Impact of the presence of HLA 1-locus mismatch and the use of low-dose antithymocyte globulin in unrelated bone marrow transplantation

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Abstract

HLA 1-locus-mismatched unrelated donors (1MMUD) have been used in allogeneic hematopoietic stem cell transplantation (allo-HCT) for patients who lack an HLA-matched donor. We retrospectively analyzed 3313 patients with acute leukemia or myelodysplastic syndrome who underwent bone marrow transplantation from an HLA allele-matched unrelated donor (MUD) or 1MMUD between 2009 and 2014. We compared the outcomes of MUD (n = 2089) and 1MMUD with antithymocyte globulin (ATG) (1MM-ATG(+); n = 109) with those of 1MMUD without ATG (1MM-ATG(−); n = 1115). The median total dose of ATG (thymoglobulin) was 2.5 mg/kg (range 1.0-11.0 mg/kg) in the 1MM-ATG(+) group. The rates of grade III-IV acute GvHD, non-relapse mortality (NRM) and overall mortality were significantly lower in the MUD group than in the 1MM-ATG(−) group (hazard ratio (HR) 0.77, P = 0.016; HR 0.74; P < 0.001; and HR 0.87, P = 0.020, respectively). Likewise, the rates of grade III-IV acute GVHD, NRM and overall mortality were significantly lower in the 1MM-ATG(+) group than in the 1MM-ATG(−) group (HR 0.42, P = 0.035; HR 0.35, P < 0.001; and HR 0.71, P = 0.042, respectively). The outcome of allo-HCT from 1MM-ATG(−) was inferior to that of allo-HCT from MUD even in the recent cohort. However, the negative impact of 1MMUD disappeared with the use of low-dose ATG without increasing the risk of relapse.

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