应用霉酚酸酯治疗异基因造血干细胞移植后移植物抗宿主病

目的 回顾性分析总结霉酚酸酯(MMF)联合环孢素A或普乐可复(CsA/FKS06)治疗异基因造血干细胞移植后急、慢性移植物抗宿主病(GVHD)的安全性和有效性.方法 44例患者中,确诊白血病的38例;骨髓异常增生综合征(MDS)4例,重症再生障碍性贫血(SAA)2例,移植方式包括同胞相合移植23例,亲缘间配型不合移植21例.预处理方案,白血病和MDS患者采用改良马利兰加环磷酰胺(BuCy)预处理方案;SAA患者采用cy加抗胸腺细胞球蛋白(ATG)方案.GVHD预防采用标准的CsA加短程甲氨蝶呤(MTX)联合MMF的预防方案.急性GVHD(aGVHD)和慢性GVHD(cGVHD)诊断和分级采用国际公认标准.MMF分别作为一线联合CsA/FKS06及皮质激素(PSE)抗GVHD治疗,以及二线挽救性抗GVHD联合治疗.结果 移植后15例患者诊为aGVHD,29例诊为cGVHD.19例(44.1%)患者应用MMF联作为一线抗GVHD治疗;25例作为二线挽救性治疗.aGVHD总有效率80%,完全有效(CR)33.33%,部分有效(PR)46.66%,其中一线治疗有效率70%,二线治疗有效率100%,有效病例中58.3%的患者实现PSE减量.cGVHD总有效率86.2%,其中CR 41.37%,PR 44.83%,一线治疗有效率100%,二线治疗有效率84.21%,有效病例中70.83%患者实现PSE减量.应用MMF联合方案过程中7例出现副作用,均为可逆性.感染并发症34.09%,仅1例因并发肺部感染和间质性肺炎而死亡.中位随访期22(10～65)个月,36例(81.82%)患者存活.结论 MMF联合CsA/FK506可有效治疗aGVHD和cGVHD,并具有较好的耐受性.

Mycophenolate mofetil in treatment of graft-versus-host disease after allogeneic hemtopoietic cell transplantation: analysis of 44 cases

Objective To retrospectively investigate the safety and efficacy of mycofenolate mofetil(MMF) in combination with cyclosporine A (CSA) or tacrolimus (FKS06) in the treatment of graft-versus-host disease(GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods 44 patientswith various hematological diseases underwent allo-HSCT: 23 received transplant from HLA-matched siblings and 21 from mismatched related donors. The conditioning regimens included modified busalphan plus cyclophosphamide (Cy) regimen for the patients diagnosed as with leukemia and myelodysplastic syndrome (MDS), and Cy plus antihuman thymocyte globulin (ATG) for severe aplastic anemia (sAA). Cyclosporine A (CsA), short term methotrexate (MTX), and MMF were used for the prophylaxis of GVHD for all patients. Acute GVHD (aGVHD) and chronic GVHD (cGYHD) were diagnosed according to the international commonly accepted GVHD diagnostic criteria. MMF was added to the standard C-sA/FK506 with prednisone (PSE) as either the first line therapy, or the second line salvage therapy. Results 15 patients were diagnosed as with aGVHD, and 29 with cGVHD. MMF was administrated as a first-line therapy drug in 19 patients and as a second-line therapy drug in 25 patients. For aGVHD the overall response rate was 80% with a complete response (CR) rate of 33.33% and a partial response (PR) rate of 46.66%. The response rates were 70% and 100% respectively for the first line and second line therapy. In 58.3% of the responsive patients the daily dose of PSE could be reduced. For chronic GVHD the overall response rate was 86.2% with a CR rate of 41.37% and a PR rate of 44.83%, and the response rate were 100% and 84.21% for the first and second line therapy respectively. PSE taper was realized in 70.83% of the responsive patients. Side effects occurred in 7 patients, all reversible. The infectious complication rate was 34.09%, only one patient died of interstitial pneumonia. The follow-up of 22 months ( 10 ～ 65 months) showed that 36 patients (81.82%) survived. Conclusion MMF combined with CSA/FKS06 is effective and well-tolerated in treatment for aGVHD and cGVHD.