According to the National Institute for Health and Care Excellence (NICE), SCA effects 1 in every 2000 live births in the UK. Sickle cell anaemia (SCA), is an autosomal recessive haemoglobin disorder caused by an inheritance of abnormal sickle beta globin genes. Haematopoietic stem cell transplantation (HSCT) is the only current curative treatment for patients with haematopoietic disorders such as sickle cell disease. HSCT treatment utilises haematopoietic stem cells removed from the bone marrow or peripheral blood of a donor and transplanted into the recipient’s bone marrow (Mehta and Hoffbrand, 2014).
In a healthy adult there are two alpha globin genes and two beta globin genes, ?2?2. If the individual is heterozygous and has one healthy gene and one mutated sickle gene, ?2??S, they are carriers and have the sickle trait (Ahmed and Blann, 2014). However, if both beta globin genes are mutated, as found in sickle cell anaemia, the individual will have HbS and is homozygous, ?2?S?S.This causes a single nucleotide replacement on the sixth position of the beta globin chain with glutamine to valine. The HbS molecule is able to carry oxygen however when deoxygenated, HbS changes the red blood cell (RBC) into a sickle shape by polymerising into long fibres (as shown in figure 1), this results in a decreased ability of the molecule to carry oxygen (Hoffbrand and Moss, 2016).
Repeated sickling of the RBCs when deoxygenated leads to premature destruction and vaso-occlusion, which leads to dactylitis, pain crisis, osteonecrosis, priapism and stroke in SCD patients. (Dubert et al) analysed the association between steady-state haemolysis and vascular complications of SCD among sub-Saharan African patients.This study showed that severe baseline anaemia, is associated with leg ulcers, microalbuminuria and echo graphic pulmonary hypertension (see figure 2). Although these complications are associated with indirect markers of increased haemolysis other factors contributing to this, in african SCD patients, include malnutrition and infectious diseases.Allo-HSCT remains the only curative approach, however it is still associated with morbidity mainly due to GVHD. Between 2010 and 2014, Cela et al, conducted a single centre descriptive study on 11 SCD patients transplanted with bone marrow from an HLA-identical sibling donor. Although none of the patients developed chronic GVHD, 6/11 patients were reported to have acute GVHD (aGVHD) of the skin, including one patient who suffered grade iv intestinal aGVHD resulting in the death of this patient.Previous studies also presented GVHD as the main cause of transplantation-related morbidity (TRM), Bernaudin et al 2007 observed the outcome of 87 SCD patients ranging from ages 2 to 22 years transplanted with grafts from a sibling donor with a median follow up of 6 years ( ranging from 2 to 18 years) and presented overall survival (OS) and event-free survival (EFS) rates of around 93% and 86%.
Stem cells for HSCT therapy can be harvested from the bone marrow or cord blood, Locatelli et al, determined whether SCD patients have different probabilities of benefiting from HLA-identical sibling cord blood transplantation (CBT) or bone marrow transplantation (BMT). The study comparatively analysed the outcome of 160 SCD patients, where 30 patients were HLA-identical sibling CBT recipients and 130 patients received BMT. Results showed that patients receiving CBT had slower neutrophil recovery and less had aGVHD, although the age of the recipients may have effected the outcome since CBT recipients were younger than BMT recipients (median age 6 vs 8 years, P = .02), and were also treated more recently. Overall, DFS did not vary between CBT and BMT patients and both showed positives outcomes in SCD.