目的 探讨异基因外周血干细胞移植(allo-PBSCT)后急性移植物抗宿主病(aGVHD)和慢性GVHD (cGVHD)的严重程度对白血病患者预后的影响及发生的相关危险因素.方法 回顾性分析2001年1月1日至2011年12月31日接受allo-PBSCT的231例白血病患者的临床资料.分析aGVHD、cGVHD的发生率及其对患者移植后总生存(OS)率、无病生存(DFS)率、移植相关死亡(TRM)率和复发率(RR)的影响.结果 ①可评估的224例患者中85例发生aGVHD,其中Ⅰ度46例,Ⅱ度25例,Ⅲ~Ⅳ度14例.生存100 d以上者213例,109例发生cGVHD,其中局限型84例,广泛型25例.②0~Ⅰ度aGVHD患者3年OS和DFS率高于Ⅱ~Ⅳ度aGVHD患者(分别为69.5%和60.7%对33.6%和33.7%,P值均<0.01);前者3年TRM率低于后者(15.0%对56.7%,P<0.01).③局限型cGVHD患者5年OS率高于无cGVHD及广泛型cGVHD患者(79.8%对55.6%,P<0.01;79.8%对56.4%,P=0.038);局限型cGVHD患者5年TRM率低于广泛型cGVHD患者(14.1%对41.1%,P=0.018);无cGVHD患者5年RR不仅高于局限型cGVHD患者(47.2%对10.9%,P<0.01),也高于广泛型cGVHD患者(47.2%对12.4%,P=0.007).④多因素分析提示供者类型、清髓性预处理是allo-PBSCT后发生aGVHD的主要危险因素;而aGVHD又是发生cGVHD的唯一危险因素.结论 aGVHD对白血病患者allo-PBSCT后长期生存有明显不良影响,尤其是Ⅲ~Ⅳ度aGVHD对患者的影响更加显著;而局限型cGVHD则是患者长期生存的有益因素,可能与之伴随的移植物抗白血病效应降低白血病复发相关.
Objective To analyze the impact of the occurrence and severity of acute and chronic graft versus host disease (GVHD) on the long-term outcome of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for leukemia. Methods A total of 231 patients with leukemia, who underwent allo-HSCT in Changhai Hospital from Jan 1st, 2001 to Dec 31th, 2011, were retrospectively analyzed. The overall survival (OS), disease-free survival (DFS), transplantation-related mortality (TRM) and relapse rate (RR) were estimated according to the degree of acute and chronic GVHD. Results (1) Among the 224 assessable patients, aGVHD was observed in 85 patients, in which 46 developed grade Ⅰ, 25 grade Ⅱ and 14 grade Ⅲ -Ⅳ. A total of 213 patients who survived beyond 100 days, cGVHD was observed in 109 patients, in which 84 developed limited cGVHD and 25 extensive cGVHD. (2)The incidence of 3-year OS and EFS of patients with aGVHD grade 0- Ⅰ was significantly higher than that of grade Ⅱ -Ⅳ (69.5% vs 33.6%, P〈0.01; 60.7% vs 33.7%, P〈0.01 ). The 3-year TRM of patients with 0- Ⅰ grade aGVHD was significantly lower than that of the grade Ⅱ -Ⅳ group ( 15.0% vs56.7%, P〈0.01 ). (3)The 5-year OS of patients with limited cGVHD was higher than patients without or with extensive cGVHD (79.8% vs 55.6% and 56.4%, P〈0.0I and P=0.038, respectively). The 5-year TRM in patients with extensive cGVHD was higher than patients with limited cGVHD (14.1% vs 41.1%, P=- 0.018). However, the 5- year RR in patients without cGVHD was higher than patients with limited cGVHD or extensive cGVHD (47.2% vs 10.9% and 12.4%, P〈0.01 and P=0.007, respectively). (4) The COX analysis showed that unrelated donor and myeloablative conditioning regimen were main factors affecting aGVHD; Meanwhile, aGVHD was the only factor affecting the cGVHD. Conclusion Our results showed that the patients with acute GVHD tended to have poor outcomes, especially with grade Ⅲ-Ⅳ. On the contrary,