非血缘造血干细胞移植中抗胸腺细胞球蛋白预防移植物抗宿主病的疗效分析

Antithymocyte globulin for graft-versus-host disease prophylaxis in hematopoietic stem cell transplantation from unrelated donors： a retrospective report

目的探讨非血缘造血干细胞移植中应用抗胸腺细胞球蛋白（ATG）预防移植物抗宿主病（GVHD）的临床疗效。方法回顾性分析1999年1月至2011年12月行非血缘造血干细胞移植患者治疗的恶性血液病（包括白血病、骨髓增生异常综合征、淋巴瘤）92例患者资料。分为ATG预防组（66例）和无ATG组（26例）。ATG剂量为1．5mg／kg，移植前第4天至移植前第1天。比较两组急性GVHD（aGVHD）和慢性GVHD（cGVHD）发生率，分析aGVHD与cGVHD发生的危险因素，并比较ATG预防对移植后总生存（0s）、治疗相关死亡（TRM）率、复发率的影响。结果Ⅱ～Ⅳ度aGVHD和Ⅲ～Ⅳ度aGVHD发生率差异无统计学意义[26．7％（16／60）比44．0％（11／25），P=0．12；13.3％（8／60）比8．0％（2／25）．P=0．74]。ATG组cGVHD及广泛型cGVHD发生率明显低于无ATG组[34．0％（17／50）比72．2％（13／18），P=0．005；10．0％（5／50）比44．4％（8／18），P=0．005]。多因素分析显示ATG预防能降低cGVHD发生f相对危险度（RR）=0．22，95％CIO．081～O．599；P=0．003}，人类白细胞抗原（HLA）不完全相合增加cGVDH发生率（RR=3．25，95％（231．39～7．61；P=0．007）。并且ATG预防显著降低广泛型cGVHD发生（RR=0．05，95％CIO．009～0．240；P〈0．001）。92例患者中位随访时间12个月（1～84个月）。ATG预防组和无ATG组间OS率（60．4％比43．1％，P=0．41）、TRM率（19．8％比34．3％，P=0．43）、复发率（40．6％比33．6％，P=0．54）差异均无统计学意义。结论总量6mg／kg的ATG预防可显著降低非血缘造血干细胞移植患者cGVHD及广泛型eGVHD的发生率，不增加疾病复发，对OS及TRM亦无影响。

Objective To assess the impact of antithymocyte globulin （ATG） on the incidence of graft-vs-host disease （GVHD） in hematopoietic stem cell transplantation from unrelated donors. Methods A total of 92 patients with hematological malignancies including leukemia, myelodysplastic syndrome （MDS） and lymphoma who underwent hemalopoietic stem cell transplantation from unrelated donors from January 1999 to December 2011 were included in this retrospective analysis. Patients were classified into ATG group （n = 66） and non-ATG group （n = 26） according to the GVHD prophylaxis regimen. The incidence of acute GVHD （aGVHD） and chronic GVHD （cGVHD）, risk factors of aGVHD and cGVHD and impact of ATG on the overall survival （OS）, treatment related mortality （TRM） and relapse rate were analyzed. Results Grade II-IV aGVHD （26.7 % vs 44.0 %, P= 0.12） or grade III-IV aGVHD （13.3 % vs 8.0 %, P= 0.74） were not significantly different between ATG and non-ATG group. However, the incidence of cGVHD in the ATG group was significantly lower （34.0 % vs 72.2 %, P = 0.005） than non-ATG group. The incidence of extensive cGVHD was also significantly reduced （10.0 % vs 44.4 %, P = 0.005） compared to non-ATG group. In multivariate analysis, the use of ATG prophylaxis significantly decreased the cGVHD （RR = 0.22, 95 %CI 0.081-0.599, P = 0.003） while one allele mismatch of human leukocyte antigen （HLA） was associated with increased risk of cGVHD （RR = 3.25, 95 % CI 1.39-7.61, P = 0.007）. As to the extensive cGVHD, the use of ATG was the only independent factor （RR = 0.05, 95 % CI 0.009-0.240, P 〈 0.001）. With a median follow-up of 12 months （1-84 mouths）, ATG prophylaxis had no impact on OS rate （60.4 % vs 43.1%, P = 0.41）, TRM rate （19.8 % vs 34.3 %, P = 0.43） and relapse rate （40.6 % vs 33.6 %, P = 0.54）. Conclusion In hematopoietic stem cell transplantation from unrelated donors, ATG prophylaxis total dose of 6 mg/kg may significantly decrease the incidence of cGVHD and extensive cGVHD without increase of TRM and relapse rate and impairment of OS.