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Outcome of children treated with haematopoietic‐stem cell transplantations from donors expressing the rare C77G variant of the PTPRC (CD45) gene
Author(s) -
Samaan Samaan,
GuérinEl Khourouj Valérie,
Auboeuf Didier,
Peltier Lucas,
Pédron Béatrice,
OuachéeChardin Marie,
Gourgouillon Nadége,
Baruchel André,
Dalle JeanHugues,
Sterkers Ghislaine
Publication year - 2011
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2011.08568.x
Subject(s) - immunology , medicine , hematology , gastroenterology , biology
Summary 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.