Beyond Biological Correction: ASTCT Experts Confront the Unfinished Work of Recovery

Gene therapy can eliminate severe vaso-occlusive crises without resolving the chronic pain a patient has lived with for years. At the 2026 American Society for Transplantation and Cellular Therapy (ASTCT) Gene Therapy Summit in Boston, Massachusetts, experts argued that biological correction is only one measure of meaningful recovery.

“An acute event control does not mean chronic pain recovery,” said Amanda Brandow, DO, MS, of the Medical College of Wisconsin and Children’s Wisconsin. Joined by Steven Hardy, PhD, a psychologist at Children’s National Hospital and George Washington University; and Catie Becker, NP, a pediatric nurse practitioner at Massachusetts General Hospital, Brandow described why treatment success must also account for patients’ daily functioning, psychological adjustment, and continued monitoring.¹

Freedom From Crises Is Not Freedom From Pain

In a pivotal trial of exagamglogene autotemcel (exa-cel, Casgevy; Vertex Pharmaceuticals) for severe sickle cell disease, 29 of 30 evaluable patients remained free of severe vaso-occlusive crises for at least 12 consecutive months.² Brandow emphasized that this striking reduction in acute events does not establish whether patients with preexisting chronic pain become pain-free.

“How does their pain impact their life? How does it interfere with their ability to do the things they want to do, their daily function, their quality of life?” she asked.¹

Pain arising from repeated ischemic injury may coexist with neuropathic pain maintained by changes in peripheral nerves, the spinal cord, and the brain. Brandow also described established joint damage and avascular necrosis as potential reasons symptoms may persist even when sickling is controlled. Her proposed post-treatment trajectories—pain resolution, partial improvement, or persistent pain—were conceptual, not percentages observed in gene therapy trials.¹

She cautioned against equating lingering symptoms with an unsuccessful intervention. “Persistent pain does not equal treatment failure,” Brandow explained. “Clinical care for these patients obviously must extend beyond just resolution of their VOCs.”¹

Brandow also addressed continued opioid treatment. “If somebody is on chronic opioid therapy, they’re doing well and have perceived benefit because that certainly happens. There’s really a shared decision making about whether they should continue it.”¹

American Society of Hematology guidelines recommend individualized opioid decisions and conditionally suggest nonopioid agents for selected chronic pain presentations, based on limited evidence.³ Pharmacists can reassess functional benefit and adverse effects rather than relying on hospitalization trends alone.

The Emotional Work Continues After Treatment

Hardy urged clinicians to consider gene therapy a major life transition shaped by experiences long before treatment. Patients may hope that improved health will also eliminate depression, restore relationships, or change how others see them. Those outcomes are less predictable than correction of the underlying hematologic disorder.

“There’s this pressure to be positive and to be grateful,” he said, describing emotional expectations that can accompany recovery. “Just because somebody is improved soon after gene therapy doesn’t mean that that’s going to be sustained over the long term.”¹

He described a family struggling after treatment because a child sought greater independence while his mother remained accustomed to monitoring his health. The adjustment reflected a changed relationship, not necessarily a failure of the therapy. Before treatment, clinicians should explore psychological readiness, coping strategies, and patients’ own goals. But Hardy rejected using those assessments as an automatic barrier to care: “This is supposed to be informative. This is not supposed to be gatekeeping.”¹

A consensus statement coauthored by Hardy recommends evaluating knowledge, motivation, and psychosocial risk and resilience to identify support needs while respecting patients’ autonomy.⁴ During the summit discussion, he warned against raising awareness without offering practical assistance: “We run a real risk of you know sort of getting people halfway there where they understand that mental health is important, but they feel helpless to do anything about it.”¹

Pharmacists can support this transition through anticipatory counseling about conditioning-related adverse effects, continued medication needs, and timely referrals when distress or treatment-related symptoms interfere with daily life.

