Beta thalassemia Major (BTM) is the most common hemoglobinopathy caused by mutations in the beta-globin gene . Worldwide, approximately 80 million people carry thalassemia gene mutation. Around 23,000 babies are affected by BTM each year, of which around 90% belong to low- or middle-income nations.

In Pakistan, the carrier prevalence of thalassemia is 5-7% resulting in a significant population of approximately 10 million carriers in the general population. There are 50,000 thalassemia patients registered in treatment facilities around the country, one of the highest global prevalence rates for transfusion dependent BTM. The average life expectancy of BTM patients in Pakistan is around 10 years of age, while life expectancy in developed countries is around 50 to 60 years. This difference is due to poor transfusion support, transfusion-transmitted infections (TTIs) and inadequate iron chelation leading to hepatotoxicity and cardiac failure.

The standard of care for BTM remains bone marrow transplantation or lifelong blood transfusions followed by iron chelation therapies. While standard care involves, challenges such as limited resources, lack of access to transplant services, and transfusion-related complications persist, particularly in low-and-middle-income countries.

Beta thalassemia Major (BTM) is the most common hemoglobinopathy caused by mutations in the beta-globin gene . Worldwide, approximately 80 million people carry thalassemia gene mutation. Around 23,000 babies are affected by BTM each year, of which around 90% belong to low- or middle-income nations.

In Pakistan, the carrier prevalence of thalassemia is 5-7% resulting in a significant population of approximately 10 million carriers in the general population. There are 50,000 thalassemia patients registered in treatment facilities around the country, one of the highest global prevalence rates for transfusion dependent BTM. The average life expectancy of BTM patients in Pakistan is around 10 years of age, while life expectancy in developed countries is around 50 to 60 years. This difference is due to poor transfusion support, transfusion-transmitted infections (TTIs) and inadequate iron chelation leading to hepatotoxicity and cardiac failure.

The standard of care for BTM remains bone marrow transplantation or lifelong blood transfusions followed by iron chelation therapies. While standard care involves, challenges such as limited resources, lack of access to transplant services, and transfusion-related complications persist, particularly in low-and-middle-income countries.

Hydroxyurea (HU), an FDA-approved inducer of fetal hemoglobin (HbF), has shown promise in reducing or eliminating the need for frequent blood transfusions in β-thalassemia patients. However, a subset of patients exhibits limited responsiveness to HU, necessitating exploration of adjunct or alternative therapies. Thalidomide, an immune modulator, has demonstrated transfusion reduction by suppressing nuclear factor-κB induction, potentially increasing HbF levels.

The primary aim of this prospective study is to determine the efficacy of the combination of thalidomide and hydroxyurea in reducing transfusion frequency in patients with β-thalassemia Major. The secondary objectives are to document the spectrum of significant adverse drug reactions as well to document any alteration in the spleen size and serum ferritin levels.

Inclusion Criteria:

• Patients suffering from Transfusion Dependent β-thalassemia (TDBT) more than two years of age of either sex will be included in the study.

Exclusion Criteria:

• Age less than two years.
• Patients having cardiac, hepatic, pulmonary, renal or neurological dysfunction or history of thrombosis.
• Both male and female participants of childbearing potential will be excluded due to the teratogenicity of thalidomide.

The investigators may share de-identified IPD upon reasonable request, beginning 9 months after publication and available for up to 24 months, following review and data-sharing agreement.

Six months after completion of study

Contact with PI