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Abstract：
T cell replete HLA-mismatched haploidentical transplantation (HIDT) with post-transplant cyclophosphamide is increasingly becoming an acceptable treatment approach for patients lacking timely access to a suitably matched related donor transplant (MRDT) or matched unrelated donor transplant (MUDT). Multiple recent registry and single-center studies have shown comparable overall survival (OS) and disease-free survival (DFS) rates among HIDT, MRDT, and MUDT with a significantly lower risk of acute and chronic graft-versus-host disease (GVHD) among HIDT recipients. Candidates for allogeneic hematopoietic stem cell transplantation (HSCT) often have access to multiple donor sources, and a relevant question is whether outcomes can be improved with a younger HLA-mismatched haploidentical donor (≤35 years) rather than an older matched related donor (≥35 years) or matched unrelated donor (≥35 years). We analyzed 406 consecutive allogenic HSCT recipients, with a median age of 54 years (range, 19 to 77), after a MRDT with a donor age of ≥35 years (n = 222), MUDT with a donor age of ≥35 years (n = 91), and HIDT with a donor age of ≤35 years (n = 93). Median follow-up time for survivors was 51.5 months. Compared with MRDT and MUDT, HIDT recipients had a similar median age at time of HSCT, hematopoietic cell transplant comorbidity index, disease risk index distribution, and donor recipient sex matching. The survival estimates and relapse incidence at 3 years post-HSCT were OS (64% for MRDT, 54% for MUDT, and 62% for HIDT), DFS (55% for MRDT, 44% for MUDT, and 58% for HIDT), Transplant related mortality (TRM) (19% for MRDT, 16% for MUDT, and 18% for HIDT), and relapse (26% for MRDT, 37% for MUDT, and 24% for HIDT). HIDT recipients had better 3-year relapse rates compared with MUDT recipients (24% versus 37%, P= .048), with similar DFS and OS in a univariate analysis. MRDT recipients had a better relapse rate (26% versus 37%, P = .042) compared with MUDT recipients. Recipients of HIDT also had significantly lower rates of moderate to severe chronic GVHD compared with MRDT and MUDT recipients (P = .01). Multivariable analysis showed no effect of donor on OS, DFS, relapse, and TRM. Recipients of HIDT from a young donor ≤35 years had similar OS, lower rates of chronic GVHD, and better chronic GVHD-free, relapse-free survival compared with patients undergoing transplantation with an MRD or a MUD donor ≥35 years. This study suggests that given a situation where a choice between a young haploidentical relative and an older matched unrelated donor is to be made, one can achieve similar survival with a haploidentical donor and significantly lower rates of chronic GVHD.
摘要：
T细胞充分的HLA不匹配的单倍体移植（HIDT）与移植后的环磷酰胺越来越成为无法及时获得适当匹配的相关供体移植（MRDT）或匹配的无关供体移植（MUDT）的患者的可接受的治疗方法。最近的多项注册和单中心研究表明，HIDT的总生存率（OS）和无病生存率（DFS）具有可比性。MRDT,和MUDT在HIDT受者中具有显著较低的急性和慢性移植物抗宿主病(GVHD)风险。异基因造血干细胞移植（HSCT）的候选人通常可以获得多个供体来源，一个相关的问题是,年轻的HLA不匹配单倍体供体(≤35岁)是否可以改善结局,而不是年龄较大的匹配相关供体(≥35岁)或匹配无关供体(≥35岁).我们分析了406名连续的同种异体HSCT接受者，平均年龄为54岁(范围，19至77），在供体年龄≥35岁(n=222)的MRDT之后，供体年龄≥35岁的MUDT（n=91），和供体年龄≤35岁的HIDT（n=93）。幸存者的中位随访时间为51.5个月。与MRDT和MUDT相比，HIDT接受者在HSCT时的中位年龄相似，造血细胞移植合并症指数，疾病风险指数分布，和捐赠者的性别匹配。HSCT后3年的生存率估计和复发率为OS（MRDT为64％，MUDT的54%，和62%的HIDT)，DFS（MRDT占55%，MUDT的44%，HIDT为58%)，移植相关死亡率（TRM）（MRDT为19％，MUDT为16%，HIDT为18%)，和复发（MRDT占26％，MUDT的37%，和24%的HIDT）。与MUDT接受者相比，HIDT接受者的3年复发率更高（24％对37％，P=.048)，在单变量分析中具有相似的DFS和OS。MRDT接受者有更好的复发率(26%对37%，P=.042）与MUDT收件人相比。与MRDT和MUDT接受者相比，HIDT接受者的中度至重度慢性GVHD发生率也显着降低（P=0.01）。多变量分析表明供体对OS没有影响，DFS,复发,和TRM。来自年轻捐赠者≤35岁的HIDT接受者有相似的OS，慢性GVHD的发生率较低，更好的无慢性GVHD，与接受MRD或MUD供者≥35岁移植的患者相比，无复发生存期。这项研究表明，考虑到在年轻的单倍体亲属和年龄较大的匹配无关供体之间进行选择的情况，使用单倍体相同的供体可以获得相似的存活率，并且慢性GVHD的发生率显着降低。
