Guiding Patients With Sickle Cell Disease Through the Transformative Era of Gene Therapy

In 2023, the FDA approved 2 milestone cell-based gene therapies for patients aged 12 and older with sickle cell disease (SCD): exagamglogene autotemcel (Casgevy; Vertex Pharmaceuticals) and lovotibeglogene autotemcel (Lyfgenia; bluebird bio). The process for administering gene therapy using these products can be painful and arduous, necessitating stem cell mobilization, collection, and myeloablative conditioning. Despite the possibly life-changing impacts of successful gene therapy, patients, caregivers, and providers alike must navigate a complex and burdensome approval and treatment process, one that many individuals are unprepared for when first considering whether to receive gene therapy.^1,2

At the 67^th American Society of Hematology Annual Meeting and Exposition, hematologists and lived experience experts met to the discuss the “To, Through, and Thereafter” of guiding patients with SCD in the era of gene therapy. Titilope Fasipe, MD, PhD, co-director of the sickle cell program at Texas Children’s Hospital moderated the panel, which featured Alexis Leonard, MD, member of the department of hematology at St. Jude Children’s Research Hospital; Alexander Ngwube, MD, director of hemoglobinopathy services at Texas Children’s Hospital; and Andrew Campbell, MD, director of the comprehensive sickle cell disease program at Children’s National Hospital.¹

Lived experience experts included Jimi Olaghere, a business owner from Atlanta, Georgia who received SCD gene therapy in 2020, and Rae Blaylark, founder and executive director of the Sickle Cell Foundation of Minnesota, whose son Treyvon was identified with SCD at 2 weeks of age. Together, the panel highlighted the nuances of gene therapy, from the initial stages of consideration and approval for administration to short- and long-term post-treatment care.^3,4

Eligibility and Psychosocial Preparation

When considering whether to initiate gene therapy for SCD, patients and their families will have a slew of questions and concerns regarding the process. Many will ultimately decide not to pursue the therapy. Despite harboring valid concerns, Alexis Leonard asserted that all patients with SCD should at least consider the treatment, noting that it is “one of the very few FDA-approved” options for patients seeking care. Still, Leonard and Fasipe noted that the FDA label is very broad, and that hematologists should consider patient factors such as their matched-donor status and overall clinical picture.¹

Just as important in Leonard’s view is the psychosocial component. Alexander Ngwube explained the long process of stem cell mobilization, which requires the use of medications (like plerixafor [Mozobil; Sanofi]) to mobilize hematopoietic stem cells into the peripheral blood for collection and use in the gene therapy products. However, the product manufacturers require a certain cell target, often necessitating 2-to-3—and sometimes more—rounds of mobilization. Ngwube cautioned that it could take 4-to-6 months to mobilize the cells alone, which Leonard said contributes to the major psychosocial burden that treated patients experience and prospective patients must consider.^1,5

“I would say that all patients should have access to psychology [resources] early on in this process, so that they can weather the highs and lows and the length of this process,” Leonard said. “If you’re one of those patients that needed 4, or 5, or 6 mobilization cycles, I can only imagine how difficult that may be.”¹

From the caregiver’s perspective, this requires care and support; but according to Rae Blaylark, the ultimate decision should still lie with the patient to ensure their motivation during this difficult process. Her son took multiple years to decide whether to move forward with gene therapy, and Blaylark emphasized that she consistently asked him his “why” for receiving therapy. Without their own personal motivations and desires for life after SCD, she said, it would only make the process more difficult for the patient and family alike.¹

“It’s a thin line between them doing it for a parent or them doing it for themselves, and frankly, I’m a caregiver and a supporter, but I’m not a cheerleader,” she said. “If they do [gene therapy] for you, you will end up cheerleading them through the whole thing.¹

Insurance, Mobilization, and Collection

Once the decision is made to move forward with SCD gene therapy, new steps arise, including mobilization, apheresis, and manufacturing. Navigating insurance eligibility is a journey in-of-itself, with Ngwube describing the financial situation simply: “This is not a cheap thing.” Private insurance is less strict with eligibility criteria than Medicaid for receiving the therapy, but the price with private insurance would be significantly higher than Medicaid, which are important considerations for patients. Across either avenue, insurance approval could take multiple months.¹

