unraveling the impact of thalidomide at diverse doses in transfusion dependent beta thalassemia

Conditions: Fetal Hemoglobin; Thalassemia Major; Genetic Disease

Summary: the project "unraveling the impact of thalidomide at diverse doses in transfusion dependent beta thalassemia" investigates the safety and efficacy of low-dose thalidomide in managing beta thalassemia, a genetic disorder causing anemia. conducted over two years at nibd hospital, the study involves 54 transfusion-dependent patients aged 8-35. the primary objective is to correlate thalidomide doses with disease severity, adverse effects, and treatment response, aiming to optimize treatment strategies and reduce side effects. data will be collected through clinical interviews and medical record reviews and analyzed using spss. key variables include hemoglobin levels, leukocyte and reticulocyte counts, platelets, liver and spleen size, genetic modifiers, and transfusion frequency. inclusion criteria are specific to beta thalassemia patients, while exclusion criteria rule out those with liver dysfunction, married patients, lactating mothers, and those with a history of thrombosis or fits.

thalassemia is an inherited monogenic blood disorder caused by improper synthesis of the hemoglobin chain, inherited in an autosomal recessive pattern. hemoglobin is essential for oxygen transport from the lungs to body tissues. initially observed in individuals of italian descent, thalassemia is characterized by anemia, enlarged spleen, and bone abnormalities. it affects approximately 1.5% of the global population, with 60,000 infants born annually with severe forms such as homozygous alpha thalassemia, beta-thalassemia, and hbh disease. patients with thalassemia major require frequent blood transfusions and iron chelation therapy to manage iron overload, which can lead to complications like cirrhosis, heart failure, and growth retardation. iron chelators such as deferasirox, deferiprone, and deferoxamine are used in pakistan either as solo or combination therapy based on iron levels. bone marrow transplantation from hla-identical siblings offers a curative option with high success rates, but non-hla identical cases are less promising. emerging therapies like hbf production reactivation, cell therapy, and gene therapy show potential for better management of thalassemia. beta thalassemia is a prevalent genetic disorder, especially in the mediterranean, middle east, and southeast asia. it causes reduced hemoglobin production, severe anemia, and dependence on regular blood transfusions, which lead to iron overload and associated complications. thalidomide, initially marketed as a sedative in 1954 and later withdrawn due to teratogenic effects, has shown efficacy in hematologic disorders. its potential in beta thalassemia, particularly for reducing transfusion requirements and managing iron overload, remains underexplored. preliminary studies suggest thalidomide could reduce transfusion needs, but comprehensive dose-dependent research is lacking. this study aims to evaluate the effects of thalidomide at various doses in transfusion-dependent beta thalassemia patients, hypothesizing that optimal dosing can improve disease management and quality of life. preliminary research indicates thalidomide might reduce transfusion frequency and manage iron overload in beta thalassemia patients. however, detailed dose-dependent studies are necessary. this research aims to fill the gap by exploring thalidomide's benefits and safety profiles at diverse doses, potentially revolutionizing the therapeutic approach to beta thalassemia. the study aims to evaluate the impact of diverse thalidomide doses on reducing transfusion dependency in beta thalassemia patients. primary objectives include assessing the efficacy of thalidomide in reducing transfusion needs. secondary objectives involve evaluating the impact on complete blood count, liver function, spleen size, serum ferritin levels, and iron overload, alongside monitoring safety profiles and adverse events. impact of genetic modifiers on thalidomide and beta thalassemia phenotype will also monitor in this study. the study will be a single-center randomized controlled clinical trial at the national institute of blood disease and bone marrow transplant hospital in karachi, pakistan, specializing in genetic disorders and hematology-oncology. participants will be divided into treatment (with two dose groups) and control groups, with a total sample size of 54 calculated using openepi. the study will span two years, from may 2024 to may 2026, involving data collection through medical records, interviews, and questionnaires. ethical approval and informed consent will be obtained, ensuring patient confidentiality and adherence to ethical standards. data will include patient demographics (age, gender, ethnicity, marital status, weight, height), clinical variables (type of thalassemia, comorbidities, previous treatment), laboratory variables (hemoglobin, leukocyte count, reticulocyte count, platelets, lactate dehydrogenase, ferritin, d-dimer, bilirubin levels, sgpt), genetic modifiers (hbb mutation, xmn polymorphism, bcl11a polymorphism, alpha chain co-inheritance), and others (spleen and liver size, fibroscan, t2 star, transfusion frequency).

Eligibility criteria:
inclusion criteria: * know case of beta thalassemia major/ intermediate ( transfusion dependent) * willing to give informed consent exclusion criteria: * patients with comorbidities such as liver dysfunction * married patients * lactating mother * h/o thrombosis and fits

Keywords: thalidomide safety and efficacy thalassemia fetal hemoglobin inducer