Boucher, Alexander A.

Background: Hematopoietic stem cell transplant (HSCT) based gene therapies (GT) have successfully demonstrated significant reduction in vasocclusive crises (VOCs) associated with sickle cell disease (SCD). The efficacy and safety of these products is well established across multiple clinical trials (Kanter et al. NEJM 2022, Frangoul et al. NEJM 2024). This led to the Food and Drug Administration (FDA) approval of the lentiviral-based gene addition product (lovotibeglogene autotemcel) and CRISPR-Cas9 based gene editing product (exagamglogene autotemcel) for patients with SCD above 12 years of age. As these therapies have a different logistical process compared to a standard allogeneic HSCT, there is a need to develop a collaborative transition of care plan for these patients and families prior to and long after completion of transformative therapies. Methods: Upper Midwest Sickle Cell Curative Therapies Consortium is a collaborative model including multiple stakeholders between 7 centers across the upper Midwest United States, the regional community-based organization (CBO) and National Marrow Donors Program (NMDP). The structure and workflow for this model was presented previously (Blaylark et al. ASH 2023). With the advent of commercial GTs, we developed a multi-specialty care model in collaboration with community stakeholders to address diverse patient and logistical needs for smoother transition to and from these therapies. Discussion: The initial transition is a period of potential gaps in medical care and often high anxiety for patients and families. Thus, when patients and families are considering GT, our care model engages a multidisciplinary team. As part of the comprehensive evaluation prior to gene therapy, an initial shared collaborative checklist includes an extensive medical history, assessment of treatment plan, an individualized pain plan and adherence, transfusion planning (simple or exchange) with setting of target hemoglobin and hemoglobin S% targets, and coordination of multi-specialty consults including apheresis, fertility preservation, child life, and social work. Additionally, pain, psychology, and integrative medicine specialists address not only ongoing concerns, but also help develop a plan for future transition back to the primary site of SCD care (“re-transition”) after GT. Patients undergo neuropsychological evaluations to establish baseline functioning and the role of chronic pain and fatigue, as GT can significantly impact long term cognitive functioning, emotional coping with transitions, and overall daily functioning. When appropriate and available, warm handoffs are encouraged between centers within each of these specialties. Our team also reviews available resources for education and ongoing support through the process and after from national and regional CBOs. Similarly, the post-GT transition is also a period of potential medical care gaps and high anticipated anxiety and concern, as patients go through significant unfamiliar adverse effects followed by the potential for persistent freedom from VOCs. In the post-GT transition, ongoing psychology, integrative medicine, and pain team support; peer mentoring; and support groups are critical for a smooth re-transition to post-GT care and further successful re-transition back into the community. Using this interdisciplinary approach across GT clinical trials, we successfully weaned opioids in 83% of patients (5/6) by day 60 post-GT infusion and successful re-transition of these patients, further highlighting the role of interdisciplinary care. Our team's collaborative approach to SCD care with sickle cell specialists, transplant team and other care providers and CBO continues into the long term follow up period, including ongoing supportive services for both patients and their families. Conclusion: As newer therapies are developed and approved for transformative SCD care, development of a transitional model with early engagement of an interdisciplinary team is critical for empowering sickle cell warriors and for their successful transition back into the community.

Introduction: Sickle cell disease (SCD) is the most common inherited hemoglobinopathy affecting populations across the United States. Several well-established patient-centered comprehensive care models have been in practice for preventive care and pain management. However, access to hematopoietic stem cell transplant (HSCT) and clinical trials for sickle cell gene therapies are limited, especially in pediatric and adult centers with limited HSCT-related resources. We describe a patient-centered collaborative model in the Upper Midwest United States to improve patient education and engagement as well as access to HSCT and gene therapy trials for patients with SCD. Collaborative Care Model: Since August 2021, centers across the Midwest meet monthly to improve access for HSCT and gene therapy as well as education about these therapies for individuals with SCD. The teams include: hematology and transplant teams from University of Minnesota, Comprehensive Sickle Cell Care team from Children's Hospital of Minneapolis, hematology and transplant team from Mayo Children's Hospital, hematology team from Essential Health, Duluth, Minnesota, hematology team from Sanford Children's Hospital Fargo and Sioux Falls and hematology team from Blank Children's Hospital, Des Moines, Iowa. This collaborative approach involves several stakeholders including an SCD community advocacy organization, hematology care providers across several rural as well as community/university hospitals, social workers, nurse coordinators, HSCT/gene therapy providers, as well as representatives from National Marrow Donor Program. Individual patient needs and available community support as well as institutional resources are discussed at length during monthly virtual meetings and a pre-intervention plan is established to ensure smooth transition of care to and from primary centers (Figure 1). Ongoing communication with the primary team helps with efficient transition of care after transplant as patients continue ongoing monitoring and care closer to home. Community partners help with early education of the families and provide necessary resources and support. Institutional partners like NMDP provide support with immune typing and discuss ongoing support and other resources available for providers and families. Results/Impact: Since the implementation of this collaborative model, there has been a steady increase in early referrals for education regarding HSCT and potential gene therapies trials for patients with SCD. There has been about 100% increase in new patient referrals since the implementation of this collaborative model compared to the average new referrals in the previous years (2021-22 vs 2018-19; Figure 2). Enrollment in HSCT as well as gene therapy clinical trials also has increased 2-3 folds since the implementation of the collaborative care model. It has helped established early discussion and longitudinal care and has also led to ongoing evaluation and discussions for availability of optimal donors, determining eligibility for HSCT and gene therapy trials as well as providing ongoing support and education to the sickle cell community and providers regarding the available therapies for SCD. This has also facilitated the transplant team establish earlier and better rapport with patients and their families and provide necessary education with an in-depth discussion regarding the potential benefits and risks of therapies such as HSCT and gene therapy. These discussions often occur over multiple visits and helps address psychological as well social barriers with a prospective evaluation. Additionally, the ongoing discussion among the providers helps with longitudinal monitoring of the patients and provide an assessment of the risks and benefits of therapies as the patient's disease course continues to evolve. This multi-stake holder collaborative approach continues to provide a well-established platform for discussion of newer therapies and access to open clinical trials, available resources for patients and families, and improve patient care and experience. The impact of this collaboration is noted in significant increase in early referrals and educational consults for HSCT and gene therapies, improved patient engagement as well as the acceptability and participation in clinical trials.

