低体重指数患者接受单倍体异基因造血干细胞移植后重度移植物抗宿主病风险增加

Increased risk of severe acute graft-versus-host disease in low body mass index patients undergoing haploidentical allogeneic stem cell transplantation

目的 探讨在单倍体相合异基因造血干细胞移植（allo-HSCT）模式下,移植前受者的BMI水平对移植后移植物抗宿主病（GVHD）的发生及预后的影响.方法 回顾性分析北京大学人民医院血液病研究所2008年8月至2011年9月接受单倍体相合allo-HSCT的253例成人急、慢性白血病患者的临床资料.所有患者均采用以白消安为主的清髓性预处理方案.按BMI分为3组：消瘦组（BMI＜ 18 kg/m2）,17例;正常体重组（BMI为18～ ＜25 kg/m2）,157例;超重组（BMI≥25 kg/m2）,79例.单因素分析纳入16个可能的影响因素：供受者性别、供受者年龄、受者BMI、受者疾病诊断、受者疾病状态分层、HLA不合位点数目、供受者关系、预处理中抗胸腺细胞球蛋白（ATG）剂量（10 mg/kg与6 mg/kg）、骨髓及外周血采集物单个核细胞数、骨髓及外周血采集物CD34＋细胞数、骨髓及外周血采集物CD3细胞数.分析这些因素与移植后GVHD、复发、治疗相关死亡及总生存之间的相关性,采用多因素Cox回归分析确定其相关的危险因子.结果 253例患者的中位年龄为31（18～56）岁,包括急性髓性白血病（AML） 128例,急性淋巴细胞白血病（ALL） 95例,慢性髓性白血病（CML） 30例.疾病状态分层：标危185例,高危68例.中位随访时间为移植后第929天（＋929 d）（＋48～＋1 762）d.252例（99.6％）获得持久的造血重建,粒细胞植活中位时间为＋12（＋9～＋45）d,血小板植活中位时间为＋16（＋7～＋180）d.Ⅱ～Ⅳ级急性GVHD累积发生率为33.2％,中位发生时间为＋ 25（＋13～ ＋88）d.多因素分析结果显示：与正常体重组相比,消瘦组重度急性GVHD发生风险明显增高（HR=5.736,95％ CI 1.779 ～ 18.491,P=0.003）,而超重组此风险并不增加（HR=1.843,95％ CI0.727～4.671,P=0.198）;受者BMI水平对移植后复发、治疗相关死亡及总生存无影响.结论 低BMI水平是单倍体相合allo-HSCT后重度急性GVHD发生的危险因子.

Objective To investigate the impact of body mass index（BMI） before transplantation on clinical outcomes of haploidentical allogeneic stem cell transplantation （allo-HSCT）.Methods We performed a retrospective cohort study of 253 adult patients with acute or chronic leukemia who received haploidentical allo-HSCT from August 2008 to September 2011.All conditioning regimens were myeloablative and bulsufan based.Patients were stratified according to BMI values （low BMI group：〈 18kg/m2; normal BMI group：≥18 and 〈 25 kg/m2; overweight BMI group：≥25 kg/m2）.Other possible risk factors correlated with GVHD,relapse,transplant related mortality （TRM） and overall survival （OS）included age and gender of donor and recipient,HLA disparity,relationship between donor and recipient,diagnosis,status of disease,ATG dose in conditioning regime （10 mg/kg,6 mg/kg）,mononuclear cells （MNC）,CD34＋ and CD3＋ cell amount from granulocyte colony-stimulating factor（G-CSF） primed bone marrow grafts（G-BM） and G-CSF mobilized peripheral blood grafts（G-PB）.Cox regression analysis was used to determine the related risk factors,Results The median age of all 253 patients was 31 （18-56） years,including 128 cases with acute myeloid leukemia （AML）,95 cases with acute lymphocytic leukemia （ALL）,and 30 cases with chronic myeloid leukemia （CML）.According to primary diseases,185 patients were classified in the standard-risk group and 68 cases in the high-risk group.Median follow-up time was 929 days （range：48-1762 days） post-transplantation.Engraftment has been attainted 252 （99.6%）recipients with the median time of granulocyte and platelet recovery 12 days （ranging from 9 to 45 days） and 16 days （ranging from 7 to 180 days）,respectively.Cumulative incidences of acute GVHD was 33.2% with median time of 25 days （range：13-88 days） after transplant.Multivariate analysis identified that low BMI was associated with an increased risk of grade Ⅲ-Ⅳ acute GVHD （HR =5.736,95% CI 1.779-18.491,P =0.003）.There was no significant impact of BMI to other manifestations of GVHD,TRM,relapse or OS in different groups.Conclusions Our findings demonstrate a correlation between pre transplant BMI and clinical outcome post-transplant.Low BMI was associated with increased risk of severe acute GVHD in leukemia patients receiving haploidentical allo-HSCT.Meticulous supportive care pre-transplantation is required for low BMI patients.