The 9-to-12-Month Decision in Curative Sickle Cell Care

For sickle cell patients without a matched sibling donor, the path to a cure used to be narrower. Now, gene therapy offers an alternative, though it comes with its own tradeoff: a 9- to 12-month timeline that isn't always an option for the sickest patients.

As Sickle Cell Disease Awareness Month draws attention to the condition, HCPLive is revisiting a conversation with Stacey Rifkin-Zenenberg, DO, pediatric hematologist/oncologist and program director of the Pediatric Hematology/Oncology Fellowship at the Joseph M. Sanzari Children's Hospital at Hackensack University Medical Center, on how she weighs gene therapy against allogeneic stem cell transplantation for individual patients.

HCPLive: Over the past few years, curative treatment options for sickle cell disease have expanded significantly. How would you describe the current treatment landscape, and what do you see as the biggest shift in care?

In the last few years, gene therapy has become more common as a curative therapy offered to sickle cell patients. Bone marrow transplant has been the standard of care since the early 1980s, starting with a patient who had sickle cell and leukemia and was cured of both. Since then, there has been a push to get patients to bone marrow transplant, initially for the most severe patients, and more recently the standard of care has been that if you have a sibling who matches you, you have the opportunity to be transplanted. The issue is that a good percentage of patients don't have a sibling or a good donor, and that's where gene therapy came from. Gene therapy uses the patient as their own donor. It's been very successful; there are a few companies doing it, multiple qualified treatment centers across the United States now, and most insurances will pay for it. Because of that, we hope it will become a more common therapy for patients.

HCPLive: In your clinical experience with both gene therapy and allogeneic stem cell transplantation now available for some patients, how do you approach determining which curative strategy may be the best fit for an individual?

The standard of care is still that if you have a matched sibling — a tissue match, not a blood group match — that's the pathway you'd go. If you don't have a matched sibling, it depends on the patient. Gene therapy is definitely a great option, but it takes longer, usually about 9 to 12 months. So if the patient is very sick, an allogeneic transplant may be an option because it can be done more quickly, but it also depends on the availability of donors outside the family.

HCPLive: What characteristics or clinical factors should prompt hematologists to refer a patient for evaluation at a specialized center, even if a curative therapy is not immediately planned?

Everybody should be talking to their patients, starting when they're babies, about both of these options, since sickle cell patients have the opportunity in their lifetime to pursue either one. For gene therapy, the criteria are the same as when patients were undergoing clinical trials: having four painful crises or other types of acute crises in the last two years. Patients with SS or S beta thalassemia can also qualify. That's the criteria most insurance companies are also going by. For transplant, it really depends on how severe the sickle cell is, how sick the patient is, and donor availability.

HCPLive: As more patients begin to undergo gene therapy and other curative approaches, what long-term outcomes are you most interested in tracking over the next several years?

There are so many. What we're now seeing is that most patients who have received gene therapy are transformed — their sickle cell is transformed, and they don't have crises. I'd like to see how they do over time with their clinical organ function, and also how they're doing from a psychosocial point of view.

HCPLive: What message would you send to community hematologists about the role of curative therapies in the future of sickle cell disease management?

If you have a sickle cell patient, it should be standard of care to discuss this when you meet them, ideally after the newborn screen. If you don't meet them then, at any point after, talk to them and give them the option of pursuing it if you're not at a qualified treatment center yourself.

Editor’s Note: Rifkin reports relevant disclosures with Bluebird Bio and Vertex Pharmaceuticals Incorporated.

References

1. Sharma A. How I treat sickle cell disease with gene therapy. Blood. 2024;144(26):2693-2705. doi:10.1182/blood.2024024519

2. Tardif M, Saby M, Forté S, Pincez T. The journey of gene therapy in sickle cell disease: how molecular advances meet clinical care. Cells. 2026;15(10):939. doi:10.3390/cells15100939