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

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.

Hydroxycarbamide for patients with silent cerebral infarcts: outcomes and patient preference

“…The HUSTLE cohort of patients in the setting of a hydroxycarbamide cohort (Nottage et al , ) and our current study in the setting of an institutional MRI screening programme and standard of care hydroxycarbamide therapy suggest a similar benefit of hydroxycarbamide for overt stroke protection in patients with SCI. Our cohort also suggests that patients with SCI and a normal MRA may prefer hydroxycarbamide to transfusion for secondary CNS protection.…”

“…Nottage et al () reported 3‐year magnetic resonance imaging (MRI) outcomes in patients who participated in a cohort study of long‐term hydroxycarbamide therapy (HUSTLE), providing early data on the potential impact of hydroxycarbamide in preventing SCI progression. Nineteen (38%) of 50 participants were identified with a SCI on HUSTLE baseline evaluation.…”

“…To complement the study reported by Nottage et al (), we performed a 15‐year Institutional Review Board‐approved retrospective study of all patients with an incident SCI at Children's of Alabama. Prior to and during SIT Trial enrolment (2004–2010), we only obtained MRI scans for clinical indication or SIT Trial participation.…”

A clinically meaningful fetal hemoglobin threshold for children with sickle cell anemia during hydroxyurea therapy

“…Previous analyses from the HUSTLE study reported that children receiving hydroxyurea escalated to MTD may have higher levels of HbF, Hb and MCV compared to children treated with lower doses of hydroxyurea 30 , and that children enrolled on HUSTLE have a low rate of new or worsening cerebrovascular disease 31 , and improved splenic 32 and renal 33,34 function. The current analysis of the HUSTLE study provides new critical clinical information regarding the optimal HbF% target during hydroxyurea therapy in children with SCA.…”

A pilot study to screen for poor academic performance in children with sickle cell disease in the outpatient setting

“…None of the patients who scored as at risk had ever used hydroxyurea as compared with 75% of those who scored as average. Low hemoglobin has been repeatedly identified as independently associated with neurocognition in sickle cell anemia across numerous studies, 6,17,18 with fetal hemoglobin being shown to be protective. 19 Not surprisingly, the SIT trial showed that the use of prophylactic simple transfusions was protective against the development of further silent infarcts with a 58% relative risk reduction.…”