含或不含全身照射的预处理方案对急性白血病allo—HSCT疗效的影响

Conditioning regimen with or without total body irradiation for allogeneic hematopoietic stem cell transplantation in acute Ieukemia

目的 探讨含或不含全身照射（TBI）的预处理方案对急性白血病异基因造血于细胞移植（allo-HSCT）疗效的影响.方法 回顾性分析2002年1月至2011年8月287例行allo-HSCT的急性白血病患者的资料,患者的原发疾病分别为急性非淋巴细胞白血病（AML） 129例,急性淋巴细胞白血病（ALL） 105例,急性未定型白血病（AUL）53例.287例中,移植前完全缓解（CR） 206例,未缓解（NR）81例.按预处理方案分为TBI＋环磷酰胺（Cy）组（199例）以及白消安＋环磷酰胺（BuCy）组（88例）,前者TBI的总剂量为9.0Gy,后者Bu的剂量为3.2 mg,kg- ·d-1,移植前7～4 d应用.结果 TBI＋ Cy组与BuCy组移植后造血重建情况、疾病无进展生存（DFS）、移植物抗宿主病（GVHD）发生率和疾病复发情况的差异均无统计学意义（P＞0.05）.AML和AUL患者无论采用TBI＋ Cy或BuCy方案行预处理,其5年总体存活率的差异均无统计学意义（P＞0.05）.而采用TBI＋ Cy与BuCy进行预处理的ALL-CR患者的移植后5年累积总体存活率分别为52.0％和31.3％（LogRank=4.249,P＜0.05）,DFS分别为50.4％和27.8％ （LogRank=4.445,P＜0.05）,差异有统计学意义.移植后1个月时TBI＋ Cy组和BuCy组CD19＋B淋巴细胞分别占（1.47±0.99）％和（4.04±1.86）％,移植后12个月两组NK细胞分别占（13.11±7.99）％和（23.38±12.9）％,移植后9个月时两组CD4＋ CD45RO＋细胞分别占（14.36±6.17）％和（9.07±3.12）％,差异均有统计学意义（P＜0.05,P＜0.05,P＜0.01）.结论 AML和AUL患者采用TBI＋ Cy方案或采用BuCy方案预处理,其存活率无差异；而ALL-CR患者采用TBI＋ Cy方案其存活率高于采用BuCy方案者.总剂量为9 Gy的TBI预处理方案不增加急、慢性GVHD的发生率.

Objective To investigate the therapeutic effects of the conditioning regimen with or without total body irradiation on allogeneic hematopoietic stem cell transplantation in acute leukemia.Methods We retrospectively evaluated clinical outcomes in 287 allo-HSCT recipients with acute leukemia （ALL- 105,AML-129,and AUL-53） who received myeloablative conditioning regimen with or without total body irradiation from January 2002 to August 2011.Two hundred and six patients obtained complete remission （CR） and 81 non-remission （NR） before transplantation.One hundred and ninety-nine patients received conditioning with total body irradiation （TBI＋ Cy group,9 Gy given over 2 days）,and 88 patients received busulfan （BuCy group,3.2 mg·kg-1 ·d-1 ）,both followed by cyclophosphamide.Results There were no statistically significant differences in hematopoietic reconstitution,regimen-related toxicity （RRT）,graft-versus-host disease （GVHD） and relapse between two groups.For patients with AML and AUL,there was no significant difference in the 5-year survival between the two regimens （P〉 0.05）,while for ALL-CR patients,the TBI ＋ Cy regimen had a higher over survival rate （52.0% vs.31.3%,LogRank=4.249,P〈0.05） and DFS （50.4% vs.27.8%,LogRank =4.445,P〈0.05） than BuCy.In TBI ＋ Cy group and BuCy group,the proportion of CD19＋ B cells at the first month after HSCT was （4.04 ± 1.86）% and （1.47 ±0.99） % （P〈0.05）,that of NK cells at 12th month after HSCT was （23.38 ± 12.19） % and （13.11± 7.99） % （P〈0.05）,and that of CD4＋ CD45RO＋ cells at 9th month after HSCT was （14.63 ±6.17）% and （9.07 ± 3.12）% （P〈0.01）,respectively.Conclusion Using TBI-containing regimen was more effective for treating ALL-CR patients than busulphan-containing regimen,but no difference was found for long-term outcomes in patients with AML and AUL between the two regimens.The 9 Gy TBI-based regimens may not affect recipients＇ thymic function,T-cells reconstitution and immune tolerance,coming out a non-increase of GVHD.