High dose chemotherapy followed by transplantation of unrelated, banked, umbilical cord blood provides curative therapy for young pediatric patients with familial erythrophagocytic lymphohistiocytosis fed
Familial erythrophagocytic lymphohistiocytosis (PEL) is an inherited disease that is uniformly fatal without myeloablation and transplantation therapy. Frequently babies and young children with this condition need to proceed to transplant rapidly before disease progression. Banked unrelated umbilical cord blood (uUCB)is a readily available source of allogeneic unrelated hematopoietic stem cells which can be used for patients who lack a matched related donor. Over the past 2 years, we have transplanted 4 babies with PEL with uUCB after cytoreduction with busulfan (40mg/mg/m2/dose PO q6 hours x 16 doses, days -9 to -6), cyclophosphamide (50mg/kg/dose IV daily, days -5 to -2) and ATG (30mg/kg/ dose, daily days -3 to -1). Prior to transplant, each baby had received at least 1 month of therapy with prednisone, VP-16 and intrathecal methotrexate. All had CNS involvement at diagnosis, but negative CSF cytopathology at the start of the preparative therapy for transplant. Prophylaxis for GvHD was provided with conventional dose cyclosporine and intermediate dose solumedrol. Supportive care was provided with G-CSF, prophylactic antiviral and antifungal therapy. TPN, RBC and platelet transfusions, and nursing under HEPA filtration. The median age and weights of the patients were 0.5 years (range 0.3-0.8) and 8.2kg (range 4.7-11.6), respectively. 75% were female and 50% were CMV negative. Two patients received a 4/6 and 2 received a 5/6 antigen matching graft. The median nucleated cell dose administered was 137 million cells/kg (range 70-215) and the median CD34 dose was 381,000 cells/kg (range 250-644K). All patients engrafted achieving an ANC of 500/mm3 at 12,12, 13, and 18 days, respectively. They achieved platelet and RBC transfusion independence in a median of 48 and 44 days repectively and achieved an untransfused platelet count of 50K/ mm3 in 31,49,69,and 75 days, respectively. 3/4 patients developed grade 1 GvHD involving skin only while the fourth had no GvHD. The average hospital stay was 45 days. All patients engrafted with 100% donor cells and are survi ving event-free and free of signs or symptoms of PEL from 75-660 days (median 451 days). These preliminary data suggest that unrelated UCB should be strongly considered as an allogeneic donor source for rapid transplantation of patients with PEL. Furthermore, it is not necessary to use total body irradiation in the preparative regimen to cure these babies of this disease.
Kurtzberg, J; Szabolcs, P; Howrey, RP; Driscoll, TA; Martin, PL
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