Gγ-Xmn I polymorphism: a significant determinant of ß-thalassemia treatment without blood transfusion.

ß-thalassemia is characterized by impaired ß-chain synthesis leading to ineffective erythropoiesis, severe anemia, and a need for blood transfusion. Presence of Xmn I polymorphism (-158 C-T nucleotide change) in γ-globin gene is associated with a higher fetal hemoglobin and a lesser clinical severity. This prospective study attempted to find out the effect of hydroxyurea (HU) on ß-thalassemia patients in the presence or absence of Xmn I polymorphism. A total of 143 consecutive ß-thalassemia patients received HU (16 mg/kg/d). Sixty-four (44.7%) had Xmn I polymorphism (either homozygous or heterozygous). Patients were evaluated at a median duration of 3 years (range, 6 mo to 9 y). Responders became transfusion independent after 6 months, partial responders had a least 50% reduction in transfusion requirement and nonresponders had no significant reduction. Of the 64 patients with Xmn I polymorphism, 44 (69%) showed response (P<0.01), whereas in those who lacked Xmn I polymorphism (n=79), only 17 (21%) were responders. This study showed that the presence of Xmn I polymorphism in ß-thalassemia is a predictor of response to HU and highlights the possibility of managing this subset of patients without blood transfusion.

Efficacy of hydroxyurea in providing transfusion independence in ß-thalassemia.

BACKGROUND: Packed red blood cell (PRC) transfusion with iron chelation is the mainstay of treatment for ß-thalassemia major. This prospective interventional trial serves as a follow up to our similar earlier study that evaluated the efficacy and safety of hydroxyurea (HU) in minimizing PRC transfusions in patients with ß-thalassemia major. METHODS: One hundred fifty-two patients with ß-thalassemia major received HU at a mean dose of 16 mg/kg/d. The results were analyzed at the end of 24 months. Transfusion requirement during the 6 months preceding the study was considered as the control. RESULTS: One hundred forty-six of 152 patients were evaluated after 24 months of follow up; 6 patients were either lost to follow-up or withdrew consent. Grade 1 myelosuppression was observed in 4 patients and diarrhea in 2 patients. Sixty children (41%) did not require any transfusion after using HU; 57 patients (39%) showed partial response with greater than 50% reduction in PRC transfusion; and 29 patients (20%) were nonresponders with less than 50% reduction in PRC transfusion. The mean volume of PRC transfused was reduced for all patients. CONCLUSIONS: HU was found to be safe in patients with ß-thalassemia major, and resulted in the reduction of transfusion requirement and in an increase in the interval between transfusions.

Efficacy of hydroxyurea (HU) in reduction of pack red cell (PRC) transfusion requirement among children having beta-thalassemia major: Karachi HU trial (KHUT).

BACKGROUND: Packed red blood cell (PRC) transfusion with iron chelation is the mainstay of treatment for patients with beta-thalassemia major. Hemoglobin F augmentation is another approach to treat this hemoglobinopathy. This study evaluates the efficacy and safety of hydroxyurea (HU) in minimizing PRC transfusions in patients with beta-thalassemia major. METHOD: Twenty-three patients with beta-thalassemia major received HU at a mean dose of 16 mg/kg/d. The results were analyzed at the end of 24 months. Transfusion requirement during the 6 months preceding the study was considered as the control. RESULT: Twenty patients were evaluable after 24 months. The mean volume of PRC transfused was reduced from 2126.45 mL to 1489.59 mL (P<0.001). The interval between transfusions was increased by 68.7%. Grade I myelosuppression was observed in 4 patients and diarrhea in 2 patients. CONCLUSIONS: HU was found to be safe in patients with beta-thalassemia major, and resulted in reduction in the transfusion requirements and in increase of the intervals between transfusions.