CsA,MTX,MMF联合ATG预防非亲缘供者外周血造血干细胞移植后GVHD的疗效观察

Prophylactic Effect of CsA,MTX,MMF Combined with ATG on GVHD in Patients Underwent Unrelated Peripheral Blood Hematopoietic Stem Cell Transplantation

本研究旨在探讨非亲缘供者外周血造血干细胞移植(URD-PBSCT)后的移植物抗宿主病(GVHD)预防方法、疗效及其对患者生存、复发的影响。对我院HLA高分辨相合或1个位点不合URD-PBSCT患者33例的临床资料进行总结,主要比较了不同GVHD防治方法下的GVHD发生率、疾病的复发率及患者的生存率。GVHD防治方法:环孢素A(CsA)+短疗程甲氨喋呤(MTX)+霉酚酸酯(MMF)+抗胸腺细胞球蛋白(URD-ATG组),其中13例加用CD25单克隆抗体(URD-ATG+CD25组)。结果显示,移植后所有患者100%植入,造血重建顺利。URD-ATG+CD25组、URD-ATG组急性GVHD的发生率分别为23.07%、45%%,慢性GVHD的发生率分别为0和47.4%,后者均显著高于前者(p<0.05);疾病的复发率分别为53.84%、15%,前者显著高于后者(p<0.05)。根据移植前患者疾病状态(稳定、进展)分层分析显示,进展期疾病的复发率显著高于稳定期(p<0.01),而URD-ATG+CD25组进展期疾病的复发率高达100%。URD-ATG+CD25组和URD-ATG组患者的1年总生存率(OS)分别为53.8%、75%;5年OS分别为38.5%、65%,URD-ATG组高于URD-ATG+CD25组(p<0.05);同时移植前疾病进展期患者的生存率显著下降。结论:在HLA相合或1个位点不合的URD-PBSCT中采用CsA+MTX+MMF+ATG的GVHD防治措施是安全可行的,对于进展期患者可考虑进一步减少ATG用量以减少复发,提高存活。

This study was aimed to investigate the prophylactic effect of CsA, MTX and MMF combined with ATG on graft versus host disease （GVHD） after unrelated donor peripheral blood hematopoietic stem cell transplantation （URD-PBHSCT）. 33 patients underwent URD-PBHSCT with unrelated donor of HLA matched or 1 locus mismatched. The clinical data of all cases were retrospectively analyzed. URD-PBHSCT recipients received cyclosporin A ＋ short term MTX ＋ mycophenolatemofetil （MMF） ＋ antithymocyte globulin to prevent GVHD（ URD-ATG group）, while 13 out of 33 patients were given additionally anti-CD25 antibody （ URD-ATG ＋ CD25 group）. The results showed that engraftment was successfully achieved in 100% of all patients. In URD-ATG ＋ CD25 group and URD-ATG group, the incidence of aGVHD were 23.07% and 45%, the incidence of cGVHD were 0 and 47.4% respectively. The latter was significantly higher than the former （p 〈 0.05 ）. The relapse rate in URD-ATG ＋ CD25 group and URD-ATG group were 53.84% and 15% respectively, the former was significantly higher than the latter （p 〈 0.05 ）. The analysis on disease status of patients before transplantation displayed that the relapse rate of patients in progression status was significantly higher than that of patients in stable status （p 〈 0.01 ）, while the relapse rate of patients in progression status in URD-ATG ＋ CD25 group reached to 100%. The overall survival （OS） at 1 year of patients in URD - ATG ＋ CD25 group and URD-ATG group were 53.8% and 75% respectively, the OS at 5 years of patients in URD-ATG ＋ CD25 group and URD-ATG group were 38.8% and 65% respectively, the OS of patients in URD-ATG group was higher than that of patients in URD-ATG ＋ CD25 group （p 〈 0.05 ）. Simultaneously the OS of patients with progression status before transplantation diclined obviously. It is concluded that adopting CsA ＋ MTX ＋ MMF ＋ ATG as the prophylaxis of GVHD for UDR-PBSCT is effective. Reducing the dose of ATG may be good for patient in progression status.