Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; PhD Program in Public Health, Department of Medicine and Surgery, University of Milano-Bicocca, Italy.
Transplant Cell Ther. 2021 Sep;27(9):776.e1-776.e13. doi: 10.1016/j.jtct.2021.05.023. Epub 2021 Jun 1.
Post-transplantation cyclophosphamide (PTCy) has emerged as a promising graft-versus-host-disease (GVHD) prophylaxis in the setting of allogeneic hematopoietic stem cell transplantation (HSCT) from haploidentical donors and more recently in matched donor transplants. Herein, we describe our real-life experience on 249 adult patients undergoing allogeneic HSCT, from HLA-matched related (MRD), HLA-matched unrelated (MUD), or mismatched related donors (MMRD). Patients received unmanipulated peripheral blood stem cells (PBSCs), using a GVHD prophylaxis with PTCy and sirolimus. Mycophenolate mofetil was added in MUD or MMRD. In the HLA-matched donor group (MRD, n = 48, MUD, n = 50), the cumulative incidence of grades II-IV and III-IV acute GvHD was 23% and 9% at 100 days, respectively. The cumulative incidence of chronic GvHD was 25% at 2 years, severe only for 5% of the patients. The cumulative incidences of relapse and transplant-related mortality (TRM) were 31% and 9% at 2 years, respectively. The 2-year overall survival (OS) was 72% and progression-free survival (PFS) 60%; the composite endpoint of GvHD/relapse-free survival (GRFS) was 52% at 2 years. In the haploidentical donor group (n = 151), we documented a cumulative incidence of grades II-IV and III-IV acute GVHD of 35% and 20% at 100 days, respectively, and a cumulative incidence of chronic GvHD of 39% at 2 years. We observed severe chronic GVHD in 15% of the patients. The cumulative incidence of relapse and TRM was 32% and 25% at 2 years, respectively. The 2-year OS was 48%, whereas PFS was 43%; GRFS was 28% at 2 years. However, more patients in the haploidentical group presented high/very high disease risk index (DRI) and higher HCT-comorbidity index. In patients classified in the low-intermediate DRI, 2-year GRFS was 53% in MRD, 65% in MUD, and 46% in haploidentical HSCT (P = .33). Sirolimus-PTCy platform deserves further investigation as an alternative to calcineurin-inhibitor-based GVHD prophylaxis for all donor sources. In patients presenting a low-intermediate DRI, this strategy translates in relevant survival independently from the transplant source.
移植后环磷酰胺（PTCy）已成为异基因造血干细胞移植（HSCT）中同种异体造血干细胞移植（HSCT）和最近匹配供体移植中预防移植物抗宿主病（GVHD）的有希望的方法。在此，我们描述了我们在 249 名接受异基因 HSCT 的成年患者中的真实经验，这些患者来自 HLA 匹配的相关（MRD）、HLA 匹配的无关（MUD）或不匹配的相关供体（MMRD）。患者接受未经处理的外周血干细胞（PBSC），采用 PTCy 和西罗莫司进行 GVHD 预防。在 MUD 或 MMRD 中添加霉酚酸酯。在 HLA 匹配供体组（MRD，n=48，MUD，n=50）中，100 天时 II-IV 级和 III-IV 级急性 GvHD 的累积发生率分别为 23%和 9%。2 年时慢性 GvHD 的累积发生率为 25%，仅 5%的患者为重度。2 年时复发和移植相关死亡率（TRM）的累积发生率分别为 31%和 9%。2 年时总生存率（OS）为 72%，无进展生存率（PFS）为 60%；2 年时 GvHD/复发无事件生存率（GRFS）的累积发生率为 52%。在半相合供体组（n=151）中，我们记录了 100 天时 II-IV 级和 III-IV 级急性 GVHD 的累积发生率分别为 35%和 20%，2 年时慢性 GvHD 的累积发生率为 39%。我们观察到 15%的患者发生严重慢性 GVHD。2 年时复发和 TRM 的累积发生率分别为 32%和 25%。2 年时 OS 为 48%，而 PFS 为 43%；2 年时 GRFS 为 28%。然而，半相合组中更多的患者存在高/极高疾病风险指数（DRI）和更高的 HCT 合并症指数。在低中危 DRI 患者中，MRD、MUD 和半相合 HSCT 的 2 年 GRFS 分别为 53%、65%和 46%（P=.33）。西罗莫司-PTCy 平台值得进一步研究，作为钙调神经磷酸酶抑制剂为基础的 GVHD 预防方案的替代方案，用于所有供体来源。在具有低中危 DRI 的患者中，这种策略可独立于移植来源转化为相关生存。
