HLA-Identical Sibling Donor Bone Marrow Transplantation for Individuals With Severe Sickle Cell Disease Using a Reduced Intensity Conditioning Regimen

Summary

Sickle cell disease (SCD) is the most common inherited blood disorder in Saudi Arabia . Its clinical severity is widely heterogeneous among patients who share the same genetic mutation . Severe frequent pain crisis, recurrent acute chest syndrome and stroke are features of severe SCD. Hydroxyurea is an effective treatment of SCD as it ameliorates the severity and frequency of pain crisis and acute chest syndrome and decreases mortality, however, it is less effective in the prevention and treatment of stroke and other end organ dysfunctions . The only readily available cure of SCD is by hematopoietic stem cell transplantation (HSCT) . Most children with SCD who are treated by HSCT receive myeloablative conditioning with excellent results. The application of reduced intensity (RIC) and non-myeloablative (NMA) conditioning regimens are reserved for patients older than 16 years of age because of the increased risks of morbidity and mortality after HSCT6. However, infertility and gonadal failure after myeloablative conditioning are important barriers to the willingness of patients and their families to undergo HSCT . The development of an effective RIC HSCT in SCD that might spare the fertility of SCD patients would have obvious merit. With the ultimate goal of expanding this curative therapy to SCD patients, we propose to investigate HSCT with a RIC conditioning regimen. We will carry out a pilot study of HSCT from HLA matched sibling donors using thymoglobulin/fludarabine/melphalan conditioning and sirolimus and mycophenolate mofetil (MMF) as GVHD prophylaxis in SCD patients with severe complications such as stroke and other severe complications. We hypothesize that HSCT from HLA matched sibling using thymoglobulin/fludarabine/melphalan conditioning in SCD will maintain a level of stable donor chimerism that is sufficient to cure SCD with minimal toxicity.

Timeline

Start

2016-05

Primary completion

2019-12

Completion

2019-12

Drugs

Indications