单倍型异基因造血干细胞移植治疗难治／复发急性白血病患者的疗效观察

Outcome of haploidentical hematopoietic stem cell transplantation for refractory/relapsed acute leukemia

目的探讨人类白细胞抗原（HLA）配型不合／单倍型供者异基因造血干细胞移植（allo—HSCT）治疗难治／复发白血病患者的疗效及影响疗效的相关因素。方法回顾性分析2003年1月至2011年6月行HLA不合／单倍型allo—HSCT的96例难治／复发急性白血病患者资料，采用以白消安／环磷酰胺（BU／CY）＋抗人胸腺细胞球蛋白（ATG）为主的预处理方案。结果96例患者中急性髓系白血病（AML）61例，Ph染色体阴性急性淋巴细胞白血病（ALL）35例，均为原发（或复发）未缓解病例；中位随访时间373（34～3157）d，33例（34．4％）存活，31例（32．3％）无病存活，35例（36．5％）复发。HSCT后预期3年总体生存（OS）率为30．2％，无病生存（DFS）率为29．0％。AML和ALL患者HSCT后预期3年OS率分别为39．2％和15．4％（P=0．005）；预防性供者淋巴细胞输注（DLI）与否患者HSCT后预期3年0s率分别为38．0％和11．8％（P=0．001）；而患者性别、年龄、预处理方案（BU／CY、ATG剂量）、供受者HLA相合位点数、输注单个核细胞数量均不是OS、DFS及复发的独立影响因素。多因素分析表明，接受预防性DLI的患者DFS率明显提高（P=0．003），ALL患者DFS率明显低于AML（P=0．037），发生慢性移植物抗宿主病（GVHD）的患者DFS率明显提高（P=0．006）。结论选择单倍型allo—HSCT治疗难治／复发急性白血病患者，可使部分患者延长无病生存乃至根治。患者预防性DLI可降低复发、提高生存；对难治／复发ALL患者，需进一步探索移植后复发的防治手段。

Objective To explore the outcome of human leukocyte antigen （HLA） -mismatchecL/hap- loidentical hcmatopoietic stem cell transplantation （HSCT） for refractory/relapsed acute leukemia （AL） pa- tients and its related risk factors. Methods 96 refractory/relapsed AL patients who received HLA-mis- matched/haploidentical HSCT following conditioning regimen comprised of modified busulfan/cyclophospha- mide （BU/CY） plus thymoglobulin （ATG） from Jan 2003 to Jun 2011 were analyzed retrospectively. Results Of the 96 patients, 61 suffered from acute myeloid leukemia（AML） , and 35 acute lymphoid leukemia （ALL） , all of them in non-remission （NR） or relapse before transplantation. With a median follow-up of 373 （ 34 - 3157） d, 33 cases（34% ） survived, 31 survived without leukemia, and 35 relapsed. The estimated 3- year overall survival （OS） and disease-flee survival （DFS） rate was 30.2% and 29.0%, respectively. The 3-year OS rate was significantly higher for AML patients （ 39.2% ） than for ALL patients （ 15.4% ） （ P = 0.005 ）. The estimated 3-year OS probabilities for patients with and without prophylactic donor lymphocyte in- fusion （DLI） were 38.0% and 11.8% , respectively （ P = 0. 001 ）. Sex, age, conditioning regimen （ BU/CY or not, dosage of ATG） , the number of HLA mismatches between the donor and recipient, and the number of infused mononuelear cells were not independent factors affecting OS, DFS and relapse. Multivariate analysis showed that DFS rate was significantly higher in patients receiving prophylactic DLI （ P = 0. 003 ）, in patients with AML（vs with ALL） （P=0.037） and with chronic GVHD（P =0.006）. Conclusions Haploidentical HSCT may prolong DFS in part refractory/relapsed AL patients and even cure them. Prophylactic DLI may re- duce relapse and increase survival; for patients with refractory/relapsed ALL, other therapy for prevention and treatment of post-transplant relapse should be explored.