A novel transplant procedure using bone marrow from a “half-matched” donor is safe and curative for adults with sickle cell disease, as well as more affordable than recently approved gene therapy products for SCD.
RT’s Three Key Takeaways:
- Safe and Effective Treatment for Sickle Cell Disease – A reduced-intensity haploidentical bone marrow transplant has shown a 95% survival rate and 88% cure rate in adults with severe sickle cell disease, offering a viable alternative to gene therapy.
- Lower Cost and Fewer Complications – This transplant procedure costs significantly less than gene therapy ($467,747 vs. $2M–$3M), requires shorter hospitalization, and has a lower risk of long-term side effects.
- Expanding Access to Treatment – Unlike gene therapy, which requires high-dose chemotherapy, this transplant is accessible to most adults with sickle cell disease, even those with end-organ damage, challenging misconceptions about donor matching and risks.
A novel bone marrow transplant process is safe and curative for adults with sickle cell disease, according to research published in The New England Journal of Medicine Evidence.
The treatment, called reduced-intensity haploidentical bone marrow transplantation, is available at multiple US medical centers and is a viable and less costly alternative to recently approved gene therapy products for sickle cell disease, according to investigators from Johns Hopkins Kimmel Cancer Center and Vanderbilt University Medical Center.
During this type of transplant, bone marrow is given by a “half-matched” donor, such as a parent, sibling, child, niece, nephew, aunt, uncle or cousin of the patient. This means the proteins that help the body’s immune system function, and which are present on a donor’s marrow cells, must match at least half of those proteins on the recipient’s cells to be a good fit and to not attack the recipient’s body after the transplant.
Before the transplant, patients are treated with low doses of chemotherapy and given total body irradiation. Following the transplant, they are given cyclophosphamide (a drug to prevent graft-versus-host disease, in which immune cells in the donor marrow attack their new host) and other drugs for up to one year.
Of 42 people with severe sickle cell disease who had the procedure during the trial, 95% were alive two years after the transplant, and 88% are considered cured and are experiencing no disease-related events, according to John Hopkins researchers.
“The findings are significant and have implications for enhancing the care of patients with sickle cell disease,” said Adetola Kassim, MD, MS, professor of Medicine, clinical director of VUMC’s Adult Stem Cell Transplant Program, and co-first author of the paper.
The trial shows very high engraftment of the donor cells and very high cure rates, the authors say.
“Our results with allogeneic transplant are every bit as good as or better than what you see with gene therapy,” says Richard Jones, MD, professor of oncology, director of the bone marrow transplantation program and co-director of the hematologic malignancies program at the Kimmel Cancer Center. Most people with sickle cell disease are eligible for the transplant, which costs a fraction of the price of gene therapy, he says.
“Many people — and maybe most adults — aren’t eligible for gene therapy because of the requirement for high dose chemotherapy that people with end organ damage can’t receive,” Jones says. “The risk of long-term side effects likely also will be higher with gene therapy, both in terms of damage to organs and a risk of leukemia.”
A common misconception in the medical field is that transplantation for sickle cell disease requires a perfect matched donor and that it can result in severe graft-versus-host disease and high mortality, which this trial and other studies have shown aren’t true, says study co-author Robert Brodsky, MD, the Johns Hopkins Family Professor of Medicine and Oncology and director of the Division of Hematology at the Johns Hopkins University School of Medicine.
Transplantation is a far less costly option for medical centers and patients, Brodsky says. With a transplant, patients are in the hospital for about eight days, as opposed to six to eight weeks for gene therapy. Also, “the median number of transfusions for a gene therapy patient is 50, while the median number of transfusions after a haploidentical bone marrow transplant is six. It’s done almost entirely outpatient,” he says.
A review paper comparing allogeneic bone marrow transplant and gene therapy, which Jones and Brodsky co-authored, was published in the Feb. 25 issue of the journal Blood Advances. The paper demonstrates that the estimated cost of gene therapy is $2 million–$3 million, compared to about $467,747 for a transplant.
The median age of participants in the phase II trial, which took place from 2017–2021, was 22; 59% were male, 92% were Black and 4% were Hispanic. The average follow-up time was 37 months. Serious side effects were uncommon and included three graft failures, moderate to severe graft-versus-host disease (22%) and two deaths in the first year post-transplantation (one from COVID-19).
