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P093 Graft vs host disease (GVHD) in hematopoetic stem cell transplants (HSCT): Effect of donor gender

HUMAN IMMUNOLOGY(2017)

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摘要
Aim Despite HLA matching at A, B, C, DR, DQ loci and in many cases DP locus by high resolution sequence based typing, GVHD occurs in ∼20% of the cases at our center. Minor histocompatibility antigen (mHA) differences are not routinely assessed in HSCT. We analyzed the GVHD pattern in our HSCT recipients to assess the impact of male-specific mHA, H-Y by using gender-based recipient/donor HSCT pairs. Previous reports have implicated H-Y antigen in antibody-mediated chronic GVHD and T cell mediated GVL. Methods Retrospective analysis of 281 HSCT recipients consisting of AML ( n  = 104), ALL ( n  = 36), NHL ( n  = 29), MDS ( n  = 24), CLL ( n  = 19), HD ( n  = 15) CML ( n  = 12) and other ( n  = 42) was done. Occurrence and grade of GVHD were assessed as outcome in specific recipient/donor HSCT pairs: Female/Female [F/F] ( n  = 56), Female/Male [F/M] ( n  = 48), Male/Male [M/M] ( n  = 98), and Male/Female [M/F] ( n  = 61). Transplants included matched related and unrelated and haploidentical recipient/donor pairs. Chi-square analysis was performed using SPSS. Results GVHD data was available in 264 HSCT recipients and 55 (21%) developed GVHD. Occurrence of GVHD Grades I-IV was observed in 10 F/F (17.85%), 10 F/M (21%), 22 M/M (22.4%) and 13 M/F (22.4%) HSCT pairs which was not significantly different ( p  u003e 0.05). Individual grades of GVHD did not show any significant difference among the specific gender recipient/donor pairs ( p  u003e 0.05). Conclusions Increased GVHD due to H-Y antigens were noted in previous reports, but the level of HLA matching was limited to A, B, DR or A, B, C, DR. In 10/12 or 12/12 matched HSCT, mHA consisting of ∼30 different antigens may trigger GVHD. While H-Y mHA can evoke a T cell response in Male recipients receiving HSCT from a Female donor, our data indicates that the occurrence or grade of GVHD was not significantly higher among any gender pairs. Impact of age and disease types, were not considered in this analysis. We also did not analyse the data for certain HLA genes in female donors based on their ability to process H-Y antigen. Lack of H-Y effect has also been shown in zero mismatched renal transplantation. While, our results indicate that male H-Y antigen does not have a significant role in inducing GVHD, the evaluation of other mHA and MHC gamma region SNPS are warranted considering that GVHD occurs in ∼25% of HSCT recipients with fully matched HLA donors.
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关键词
hematopoetic stem cell transplants,host disease,gvhd,gender
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