移植前状态对难治复发急性淋巴细胞白血病异基因造血干细胞移植预后的影响

Effect of disease status on outcome of allogeneic hematopoietic stem cell transplantation in treatment of refractory and relapsed acute lymphoblastic leukemia

目的探讨难治复发急性淋巴细胞白血病（acute lymphocytic leukemia,ALL）的缓解状态对异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation,allo-HSCT）预后的影响。方法回顾性分析我研究所不同缓解状态下行allo-HSCT的52例难治复发ALL患者,其中19例处于未缓解（non-remission,NR）状态,33例达到第2次及以上完全缓解（complete remission,≥CR2）。所有患者均采用清髓性预处理,其中改良白消安加环磷酰胺37例,全身照射加环磷酰胺14例。结果除1例患者早期死亡外,其余51例均获得造血重建,NR和≥CR2患者100 d内移植相关死亡为10.5%和12.1%（P=1.000）。移植后急性移植物抗宿主病（graft versus host disease,GVHD）发生率为52.6%和57.6%（P=0.730）,其中Ⅰ~Ⅱ度为42.1%和33.3%（P=0.527）,Ⅲ~Ⅳ度为10.5%和24.3%（P=0.399）,慢性GVHD发生率为41.6%和57.9%（P=0.660）。中位随访时间为12（1.8~44.5）个月,26例患者无白血病生存至今。NR与≥CR2患者的预计2年总生存（overall survival,OS）和无白血病生存（leukemia-free survival,LFS）分别为42.6%、45.7%（P=0.740）和46.3%、46.2%（P=0.998）,累积复发率为47.0%、34.3%（P=0.425）。影响预后的单因素和多因素分析显示,移植前疾病缓解状态与生存无关,移植后发生慢性GVHD才是影响OS、LFS的独立预后因素。结论移植前NR患者与≥CR2患者相比,移植预后无统计学差异,提示allo-HSCT挽救性治疗NR状态下难治复发的ALL是可行的。

Objective To determine the effect of disease status on the outcomes of allogeneic hematopoietic stem cell transplantation（ allo-HSCT） in the treatment of patients with refractory and relapsed acute lymphoblastic leukemia（ ALL）. Methods Fifty-two patients with refractory and relapsed ALL,including 19 cases in non-remission（ NR） and 33 cases in more than or equal to second complete remission（ ≥CR2） after allo-HSCT admitted in our department from January 2012 to June 2015 were enrolled in this study. All patients were treated with myeloablative conditioning. Of them,37 cases received improved busulfan and cyclophosphamide treatment,and the left 14 cases total body irradiation plus cyclophosphamide.Results Beside 1 patient died early,the other 51 patients engrafted successfully. The transplantation-related mortality（ TRM） within 100 d was 10. 5% and 12. 1% respectively for the NR and ≥ CR2 groups（ P =1. 000）. The incidence of acute graft versus host disease（ a GVHD） was 52. 6% and 57. 6%（ P = 0. 730）,including 42. 1% and 33. 3%（ P = 0. 527） with mild（ grade Ⅰ ~ Ⅱ）,and 10. 5% and 24. 3%（ P =0. 399） with severe（ grade Ⅲ ~ Ⅳ）. While,the incidence of c GVHD was 41. 6% and 57. 9% respectively for the 2 groups（ P = 0. 660）. During a median follow-up period of 12（ 1. 8 ~ 44. 5） months,26 patients were leukemia-free survival（ LFS） till now. The estimated 2 year overall survival（ OS） and 2 year LFS rate were 42. 6% and 45. 7%（ P = 0. 740）,and 46. 3% and 46. 2%（ P = 0. 998） respectively,and the cumulative relapse rate was 47. 0% and 34. 3%（ P = 0. 425） respectively in the NR and ≥ CR2 groups.Multivariate and univariate analyses showed that the disease status had no effect on the OS after all-HSCT,and appearance of c GVHD was an independent prognostic factor for OS and LFS. Conclusion No significant difference is seen in the prognosis of allo-HSCT in the NR and ≥CR2 patients with refractory and relapsed ALL. Our results indicate that al Io-HSCT is an effective salvage therapy for the patients,and the overall outcome seems unrelated to the disease status（ NR or CR） before transplantation.