title: Comparison of in-vitro and in-vivo response to fetal hemoglobin production and γ-mRNA expression by hydroxyurea in Hemoglobinopathies.
abstract: BACKGROUND
  Hydroxyurea, which induces Fetal hemoglobin (HbF) synthesis, is the only drug widely used in different hemoglobinopathies; however, the response is very variable. We compared the efficacy of hydroxyurea in-vitro in erythroid cultures and in-vivo in the same patients with different hemoglobinopathies to induce HbF production and enhance γ-messenger RNA expression.
  
  
  METHODS
  A total of 24-patients with different Hemoglobinopathies were given hydroxyurea and their response was studied in-vivo and in-vitro on mononuclear cells collected from them simultaneously.
  
  
  RESULTS
  A total of 57.7% of patients (responders) showed no further crisis or transfusion requirements after hydroxyurea therapy with a mean increase in fetal cells (F-cells) of 63.8 ± 59.1% and γ-mRNA expression of 205.5 ± 120.8%. In-vitro results also showed a mean increase in F-cells of 27.2 ± 24.7% and γ-mRNA expression of 119.6% ± 65.4% among the treated cells. Nearly 19.0% of the partial-responders reduced their transfusion requirements by 50% with a mean increase in F-cells of 61.2 ± 25.0% and 28.4 ± 25.3% and γ-mRNA-expression of 21.0% ± 1.4% and 80.0% ± 14.1% in-vivo and in-vitro respectively. The non-responders (15.3%) showed no change in their clinical status and there was no significant increase in F-cells levels and γ-mRNA expression in-vivo or in-vitro.
  
  
  CONCLUSIONS
  Thus, this method may help to predict the in-vivo response to hydroxyurea therapy; however, a much larger study is required.
authors.affiliation: National Institute of Immunohematology, Hematogenetics, 13 Floor, K.E.M. Hospital Campus, Parel, Mumbai, India.
authors.forename: Khushnooma
authors.initials: K
authors.lastname: Italia
authors.forename: Farah
authors.initials: F
authors.lastname: Jijina
authors.forename: Rashid
authors.initials: R
authors.lastname: Merchant
authors.forename: Suchitra
authors.initials: S
authors.lastname: Swaminathan
authors.forename: Anita
authors.initials: A
authors.lastname: Nadkarni
authors.forename: Maya
authors.initials: M
authors.lastname: Gupta
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.forename: Roshan
authors.initials: R
authors.lastname: Colah
keywords: 2 phase liquid erythroid cell culture; hydroxyurea; sickle cell disease; β-thalassemia syndromes; γ-mRNA expression
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