Miyakoshi Shigesaburo, Kami Masahiro, Tanimoto Tetsuya, Yamaguchi Takuhiro, Narimatsu Hiroto, Kusumi Eiji, Matsumura Tomoko, Takagi Shinsuke, Kato Daisuke, Kishi Yukiko, Murashige Naoko, Yuji Koichiro, Uchida Naoyuki, Masuoka Kazuhiro, Wake Atsushi, Taniguchi Shuichi
Department of Hematology, Toranomon Hospital, Tokyo, Minato-ku, Japan.
Transplantation. 2007 Aug 15;84(3):316-22. doi: 10.1097/01.tp.0000269796.23593.16.
Myeloablative cord blood transplantation (CBT) for adult patients offers a 90% chance of engraftment with a 50% rate of transplant-related mortality, mostly attributable to infection. We have demonstrated the feasibility of reduced-intensity CBT (RI-CBT) for adult patients, in which cyclosporine was used for acute graft-versus-host disease (GVHD) prophylaxis. Transplantation-related mortality (TRM) was 27% within 100 days. Therefore our objective was to evaluate the feasibility of RI-CBT with tacrolimus as GVHD prophylaxis for adult patients with hematologic malignancies.
Thirty-four patients with a median age of 56.5 years (range; 22-68) with hematologic diseases underwent RI-CBT at Toranomon Hospital between November 2003 and September 2004. Preparative regimen comprised fludarabine 25 mg/m2 on days -7 to -3, melphalan 80 mg/m2 on day -2, and 4 Gy total body irradiation on day -1. GVHD prophylaxis was continuous intravenous infusion of tacrolimus 0.03 mg/kg, starting on day -1.
Thirty-one patients achieved neutrophil engraftment at a median of day 20. Median infused total cell dose was 2.4 x 10E7/kg (range; 1.6-4.8). Thirty-two patients achieved complete donor chimerism at day 60. Grade II-IV acute GVHD occurred in 45% of patients, with a median onset of day 26. Primary disease recurred in five patients, and TRM within 100 days was 12%. Estimated 1-year overall survival was 70%.
This study demonstrated the possible improvement in transplant-related mortality by tacrolimus as GVHD prophylaxis in adult RI-CBT recipients.
成人患者的清髓性脐血移植（CBT）有90%的植入机会，但移植相关死亡率为50%，主要原因是感染。我们已经证明了成人患者采用降低强度的CBT（RI-CBT）的可行性，其中环孢素用于预防急性移植物抗宿主病（GVHD）。100天内的移植相关死亡率（TRM）为27%。因此，我们的目标是评估以他克莫司作为GVHD预防措施对血液系统恶性肿瘤成人患者进行RI-CBT的可行性。
2003年11月至2004年9月期间，34例中位年龄为56.5岁（范围22-68岁）的血液系统疾病患者在虎之门医院接受了RI-CBT。预处理方案包括在-7至-3天给予氟达拉滨25mg/m²，在-2天给予美法仑80mg/m²，在-1天给予4Gy全身照射。GVHD预防措施是从-1天开始持续静脉输注他克莫司0.03mg/kg。
31例患者在中位第20天实现中性粒细胞植入。中位输注的总细胞剂量为2.4×10⁷/kg（范围1.6-4.8）。32例患者在第60天实现完全供体嵌合。45%的患者发生II-IV级急性GVHD，中位发病时间为第26天。5例患者原发性疾病复发，100天内的TRM为12%。估计1年总生存率为70%。
本研究表明，在成人RI-CBT受者中，他克莫司作为GVHD预防措施可能会改善移植相关死亡率。
