Haploidentical hematopoietic stem cell transplantation for lymphoma with monosomy of chromosome 6 (loss of heterozygosity in the HLA region) — Who should be a donor?

Hematopoietic stem cell transplantation (HSCT) from an HLA haploidentical family donor is an option for patients who do not have a full HLA matched donor and lack the time to find an unrelated one [1] and [2]. Furthermore, it may facilitate a powerful graft versus leukemia/lymphoma (GVL) effect to help combat hematological malignancies by directly targeting the mismatched HLA expressed on leukemia/lymphoma cells [3]. On the contrary, leukemia/lymphoma cells escape from the surveillance of the donor-derived GVL effect by losing the target HLA (mismatched HLA in GVH direction). This mechanism has been called loss of heterozygosity (LOH) in the HLA gene region on chromosome 6 [4,5]. Taking the above into account, in this case report, we present a case of lymphoma with monosomy 6, which means natural LOH of HLA, and suggest that selection of a haploidentical family donor matched with the missing HLA haplotype seems to be very effective.

► Some leukemia/lymphoma cells originally have a chromosomal abnormality of monosomy 6. ► One of the HLA haplotype should be lost on the lymphoma cells with monosomy 6. ► LOH of HLA haplotype is one of the mechanisms of relapse in haploidentical transplantation. ► The donor who could directly target the residual HLA on the lymphoma cells should be a donor in the case of monosomy 6.