Tacrolimus plus sirolimus with or without ATG as GVHD prophylaxis in HLA-mismatched unrelated donor allogeneic stem cell transplantation
Tacrolimus plus sirolimus with or without ATG as GVHD prophylaxis in HLA-mismatched unrelated donor allogeneic stem cell transplantation
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DOI：
10.1038/bmt.2016.269
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发表时间：
2017-03-01
影响因子：
4.8
通讯作者：
Perez-Simon, J. A.
中科院分区：
文献类型：
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作者：
Kharfan-Dabaja, M. A.;Parody, R.;Perez-Simon, J. A.
hla匹配的亲属或非亲属供体并不是普遍可用的。因此，可以为患者提供来自其他供体的造血干细胞移植（HSCT），包括不匹配的非亲属供体（MMURD），已知会导致更高的急性GVHD （aGVHD）和慢性GVHD发生率。体内t细胞消耗策略，如抗胸腺细胞球蛋白（ATG）治疗，可显著降低GVHD的风险。我们对104例接受MMURD HSCT的患者（TAC-SIR = 45, TAC-SIR-ATG = 59）进行了一项多中心、回顾性研究，比较了他克莫司（TAC）和西罗莫司（SIR）联合或不联合ATG。使用ATG与2-4级aGVHD发生率较低（46%对64%，P= 0.09）、3-4级aGVHD发生率无差异（10%对15%，P= 0.43）、中/重度慢性GVHD发生率较低（16%对37%，P= 0.09）和更频繁的Epstein-Barr病毒再激活（54%对18%，P= 0.0002）相关。3年总生存率（OS） (TAC-SIR- atg = 40%（95%可信区间（CI) = 24-56%）与TAC-SIR = 54% (95% CI = 37-70%)， P= 0.43）或3年累积复发/进展发生率（TAC-SIR- atg = 40% （95% CI = 28-58%）与TAC-SIR = 22% (95% CI = 13-39%)， P= 0.92）无统计学差异。国际血液和骨髓移植研究中心的中间疾病风险导致3年的非复发死亡率显著降低，生存期更好。我们的研究表明，在MMURD HSCT中，与单独使用TAC-SIR相比，在TAC-SIR中添加ATG不会影响OS。
HLA-matched related or unrelated donors are not universally available. Consequently, patients can be offered hematopoietic stem cell transplantation (HSCT) from alternative donors, including mismatched unrelated donors (MMURD), known to cause a higher incidence of acute GVHD (aGVHD) and chronic GVHD. In vivo T-cell-depletion strategies, such as antithymocyte globulin (ATG) therapy, significantly decrease the risk of GVHD. We performed a multicenter, retrospective study comparing tacrolimus (TAC) and sirolimus (SIR) with or without ATG in 104 patients (TAC-SIR = 45, TAC-SIR-ATG = 59) who underwent MMURD HSCT. Use of ATG was associated with a lower incidence, albeit not statistically significant, of grades 2-4 aGVHD (46% vs 64%, P= 0.09), no difference in grades 3-4 aGVHD (10% vs 15%, P= 0.43), a trend for a lower incidence of moderate/severe chronic GVHD (16% vs 37%, P= 0.09) and more frequent Epstein-Barr virus reactivation (54% vs 18%, P= 0.0002). There were no statistically significant differences in 3-year overall survival (OS) (TAC-SIR-ATG = 40% (95% confidence interval (CI) = 24-56%) vs TAC-SIR = 54% (95% CI = 37-70%), P= 0.43) or 3-year cumulative incidence of relapse/progression (TAC-SIR-ATG = 40% (95% CI = 28-58%) vs TAC-SIR = 22% (95% CI = 13-39%), P= 0.92). An intermediate Center for International Blood & Marrow Transplant Research disease risk resulted in a significantly lower non-relapse mortality and better OS at 3 years. Our study suggests that addition of ATG to TAC-SIR in MMURD HSCT does not affect OS when compared with TAC-SIR alone.