雷帕霉素治疗难治性广泛性慢性移植物抗宿主病

背景：难治性广泛性慢性移植物抗宿主病是异基因造血干细胞移植晚期的主要并发症，目前一线治疗药物为糖皮质激素，但对于糖皮质激素治疗无效或激素依赖的患者临床上尚缺乏有效且长期使用毒副作用较小的治疗方法。目的：观察雷帕霉素在治疗糖皮质激素无效或激素依赖的难治性广泛性慢性移植物抗宿主病中的临床疗效及毒副作用。方法：从1998年1月至2012年6月在中山大学附属第三医院血液科增加72例接受异基因造血干细胞移植患者中发现5例经糖皮质激素治疗无效或激素依赖的难治性广泛性慢性移植物抗宿主病的患者给予雷帕霉素口服，观察治疗效果及使用过程中出现的毒副作用。结果与结论：使用雷帕霉素后5例患者中1例症状获得完全缓解，3例明显改善，1例病情稳定。服用雷帕霉素最长时间为14个月，中位时间为9．4个月（4—14个月）。随访中位时间为18个月，随访期间5例患者均存活。使用过程中毒副作用轻，1例患者出现高脂血症，1例出现轻度贫血，未出现肝功能损害及高血糖。说明雷帕霉素在糖皮质激素治疗无效或激素依赖的难治性广泛性慢性移植物抗宿主病的治疗上有较好的疗效，且血液学毒性、肝功能损害、高血脂等不良反应较轻，多数患者能耐受。

Rapamycin for the treatment of refractory extensive chronic graft-versus-host disease

BACKGROUND： Refractory extensive chronic graft-versus-host disease is the mainly late complication of allogeneic hematopoietic stem cell transplantation and glucocorticoid is the first choice for the therapy. But now, there are few effective and less side effect methods for glucocorticoid-resistant or hormone-dependent patients. OBJECTIVE： To observe clinical effects and side effects of rapamycin on patients suffering from refractory extensive chronic graft-versus-host disease that resistant or dependent on glucocorticoid. METHODS： Seventy-two cases received a~logenic hematopoietic stem cells transplantation in the Department of Hematology, the Third Affiliated Hospital of Sun Yat-sen University between January 1998 and June 2012. Among them, five patients with refractory extensive chronic graft-versus-host disease were resistant to glucocorticoid or dependent on hormone, and these five patients were treated with rapamycin. The treatment effects and side effects were observed. RESULTS AND CONCLUSION： Among the five cases treated with rapamycin, one case received complete remission, three cases improved obviously, and the last one case received stable condition. The longest and median time for taking rapamycin was 14 and 9.4 （4-14） months respectively. The median follow-up time was 18 months, and five patients were all alive during the follow-up. The rapamycin had fewer side effects, hyperlipidemia and mild anemia were observed in one case separately, and the hepatic dysfunction and hyperglycemia were not observed. The results show that rapamycin has better effect on refractory extensive chronic graft-versus-host disease that resistant or dependent on glucocorticoid, and results in fewer side effects. Hematologic toxicity, hepatic dysfunction and high cholesterolcan can be tolerant well for patients.