Sickle cell disease (SCD) is a recessive hereditary red blood cell disorder (homozygosity for the haemoglobin S gene – HbS confers the disease) that is characterized by early mortality and severe morbidity, including debilitating painful crises and organ involvement, particularly chronic kidney injury that can progress to renal failure and dialysis. Sickle cell is prevalent in regions of the world where malaria is endemic as heterozygosity for the HbS gene confers some protection from malaria.

Mortality has improved significantly with improved care and particularly since the introduction of hydroxyurea therapy. Hydroxyurea is an antimetabolite that helps prevent the formation of sickle-shaped red cells. However, HSCT remains the only curative treatment currently available for SCD. Not only is HSCT curative, it abates progressive organ dysfunction.

HSCT for sickle cell is usually reserved for children with major complications, such as stroke and who have a fully HLA-matched sibling donor. Older patients with significant co-morbidities are usually excluded from HSCT. In a small clinical trial (the SCURT trial) of matched unrelated donor (MUD) transplantation, children had a 2-year survival of 79%. One-year incidence of GvHD was high. In general, a MUD donor is only used if there is no HLA-matched sibling donor and there is recurrent severe pain episodes despite hydroxyurea therapy and there is overt stroke or any neurologic deficit lasting >24 h. It is recommended that MUD transplants take place in the context of a clinical trial.

In the UK, use of other alternative donors such as 11/12 MUD and cord require approval from a national panel. In addition, there have been a small number of haplo transplants that have recently been undertaken successfully.