Hydroxycarbamide treatment and brain MRI/MRA findings in children with sickle cell anaemia.
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.
Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Kerri A
KA
Nottage
Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Russell E
RE
Ware
Division of Pediatric Hematology/Oncology and Stem Cell Transplantation, Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park, NY, USA.
Banu
B
Aygun
Department of Epidemiology and Biostatistics, University of Memphis, Memphis, TN, USA.
Matthew
M
Smeltzer
Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Guolian
G
Kang
Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Joseph
J
Moen
Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Winfred C
WC
Wang
Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Jane S
http://orcid.org/0000-0003-4439-7321
JS
Hankins
Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN, USA. kathleen.helton@stjude.org.
Kathleen J
KJ
Helton
D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy*; D058070:Asymptomatic Diseases; D020520:Brain Infarction / Q000000981:diagnostic imaging* / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D007223:Infant; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D008297:Male; D016896:Treatment Outcome
D005319:Fetal Hemoglobin; D006918:Hydroxyurea
brain MRA; brain MRI; hydroxycarbamide; sickle cell anaemia; silent cerebral infarct