False homozygous HLA genotyping results due to copy number neutral loss of heterozygosity in acquired aplastic anaemia

Abstract

The aim of this case report is to draw attention on possible false human leucocyte antigen (HLA) genotyping in acquired aplastic anaemia prior to allogeneic haematopoietic stem cell transplantation. In acquired aplastic anaemia loss of heterozygosity (LOH) of chromosome 6p is known to occur in around 12%. We report false HLA genotyping results due to LOH and a coinciding steep rise in neutrophils following filgrastim stimulation in a patient with very severe aplastic anaemia. At diagnosis we obtained heterozygous results on peripheral blood. Failing to reach a partial response at 6 months with immune-suppressive therapy we repeated HLA genotyping, obtaining homozygous results. Repeated testing confirmed loss of HLA genotype heterozygosity. HLA genotyping on cells obtained by a buccal swab confirmed the previous HLA heterozygosity. A second course of filgrastim at the time of homozygous HLA genotyping resulted in a steep rise in neutrophils. Stopping filgrastim resulted in an equally steep drop.

HLA‐B gene somatic insertion/deletion mutations in patients with acute myelogenous leukaemia

“…On the other hand, the same authors point out that HLA somatic mutations are probably underestimated, because they are only detected in blood samples with a substantial proportion of malignant cells, but not in the remission samples. There have also been several further single case reports on somatic HLA mutations of various types in haematological diseases (Dubois et al, 2012;Heyrman, De Becker, Verheyden, & Demanet, 2017;Jeong et al, 2017;Mrazek et al, 2014;Planelles et al, 2016;Sayer et al, 2004;Venigova, Jindra, & Koza, 2011). At present, we are almost completely lacking in the relevant data on the biological importance of the pretransplant HLA somatic mutation in tumour cells in the context of clinical aHSCT.…”