巴利昔单抗在骨髓移植中防治急性移植物抗宿主病和免疫功能重建中的作用

Effect of anti-CD25 monoclonal antibody for prophylaxis and therapy of acute GVHD and immune reconstitution following HLA haplotype related T-cell undepleted allogeneic bone marrow transplantation

目的 探讨抗CD25单克隆抗体（巴利昔单抗）在单倍体未去除T细胞的骨髓移植中防治重度急性移植物抗宿主病（aGVHD）的作用以及对免疫重建的影响。方法 1999年2月至2004年3月，对87例白血病患者进行了HLA单倍体未去T细胞的亲缘骨髓移植，其中2000年9月以前移植的15例受者预处理没有使用巴利昔单抗（对照组），2000年11月以后的72例预处理中加用巴利昔单抗（单抗组）。用流式细胞分析仪对受者移植术后1、3、6、9、12、18、24个月的外周血淋巴细胞亚群进行动态测定，对两组的结果进行比较。结果 移植后单抗组和对照组Ⅱ～Ⅳ度aGVHD的发生率分别为12．5％和33．3％（P=0.045）；与aGVHD相关的死亡率分别为6．9％和20％，两组差异有统计学意义。单抗组中9例临床诊断为Ⅱ～Ⅳ度aGVHD的患者因激素耐药再次使用巴利昔单抗治疗，缓解6例（66．7％），部分缓解2例，无效1例。移植后两组CD4^＋ T细胞的恢复均迟缓。单抗组CD4^＋ T细胞＞200个／μ1的时间为移植后6个月，在移植后18个月绝对数恢复正常。CD3^＋、CD8^＋和CDl9^＋ B细胞在9～12个月恢复正常水平，两组淋巴细胞亚群的恢复情况差异无统计学意义。结论 使用抗CD25单克隆抗体预防和治疗受者严重的aGVHD有一定疗效；受者白血病的复发率和移植后的感染率无明显增加；对骨髓移植后淋巴细胞亚群数量的重建无明显的影响。

Objective To investigate the contribution of a novel anti-CD25 （IL-2 receptor α） monoclonal antibody, Basiliximab, on reducing the incidence of acute GVHD and the recovery kinetics of immune reconstitution. Methods Eighty-seven consecutive high risk leukemia patients （age 3-50 years） underwent haploidentical G-CSF primed bone marrow transplantation without ex-vivo T cell depletion. Seventy-two patients underwent the transplants with the addition of CD25 mAb （Basiliximab Novartis） for GVHD prophylaxis designated as CD25 mAb group. The remaining 15 patients without Basiliximab for GVHD prophylaxis served as the control group. By using flow cytemetry （FCM）, lymphocyte subsets of some recipients were detected at 1st, 3rd, 6th, 9th, 12th, 18th and 24th month after BMT. Results All patients achieved trilineage engraftment. The incidence of grade Ⅱ-Ⅳ GVHD- was 12.5% vs 33.3% respectively with the Basiliximab treated vs non-treated group. The GVHD- related mortality was 6.9% vs 20% respectively in Basiliximab group vs control group. Eight of 9 patients were responded to Basiliximab, 6/9 （66. 7% ） had a complete response （CR） of acute GVHD, 2/9 had a partial response and 1/9 had no response. Three deaths were acute GVHD related. Five of 6 patients in GVHD CR were alive in leukemia-free situation. Rate of relapse and mortality of infection had no statistically significant difference between two groups （P〉0.05）. It was noted that the number of CD4^＋ T cells was less significantly throughout the 18 months after BMT in two groups. The time to reach 200 CD4^＋ cells/μ1 was 6 months, and that to reach normal number of CD4^＋ was 18 months. Median time to reach normal CD3^＋ CD8^＋ and CD19^＋ was 9-12 months, and there was no significant difference between two groups. Conclusions The incidence of severe lethal aGVHD and GVHD-related deaths tended to be less in patients with Basiliximab group than un-treated group in haploidentical BMT. It is useful to use Basiliximab to treat sever GVHD. CD4^＋ reconstitution appeared significantly delayed in two groups. CD4^＋ reconstitution is crucial to control post transplant opportunistic infections and leukemia relapse. Nevertheless, there was no significant difference in immune reconstitution and the incidence of infection and relapse between the two groups.