Genotype of Beta Thalassemia Patients As Predictors for Prognosis & Management without Blood Transfusion,
Authors: Ansari Saqib Hussain , Shamsi Tahir S , Khan Mohammed Tahir , Bohray Muneera , Farzana Tasneem , Perveen Kousar , Erum Sajida 
Published: October 2019

Abstract 3199

Introduction:

Packed red blood cell (PRC) transfusion with iron chelation, despite their undesirable effects, has been the mainstay of treatment for patients with beta-thalassaemia major. In the recent past introduction of oral medications that augment Hemoglobin F (HbF) has opened new horizons in the management & prognosis of these patients sparing many of them from the hardtimes of blood transfusions & related adversities.

Methods:

On the basis of our previous studies evaluating the safety & efficacy of Hydroxyurea (HU) in beta thalassemia patients which is an oral HbF augmentation agent, at 10–15 mg/kg/day was used on 238 patients for 24 months 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 3 groups on the basis of response, Group 1 consisted of Complete Responders, group 2 were partial responders & group 3 were non-responders. Group1 patients needed regular blood transfusions prior to HU therapy while after 24 months they never required transfusion as they maintained their mean Hb at ≥7gm/dL. Partial responders substantially decreased their need for transfusion (less than 50 %), while Non-responders had no decrease in their need for transfusions. All patients' genetic mutation profiles were investigated upon.

Results:

Most common genetic mutations observed were IVS1-5 (48%) either homozygous or heterozygous, Fr 8–9 (11.8%), IVS1-1 (10.5%), Cd 30 (7.6 %), Fr 41–42 (6.3%), Cap+1 (3.3%) & Del-619 (8%). Homozygous Xmn-polymorphism was found in 20% & heterozygous Xmn polymorphism was observed in 26% of the patients, while rest 54% had no Xmn polymorphism. Astounding results were observed when these mutations were correlated with response of HU. Response rate was found to be most closely related with gene mutations IVS1-1 (68% Responders), Cd-30 (56% Responders), Cap+1 (38% Responders)IVS1-5 (37% Responders). Xmn polymorphism was found to be significantly associated with Response rate 73% (p-value 0.00).

Discussion:

It was observed from our study that certain genetic mutations in beta-thalassemia & presence of Xmn polymorohism responds exceptionally well to oral HbF augmentation agents, sparing the patients from the adversities of blood transfusion. Most notably presence of IVS1-1 spared 68% of the patients from blood transfusions while Xmn polymorphism spared 73% of them. It is recommended, therefore, that a new classification be made on the basis of genetic profile of beta thalassemia patients for better treatment & prognosis preventing unnecessary blood transfusions.

Disclosures:

Ansari: National Institute of Blood Diseases & Bone Marrow Transplantation: Consultancy. Off Label Use: We used Hydroxyurea or hydroxy carbamide. Hydroxycarbamide increases the concentration of fetal hemoglobin. The precise mechanism of action is not yet clear, but it appears that hydroxycarbamide increases nitric oxide levels, causing soluble guanylyl cyclase activation with a resultant rise in cyclic GMP, and the activation of gammaglobin synthesis necessary for fetal hemoglobin. Shamsi:National Institute of Blood Diseases & Bone Marrow Transplantation: Consultancy. Bohray:National Institute of Blood Diseases & Bone Marrow Transplantation: Consultancy. Farzana:National Institute of Blood Diseases: Employment. Erum:National Institute of Blood Diseases: Employment.