PDF(Pubmed)
Abstract：
Post-transplant cyclophosphamide (PTCY) alone as graft-versus-host disease (GVHD) prophylaxis may avoid/reduce short- and mid-term toxicities of drugs commonly used for GVHD prophylaxis, accelerate immune reconstitution after the graft to decrease infections and facilitate the early integration of adjunct maintenance therapies to prevent relapse.
A prospective phase 2 study was designed in order to assess the feasibility and safety of PTCY as a sole GVHD prophylaxis in adult patients receiving a Baltimore-based reduced-intensity conditioning (RIC) peripheral blood (PB) allogeneic hematopoietic stem cell transplantation (Allo-HSCT) with a matched donor.
Patients were planned to be included stepwise up to 59 evaluable PTCY recipients, in order to be able to stop the protocol in case of excessive corticosteroid resistant grade 3-4 severe acute GVHD (aGVHD). Because a high incidence of grade 2-4 aGVHD was observed after analysis of the first 27 patients, the protocol was amended to test the addition of 1 day of anti-thymoglobulin to PTCY. In spite of this, the trial had to be stopped after 38 treated patients, because of an unacceptable rate of grade 3-4 aGVHD. Donors were matched related to 12 patients and unrelated to 26.
With a median follow-up of 29.6 months, 2-year overall, disease-free and GVHD-free relapse-free (GRFS) survivals were respectively 65.4%, 62.1% and 46.9%. Cumulative incidences of grade 2-4 and 3-4 aGVHD at day 100 were 52.6% and 21.1%, respectively, while that of moderate/severe chronic(c) GVHD was 15.7% at 2 years. Addition of ATG to PTCY did influence neither aGVHD, cGVHD nor GRFS.
Despite paradoxically good survivals, especially GRFS, this study failed to demonstrate that PTCY (± ATG) alone can be used for Baltimore-based RIC PB Allo-HSCT with matched donors. Other combinations should be tested to try and avoid long-term use of immunosuppressive drugs following Allo-HSCT in this setting.
A prospective phase 2 study was designed in order to assess the feasibility and safety of PTCY as a sole GVHD prophylaxis in adult patients receiving a Baltimore-based reduced-intensity conditioning (RIC) peripheral blood (PB) allogeneic hematopoietic stem cell transplantation (Allo-HSCT) with a matched donor.
Patients were planned to be included stepwise up to 59 evaluable PTCY recipients, in order to be able to stop the protocol in case of excessive corticosteroid resistant grade 3-4 severe acute GVHD (aGVHD). Because a high incidence of grade 2-4 aGVHD was observed after analysis of the first 27 patients, the protocol was amended to test the addition of 1 day of anti-thymoglobulin to PTCY. In spite of this, the trial had to be stopped after 38 treated patients, because of an unacceptable rate of grade 3-4 aGVHD. Donors were matched related to 12 patients and unrelated to 26.
With a median follow-up of 29.6 months, 2-year overall, disease-free and GVHD-free relapse-free (GRFS) survivals were respectively 65.4%, 62.1% and 46.9%. Cumulative incidences of grade 2-4 and 3-4 aGVHD at day 100 were 52.6% and 21.1%, respectively, while that of moderate/severe chronic(c) GVHD was 15.7% at 2 years. Addition of ATG to PTCY did influence neither aGVHD, cGVHD nor GRFS.
Despite paradoxically good survivals, especially GRFS, this study failed to demonstrate that PTCY (± ATG) alone can be used for Baltimore-based RIC PB Allo-HSCT with matched donors. Other combinations should be tested to try and avoid long-term use of immunosuppressive drugs following Allo-HSCT in this setting.
摘要：
背景：移植后环磷酰胺（PTCY）单独作为移植物抗宿主病（GVHD）的预防可以避免/减少常用于GVHD预防的药物的短期和中期毒性，加速移植后的免疫重建，以减少感染，并促进辅助维持疗法的早期整合，以防止复发。
目的：设计了一项前瞻性2期研究，以评估PTCY作为GVHD预防的可行性和安全性，用于接受巴尔的摩基础的低强度预处理（RIC）外周血（PB）异基因造血干细胞移植（Allo-HSCT）的成年患者。
方法：计划逐步纳入59名可评估的PTCY接受者，为了能够在过度的皮质类固醇耐药3-4级严重急性GVHD（aGVHD）的情况下停止该方案。因为在分析前27名患者后观察到2-4级aGVHD的高发病率，对方案进行了修改,以测试在PTCY中添加1天抗胸腺球蛋白.尽管如此,在38名患者接受治疗后，试验不得不停止，因为3-4级aGVHD的比率不可接受。捐赠者与12名患者相关，与26名患者无关。
结果：中位随访时间为29.6个月，2年整体,无病和无GVHD无复发(GRFS)生存率分别为65.4%,62.1%和46.9%。第100天2-4级和3-4级aGVHD的累积发生率分别为52.6%和21.1%，分别,而中度/重度慢性（c）GVHD在2年为15.7％。将ATG添加到PTCY并不影响aGVHD，cGVHD或GRFS。
结论：尽管生存异常良好，尤其是GRFS,这项研究未能证明PTCY（±ATG）可单独用于具有匹配供体的基于巴尔的摩的RICPBAllo-HSCT。在这种情况下，应测试其他组合，以尝试并避免在Allo-HSCT后长期使用免疫抑制药物。
目的：设计了一项前瞻性2期研究，以评估PTCY作为GVHD预防的可行性和安全性，用于接受巴尔的摩基础的低强度预处理（RIC）外周血（PB）异基因造血干细胞移植（Allo-HSCT）的成年患者。
方法：计划逐步纳入59名可评估的PTCY接受者，为了能够在过度的皮质类固醇耐药3-4级严重急性GVHD（aGVHD）的情况下停止该方案。因为在分析前27名患者后观察到2-4级aGVHD的高发病率，对方案进行了修改,以测试在PTCY中添加1天抗胸腺球蛋白.尽管如此,在38名患者接受治疗后，试验不得不停止，因为3-4级aGVHD的比率不可接受。捐赠者与12名患者相关，与26名患者无关。
结果：中位随访时间为29.6个月，2年整体,无病和无GVHD无复发(GRFS)生存率分别为65.4%,62.1%和46.9%。第100天2-4级和3-4级aGVHD的累积发生率分别为52.6%和21.1%，分别,而中度/重度慢性（c）GVHD在2年为15.7％。将ATG添加到PTCY并不影响aGVHD，cGVHD或GRFS。
结论：尽管生存异常良好，尤其是GRFS,这项研究未能证明PTCY（±ATG）可单独用于具有匹配供体的基于巴尔的摩的RICPBAllo-HSCT。在这种情况下，应测试其他组合，以尝试并避免在Allo-HSCT后长期使用免疫抑制药物。