Healthcare inequities are often attributed to large-scale structural barriers for access to medical care or patient-medical staff interactions. However, the role of the electronic medical record (EMR) in perpetuating hidden biases has been poorly characterized. This passive form of sharing implicit biases with unknown readers may have profound ripple effects asynchronous in place and time from the note writer. This study aims to illustrate racial imbalances in ad hominem patient characterizations as documented by medical staff, regardless of role, in a large metro healthcare system. The use of certain potentially stigmatizing language in emergency department (ED) and inpatient notes for hematology/oncology patients was investigated. Retrospective chart review of four hospitals within a university network in a major metro area between 1/1/2019 - 6/30/2021 was undertaken. Patients ≥22 years old were included with two primary hypotheses in mind: 1) Negative terms are used more frequently for underrepresented minorities, and 2) words with shock value (i.e. curse words) are used more often than more general descriptors of these terms (e.g. “cursing” or “profanity”). Nine positive and twelve negative terms were evaluated, based on the authors' observations of their use in the EMR in past encounters (Table 1). Some were personal descriptors in which the ED or inpatient note writer would be less likely than outpatient providers to have a full sense of outpatient care or social determinants of health (e.g. compliant). Others were behavioral descriptions (e.g. hostile) or words with minimal medical relevance (e.g. curse words). If multiple notes in an encounter included the same word(s), the encounter was only analyzed once for each word to avoid word count inflation, though re-occurrences for the same patient in subsequent encounters were counted. Authors' manual data review using natural language processing software confirmed appropriate use of terms. Generalized estimating equations were used for race-based comparisons to account for same-patient clustered encounters. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for self-reported demographic comparisons with White as the reference category. P≤0.05 was considered significant. A total of 1,059 encounters for 889 hematology/oncology patients were analyzed. Mean age was 61 years (standard deviation 16.7) and 49.4% were female. White race was reported for 80.2% of patients (72% system-wide prevalence during same timeframe) and Black for 11.4% (15.2% system-wide); all others were ≤4% so only White/Black comparisons were included. Positive terms were more prevalent than negative ones (n=535 vs 459). However, negative terms were found more often for Black individuals (OR 2.24, CI 1.41 - 3.56, P<0.001), while the positive terms were less frequently documented in Black patients relative to White patients (OR 0.51, CI 0.33 - 0.77, P=0.001), and neither category was concordant with the overall patient racial demographics. Other significant racial differences existed for the terms “Argumentative”, “Disrespectful”, “Noncompliant”, and “Polite”, all discrepancies which favored White patients (Table 2). Specific curse words were documented nearly as often as “cursing”, “swearing”, or “profanity”, but no racial differences were observed. Some words in the initial search (“Brave”, “Courageous”, “Empathetic”, and “Ambitious”) were not found in hematology/oncology notes in this timeframe. EMR documentation in hospital-based hematology/oncology care demonstrated evidence of racial discrepancies in language that may carry stigma, positively or negatively. Importantly, many of these terms have questionable, if any, medical relevance. The use of stigmatizing terminology in the EMR may reflect implicit biases that extend past the direct patient encounter, passively and subconsciously prejudicing future care from other staff members. Time-saving heuristics and documentation shortcuts like copy-forwarding may further ossify healthcare inequities. This phenomenon is undoubtedly not limited to this hospital system or the hematology/oncology field, but quantitative real-world evidence has been scant. Improved awareness of stigmatizing language in documentation may be one step towards mitigating this contributor to unequal care for hematology/oncology providers and their patients.