Stacey Rifkin-Zenenberg, DO, is a Pediatric Hematologist Oncologist in Hackensack, NJ. She has 30 years of experience and is board certified in Hospice Care and Palliative Medicine.

Stacey Rifkin Zenenberg, DO

Gene therapy, which uses a patient's own genetically modified cells as a curative treatment, avoiding the need for a matched donor, has produced strong early results for patients with 

, freeing many from the vaso-occlusive crises that previously defined their disease course. Even so, 2 areas of outcome remain under active study: organ function over time, and psychosocial adjustment following treatment.

Stacey Rifkin-Zenenberg, DO, MS, FAAP, FAAHPM, Section Chief of Pediatric Pain and Palliative Care and a pediatric hematologist/oncologist in Hackensack, NJ, discussed both the current landscape and the long-term questions researchers are still working to answer.

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

After the Cure: What We Still Don't Know About Sickle Cell Gene Therapy

"What we're now seeing is that most of the patients that have received gene therapy are actually transformed," Rifkin-Zenenberg said. "Their sickle cell is transformed. They don't have crises."

At the same time, she pointed to 2 areas she is watching closely as more patients move further out from treatment:

"I'd like to see how they do as they go through time with their clinical organ function, and how they are also doing from a psychosocial point of view."

Rifkin-Zenenberg did not specify which organ systems concern her most, but her point tracks with what the broader literature has found so far. 

Sickle cell disease can cause progressive organ damage well before a curative treatment ever happens, so a patient's post-treatment organ trajectory reflects both that pre-existing burden and whatever longer-term effects gene therapy itself may carry. 

Trials to date have shown durable disease modification, but the toxicity data available so far is largely short-term, meaning long-term organ outcomes are still being collected rather than fully known.

Psychosocial Outcomes After Curative Treatment

A cure doesn't necessarily mean an easy transition. In a mixed-methods study of adult sickle cell disease patients after allogeneic stem cell transplantation, most reported improvements in social health, but emotional struggles and feelings of being overwhelmed were also common, and many wanted more psychological counseling.¹

Whether gene therapy recipients face a similar adjustment is unclear — this evidence comes from transplant patients, and comparable research on gene therapy patients doesn't yet exist.

Tracking Long-Term Outcomes: STELLAR and CureSCi

Two efforts are specifically structured to follow these outcomes over time:

 (Sickle Cell Transplantation Evaluation of Long-term and Late Effects Registry) compares long-term outcomes after transplant against both unaffected siblings and non-transplanted patients with sickle cell disease.

 has developed standardized data elements for gene therapy trials, including patient-reported outcome instruments covering pain, sleep, fatigue, anxiety, depression, and cognition, alongside clinical endpoints such as organ function.

Sickle Cell Disease: Clinical Implications for Curative Treatment

Rifkin-Zenenberg noted that discussion of curative options should begin early, regardless of the current state of long-term outcome data.

For patients and families, that leaves 2 distinct pieces of information: sustained elimination of crises has been observed in most treated patients so far, and organ function and psychosocial outcomes remain under active follow-up rather than fully characterized.

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

Sharma A. How I treat sickle cell disease with gene therapy. 

. 2024;144(26):2693-2705. doi:10.1182/blood.2024024519

Tardif M, Saby M, Forté S, Pincez T. The journey of gene therapy in sickle cell disease: how molecular advances meet clinical care. 

. 2026;15(10):939. doi:10.3390/cells15100939

Krishnamurti L, Arnold SD, Haight A, et al. Sickle Cell Transplantation Evaluation of Long-term and Late Effects Registry (STELLAR) to compare long-term outcomes after hematopoietic cell transplantation to those in siblings without sickle cell disease and in nontransplanted individuals with sickle cell disease: design and feasibility study. 

Lanzkron S, Coleman-Cowger VH, Thompson AA, Carroll CP, Clemons T, DeBaun M, Kanter J, Malik P, Manwani D, Pierciey FJ, Walters MC, Alai S. Cure Sickle Cell Initiative recommendations on common data elements for sickle cell disease gene therapy trials. 

. 2026;10(11):3960-3965. doi:10.1182/bloodadvances.2025019400

Videos

Stacey Rifkin-Zenenberg, DO, on early gene therapy outcomes and the long-term questions still being tracked in sickle cell disease.

After Sickle Cell Gene Therapy, What Comes Next?

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

: 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.

: 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.

: 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.

: 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.

: 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.

. 2026;15(10):939. doi:10.3390/cells15100939


Stacey Rifkin-Zenenberg, DO, on gene therapy vs stem cell transplant and when to refer for sickle cell disease. 

Stacey Rifkin Zenenberg, DO

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