Neurologic Stability Can Carry New Uncertainty

Becker described a different challenge in cerebral adrenoleukodystrophy (CALD), where irreversible neurologic injury can accumulate rapidly. Unlike decisions about symptom burden in sickle cell disease, timing may determine whether children with early CALD can receive therapy before substantial deterioration.

“The question becomes more about whether or not we’re in time,” Becker said.¹

A study of elivaldogene autotemcel (eli-cel, Skysona; bluebird bio, Inc) reported that all 29 patients completing 24-month follow-up remained free of major functional disabilities, although outcomes require continued surveillance.⁵ Becker explained why disease stabilization is not the same as restoration of abilities already lost: “I often tell parents to think of it as like you’ve had an injury, you’ve had a stroke. Now we’re going to see how much we can get back.”¹

Families also remain vulnerable to the anxiety of repeated testing. Becker characterized the pretreatment surveillance experience as “living MRI to MRI.” Following gene therapy, the threat of treatment-associated hematologic malignancy introduces another long-term concern.¹

In August 2025, the FDA strengthened eli-cel’s labeling after 10 of 67 treated clinical trial participants (15%) developed hematologic malignancies as of July 2025. The FDA calls for lifelong surveillance, including complete blood counts at least every 3 months and periodic assessments for clonal expansion.⁶

Redefining Success in Long-Term Care

The speakers did not suggest that persistent pain, anxiety, or neurologic impairment negate the benefits of gene therapy. Instead, their presentations challenged clinicians to measure outcomes beyond acute-event reduction and to explain what treatment can—and cannot—reverse.

Brandow described a planned long-term observational sickle cell cohort targeting approximately 300 transplant and gene therapy recipients, with patient-reported pain and functional assessments.¹ Separately, 2026 ASTCT and International Society for Cell & Gene Therapy recommendations emphasize psychosocial support and lifelong monitoring following sickle cell gene therapy.⁷

For pharmacists, those priorities translate into longitudinal medication reviews, thoughtful opioid stewardship, surveillance coordination, and counseling that validates symptoms even after successful biological correction. The aim is not to redefine gene therapy as incomplete treatment, but to ensure that recovery includes the person receiving it.

REFERENCES

1. Brandow AM, Hardy SJ, Becker C. Real-life sequelae of seeking transformative therapy: biologic correction vs. lived experience. Presented at: ASTCT Gene Therapy Summit; November 4, 2026; Boston, MA.

2. Frangoul H, Locatelli F, Sharma A, et al. Exagamglogene Autotemcel for Severe Sickle Cell Disease. N Engl J Med. 2024;390(18):1649-1662. doi:10.1056/NEJMoa2309676

3. Brandow AM, Carroll CP, Creary S, et al. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain. Blood Adv. 2020;4(12):2656-2701. doi:10.1182/bloodadvances.2020001851

4. Hardy SJ, Crosby LE, Porter JS, et al. Assessing Psychosocial Risk and Resilience to Support Readiness for Gene Therapy in Sickle Cell Disease: A Consensus Statement. JAMA Netw Open. 2024;7(8):e2429443. Published 2024 Aug 1. doi:10.1001/jamanetworkopen.2024.29443

5. Eichler F, Duncan CN, Musolino PL, et al. Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy. N Engl J Med. 2024;391(14):1302-1312. doi:10.1056/NEJMoa2400442

6. US Food and Drug Administration. FDA approves required labeling changes for increased risk of hematologic malignancy following treatment with Skysona (elivaldogene autotemcel). August 7, 2025. Accessed November 4, 2026. https://www.fda.gov/vaccines-blood-biologics/fda-approves-required-labeling-changes-increased-risk-hematologic-malignancy-following-treatment

7. Sharma A, Kassim A, Thompson A, et al. Gene Therapy for Sickle Cell Disease: Practice Recommendations from the American Society for Transplantation and Cellular Therapy and the International Society for Cell & Gene Therapy. Transplant Cell Ther. 2026;32(7):778-791. doi:10.1016/j.jtct.2026.03.019