Genetic Modifiers Of Beta-Thalassaemia Associated With Management Without Blood Transfusion: Ten Years Experience

Long survival with improve quality life in treatment of thalassaemia patients can be procure by blood transfusion and sedulous chelation but, it is cumbrous. Therapeutic manoeuvers designed to stabilize or increase hemoglobin without transfusion and to reduce the blood transfusion. Efforts have been undertaken to find an alternative approach to transfusion in β-thalassaemia.

On the basis of our previous studies evaluating the safety & efficacy of Hydroxyurea (HU) in beta thalassemia patients which is an oral Hb-F augmentation agent, at 10-15 mg/kg/day was used on 473 patients for Mean duration of 3 years under the guidelines of Helsinki’s declaration. Response was measured by using transfusion requirement prior to 6 months period of enrollment in the study as control. Patients were finally divided into Complete Responders (CR), partial responders (PR) and non-responders(NR).Patients’ genetic profile was investigated. Chi square test was applied to check association between variables, p-value ≤0.05 considered significant.

Complete responders were 176, PR were 194 while 103 were NR.  Most common genetic mutations observed were IVS1-5 (46%) either homozygous or heterozygous, Fr 8-9 (14.3%), IVS1-1 (11%), Cd 30 (5.5%), Fr 41-42 (5.5%), Del-619 (5%) &Cap+1 (1.9%). Astounding results were found when association of these mutations with response of HU was observed. Response was found to be closely related with gene mutations Cd-30 (61.5 % Responders), IVS1-1 (58 % Responders), Cap+1 (44.4 % Responders), IVS1-5 (33.6 % Responders). Homozygous Xmn-I polymorphism was observed in 21% & heterozygous in 24% of the patients, while 55 % had no Xmn-I polymorphism. Xmn-I polymorphism was found to be significantly associated with Response 67 % (p-value 0.00).

Hydroxyurea showed promising results in this long term follow up of large cohort of patients. We suggest screening all newly diagnosed thalassaemic children for Genetic characteristic in order to offer Hb-F Augmenting agent as an alternative to blood transfusion.

No relevant conflicts of interest to declare.