异基因外周血干细胞移植(S999方案)治疗白血病的临床观察

Allogeneic peripheral blood stem cell transplantation in treatmemt of leukemia

目的 采用S999方案中异基因外周血干细胞移植 (allo PBSCT)治疗白血病 ,评价其疗效并观察移植物抗宿主病 (GVHD)等并发症。方法 1999年 9月～ 2 0 0 2年 9月间 ,共完成allo PBSCT治疗成人白血病 5 0例 ,其中慢性粒细胞白血病 (CML) 2 8例 ,急性髓细胞白血病 (AML) 13例 ,急性淋巴细胞白血病 (ALL) 9例。外周血干细胞动员方案 :格拉诺赛特 (G CSF) 5 μg·kg- 1 ·d- 1 × 5d ;移植预处理主要采用环磷酰胺 (CTX) +足叶乙甙 (VP16) +全身照射 (TBI)方案 :CTX 5 0～ 60mg·kg- 1 ·d- 1 × 2d ;VP162 0mg·kg- 1 ·d- 1 × 2d或 5 0mg·kg- 1 ·d- 1 × 1d ,TBI 6.5～ 8.0Gy单次照射或l2 .0Gy分 3次照射 ;GVHD预防采用常规环孢素A(CsA)+短程氨甲喋呤 (MTX)和霉酚酸脂 (MMF)联合CsA +MTX两种方案。结果 本组患者除 1例移植早期因并发真菌感染而导致败血症死亡外 ,余 49例均获得完全供体型造血功能重建。中性粒细胞恢复至 0 .5× 10 9/L及血小板恢复至 2 0× 10 9/L的中位时间分别为移植后 14d( 10～ 2 2d)及 19d( 10～ 68d)。 49例移植成功者发生急性GVHD 16例 ( 3 2 .7% ) ,其中Ⅲ～Ⅳ度 5例 ( 10 .2 % )。 3 6例生存 6个月以上者发生慢性GVHD 2 4例( 66.7% ) ,其中广泛性 5例 ( 13 .9% )。MMF +CsA

Objective To evaluate the efficacy and the complication of allogeneic peripheral blood stem cell transplantation (allo PBSCT) in the treatment of leukemia. Methods 50 patients with acute or chronic leukemia (CML n =28, AML n =13, ALL n =9) were treated with allo PBSCT. PBSC were mobilized with G CSF ( 5 μg·kg -1 ·d -1 ) for 5 days. The preconditioning regimens included CTX(60 mg·kg -1 ·d -1 ×2 d) and VP16 (20 mg·kg -1 ·d -1 ×2 d) plus TBI(6.5～12.0 Gy). Two regimens were used for prophylaxis of acute GVHD, one was the conventional low dose cyclosporine(CsA)plus short course methotrexate(MTX)(CsA+MTX group), the other was short course mycophenolate mofetil(MMF)plus CsA and MTX(MMF+CsA+MTX group). Results All patients were successfully engrafted and the median time for ANC>0.5×10 9/L and platelet>20×10 9/L was 14 (10～22) and 19 (10～68) days, respectively post PBSCT. The incidence of acute graft versus host disease (GVHD) was 32.5% (16/49) with grade Ⅲ～Ⅳ 10.2% (5/49). Chronic GVHD occurred in 24 out of 36 patients (66.7%) and lived longer than 6 months post transplantation, 5 including of extensive chronic GVHD (13.9%). The incidence of acute GVHD with grade Ⅲ～Ⅳ in MMF+CsA+MTX group was significantly lower than that of CsA+MTX group (0% vs 21.7%, P <0.05). 37(74%) patients are still alive in complete remission with a median follow up of 18 (3～39) months, with the probability of disease free survival (DFS) at 3 year was 65%. 17(26%) died with complications of acute GVHD, infection or interstitial pneumonitis and relapse which were the main causes of death. Conclusion Allo PBSCT is a safe and effective therapy for leukemia. The incidence of acute GVHD in allo PBSCT is low, but that of chronic GVHD is high. The MMF+CsA+MTX regimen for prevention of acute GVHD is more effiective than CsA+MTX.