Severe graft-versus-host disease post allogeneic hematopoietic stem cell transplantation due to loss of HLA heterozygosity in recipient lymphocytes after full graft rejection

Germ cell tumors complicated by hematological malignancy (HM) are a rare clinical phenomenon. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially effective therapy, but graft-versus-host disease (GVHD) is a life-threatening complication. We report a case of a 13-year-old female patient diagnosed with germ cell tumors followed by acute lymphoblastic leukemia. After chemotherapy, she received allo-HSCT and her chimerism rate decreased rapidly to near zero by 6 months without evidence of HM recurrence. However, she developed severe, multiorgan GVHD-like manifestations. DNA analysis revealed the pathogenesis of GVHD to be loss of HLA heterozygosity in recipient hematopoietic cells. This paper presents a unique case of a 13-year-old female patient diagnosed with concomitant germ cell tumors and acute lymphoblastic leukemia, who underwent allogeneic hematopoietic stem cell transplantation and subsequently developed severe graft-versus-host disease (GVHD)-like manifestations (hereon, we call GVH-like-disease, GVHLD) despite the absence of donor chimerism and recurrent hematological malignancy. The underlying etiology was found to be HLA loss of heterozygosity (HLA-LOH) in the patient's newly reconstituted hematopoietic lineage. This is the first report of fatal GVHLD caused by HLA-LOH in the recipient's own immune system without donor chimerism. The paper highlights the importance of understanding the role of HLA-LOH in GVHLD pathogenesis. image