Hydroxycarbamide treatment and brain MRI/MRA findings in children with sickle cell anaemia

Br J Haematol. 2016 Oct;175(2):331-338. doi: 10.1111/bjh.14235. Epub 2016 Sep 8.

Abstract

Silent cerebral infarction (SCI) is the most common neurological abnormality among children with sickle cell anaemia (SCA). The effect of hydroxycarbamide (also termed hydroxyurea) on the development and progression of SCI is unclear. We evaluated brain magnetic resonance imaging/angiography (MRI/MRA) in children with SCA receiving long-term hydroxycarbamide therapy. Fifty participants (median 9·4 years, range 1·1-17·3) enrolled in the Hydroxyurea Study of Long-Term Effects (HUSTLE; NCT00305175) underwent brain MRI/MRA and laboratory evaluations before hydroxycarbamide initiation and after 3 and 6 years of treatment to maximum tolerated dose. SCI and vascular stenosis were evaluated. At baseline, 3 and 6 years, SCI were present in 19/50 (38%), 20/49 (41%), and 7/17 (41%), respectively. At 3 years, one child developed a SCI lesion, and another progressed (single lesion to multiple). Lower haemoglobin (Hb) (80 g/l vs. 86 g/l, P = 0·049), fetal Hb (5·0% vs. 10·4%, P < 0·001) and oxygen saturation (97% vs. 98%, P = 0·027) before hydroxycarbamide initiation were associated with SCI. No patients had vascular stenosis identified on MRA, transient ischaemic attack or stroke. Our data indicate that children receiving hydroxycarbamide over a 3- to 6-year period have a low rate of new or worsening cerebrovascular disease. Further studies are needed to confirm that hydroxycarbamide can prevent the onset and progression of SCI.

Keywords: brain MRA; brain MRI; hydroxycarbamide; sickle cell anaemia; silent cerebral infarct.

MeSH terms

  • Adolescent
  • Anemia, Sickle Cell / complications*
  • Anemia, Sickle Cell / diagnosis
  • Anemia, Sickle Cell / drug therapy*
  • Asymptomatic Diseases
  • Brain Infarction / diagnostic imaging*
  • Brain Infarction / etiology*
  • Child
  • Child, Preschool
  • Female
  • Fetal Hemoglobin / genetics
  • Humans
  • Hydroxyurea / therapeutic use*
  • Infant
  • Magnetic Resonance Angiography*
  • Magnetic Resonance Imaging*
  • Male
  • Treatment Outcome

Substances

  • Fetal Hemoglobin
  • Hydroxyurea