Role of hydroxyurea in thalassemia intermedia
Background: Thalassemia intermedia is a term used to define a group of patients with β thalassemia in whom the clinical severity of the disease is somewhere between the mild symptoms of the β thalassemia trait and the severe manifestations of β thalassemia major.1,2 Thalassemia intermedia encompasses a wide clinical spectrum. Mildly affected patients are completely asymptomatic until adult life, experiencing only mild anemia and maintaining hemoglobin levels between 7-10g/dL. These patients require occasional blood transfusions, during acute infections or blood loss. Patients with severe thalassemia intermedia generally presents between the ages of 2 to 6 years and although they are able to survive without regular transfusion therapy, growth and development can be retarded.2 There is currently no definitive treatment to correct the globin chain imbalance in thalassemia, but the promising approach involves the use of therapeutic agents to definitively correct the globin chain imbalance by re-activating the fetal globin genes. Hydroxyurea, a cytotoxic drug, is reported to be useful in reducing this degree of imbalance, thus decreasing the disease severity. Due to the lesser α/β globin imbalance in β-thalassemia intermedia (TI), compared with thalassaemia major, better clinical responses are expected in patients with TI.3,4
Objective: To determine the clinical response and frequency of side effects of hydroxyurea in thalassemia intermedia patients in local population.
Patients and methods: Descriptive case series study was conducted in Pediatrics Department of Fatima Memorial Hospital, Lahore from August to December 2016. Total 150 patients clinically diagnosed to have thalassemia intermedia fulfilling inclusion criteria were enrolled, interviewed and examined. Baseline investigations were sent to monitor the side effects of hydroxyurea. Hydroxyurea was started at dose of 15mg/kg/day and patients were called after every fortnight for first 8 weeks and then monthly for 4 months. If no response seen on first visit, dose was increased to 20mg/kg/day and called again after 2 weeks. If still no rise in Hb observed, labelled as” no response”, if Hb increase then label as according to clinical response criteria. Patients were graded according to clinical response criteria after 3 months starting of hydroxyurea. For blood transfusion frequency, patients’ blood transfusion record was explored for their mean pre-transfusion Hb levels and red cell consumption after and before start of hydroxyurea in 3 months. For leucopenia, complete blood count was repeated after 1 month starting hydroxyurea. For diarrhea, clinical examination and assessment was done after 1 month of starting hydroxyurea. For neuropathy clinical assessment was done periodically on monthly visits.
Results: Out of 150 patients, 79 (53%) were transfusion dependent and 71 (47%) were transfusion independent. Total of 123 (82%) showed response and 27 (18%) showed no response even after increasing dose from 15mg/kg/day to 20mg/kg/day. Out of 123 responders, 74 (49.3%) were good responder, 49 (32.7%) were partial responder. In good responders mean increment in hemoglobin ranged between 1.5g/dl to 2.5g/dl.
Conclusion: Hydroxyurea is an effective and well tolerated drug for the treatment of thalassemia intermedia with very few side effects. With use of this medicine, regular blood transfusions and its hazards can be prevented in these patients.