Marcoux Curtis, Marin David, Ramdial Jeremy, AlAtrash Gheath, Alousi Amin M, Oran Betul, Kebriaei Partow, Popat Uday R, Rezvani Katayoun, Champlin Richard E, Shpall Elizabeth J, Mehta Rohtesh S
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Am J Hematol. 2023 May;98(5):712-719. doi: 10.1002/ajh.26870. Epub 2023 Feb 13.
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.
最佳供体选择是异基因造血细胞移植（HCT）成功的基础，供体年龄会影响匹配无关供体（MUD）和单倍体相合供体HCT后的生存率。尽管最近的研究表明MUD和单倍体相合HCT的结果相似，但与年龄较大的MUD供体HCT相比，年龄较小的单倍体相合供体HCT后的结果是否不同尚不清楚。因此，我们进行了一项回顾性分析，比较接受年龄较小（≤35岁）单倍体相合供体（n = 494）或年龄较大（>35岁）MUD供体（n = 1005）HCT的骨髓增生异常综合征（MDS）和急性髓系白血病（AML）患者的结果。单倍体相合组和MUD组的患者分别接受移植后环磷酰胺（PTCy）和传统的移植物抗宿主病（GVHD）预防。在多变量分析中，使用年龄较小的单倍体相合供体与总生存率提高相关（风险比[HR] 0.81，95%置信区间[CI] 0.69 - 0.95，p = 0.01），II-IV级急性GVHD发生率较低（HR 0.64，95% CI 0.53 - 0.77，p < 0.001），III-IV级急性GVHD发生率较低（HR 0.37，95% CI 0.25 - 0.53，p < 0.001），慢性GVHD发生率较低（HR 0.49，95% CI 0.40 - 0.60，p < 0.001）。接受清髓性预处理的患者复发率相似，但接受减低强度预处理的年龄较小的单倍体相合组患者复发率较高（HR 1.49，95%CI 1.18 - 1.88，p = 0.001）。年龄较小的单倍体相合组在HCT后≥3个月时非复发死亡率显著较低（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，使用年龄较小的单倍体相合供体联合PTCy优于使用年龄较大的MUD供体联合传统预防措施。有必要进一步研究供体年龄在采用PTCy预防的单倍体相合和MUD HCT中的重要性。
