Psychosocial considerations during and after gene therapy for sickle cell disease: Building on consensus to guide comprehensive care

Abstract

Abstract Introduction: The Cure Sickle Cell Initiative (CureSCi) Patient Readiness and Resilience Working Group (PRR) was formed in 2020 by the National Heart, Lung, and Blood Institute (NHLBI) to develop consensus recommendations for the assessment and support of psychosocial health during the gene therapy process for people living with sickle cell disease (SCD). The working group previously developed consensus recommendations guiding implementation of pre-gene therapy patient readiness assessments and support strategies (Hardy et al., 2024). The current objective of the PRR Working Group is to build on this document to provide guidance on patient assessments and recommendations for psychosocial support during and post-gene therapy. Methods: The PRR Working Group consists of 12 members including mental health clinicians, patient care providers, researchers, patient advocates, and people living with SCD. The working group is using a modified Delphi method to develop best practice recommendations for psychosocial assessment and support during and post-gene therapy for SCD. First, the PRR Working Group developed a set of core questions to be asked during and post-gene therapy by a psychosocial care clinician with training and expertise in clinical interviewing and psychosocial assessment. The NHLBI CureSCi Community Input Panel (CIP), which consists of people who represent the varied voices of people living with SCD as well as their caregivers, provided feedback on the core questions. The PRR Working Group also reviewed the research literature to establish key areas that may influence the gene therapy process and inform recommendations concerning implementation of psychosocial assessments and support. Literature review search topics included: 1) psychosocial concerns during and after gene therapy in SCD, 2) psychosocial challenges experienced by individuals with SCD undergoing hematopoietic cell transplantation (HCT), 3) psychosocial concerns experienced by individuals receiving gene therapy and HCT in non-SCD samples, and 4) psychosocial consequences of prolonged hospitalizations. Results: PRR Working Group discussions and CIP input emphasized the following areas to be assessed during and post-gene therapy: ongoing emotional and physical functioning, health challenges, emotional support, stress management and coping, changes in expectations and life goals, impact on identity, positive aspects, and challenges and drawbacks. The literature reviews yielded evidence that: 1) psychosocial challenges can persist despite improvement of physical health outcomes; 2) currently available mental health support is often insufficient for patients; and 3) changes in self-perception and identity are notable. In addition to anxiety and depression, broader social determinants and functional outcomes such as financial strain, educational and vocational disruptions, and difficulties with social reintegration warrant attention. Evidence also suggests that prolonged hospitalizations contribute to emotional distress, hinder recovery and complicate reintegration, highlighting the need for pre- and post-discharge support including mental health and rehabilitative care. All of this information has been integrated, and preliminary guidelines have been developed that include both a core set of assessment questions for during and after gene therapy, in addition to implementation recommendations for psychosocial assessments and support. Conclusions: Overall, current findings highlight the need for holistic care, integration of mental health guidance and development of supportive interventions throughout the gene therapy process to optimize psychosocial health outcomes. With the initial development of guidelines for assessing psychosocial health during and after the gene therapy process, the PRR Working Group has initiated the next stage of the development process. This includes soliciting additional feedback from the CIP as well as soliciting feedback from key stakeholder populations partnering with health care and community organizations (e.g., the Sickle Cell Consortium, the National Alliance of Sickle Cell Centers). After that feedback is processed and integrated by the PRR Working Group, a draft of the consensus document will be released for public comment for further refinement.