Rapamycin (sirolimus) for treatment of chronic graft-versus-host disease
Rapamycin (sirolimus) for treatment of chronic graft-versus-host disease
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DOI：
10.1016/j.bbmt.2004.10.004
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发表时间：
2005-01-01
影响因子：
4.3
通讯作者：
Chao, NJ
中科院分区：
文献类型：
--
作者：
Johnston, LJ;Brown, J;Chao, NJ
我们在19例慢性移植物抗宿主病（cGVHD）患者中进行了一项II期试验，使用雷帕霉素、钙调磷酸酶抑制剂和泼尼松，目的是控制cGVHD，减少泼尼松的使用，并确定该方案的安全性。雷帕霉素开始作为二线（n = 9）或超过二线（n = 10）治疗。中位随访时间为42个月，16例患者可评价反应。9例患者因依从性差/患者要求（n = 2）或不良事件（n = 7）而停用雷帕霉素，其中3例因停药少于或等于1个月或不依从而无法评估。不良事件包括血清肌酐≥ 2.4 mg/dL（n = 4）、溶血性尿毒症综合征（n = 2）和恶性肿瘤复发（n = 1）。16例可评价患者中有15例出现临床缓解。16例中有5例停药，1例死于复发性白血病。在10名继续使用雷帕霉素的患者中，2名患者停止使用雷帕霉素，1名患者成功地减少了所有全身性免疫抑制。10例患者中有3例发生进行性cGVHD，免疫抑制逐渐减弱;所有患者均对恢复既往药物治疗有反应。10例患者中有4例在接受雷帕霉素治疗时需要替代治疗持续性或进行性cGVHD;泼尼松停药（n = 2）或在疾病进展时逐渐减少（n = 2）。19例原始患者中有17例存活。1例死于恶性肿瘤复发，1例死于充血性心力衰竭。在雷帕霉素作为cGVHD治疗的这份报告中，有雷帕霉素疗效的证据。考虑到所描述的显著毒性，在未来的cGVHD试验中应继续研究雷帕霉素和钙调磷酸酶抑制剂的改变给药。(C)2005年美国血液和骨髓移植学会。
We conducted a phase II trial in 19 chronic graft-versus- host disease (cGVHD) patients with rapamycin, calcineurin inhibitors, and prednisone with the goals of controlling cGVHD, reducing prednisone use, and defining the safety of this regimen. Rapamycin was begun as second-line (n = 9) or more than second-line (n = 10) therapy. With a median follow-up of 42 months, 16 patients were evaluable for response. Nine patients discontinued rapamycin because of poor compliance/patient request (n = 2) or an adverse event (n = 7), 3 of whom were not evaluable because of withdrawal at less than or equal to1 month or noncompliance. The adverse events included serum creatinine greater than or equal to2.4 mg/dL (n = 4), hemolytic uremic syndrome (n = 2), and relapse of malignancy (n = 1). Fifteen of 16 evaluable patients had a clinical response. Five of the 16 discontinued the drugs and 1 died of relapsed leukemia. Of the 10 patients who continued rapamycin, 2 discontinued and 1 successfully tapered all systemic inmunosuppression. Three of the 10 developed progressive cGVHD with tapering immunosuppression; all responded to resumption of prior medications. Four of the 10 patients required alternate therapy for persistent or progressive cGVHD while receiving rapamycin; prednisone was discontinued (n = 2) or tapered at the time of progressive disease (n = 2). Seventeen of 19 original patients were alive. One death was due to relapsed malignancy, and 1 was due to congestive heart failure. In this report of rapamycin as cGVHD therapy, there is evidence of rapamycins efficacy. Given the significant toxicities described, investigation of altered administration of rapamycin and calcineurin inhibitors should be pursued in future cGVHD trials. (C) 2005 American Society for Blood and Marrow Transplantation.