Sickle cell disease is the most commonly inherited hemoglobinopathy (1).Disease modifying drug therapies such as hydroxyurea,L-glutamine,voxelotor and crizanlizumab reduce pain crises and severe complications(2).Hematopoietic stem cell transplantation (HSCT) is the only curative treatment option. In 1984, the first report of HSCT in a patient with SCD who was transplanted for AML demonstrated the efficacy of HSCT as a curative treatment option for SCD patients with severe disease.In 1996,Walters and colleagues first reported the curative benefits of treatment in a 22-year-old patient with severe sickle cell disease who had an HLA-identical sibling donor(3).

INDICATIONS FOR HEMATOPOIETIC STEM CELL TRANSPLANTATION

Indications for HSCT are summarized in the Table 1.

According to the expert panel,(1) any young patient with symptomatic SCD who has an HLA-identical sibling donor should be transplanted as early as possible, preferably at preschool age; (2)bone marrow and umbilical cord blood from HLA-identical sibling donors are the recommended stem cell sources;(3)for patients who need to use an alternate donor source,more stringent indications are still recommended, and these patients should only have HSCT under a clinical trial and at a center where the staff are experienced in the procedure(3).

DONOR SELECTION AND STEM CELL SOURCES

Current recommendations by the National Marrow Donor Program recommend high-level matching at the HLA-A,HLA-B,HLA-C and HLA-DRB1 loci for unrelated donors.20 Matching in all the loci is referred to as an 8/8 match (3).Unfortunately, <%20 of patients have HLA-matched donors.In the absence of a matched sibling donor, HLA-matched unrelated donors,HLA-identical sibling cord blood donors and haploidentical donors are alternatives.Two trials, Sickle Cell Transplant To Prevent Disease Exacerbation (STRIDE) and Sickle Cell Unrelated Transplant trial (SCURT), are evaluating the use of matched unrelated donors in different age groups and with different conditioning regimens.The STRIDE trial started in 2012 for reduced intensity myeloablative transplantation in patients with SCD aged 15-40 years and reported excellent outcomes (OS and EFS of %95) at 12-month follow-up.32 The SCURT trial opened in 2008 and demonstrated no difference in graft rejection rates with matched unrelated donors compared to HLA-identical sibling donors; however, significant morbidity from chronic GVHD (%62) was reported.

CONDITIONING REGIMENS

Conditioning regimens are categorized as being myeloablative,reduced intensity,or nonmyeloablative.

Myeloablative Conditioning Regimen The most commonly used myeloablative conditioning regimen for SCD consists of busulfan 14-16 mg/kg and cyclophosphamide 200 mg/kg ± ATG.Cryopreservation of sperm and ovarian tissue is recommended in these types of HSCT(1).

Reduced Intensity and Nonmyeloablative Conditioning Regimens Reports of SCD symptoms resolving even in patients with mixed chimerism suggest that complete donor chimerism is not necessary and have led to interest in using reduced intensity and nonmyeloablative conditioning regimens for this population(3).