We describe a patient with homozygous β°thalassemia who experienced a prolonged hématologie response to therapy with Hydroxyurea (HU) and recombinant human erythropoietin (Epo). A term female infant born to non-consanguineous Iranian parents manifested transfusion-dependent anemia in the first year of life. Transfusions were administered at 4 week intervals and at 3-1/2 years of age her Ht was <5%,weight 25%, ferritin-1338. She received Desferrioxamine 1,000 mg by overnight subcutaneous infusion every other day. She had hepatosplenomegaly. The Mb analysis of the patient and her parents showed: Father Mother Patient %Hb A 93.5 93.5 0 %Hb A2 5.1 4.9 1.3 %Hb F 1.4 1.6 98.7 After transfusion therapy was stopped for 10 weeks the Hgb level was 6.6 gm/dl. This value remained unchanged for two additional weeks. After undergoing splenectomy and liver biopsy (iron content: 18,140 mcg/gm dry Wt.), she was started on Epo/HU therapy. Epo was given as 400 u/kg subcutaneously for 3 consecutive days, followed by HU (500 mg) X 2 days. After 3 months of Epo/HU therapy the Hb was maintained above 10 gm/dl and the reticulocyte count between 6%-10%. She has now been treated with Epo/HU for a total of 63 months, and has had no blood transfusions administered during this interval. The Hgb levels have ranged between 9.8-11.0 gm/dl. Her height is now between the 5%-10% for age. Although her weight has doubled, the dose of Epo remains unchanged and is now 223 u/kg. The dose of HU remains at 500 mg (16.3 mg/kg). She has experienced two transient episodes of neutropenia (ANC=960 and 806) which responded rapidly to temporary cessation of HU therapy. The current schedule of therapy is Epo on days 1 and 2 and HU on days 3 and 5. The cycle is repeated weekly. B-globin DNA sequencing of the patient and her parents revealed homozygosity in the patient for the IVS-II-1-(G→A) mutation. This mutation occurs on Mediterranean haplotype III with an Xmnl site in the G gamma promoter which is associated with a higher Hb F response to erythropoeitic stress. The combination of HU and Epo probably acts to further augmenting gamma globin synthesis, thereby reducing the chain imbalance and improving the hematology.
|Original language||English (US)|
|Issue number||11 PART II|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Cell Biology