Response to hydroxyurea therapy in beta-thalassemia.
Although a relatively small number of previous studies suggest a modest response to hydroxyurea (HU) therapy in beta-thalassemia, more recent investigations have revealed that some transfusion-dependent patients can become transfusion-independent following HU therapy. Patients with Ggamma XmnI polymorphism, several beta-globin mutations, and alpha-thalassemia deletions were inconsistently reported to have significant responses to HU therapy. To better predict who may respond, we retrospectively evaluated the clinical response and the molecular background of 18 beta-thalassemia patients treated with HU for a mean of 46 months. The majority of transfusion-dependent patients responded to HU therapy with 9 out of 11 (82%) becoming transfusion-independent. Five thalassemia intermedia (TI) patients receiving occasional blood transfusion did not require any additional transfusions following therapy and two TI patients who had never received transfusions had a 2 g/dl increase in their hemoglobin level. The majority of beta-thalassemia major patients who became transfusion-independent (7/9) were either homozygous (5) or heterozygous (2) for the XmnI polymorphism. No correlation was identified between response to therapy and the presence of specific beta-thalassemia mutations or alpha-globin deletions. We conclude that further analysis of the degree of response of transfusion-dependent beta-thalassemia patients to HU therapy, as well as, the impact of their genetic background on this response is required to identify patients likely to have significant response.
Koren
Ariel
A
Pediatric Hematology Unit and Pediatric Department B, Ha'Emek Medical Centre, Afula, Israel. koren_a@clalit.org.il
Levin
Carina
C
Dgany
Orly
O
Kransnov
Tatyan
T
Elhasid
Ronit
R
Zalman
Lucia
L
Palmor
Haya
H
Tamary
Hannah
H
D000293:Adolescent; D000328:Adult; D001803:Blood Transfusion; D002648:Child; D015331:Cohort Studies; D003131:Combined Modality Therapy; D015252:Deoxyribonucleases, Type II Site-Specific; D004341:Drug Evaluation; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D012189:Retrospective Studies; D017085:alpha-Thalassemia / Q000188:drug therapy / Q000235:genetics; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy
D006454:Hemoglobins; D005914:Globins; D005319:Fetal Hemoglobin; C028649:endodeoxyribonuclease XmnI; D015252:Deoxyribonucleases, Type II Site-Specific; D006918:Hydroxyurea