For centuries, sickle cell disease (SCD) has imposed significant morbidity and reduced life expectancy, disproportionately affecting African American and Hispanic communities. Although disease-modifying treatments such as hydroxyurea and chronic blood transfusions have improved outcomes, they fall short of being curative.
Hematopoietic stem cell transplantation (HSCT) remains the only established cure, offering greater than 90% event-free survival when using human leukocyte antigen (HLA)-identical sibling donors. However, donor scarcity and complications such as graft rejection, graft-versus-host disease, and conditioning regimen toxicities restrict the use of HSCT to a minority of patients.
Gene therapy is an emerging frontier, with approaches like gene editing and anti-sickling beta-globulin gene addition showing promise. The U.S. Food and Drug Administration’s approval of gene therapy and media coverage of high-profile cases, such as the 2024 report of a teenager cured of SCD through a single gene-editing procedure, has garnered global attention. The New York Times aptly described this as “a moment of hope,” while cautioning against overstating the accessibility of gene therapy.
On the horizon of new curative therapies for SCD, clinicians and their patients have many unanswered questions: Which therapy is safest? Am I eligible for this therapy? Will my insurance company cover this new treatment? What if I don’t have a matched-sibling donor?
Santosh L. Saraf, MD, and Payal Desai, MD, explored these questions and more in their session Curative Therapies for Sickle Cell Disease: Option for Some but Not Quite All, which spotlighted the clinical breakthroughs and systemic challenges surrounding curative treatments for SCD. The conversation included patient selection, modality choice, referral timing, systemic barriers to access, and the need for integrated care.
The Complexities of Patient Selection and Referral
There is significant nuance to patient selection for curative therapies. “When to refer” remains a critical question for hematologists. While early transplantation in children with HLA-matched sibling donors has produced excellent outcomes, the equation becomes more complex for adults, those with comorbidities, or patients without matched donors.
Furthermore, advancements in alternative donor approaches, such as haploidentical HSCT and umbilical cord blood transplants, are gradually expanding the donor pool. However, these approaches carry increased risks of complications. Reduced-intensity and non-myeloablative conditioning regimens have shown promise for patients who may not tolerate traditional conditioning.
Dr. Saraf presented a roadmap for navigating these discussions — personalizing these therapy options with your patients and optimizing disease-modifying therapies to help prevent disease progression. In an interview before yesterday’s presentation, Dr. Saraf advised that such discussions “should happen earlier, even annually” and that patients “may have better outcomes with these kinds of curative and transformative therapies.” With gene therapy trials underway and initial outcomes appearing promising, the interplay between HSCT and gene therapy in treatment decision-making will soon take center stage.
During the session, Dr. Saraf also highlighted the need for thorough neuropsychological evaluation and psychosocial support, as these treatments can be mentally and logistically challenging for patients and families.
Systemic Barriers: The Unfinished Battle
While curative therapies are scientifically groundbreaking, systemic barriers impede equitable access. Understanding that SCD disproportionately affects populations with limited access to specialized care, the result is that only a tiny fraction of eligible patients can benefit from curative options.
Dr. Desai’s presentation examined the systemic hurdles that hinder equitable care delivery. From providers' lack of awareness to the financial burden of advanced therapies, these barriers highlight persistent disparities in health care access. For instance, Medicaid policies often do not align with the high costs associated with curative treatments, making insurance coverage inconsistent across the U.S.
Additionally, structural racism in health care contributes to delays in diagnosis, referral, and treatment for SCD patients. Integrated care models aligning hematology with social work, primary care, and community advocacy are critical to overcoming these barriers. Dr. Desai’s insights into potential solutions, including policy reforms and multidisciplinary care teams, resonated widely among the session attendees.
This important session underscored the dual narrative of hope and challenge in SCD treatment. On one hand, curative therapies promise to transform the lives of thousands living with this debilitating condition. On the other, systemic and logistical barriers prevent these therapies from reaching all who need them, ultimately creating a mix of anxiety and hope for patients and providers alike.
The path forward will require collaboration among researchers, clinicians, policymakers, and patient advocates to ensure that scientific progress translates into real-world impact. Sessions like these remind us that hematology is about innovation and justice—ensuring that advancements benefit all, not just a fortunate few.
If you missed this session, make sure to watch the recording on the online platform to gain deeper insights into the evolving landscape of curative therapies for SCD and witness the discussions shaping the future of hematology.
