Unique Reversible but Serious Adverse Events in Very Young Infants Undergoing Unrelated Donor Umbilical Cord Blood Transplantation for Non-Malignant Conditions: Increased Autoimmune Cytopenias and Hypertrophic Cardiomyopathy.

Between September 1998 and June 2004, 15 young infants, <3 months of age, 60% males, 14 Caucasian, 1 African American, underwent unrelated donor umbilical cord blood transplantation for treatment of non-malignant conditions [early infantile Krabbe disease (n = 9), MLD (n = 1), MPS I (n = 1), MPS II (n = 2), Tay Sachs Disease (N = 1) or Beta Thalassemia major (n = 1)]. All infants were prepared for transplant with oral busulfan 20mg/m2/dose (targeting a steady state of 600–900ng/ml), cyclophosphamide 50mg/kg/dose daily x 4, and equine ATG 30mg/kg/dose daily x 3. Cyclosporine and solumedrol were used for prophylaxis against GvHD. All infants engrafted with donor cells, although 1 patient with MPS II never achieved >50% donor chimerism. Two patients died 3 and 5 years post transplant from respiratory failure (1 patient with MPS II and incomplete chimerism) and progressive Tay Sachs Disease, respectively. Grafts were mismatched at 1 (n = 8) or 2 (n = 7) HLA loci and 8/15 donor/recipient pairs were ABO mismatched. Nine patients developed mild to moderate acute GvHD. Within 6–10 months of transplant, six of the 15 patients developed autoimmune cytopenias (autoimmune hemolytic anemia +/− ITP), diagnosed clinically by Coombs positivity and antiplatelet antibodies respectively. They required therapy with steroids, imuran, dacluzimab, rituximab, and in one patient, splenectomy. There was no correlation with ABO or HLA matching or GvHD and the incidence of autoimmune disease. All patients recovered within 3–24 months. Eight of the 15 newborns developed concentric cardiomyopathy while on solumedrol and either cyclosporine or FK506 for GvHD treatment and/or prophylaxis. One patient required intubation and prolonged mechanical ventilation. The others remained relatively asymptomatic. Over time and with weaning of steroid therapy, their left ventricular hypertrophy resolved and heart function returned to normal. Both autoimmune cytopenias and hypertrophic cardiomyopathy occur in higher frequency in very young infants undergoing unrelated donor umbilical cord blood transplantation. The etiology of the autoimmune disease is not currently known while the cardiac disease is a result of therapies used to treat and prophylax against GvHD.

Duke Scholars

Author Joanne Kurtzberg Pediatrics, Transplant and Cellular Therapy