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A recent clinical trial co-developed by researchers at the Johns Hopkins Kimmel Cancer Center has demonstrated that a novel bone marrow transplant method is both safe and potentially curative for adults suffering from sickle cell disease. Conducted at Johns Hopkins alongside nearly 20 other cancer centers in the U.S. and London, the findings suggest this treatment offers a promising and more affordable alternative compared to the newly approved gene therapy solutions for this condition.
The transplant approach in focus is known as reduced-intensity haploidentical bone marrow transplantation. This procedure involves using bone marrow from a “half-matched” donor—a relative such as a parent, sibling, or child. The compatibility of the donor’s and recipient’s immune system proteins is essential, with at least half matching to minimize the risk of rejection and complications during the transplant process.
Prior to the transplant, patients undergo treatment involving low doses of chemotherapy and total body irradiation. Post-transplant, they receive cyclophosphamide, among other medications, for a duration of up to one year to prevent complications such as graft-versus-host disease, where the donor’s immune cells attack the recipient’s body.
Among the 42 participants with severe sickle cell disease who received this transplant during the trial, an impressive 95% survived for at least two years post-procedure, with 88% classified as cured and free from disease-related complications. These significant results are set to be published in the February 25 issue of The New England Journal of Medicine Evidence, following preliminary presentations at the American Society of Hematology meeting in December 2023.
The high rate of donor cell engraftment and the favorable cure rates indicate the procedure’s promise, according to the study’s authors. “The success rate of our allogeneic transplant is comparable to, if not better than, that of gene therapy,” remarked Dr. Richard Jones, a professor of oncology and director of the bone marrow transplantation program at the Kimmel Cancer Center. He emphasized that the majority of individuals with sickle cell disease qualify for this transplant option, which is significantly less expensive than gene therapy alternatives.
Dr. Jones noted, “Many individuals, particularly adults, may not be eligible for gene therapy due to the high-dose chemotherapy requirements, which can be unsuitable for patients with significant organ damage. Moreover, gene therapy may carry a greater risk of long-term side effects, including organ damage and potential leukemia.” This statement challenges prevalent misconceptions within the medical community that a perfectly matched donor is essential for successful transplantation, as well as concerns surrounding graft-versus-host disease and associated mortality risks.
Transplants prove to be more economical for both healthcare facilities and patients. As Dr. Robert Brodsky, a co-author of the study, explained, “Patients typically spend about eight days in the hospital for a transplant, compared to six to eight weeks required for gene therapy. Furthermore, the median number of transfusions needed for patients undergoing gene therapy is 50, whereas those receiving haploidentical bone marrow transplants only require about six transfusions, many of which can occur on an outpatient basis.”
A review article co-written by Drs. Jones and Brodsky and published in the February 25 issue of Blood Advances provides a comparative overview of allogeneic bone marrow transplant versus gene therapy, revealing that gene therapy costs range from $2 million to $3 million, contrasted with approximately $467,747 for a transplant.
Participants in the phase II trial, conducted from 2017 to 2021, had a median age of 22. The demographic breakdown included 59% males, 92% Black individuals, and 4% Hispanic individuals, with an average follow-up period of 37 months. Notably, serious side effects were rare, with incidents confined to three graft failures, moderate to severe graft-versus-host disease affecting 22% of participants, and two fatalities in the first year post-transplant (one attributed to complications from COVID-19).
Sickle cell disease, a disorder characterized by crescent-shaped red blood cells that obstruct blood flow, impacts approximately 100,000 individuals in the United States, predominantly affecting the Black community, according to the Centers for Disease Control and Prevention.
The clinical trial received funding from the Blood and Marrow Transplant Clinical Trials Network, along with support from the National Institutes of Health, the National Heart, Lung, and Blood Institute, and the National Cancer Institute through grant numbers U10HL069294 and U24HL138660.
Other participating institutions in this significant trial included Vanderbilt University Medical Center in Tennessee, University of California San Francisco School of Medicine, Medical College of Wisconsin, Northside Hospital in Atlanta, Children’s Hospital Colorado, H. Lee Moffitt Cancer Center in Florida, and several others across the United States and the United Kingdom, as well as contributions from the Emmes Company in Maryland and the National Heart, Lung, and Blood Institute.
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