Effect of hydroxyurea on the transfusion requirements in patients with severe HbE-beta-thalassaemia: a genotypic and phenotypic study.
BACKGROUND
Haemoglobin E (HbE)-beta-thalassaemia has a very variable clinical presentation. The management of severe cases that are often transfusion dependent is similar to that of cases of beta-thalassaemia major; however, this is often not possible in India because of its high cost and the lack of availability of safe blood at many places. Thus there was a need for a drug such as hydroxyurea, which is known to reduce the transfusion requirements of patients with thalassaemia intermedia. This study was undertaken to evaluate the response of Indian patients with HbE-beta-thalassaemia to hydroxyurea.


METHODS
11 patients with HbE-beta-thalassaemia receiving regular transfusion plus two less frequently transfused patients were selected for hydroxyurea therapy. Clinical and haematological evaluation was performed before and after treatment for 2 years. Molecular studies included beta-globin genotype, beta-globin gene haplotype, Xmn I polymorphism and alpha-genotyping.


RESULTS
Four clinically severe patients became transfusion independent (responders) after hydroxyurea therapy, four patients showed a reduction in their transfusion requirements (partial responders), and three patients were non-responders. Responders showed a statistically significant increase in Hb, mean corpuscular volume, mean cell Hb, fetal Hb and F cells with a reduction in their transfusion requirements. A reduction in serum ferritin concentration was also seen in responders and non-responders.


CONCLUSIONS
Genetic markers such as Xmn I polymorphism and alpha-gene deletions were not always beneficial for the response to hydroxyurea therapy. Thus many more markers and a larger cohort need to be studied to predict the response in these patients.
National Institute of Immunohaematology, K E M Hospital Campus, Parel, Mumbai, India.
Khushnooma Y
KY
Italia
Farah F
FF
Jijina
Rashid
R
Merchant
Sangeeta
S
Panjwani
Anita H
AH
Nadkarni
Pratibha M
PM
Sawant
Sona B
SB
Nair
Kanjaksha
K
Ghosh
Roshan B
RB
Colah
D000293:Adolescent; D000328:Adult; D001803:Blood Transfusion; D002648:Child; D003131:Combined Modality Therapy; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D005293:Ferritins / Q000097:blood; D005838:Genotype; D006446:Hemoglobin E / Q000032:analysis*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D009154:Mutation; D011110:Polymorphism, Genetic; D016896:Treatment Outcome; D055815:Young Adult; D055544:beta-Globins / Q000235:genetics; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy
D055544:beta-Globins; D005293:Ferritins; D006446:Hemoglobin E; C028649:endodeoxyribonuclease XmnI; D015252:Deoxyribonucleases, Type II Site-Specific; D006918:Hydroxyurea