Outcome of children treated with haematopoietic-stem cell transplantations from donors expressing the rare C77G variant of the PTPRC (CD45) gene.

The uncommon C77G polymorphism of the Protein-Tyrosine Phosphatase (PTPRC) gene (PTPRC; previously termed CD45) could confer an increased risk of immunopathology. This study compared the outcome of children following human leucocyte antigen-matched unrelated haematopoïetic-stem cell transplantations (HSCT) from donors carrying (C77G cases: n = 8) or not (controls: n = 36) the PTPRC C77G polymorphism. Transmission of the PTPRC C77G polymorphism through the graft was suggested by unusual CD45RA phenotype in the donors and/or in the recipients after, but not before HSCT. Restriction-Fragment Length Polymorphism and sequencing confirmed the polymorphism. Overall survival rates were similar in C77G cases and controls (63% vs. 61%). Acute leukaemia relapse tended to be less frequent in C77G cases (0% vs. 32%; P = 0·09). Among recipients surviving ≥ 30 d, acute GVHD (aGVHD) ≥ grade 2 tended to be more frequent (100% vs. 58%; P = 0·07) and the rate of steroid-refractory or -dependant aGVHD higher (67% vs. 28%) in C77G cases. Finally, extensive chronic GVHD tended to occur more frequently (40% vs. 9%) in C77G cases. Recovery of lymphocyte subsets and virus-specific CD4 was similar in C77G cases and controls while interleukin 2 (IL2)-responses through CD3 stimulation were higher in C77G cases (P = 0·004). In conclusion, HSCT from PTPRC C77G donors could increase GVHD risk without compromising overall survival. Altered IL2-responses could be involved in this process.