II-IV acute GVHD (HR 0.64, 95% CI 0.53-0.77, p < .001), grade III-IV acute GVHD (HR 0.37, 95% CI 0.25-0.53, p < .001), and chronic GVHD (HR 0.49, 95% CI 0.40-0.60, p < .001). Relapse rates were similar among those who received myeloablative conditioning but were higher in patients of the younger haploidentical group who received reduced intensity conditioning (HR 1.49, 95%CI 1.18-1.88, p = .001). The younger haploidentical group had significantly lower non-relapse mortality ≥3 months post-HCT (HR 0.59, 95% CI 0.38-0.90, p = .02). Our data support the use of younger haploidentical donors with PTCy over older MUDs with conventional prophylaxis in patients with MDS or AML. Further studies on the importance of donor age in haploidentical and MUD HCT with PTCy prophylaxis are warranted.