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.