异基因外周血造血干细胞移植治疗急性淋巴细胞白血病95例疗效分析

Clinical analysis of allogeneic peripheral blood stem cell transplantation for 95 patients with acute lymphoblastic leukemia

目的探讨异基因外周血造血干细胞移植（a110_PBSCT）治疗急性淋巴细胞白血病（ALL）的疗效。方法2002年2月至2014年2月采用HLA相合allo-PBSCT治疗ALL95例。采用全身照射（TBI）＋环磷酰胺（Cy）或白消安＋Cy为主的预处理方案。同胞供者68例，非血缘供者27例。存活受者的中位随访期为57个月（4-148个月）。结果95例受者均造血功能完全重建，中性粒细胞和血小板植活时间中位数分别为移植后12d（9-22d）和16d（9-39d）。Ⅱ～Ⅳ度急性移植物抗宿主病（aGVHD）累积发生率为19．4％，慢性移植物抗宿主病（cGVHD）累积发生率为43．3％。累积白血病复发率为30．2％，累积移植相关死亡率为24．0％。5年预期总体存活率（0s）及无自血病复发存活率（DFS）分别为54．3％和51．2％，其中第1次完全缓解（CR-）期接受移植者移植后5年预期OS和DFS分别为65．5％和64．0％。无白血病复发存活时间超过1年的59例受者中，发生eGVHD者的OS和DFS显著低于未发生cGVHD者（P〈0．05）。多因素分析显示，与白血病复发相关的危险因素是移植前处于白血病复发后多次CR（CR2）、移植前未缓解（NR）和未采用TBI方案，与移植相关死亡的危险因素是发生Ⅱ～Ⅳ度aGVHD和cGVHD，移植前NR和发生Ⅱ～Ⅳ度aGVHD是影响OS的独立危险因素，CR2期接受移植、NR期接受移植和发生Ⅱ～Ⅳ度aGVHD是影响DFS的独立危险因素。结论Allo-PBSCT是治疗ALL的有效方法，如有HLA相合供者，Allo-PBSCT可作为成人ALL患者的治疗首选在CR1期进行；预防发生严重aGVHD和cGVHD有可能进一步提高HLA相合allo-PBSCT的疗效。

Objective To analyze the outcomes and the prognostic factors of allogeneic peripheral blood stem cell transplantation （allo-PBSCT） for acute lymphoblastic leukemia （ALL）. Method From Feb. 2002 to Feb. 2014, a total of 95 patients with ALL were treated with alloPBSCT in our hospital. Of these, 73 cases obtained the first CR （CR1）, 11 cases obtained late CR, 7 patients were in relapse and 3 patients suffered from primarily refractory disease （PRD） boefore transplant. The median age was 26 （4-57） years. Conditioning regimens including total body irradiation （TBI）/ etoposide/semustine/cyclophosphamide or busulfan/semustine/cyclophosphamide were used. Matched sibling transplantation was performed on 68 patients, and matched unrelated donor transplantation was performed on 27 patients. Combination of CsA, MTX and low-dose, shortcourse mycophenolate mofetil was used for graft-versus-host disease （GVHD） prophylaxis. The average fellow-up was 57 months. Result Hematopoietic reconstitution was achieved in all 95 patients. Five-year estimate of overall survival （OS） was 54. 3%, disease free survival （DFS） was 51.2%, relapse rate （RR） was 30. 2% and transplant-related mortality （TRM） was 24. 0%. The 5- year OS and DFS were significantly longer in patients with CR1 than in late CR and relapse/PRD patients before allo-PBSCT （P〈0. 001）. There was no significant difference in OS between the two different conditioning regimens. Multivariate analyses revealed that Ⅱ- Ⅳ aGVHD and cGVHD were correlated with higher TRM, CR1 before allo-PBSCT and TBI were associated with a lower RR, and non Ⅱ- Ⅳ aGVHD and CR1 before allo-PBSCT were favorable factors which were associated with OS and DFS. In the patients with DFS≥1 year after allo-PBSCT, DFS and OS were shorter in patients with cGVHD （P = 0. 008）. Conclusion Allo-PBSCT in adult ALL patients should be performed in CR1. Severe acute and chronic GVHD are not associated with improved survival.