Vasculopathy of small muscular arteries in pediatric patients after bone marrow transplantation

Abstract

Bone Marrow Transplant (BMT) is a critical therapeutic intervention for a variety of diseases occurring in the pediatric patient. Complications of allogeneic BMT include graft-versus-host disease (GVHD), infection, drug toxicity, thrombotic microangiopathy, and veno-occlusive disease. With solid organ transplantation, chronic vascular rejection has emerged as a major factor limiting long-term survival of the graft. We present a vasculopathy of small muscular arteries in 6 patients after allogeneic BMT. Cases include 4 boys and 2 girls ranging in age from 4 months to 13 years with full or partial human leukocyte antigen matching. Five of the 6 transplants were from related donors. The vasculopathy occurred 13 to 418 days after transplant and was noted in surgical specimens (2) and at autopsy (4). It was seen in the gastrointestinal tract and lung in 3 cases each. Vascular changes in small muscular arteries include concentric intimal or medial hyperplasia with luminal narrowing, prominent myxoid change, extravasated red blood cells, and presence of some foamy histiocytes with no evidence of thrombotic microangiopathy. Vasculopathy contributed to intestinal compromise requiring surgical intervention 3 times in 1 patient, and diffuse alveolar damage with hemorrhage in another. All 6 patients are dead. The cause of this unusual vasculopathy present in patients after BMT is likely to be multifactorial, involving effects of irradiation, chemotherapy, cyclosporine, and GVHD. Together these may create a negative synergy which produces an obliterative arteriopathy that should be recognized as a pathological entity and may be a harbinger of a poor prognosis.