Graft Versus Host Disease of the Brain Following Allogeneic Stem Cell Transplant for Myelodysplastic Syndrome

Graft-versus-host disease (GVHD) is a frequent cause of morbidity and mortality following bone marrow transplantation (BMT). GVHD, which can present either acutely or chronically, typically involves the skin, gastrointestinal tract, and liver. In contrast, GVHD involving other organs such as the heart and kidney is highly uncommon and involvement of the central nervous system has only rarely been described in the literature. We report an unusual case of GVHD that involved the heart, kidney, adrenals, and the brain of a recipient of a dual haploidentical stem cell transplant for myelodysplastic syndrome. Premortem, the patient developed GVHD of the skin and liver. The clinical course was also complicated by fungal infection (Rhizopus). GVHD of the CNS was characterized by a lymphocytic leptomeningitis with few perivascular multinucleated giant cells. Immunohistochemical studies demonstrated both CD8+ and CD4+ lymphocytes in the leptomeninges and the brain parenchyma with a marked predominance of CD8+ lymphocytes. CD20 and VZV immunohistochemistry was negative. Post-mortem PCR analysis of short tandem repeat (STR) polymorphisms demonstrated a range of ~20-50% of both donors' lymphocytes in multiple organs. However, due to prolonged formalin fixation, no PCR signal could be detected in the brain. GVHD of the CNS is rare and likely underreported due to the declining autopsy rate and a lack of recognition of the salient histologic features. RESULTS