Response to hydroxycarbamide in pediatric β-thalassemia intermedia: 8 years’ follow-up in Egypt

Abstract

Hydroxycarbamide (hydroxyurea or HU) has been shown to increase fetal hemoglobin (HbF) in patients with β-thalassemia intermedia (TI). The reported effects of HU in increasing the total hemoglobin (Hb) have been inconsistent. Studies of long-term therapy with HU in pediatric TI are rather uncommon. A retrospective observational study was carried out to evaluate the clinical responses to HU in Egyptian patients with β-TI. One hundred patients; children (n = 82, mean age 9.9 ± 4.1 years) and adults (n = 18) were studied for the mean Hb, HbF%, median serum ferritin, transfusion history, and splenic size before and after HU therapy (mean dose 20.0 ± 4.2 mg/kg/day, range 10-29 mg/kg/day) over a follow-up period 4 to 96 months (mean 35.4 ± 19.2 months). Molecular studies were also done for group of patients (n = 42). The overall response rate to HU was 79 %; 46 % were minor responders (with a reduction in transfusion rate by 50 % or more and/or an increase in their total hemoglobin level by 1-2 g/dl) and 33 % major responders (becoming transfusion-free and/or having an increase in total hemoglobin level by >2 g/dl). Mean hemoglobin increased among responders from 6.9 ± 0.9 g/dl to 8.3 ± 1.4 g/dl (p < 0.001). A significant rise in mean HbF (27.0 vs. 42.5 %; p < 0.011) and a decrease in median serum ferritin (800 vs. 644 ng/ml; p < 0.001) were also observed among responders (n = 45). Transfusions stopped in 44 % of pretreatment frequently transfused responders (n = 11/25). Splenic size decreased in 37 % of patients (n = 30/81). The predominant β-thalassemia mutation was 1-6 (T > C) in 32/42 (76 %) of studied patients; 28/32 were responders. Bivariate analysis showed no predictors of response as regards sex, pediatric and adult age, splenic status, or genotype. Hydroxycarbamide is a good therapeutic modality in the management of pediatric as in adult TI patients. It can minimize the need for blood transfusion, concomitant iron overload, and blood-born viral transmission especially in developing countries like Egypt.

The Genetic Determinants for Long-term Response to Hydroxyurea Therapy in Indian β-Thalassemia Patients

“…No correlation could be established with respect to age, sex, or genotype toward the prediction of response to hydroxyurea therapy. [27] Our study also showed a reduction in serum ferritin levels in both the groups after hydroxyurea therapy. This is in agreement with our earlier report where hydroxyurea has been shown to be a potential iron chelator in an animal model and transfusion-dependent β-thalassemia patients.…”

ATG vs thiotepa with busulfan and cyclophosphamide in matched-related bone marrow transplantation for thalassemia

“…39,41,42 Many patients, particularly in the ATG-BuCy group, were treated with Hu in order to minimize both liver and spleen size as well as extramedullary hematopoiesis. 43,44 There is a general perception that BMT centers need complex engineering standards requiring undue investments, even more so in developing countries, where the risk of infection might be greater. In fact, there is no evidence that the latter is true.…”

Thalidomide for Patients With Thalassemia Intermedia: A Retrospective Multicenter Clinical Study

“…For patients with TDT, the groups were defined by the following parameters: MaR, removal from the blood transfusion, MiR, ≥50% reduction in transfusion requirement, and NR, <50% reduction in transfusion requirement. 4,7 Statistical analysis. SPSS Statistics 21.0 (SPSS Inc., Chicago, IL, USA) was applied for data analysis.…”

“…Hydroxyurea, approved by the FDA for the treatment of sickle cell disease (SCD), is also the most widely used HbF inducer in β-thalassemia. However, the clinical application of hydroxyurea is limited by the low number of significant responders, 7,8 reduced clinical response with long follow-up, 9,10 and bone marrow suppression. 11 Therefore, better treatments facilitating improved outcomes are increasingly important.…”