#2-OR
RELEVANCE OF AMINO ACID 116 SUBSTITUTIONS ON THE OUTCOME OF HLA CLASS I MISMATCHED BONE MARROW TRANSPLANTS.
Guido Frumento Dr. , Andrea Bacigalupo Dr. , Teresa Lamparelli Dr. , Edoardo Lanino Dr. , Laura Delfino Lab. Technician , Anna Morabito Lab. Technician , Anna Maria Parodi Lab. Technician , Cinzia Pera Dr. , Sarah Pozzi Dr. , Maria Pia Sormani Dr. , Paolo Bruzzi Dr. , Anna A. Colombo, Dr. , Paolo Alessandrino Dr. , Miriam Martinetti Dr. , Jean D. Bignon, Dr. , Giuseppe Bandini Dr. , Andrea Bontadini Dr. , Raimondo Marceno
Dr. , Alessandro Rambaldi Dr. , Mario Bontempelli Dr. , Tom Fuller Dr. and Giovanni B. Ferrara, Prof. . Genoa Italy, National Cancer Research Institute, 16132, Immunogenetics and Genoa Italy, University of Genoa, 16132, Oncology, Biology and Genetics .
We have previously suggested (Blood, 98:3150,2001) that amino acid substitution in position 116 within Class I heavy chain would have an impact on unrelated BMT outcome. However, the relatively small size of the cohort analysed required further studies in a larger and independent data set.
152 new donor-recipient pairs, all matched for DRB1/3/4/5, DQA1, and DQB1 loci were typed by SBT for the HLA-A, -B, and -C loci.
The cohort was then divided in three groups: i) pairs that were also matched at Class I, ii) pairs having a Class I mismatch not involving the amino acid at position 116, and iii) pairs having a Class I mismatch involving the replacement of the residue at position 116.
The risk of acute GvHD grade III-IV was increased in pairs having a replacement of the amino acid at position 116, as compared to fully matched pairs, with the group of pairs having a Class I mismatch not involving position 116 in between. Differences were statistically significant.
The impact on severe acute GvHD differently affected TRM and overall survival, depending on GvHD prophylaxis adopted. Instead, relapse was not affected.
Our data confirm the finding that substitutions at position 116 of Class I heavy chain increase the risk of severe acute GvHD. The occurrence of donor recipient pairs having a Class I mismatch involving the replacement of the amino acid at position 116 should be avoided.