异基因造血干细胞移植治疗复发难治性淋巴瘤的临床研究

Clinical research of allogeneic hematopoietic stem cell transplantation for relapsed or refractory lymphoma

目的 探讨异基因造血干细胞移植（allo-HSCT）治疗复发难治性淋巴瘤的疗效和安全性.方法 北京军区总医院血液科2007年1月至2012年1月应用allo-HSCT共治疗7例复发难治性淋巴瘤患者,其中男4例,女3例,年龄18～ 48岁,平均年龄33.7岁.原发病为非霍奇金淋巴瘤6例,其中弥漫大B细胞淋巴瘤（DLBCL）2例,T淋巴母细胞淋巴瘤（T-LL）1例,皮肤结外鼻型NK/T细胞淋巴瘤（ENKTCL-N）1例,肝脾T细胞淋巴瘤（HSTCL）1例,伯基特淋巴瘤（BL）1例；霍奇金淋巴瘤1例,为混合细胞型.首次复发4例,2次及以上复发2例,原发难治1例；自体移植后复发2例（均为2次及以上复发者）；移植时有3例缓解,4例未取得缓解.供受者HLA全相合3例,HLA不全相合4例,采用骨髓加外周血干细胞联合移植,预处理均采用氟达拉滨替代环磷酰胺（Cy）的改良白消安（Bu）＋Cy方案,移植物抗宿主病（GVHD）的预防采用经典环孢素（CsA）和甲氨蝶呤（MTX）,移植后观察患者并发症和无病生存等情况.结果 6例患者能较好耐受预处理方案,均获造血重建,植入证据检测证实100％为完全供者造血,1例预处理后死亡.全部患者中位随访29.6个月（1～70个月）.共5例发生急性GVHD,4例发生慢性GVHD;死亡2例（因感染死亡1例、复发死亡1例）,其余5例患者无病生存,无病生存率为71.4％,最长无病生存时间已达70个月.结论 allo-HSCT治疗复发难治性淋巴瘤安全有效,可作为挽救治疗的关键技术,可在临床广泛开展.

Objective To explore the efficacy and safety in the treatment of relapsed or refractory lymphoma after allogeneic hematopoietic stem cell transplantation （allo-HSCT）.Methods The method of allo-HSCT was adopted to treat 7 patients with relapsed or refractory lymphoma from January 2007 to January 2012 in the General Hospital of Beijing Military.The primary disease included 6 cases of NHL and 1 case of HL.4 cases had one recurrence,2 cases had two or more relapses,and 1 case was primary refractory.The patients had an average age of 33.7 years old （ranging froml8 to 48-year-old） and included 4 males and 3 females.The patients included 2 cases of diffuse large B-cell （DLBCL） and 1 for each case of T lymphoblastoid cell type （T-LL）,skin extranodal NK/T cell type （ENKTCL-N）,hepatosplenic T-cell type （HSTCL）,Burkitt＇ s type （BL）,and HL mixed cell type.3 patients were in remission while 4 patients did not achieve remission at the time of transplantation.3 cases had donor and recipient HLA matching while the remaining 4 mismatched.Bone marrow and peripheral blood stem cell transplantation were used in this study.Patients were pretreated with fludarabine,melphalan,anti-human thymocyte globulin cyclosporin A （CsA） and methotrexate （MTX） to prevent graft-versus-host disease （GVHD）.Toxicity,GVHD and disease-free survival were monitored in patients after transplantation.Results 6 patients tolerated conditioned regimen and achieved hematopoietic reconstitution.Implantation evidence testing confirmed 100 % hematopoietic from donors.Follow-up was up to January 2011 with a median of 29.6 months （1-70 months）.The overall survival rate was 71.4 %.5 patients had acute GVHD and 4 experienced chronic GVHD.1 patient died of infection and 1 died of relapse,and the rest patients were alive.The longest disease-free interval was up to 70 months.Conclusion allo-HSCT is effective and safe for relapsed or refractory lymphoma.It can be a key technology of extensive clinical use for treating relapsed or refractory lymphoma.