New transplantation methods show promise as an accessible treatment for sickle cell disease

According to a nationwide clinical trial, a bone marrow transplant technology refined by Johns Hopkins Medical researchers has proven to be a viable, more affordable alternative for recently approved gene therapy for sickle cell disease.

The treatment was called a reduced intensity haploid bone marrow transplant, and the survival rate was 95% after two years of transplantation in the trial participants. More importantly, after the surgery, 88% of patients were considered cured and had no disease-related events.

The findings, published February 25 in the New England Journal of Medicine, are at a critical moment when new gene therapy treatments for sickle cell disease have captured headlines, but are still very expensive for many patients.

“Our allograft results are as good or better than what you’ve seen with gene therapy,” said Richard Jones, director of the bone marrow transplant program at the Johns Hopkins Kimmel Cancer Center.

Unlike traditional grafts that require perfectly matched donors, this approach uses “half-matched” donors, such as parents, siblings and even cousins. This greatly expands the population of potential donors, a key advancement in a disease that primarily affects Black Americans, who are historically facing the challenge of finding matching donors at transplant registries.

Another way to condition

What makes the treatment particularly noteworthy is that it uses lower intensity pre-transplant regulation. Prior to transplantation, the patient received chemotherapy and systemic exposure doses, followed by cyclophosphamide, to prevent grafts and host disease.

This milder approach qualifies more adults with sickle cell disease for treatment, including those who have caused organ damage since the years of suffering from the disease.

“Many people (perhaps most adults) are not eligible for gene therapy because the ultimate organ damage that requires high doses of chemotherapy cannot be subject to,” explains Jones. “The risk of long-term side effects of gene therapy may also be higher in terms of organ damage and leukemia risks.”

The trial included 42 people with severe sickle cell disease, with a median age of 22 years. The majority of participants (92%) were black and 4% were Hispanic, reflecting the demographics of the people most affected by the disease. The trial spans several medical centers in the United States and includes a location in London.

Cost Difference

The financial contrast between this approach and gene therapy is sharp. According to the peer review paper, blood therapy was also published on February 25, with gene therapy for sickle cell disease costing between $2 million and $3 million per patient. Meanwhile, the estimated haploid bone marrow transplant is about $467,747.

Robert Brodsky, MD, professor of medicine and oncology family, Johns Hopkins, and co-author of the study highlights other practice advantages: “With transplants, patients stay in the hospital for about eight days, while gene therapy is six to eight weeks. Similarly, the median transfusion for gene therapy patients is 50, while the median transfusion after haploid bone marrow transplant is 6. It is almost entirely outpatient.”

These factors may make transplantation methods more readily a healthcare system serving a diverse population, in which case sickle cell disease is more prevalent, but resources may be more limited.

Solve past problems

Researchers noted that many doctors still maintain an outdated belief in bone marrow grafts for sickle cell disease.

“A common misconception in the medical field is that transplants of sickle cell disease require a perfectly matched donor, which can lead to severe grafts with host disease and high mortality, and this trial and other studies suggest that this is not true.”

The trial did document some complications, including three graft failures and moderate to severe graft-versus-host disease in 22% of participants. There were two deaths in the first year after the transplant, one of which was attributed to the age of 19.

Lifetime situation

According to the Centers for Disease Control and Prevention, sickle cell disease affects about 100,000 Americans. Genetic conditions can cause red blood cells to form crescent shapes rather than normal disc shapes, causing them to clog blood vessels and cause painful attacks, organ damage and shorter life spans.

Until recently, treatment options were largely limited to managing symptoms and preventing complications. The development of multiple curing methods represents a significant improvement in patients.

The clinical trials are supported by the Blood and Bone Marrow Transplant Clinical Trials Network, the National Institutes of Health, the National Institutes of Heart, Lung and Blood, and the National Cancer Institute.

As medical centers across the country begin implementing this transplant, more patients with sickle cell disease may now have access to a therapeutic approach that does not require a large number of resources associated with newer gene therapies.

For a disease that has historically received attention and research funding compared to the conditions that primarily affect white populations, this development represents a fair step towards therapeutic treatment.