A bone marrow transplant process co-developed by investigators at the Johns Hopkins Kimmel Cancer Center is safe and curative for adults with sickle cell disease, according to results of a trial completed at Johns Hopkins and about 20 additional cancer centers nationwide and in London. The treatment, available at multiple U.S. medical centers, is a viable and less costly alternative to recently approved gene therapy products for sickle cell disease, the authors say.
During this type of transplant, called reduced-intensity haploidentical bone marrow transplantation, 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. These results will be published in the Feb. 25 issue of The New England Journal of Medicine Evidence. Early results were presented in December 2023 during the American Society of Hematology annual meeting.
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, M.D. , 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, M.D. , 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 posttransplantation (one from COVID-19).
Sickle cell disease — a painful blood disorder in which red blood cells are shaped like crescents instead of discs and tend to clog up blood vessels — affects about 100,000 Americans (primarily Blacks), according to the federal Centers for Disease Control and Prevention.
The clinical trial was supported and sponsored by the Blood and Marrow Transplant Clinical Trials Network; the National Institutes of Health; the National Heart, Lung and Blood Institute and the National Cancer Institute (grants U10HL069294 and U24HL138660).
Other centers participating in the trial were the Vanderbilt University Medical Center in Nashville, Tennessee; the University of California San Francisco School of Medicine; Medical College of Wisconsin in Milwaukee; Northside Hospital in Atlanta; Children's Hospital Colorado; H. Lee Moffitt Cancer Center in Tampa, Florida; the Roswell Park Comprehensive Cancer Center in Buffalo, New York; Atrium Health Levine Children's Hospital in Charlotte, North Carolina; University of Michigan in Ann Arbor; the University of Washington in Seattle; the Nicklaus Children's Hospital in Miami; Methodist Hospital in San Antonio; the University of Alabama at Birmingham; the University of Pittsburgh Medical Center; Orlando Health Cancer Institute in Florida; Children's National Hospital in Washington, D.C.; St. Mary's Hospital in London; the Cleveland Clinic; the Yale Cancer Center in New Haven, Connecticut; the Duke University Medical Center in Durham, North Carolina; and Washington University in St. Louis. Additional study authors were from the Emmes Co. in Rockville, Maryland, and the National Heart, Lung and Blood Institute.
