The first randomised double-blind trial to examine the effect of hydroxycarbamide (previously hydroxyurea) in very young children with sickle-cell anaemia shows that the drug is safe and significantly reduces pain and other common complications of the disease as well as hospitalisations and transfusions. The findings, published in this week's edition of The Lancet, suggest that hydroxycarbamide is underused in young patients and should now be the standard of care for all children with the disease.
Sickle-cell anaemia causes bone marrow to produce red blood cells with defective haemoglobin, resulting in sickle-shaped red blood cells. These deformed cells block small blood vessels causing a number of complications including pain, strokes, organ dysfunction, and premature death. Hydroxycarbamide is the recommended treatment in adults and substantially reduces symptoms, admissions to hospital, and transfusions, with no evidence of long-term toxicity. However, little is known about its effects in infants, although previous small studies have reported its benefits in reducing symptoms in school-age children and adolescents.
The BABY HUG trial was designed to assess whether liquid hydroxycarbamide (20 mg/kg daily) safely prevents early organ damage (particularly of the spleen and kidney) in very young children with sickle-cell anaemia. Between October 2003 and September 2007, 193 patients aged 9 months were enrolled from 13 centres across the USA and randomly assigned to hydroxycarbamide (96) or placebo (97) for 2 years.
Hydroxycarbamide therapy significantly reduced the most common complications and decreased the occurrence of hospitalisations and transfusions. Pain was nearly twice as frequent, dactylitis (painful inflammation of the hands or feet) five times as common, and acute chest syndrome three times higher in the placebo group. The authors also reported some benefit for spleen, kidney, and neurological function, but the results were not conclusive.
Hydroxycarbamide therapy was well tolerated, with mild-to-moderate neutropaenia (low levels of neurophils, a type of white blood cell) the only adverse effect associated with treatment.
The authors say: "The laboratory and clinical benefits of hydroxycarbamide for children and adolescents with sickle-cell anaemia, coupled with an excellent short-term and long-term safety profile, suggest that hydroxycarbamide is underused in young patients."
They conclude: "The results of the BABY HUG study should have a major effect on guidelines for the management of children with sickle-cell anaemia… hydroxycarbamide therapy can now be considered for all very young children with sickle-cell anaemia whether or not they have clinical symptoms."
In a Comment, David Weatherall from the University of Oxford, Oxford, UK says: "Hydroxycarbamide is inexpensive and could certainly be made available in low-income countries in which sickle-cell anaemia is so common. Although there is still a long way to go in the management of sickle-cell anaemia, enough can be achieved such that establishment of international partnerships between richer countries and low-income countries for the better management of sickle-cell anaemia is now vital. In view of the early deaths that result from this disease in sub-Saharan Africa, the success of this trial in early infancy is particularly encouraging."
Dr Winfred C Wang, St Jude Children's Research Hospital, Memphis, USA. T) +1 901 595 2051 E) Winfred.wang@stjude.org
Or St Jude Children's Research Hospital Public Relations T) +1 901 595 3306 E) media@stjude.org
Professor David Weatherall, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. E) liz.rose@imm.ox.ac.uk
Journal
The Lancet