With 2 Curative Pathways, Sickle Cell Intervention Can Start in Infancy

Curative treatment for sickle cell disease has moved well past the era when allogeneic stem cell transplant was the only option on the table. With gene therapy now available at qualified treatment centers across the United States and increasingly covered by insurance, hematologists have 2 distinct curative pathways to weigh for eligible patients, each with its own timeline, donor requirements, and ideal candidate profile.

In this Q&A, Stacey Rifkin-Zenenberg, DO, MS, FAAP, FAAHPM, Section Chief of Pediatric Pain and Palliative Care and a pediatric hematologist/oncologist at Hackensack, breaks down how clinicians should approach that decision: when a matched sibling donor still makes transplant the faster route, what specific criteria determine gene therapy eligibility, and why the conversation about curative options shouldn't wait until a patient is in crisis.

Rifkin-Zenenberg also discusses what early outcomes from gene therapy are showing so far, and what questions remain unanswered as more patients move through treatment — insight that has direct implications for how and when community hematologists refer patients for specialized evaluation.

Q&A: With 2 Curative Pathways, Sickle Cell Intervention Can Start in Infancy

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?

Rifkin: I think that in the last few years, gene therapy has become more common as a curative therapy that's offered to sickle cell patients. Bone marrow transplant really was the standard of care since the early '80s, starting with a patient who had sickle cell and leukemia and was cured of both. Since then, there's been a push to have patients go to bone marrow transplant, and this was for our most severe patients. Recently, the standard of care is: if you have a sibling who matches you, you have the opportunity to be transplanted. The thing is, there's a good percentage of patients that don't have a sibling and don't have a good donor, and that's where gene therapy came from. Gene therapy is using the patient as their own donor for this treatment. It's been very successful — there are a few companies doing it, there are multiple qualified treatment centers across the United States now, and most insurances will pay for it. Because of that, we hope this 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?

Rifkin: That's a great question. Still, the standard of care is: if you have a matched sibling — meaning it's a tissue match, not a blood group match — that would be the pathway you'd go. If you do not have a matched sibling, then depending on the patient, gene therapy is definitely a great option. But gene therapy does take a longer period of time — it usually takes about nine to 12 months to actually happen. So if the patient is very sick, an allogeneic transplant may be an option because it can be done quicker. But it also depends on the patient's donors outside their family and the availability of those donors.

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

Rifkin: I think everybody should be talking to their patients when they're babies about both of these options, and that sickle cell patients have the opportunity in their lifetime to have either one of these options. For patients who undergo gene therapy, the criteria really is the same as when patients were undergoing clinical trials — having four painful crises or other types of acute crises that sickle cell patients can have in the last two years. Patients who have SS, who have S beta thalassemia, can also qualify for gene therapy. That really is the criteria, and that's the criteria most insurance companies are also going by. For a transplant, again, it really depends on how severe the sickle cell is, how sick the patient is, and then what donor availability is — that could be an option also.

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?

Rifkin: There's so many. I think what we're now seeing is that most of the patients who have received gene therapy are actually transformed — their sickle cell is transformed, they don't have crises. I'd like to see how they do as they go through time with their clinical organ function, and how they're also 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?

Rifkin: What I would send to community hematologists is that if you have a sickle cell patient, I think it should be standard of care to discuss this when you meet them — after the newborn screen — and if you don't meet them then, whenever you do meet them, talk to them and give them the option of pursuing it if you're not at a qualified treatment center.