Efficacy of Hydroxyurea (HU) in Reduction of Pack Red Cell (PRC) Transfusion Requirement Among Children Having Beta-thalassemia Major: Karachi HU Trial (KHUT) Saqib H. Ansari, MBBS, DCH, DPGN, MPhil, Tahir S. Shamsi, MBBS, FRCPath, Fahad J. Siddiqui, MBBS, MSc, Muhammad Irfan, MBBS, FCPS, Kausar Perveen, BSc, Tasneem Farzana, MBBS, MCPS, Vinodh K. Panjwani, MBBS, Ayesha Yousuf, MBBS, and Tabassum Mehboob, PhD Background: Packed red blood cell (PRC) transfusion with iron chelation is the mainstay of treatment for patients with beta- thalassemia major. Hemoglobin F augmentation is another approach to treat this hemoglobinopathy. This study evaluates the efficacy and safety of hydroxyurea (HU) in minimizing PRC transfusions in patients with beta-thalassemia major. Method: Twenty-three patients with beta-thalassemia major received HU at a mean dose of 16 mg/kg/d. The results were analyzed at the end of 24 months. Transfusion requirement during the 6 months preceding the study was considered as the control. Result: Twenty patients were evaluable after 24 months. The mean volume of PRC transfused was reduced from 2126.45 mL to 1489.59 mL (P <0.001). The interval between transfusions was increased by 68.7%. Grade I myelosuppression was observed in 4 patients and diarrhea in 2 patients. Conclusions: HU was found to be safe in patients with beta-thalassemia major, and resulted in reduction in the transfusion requirements and in increase of the intervals between transfusions. Key Words: hydroxyurea, beta-thalassemia major, transfusion volume (J Pediatr Hematol Oncol 2007;29:743–746) B eta-thalassemia is the most prevalent genetically transmitted blood disorder with a carrier rate of 5% to 8%; around 5000 children are diagnosed each year in Pakistan. 1,2 Efforts are being made to prevent this disorder. 3 Limited supply of blood and risk of transfu- sion-transmitted viral infections prompted researchers to look for alternative approaches to manage beta-thalasse- mia. 4 Affected infants maintain normal hemoglobin levels till the first couple of months after birth. Methylation of gamma-globin gene at this time switches off its synthesis. Mutated beta-globin gene is unable to provide functional beta-globin chains to combine with alpha-globin chains, resulting in severe anemia. Hemoglobin F (HbF) aug- mentation is an exciting concept; if gamma-globin gene can be reactivated in postnatal life, then gamma-globin chain synthesis will restart. This will reduce the imbalance of alpha-beta/nonalpha globin chain ratio in red cells and ameliorate the biochemical defects in hemoglobin mole- cule and partially correct the ineffective erythropoiesis. 5 There are a number of pharmacologic agents at different stages of development that can induce HbF production. 6,7 5-Azacytidine was the first HbF-inducing agent tested in patients with sickle cell disease (SCD). 6,7 Further studies were abandoned because of the concerns regarding its carcinogenic potential. rHuEPO treatment has shown an increase in HbF levels in transfusion dependent beta-thalassemia patients in various studies. 8 Variable degree of response has also been seen in small groups of patients during therapy with arginine buty- rate in homozygous beta-thalassemia. 9,10 In contrast to 5-azaC, hydroxyurea (HU) is an oral agent widely used in the treatment of myeloproliferative disorders with a good safety profile. HU was first used in a number of small- scale nonrandomized clinical studies that confirmed its Copyright r 2007 by Lippincott Williams & Wilkins Received for publication July 19, 2006; accepted July 26, 2007. From the Bismillah Taqee Institute of Health Sciences and Blood Disease Center. Contribution of authors: Dr Saqib H. Ansari designed the protocol and was involved directly in patient care throughout the study. He did the literature search and wrote the manuscript. Dr Tahir S. Shamsi is the mentor of the group. He gave intellectual input, defined strategy, and defined questions that needed to be addressed. He was involved in patient care and contributed in writing and editing the manuscript. Dr Fahad J. Siddiqui is a Biostatistician. He contributed in the statistical analysis of data. Dr Muhammad Irfan was involved in patients care and contributed in data collection and literature search. Ms Kausar Perveen was actively involved in data collection and biostatistical analysis. Dr Tasneem Farzana participated in patient care and manuscript writing. Dr Vinodh K. Panjwani was actively involved in patient care, data collection, and literature search. Dr Ayesha Yousuf participated in writing the protocol and designing patient data form. She was also involved in patient care. Dr Tabassum Mehboob participated in manuscript writing. Reprints: Dr Saqib H. Ansari, MBBS, DCH, DPGN, MPhil, Bismillah Taqee Institute of Health Sciences and Blood Disease Center, ST-19, Block-5, Rashid Minhas Road, Gulshan-e-Iqbal, Karachi (e-mail: ansarisaqib@hotmail.com). ORIGINAL ARTICLE J Pediatr Hematol Oncol  Volume 29, Number 11, November 2007 743