Kim Haesook T, Liney Deborah J, Rizza Kristen, Cutler Corey S, Koreth John, Nikiforow Sarah, Shapiro Roman M, Kelkar Amar H, Gooptu Mahasweta, Romee Rizwan, Wu Catherine J, Antin Joseph H, Ritz Jerome, Soiffer Robert J, Ho Vincent T
Department of Data Science, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, Massachusetts, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, Massachusetts, USA.
Am J Hematol. 2025 Sep;100(9):1513-1522. doi: 10.1002/ajh.27741. Epub 2025 Jun 12.
Patients with myelofibrosis (MF) often have impaired engraftment after allogeneic hematopoietic cell transplantation (alloHCT). To determine whether posttransplant cyclophosphamide (PTCY) exerts a detrimental impact on engraftment, we compared clinical outcomes of all patients receiving PTCY (N = 49) and no-PTCY (N = 89) regimens as GVHD prophylaxis after first alloHCT for MF from 2016 to 2023. Median age was 64 in both groups, and baseline characteristics were balanced except that the PTCY group received more haploidentical transplants and were more likely to have secondary MF. Among engrafted individuals, median time to neutrophil engraftment was D + 18 for PTCY and D + 15 for no-PTCY (p < 0.0001). Median time to platelet recovery was D + 33.5 and D + 26 for PTCY and no-PTCY, respectively (p = 0.0006). The graft failure rate was higher for PTCY but did not reach statistical significance (27% for PTCY and 15% for non-PTCY, p = 0.095). The need for donor lymphocyte infusion, CD34 boost, or second transplant was significantly higher for PTCY (33% vs. 13% at 1-year, respectively, p = 0.004). Most cases of graft failure in both cohorts were due to prolonged cytopenias in the absence of relapse. While T-cell chimerism at D + 30 and D + 100 was robust after PTCY, the proportion of patients with granulocyte chimerism ≥ 90% at Day + 100 was significantly lower in PTCY (76% vs. 98.2%, respectively, p = 0.0028). All other outcomes were similar except for a significantly lower chronic GVHD rate in PTCY compared with no-PTCY (p = 0.0002). GVHD prophylaxis with PTCY in patients with MF is associated with delayed engraftment, lower donor granulocyte chimerism, and increased need for additional donor cell infusions after transplant without compromising survival.
骨髓纤维化(MF)患者在异基因造血细胞移植(alloHCT)后常出现植入受损的情况。为了确定移植后环磷酰胺(PTCY)是否对植入产生不利影响,我们比较了2016年至2023年期间首次alloHCT治疗MF后接受PTCY方案(N = 49)和非PTCY方案(N = 89)进行移植物抗宿主病(GVHD)预防的所有患者的临床结局。两组的中位年龄均为64岁,除PTCY组接受更多单倍体移植且更可能患有继发性MF外,基线特征均衡。在植入的个体中,PTCY组中性粒细胞植入的中位时间为移植后第18天(D + 18),非PTCY组为第15天(D + 15)(p < 0.0001)。PTCY组和非PTCY组血小板恢复的中位时间分别为D + 33.5天和D + 26天(p = 0.0006)。PTCY组的移植物失败率较高,但未达到统计学意义(PTCY组为27%,非PTCY组为15%,p = 0.095)。PTCY组对供体淋巴细胞输注、CD34增强或二次移植的需求显著更高(1年时分别为33%和13%,p = 0.004)。两个队列中的大多数移植物失败病例是由于在无复发情况下血细胞减少持续时间延长所致。虽然PTCY治疗后第30天和第100天的T细胞嵌合率较高,但PTCY组在第100天时粒细胞嵌合率≥90%的患者比例显著较低(分别为76%和98.2%,p = 0.0028)。除PTCY组的慢性GVHD发生率显著低于非PTCY组外(p = 0.0002),所有其他结局相似。MF患者采用PTCY进行GVHD预防与植入延迟、供体粒细胞嵌合率降低以及移植后对额外供体细胞输注的需求增加相关,但不影响生存率。