Therapy
All of the patients have required transfusions, most chronically and beginning in the neonatal period or infancy (Table 3). Of the 28 patients in whom data are available, 2 patients received their first transfusions in utero (13.1 and 22.4), 12 in the neonatal period, 11 in infancy, and 3 between age 4- and 8-years. All but one was maintained on regular transfusions with a transfusion interval of between 2 and 8 weeks. In 20 of 20 patients for whom oral pyridoxine was prescribed, there was no improvement in the hemoglobin (HGB). All patients surviving early childhood have developed secondary iron overload and have required chelation. A variety of agents including deferoxamine, deferisirox, deferiprone alone or in combination have been employed. One patient (2.1), poorly compliant with chelation, died at age 18 from cardiomyopathy. Another (17.1), age 3, died of line-associated sepsis. Three patients who were status-post splenectomy experienced thrombocytosis and/or thrombotic events. The median age of patients alive at the time of last follow-up is 11 years (range 1-39 years).
Nine patients have undergone allogeneic hematopoietic stem cell transplantation (Table 4) with a median follow up of 7 years (range 1 mos. to 17 yrs.). All transplanted patients are alive; 8 of 9 had full engraftment and became transfusion independent. One patient (14.1) had secondary graft failure at 18-months post-transplant with auto recovery; she is transfusion dependent and being prepared for second transplant. Four patients received myeloablative conditioning, and 4 other received reduced intensity conditioning. Donors were matched unrelated donor (n=4), matched related donors (one matched family donor and three were matched sibling donors), and one patient had one antigen mismatch sibling donor. Methotrexate and a calcineurin inhibitors were the most common graft versus host disease prophylaxis. Acute and chronic graft versus host disease were seen in 1 and 3 patients, respectively. One patient developed chronic post-transplant autoimmune hemolytic anemia requiring transfusion.