title: Alpha-thalassaemia and response to hydroxyurea in sickle cell anaemia.
abstract: BACKGROUND
  Hydroxyurea (HU) reduces vaso-occlusive crises (VOC) and other complications of sickle cell anaemia (SCA). Alpha-thalassaemia is a known modifier of SCA. Studies on the efficacy of HU in SCA patients with α-thalassaemia have yielded varying results.
  
  
  OBJECTIVE
  To determine the effect of α-thalassaemia in response to HU therapy in the Multicenter Study of Hydroxyurea (MSH) cohort.
  
  
  METHODS
  We compared the laboratory parameters and VOC incidence in the MSH cohort stratified by the presence or the absence of α-thalassaemia.
  
  
  RESULTS
  Hydroxyurea showed significant (P = 0.001 for all baseline vs. follow-up comparisons) treatment effect on red cell indices irrespective of α-globin gene deletion. The magnitude of the HU-related changes was similar for mean corpuscular volume (MCV) (no α-thalassaemia 13 fl and α-thalassaemia 13 fl) and mean corpuscular haemoglobin (MCH) (no α-thalassaemia 4 pg and α-thalassaemia 4 pg) in both groups. Foetal haemoglobin (HbF) and F-cells also increased significantly with HU treatment in both groups. Total haemoglobin increased after HU treatment in both groups, but the increase was smaller and not statistically significant in patients with α-thalassaemia. In contrast, HU-related reduction in VOCs was more pronounced in patients with α-thalassaemia (VOC incidence rate ratio HU/placebo: 0.63 for α-thalassaemia and 0.54 for no α-thalassaemia (P for interaction 0.003).
  
  
  CONCLUSIONS
  Hydroxyurea decreases VOCs in SCA patients with and without α-thalassaemia, and the degree of VOC reduction was more pronounced in the patients with alpha-thalassaemia. Despite the lower baseline values, changes in standard laboratory parameters such as MCV and HbF percent remain useful in monitoring HU therapy in the presence of α-thalassaemia.
authors: Division of Haematology, Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC, USA; Department of Paediatrics, The George Washington University Medical Center, Washington, DC, USA.
authors: Deepika S
authors: DS
authors: Darbari
authors: Mehdi
authors: M
authors: Nouraie
authors: James G
authors: JG
authors: Taylor
authors: Carlo
authors: C
authors: Brugnara
authors: Oswaldo
authors: O
authors: Castro
authors: Samir K
authors: SK
authors: Ballas
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000188:drug therapy*; D000986:Antisickling Agents / Q000627:therapeutic use*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D008297:Male; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D055542:alpha-Globins / Q000235:genetics; D017085:alpha-Thalassemia / Q000150:complications* / Q000235:genetics
chemical_list: D000986:Antisickling Agents; D055542:alpha-Globins; D006918:Hydroxyurea
keywords: alpha-thalassaemia; hydroxyurea; sickle cell anaemia; vaso-occlusive pain crisis