Reduced-Intensity Transplant Regimen Expands Donor Access in Sickle Cell Disease

Sickle cell disease is a hereditary blood disorder that deforms red blood cells, causes vaso-occlusion, and shortens life expectancy. Many candidates for curative transplantation lack fully matched donors, and intensive conditioning can injure organs and fertility. Hospitals therefore need regimens that expand donor options while limiting toxicity. To help address this challenge, physicians at Johns Hopkins have developed a reduced-intensity bone marrow transplant approach designed to provide durable cures with lower rejection risk.

A study conducted by Johns Hopkins Kimmel Cancer Center (Baltimore, MD, USA) investigators evaluated a regimen that enables use of haploidentical, or half-matched, related donors such as a parent, child, or sibling. Patients receive low-dose chemotherapy and total body irradiation before transplant to temper host immunity, followed by posttransplant immunosuppression to prevent graft-versus-host disease. The protocol incorporates posttransplantation cyclophosphamide and 400 centigray total body irradiation.

In a new study published in Blood Advances, 43 individuals with sickle cell disease aged 5 to 41 underwent transplantation at a single center between November 2014 and January 2025. Seven had fully matched donors and 36 had half-matched donors. All participants had more than two serious disease complications, including stroke or avascular necrosis.

At an average follow-up of 2.43 years, the probability of five-year overall survival was 95.5%, and the probability of two-year disease-free survival was 94.5%. Graft failure occurred in 5% of patients. Severe graft-versus-host disease occurred in 2.4% and moderate cases in 7.3%. Patients discontinued immunosuppression at a mean of 354 days, and 10 adults were able to stop by six months.

The study also examined fertility outcomes after transplant. Among 27 females, 12 resumed menses or normalized hormone levels, and two had successful pregnancies within five years. Among seven males, five achieved normalized hormone levels; all patients were offered fertility preservation before transplant.

Operationally, adults stayed in the hospital a mean of 12 days, and 67% of prior opioid users discontinued opioids after the procedure. The investigators note the regimen’s potential accessibility relative to gene therapy, citing substantially lower costs.

“The survival rate in the long run in our study was about 95%, so we are curing the overwhelming majority of people who are transplanted, with mismatched donors. Essentially, nearly everybody who has either sickle cell disease or thalassemia, an inherited blood disorder, can be cured, because nearly everybody has a donor,” said Javier Bolaños-Meade, M.D., professor of oncology at the Johns Hopkins University School of Medicine.

Related Links
The Johns Hopkins Kimmel Cancer Center