Clinical relevance of the newly reclassified HLA-C*04:09L low-expression allele in allogeneic hematopoietic cell transplantation: a case report.

In the context of allogeneic hematopoietic cell transplantation (allo-HCT), misclassifying null- and low-expression alleles could result in an HLA mismatch with life-threatening clinical consequences. HLA-C*04:09N was considered one of the most frequent null alleles, but it was recently reclassified as a low-expression allele, HLA-C*04:09L, based on a recent work which described that could be detected at the cell surface and capable of inducing peptide-specific T-cell activation in vitro. The authors suggested that these findings could imply clinical consequences in the field of transplantation, but without including any real clinical case. In this report we describe a patient carrying HLA-C*02:02:02,04:09N (now C*04:09L) who underwent an allo-HCT from a mismatched unrelated donor HLA-C*02:02:02,- that was considered functionally 10/10 matched due to the supposed lack of expression of HLA-C*04:09N. The post-transplant clinical course was complicated by graft-versus-host-disease, progression to secondary acute myeloid leukemia, and death.