After the patient is approved, Ngwube says that there should be a multi-visit interval where discussions are held on the process, resources are given to the patient, and time is allowed for deliberation. If the patient decides to move forward, hydroxyurea is administered prior to mobilization. The mobilization process itself requires multiple months, and cell collection necessitates a 4-to-5 day stay in the hospital. Next, the cells are sent to the manufacturer, which could take over 6 months, especially if they require additional mobilization and collection. Ngwube explained that, from approval to infusion, the process could take an average of 9 months.¹

Ngwube expressed gratitude towards Leonard and the field at large for focusing more on the psychosocial aspect of gene therapy given the immense challenges that patients and caregivers face. Through this phase, health care providers, pharmacists, and members of the multidisciplinary care team can work together to provide physical and emotional support for patients and their families.¹

“In the beginning, we didn’t put too much attention on the psychology and social aspect of it, but I’m glad [Alexis] talked about it and that we’re now emphasizing it,” Ngwube said. “You can imagine, you’re asking them to [mobilize] again, you’re asking them to put lines in again, and there is no hope.”¹

“I think we’re doing a better job of preparing them for this process,” he continued.¹

Addressing Unmet Needs and Ensuring Post-Treatment Monitoring

Gene therapy provides transformational, functional cures from SCD for patients desperately seeking relief. But Andrew Campbell explained to the panel that once gene therapy is completed, there are numerous short- and long-term considerations. Most prominent is the consistent disease and lab monitoring following gene therapy to ensure that key parameters, such as white and red blood cell counts and platelet levels are stable. Another important consideration for Campbell is school reentry, which is essential to initiate but with proper safeguards in place for infectious disease prevention.¹

“I would say it’s an individualized, case-by-case basis,” Campbell explained regarding school reentry. “Lab monitoring, monitoring their energy level, and medical management are things that I think are [also] important.”¹

Long-term concerns are sure to be abound for any patient who has completed gene therapy. The reality of the field is that no patient in any gene therapy clinical trial has surpassed the 15-year mark post-therapy, Fasipe noted, making these assessments difficult to predict. But Campbell provided a salient example of an issue hematologist sickle cell providers must consider for years after therapy: pain management. Campbell explained that he has seen many patients require postulator conditioning and physical therapy post-transplant, with continued psychological counseling remaining crucial.¹

Campbell shifted the attention back to a major unmet need for patients’ post-transplant: reestablishment of their identity. The panel consistently spoke of how a patient’s identity becomes intertwined in SCD, and Leonard said that patients must have an “understanding of…what that looks like after gene therapy.” She later recounted the experience of a mother as she traveled with her child for an allogeneic transplant, who described it as feeling “like a divorce…because they no longer saw their hematology team that had followed them since birth.”¹

Leonard, Campbell, and Ngwube collectively emphasized the importance of multidisciplinary collaboration to ensure that hematologists are staying involved with patients while allowing other specialties to intervene when necessary. At their respective centers, dedicated nurse care coordinators are assigned to manage the intricacies of cross-disciplinary monitoring and act as a point-of-contact for patients seeking clarity through the ocean of appointments and medications.¹

“I would say shared-decision making with the emergency room, with the patient, with the hematology provider, and coming up with a plan, but most importantly, having a long-term plan to treat the patient,” Campbell said.¹

REFERENCES

1. Fasipe T, Leonard A, Ngwube A, et al. “To, Through, and Thereafter: Guiding Sickle Cell Disease Patients Considering Gene Therapy.” Presented: 67th American Society of Hematology (ASH) Annual Meeting and Exposition; December 7, 2025; Orlando, FL; Orange County Convention Center; W311. Accessed via ASH Virtual Platform on December 7, 2025.

2. FDA approves first gene therapies to treat patients with sickle cell disease. News Release. FDA. Released December 8, 2023. Accessed December 7, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease

3. Sickle cell patient cured with CRISPR summits Kilimanjaro, setting world record. Timmerman Report. Published September 17, 2024. Accessed December 7, 2025. https://timmermanreport.com/2024/09/sickle-cell-patient-cured-with-crispr-summits-kilimanjaro-setting-world-record/

4. Personal story: Rae. CDC—Sickle cell disease (SCD). Published May 15, 2024. Accessed December 7, 2025. https://www.cdc.gov/sickle-cell/stories/rae-blaylark.html

5. Halpern L. Navigating the complex landscape of sickle cell gene therapy: Operational challenges and collaborative solutions. Pharmacy Times. Published September 11, 2025. Accessed December 7, 2025. https://www.pharmacytimes.com/view/navigating-the-complex-landscape-of-sickle-cell-gene-therapy-operational-challenges-and-collaborative-solutions