Citations

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.

Abstract Presentation Date: 6/8/2024 Presentation Start Time: 6:00 PM Background Sickle cell disease patients often lack awareness of how the disease progresses in their bodies, leading to inadequate self-care and adherence to treatment recommendations. This can result in irreversible damage, such as stroke, and affect their psychological health, leading to feelings of isolation, depression, anxiety, and frustration. The 3D Sickle Cell Patient Education Model can help bridge the gap by providing patients with a comprehensive and detailed explanation of their disease, illustrating how red blood cells function within different areas of the body, and showcasing the complications and ramifications of the disease. It can also promote consistency with treatment programs for all patients, making it an essential tool for SCD communities and healthcare industries worldwide. Methods Rochester, MN, Mayo Clinic Comprehensive Pediatric Sickle Cell Clinic, we utilized an innovative approach by incorporating a 3D model to educate children diagnosed with SCD. Results During our session at the Mayo Clinic Comprehensive Pediatric Sickle Cell Clinic, we utilized an innovative approach by incorporating a 3D model to educate children diagnosed with SCD. We were pleasantly surprised to witness a significant improvement in their understanding of SCD. The 3D Sickle Cell Patient Education Model is an incredibly effective tool that SCD communities and healthcare industries can leverage to promote better education and awareness of SCD. Conclusions SCD can be complex for patients and their loved ones to manage. However, with proper care and management, those affected by the disease can still live a better life. These Sickle Cell Patient Learning resources can provide valuable tools and resources for caregivers and healthcare providers to manage the condition more effectively, leading to improved patient outcomes. Additionally, this model can also serve as an educational tool in schools from diverse backgrounds, including urban, rural, and suburban areas where access to education resources may be limited. By utilizing these resources, we can help ensure that those affected by SCD have the support and tools they need to thrive. 3D Sickle Cell Patient Education Model

AbstractBackgroundΕ‐Aminocaproic acid oral solution (EACA OS) is the only commercially available antifibrinolytic for patients who cannot swallow tablets. Insurance denials and high costs remain barriers to its use.ObjectivesTo determine the safety and efficacy of crushed tranexamic acid tablets in water (cTXAw) for children with bleeding disorders.MethodsWe retrospectively reviewed records of children (<10 years) with bleeding disorders who received cTXAw or EACA OS from 1 December 2018, through 31 July 2022, at Mayo Clinic (Rochester, Minnesota). Bleeding outcomes were defined according to ISTH criteria.ResultsThirty‐two patients were included (median age, 3 years; male, n = 23). Diagnoses were VWD (n = 17), haemophilia (n = 5), FVII deficiency (n = 3), inherited platelet disorder (n = 4), ITP (n = 2), and combined FV and FVII deficiencies (n = 1). Thirty‐two courses of cTXAw (monotherapy 24/32; mean duration 6 days) and fifteen courses of EACA (monotherapy 12/15; mean duration 5 days) were administered. No surgical procedures (n = 28) were complicated by bleeding. Of the 19 bleeding events, 16 had effective haemostasis, two had no reported outcome, and one had no response. cTXAw and EACA were equally effective in preventing and treating bleeding (p value > .1). No patients had adverse effects. Eight of 19 patients (42%) who were initially prescribed EACA OS did not receive it because of cost or insurance denial.The estimated average wholesale price of one treatment was $94 for cTXAw and $905 for EACA OS.ConclusionsCTXAw appears to be an effective, safe, and low‐cost alternative option to EACA OS for young children with bleeding disorders.

A 13-year-old male undergoing maintenance chemotherapy with methotrexate and 6-mercaptopurine (6MP), for very high-risk B-cell acute lymphoblastic leukemia (ALL), presented with vomiting due to severe hypoglycemia with metabolic acidosis. While his laboratory values were concerning for a critically ill child, the patient was relatively well appearing. Hypoglycemia is a rare but serious side effect of 6MP with an unexpectedly variable presentation; therefore, a high index of suspicion is needed for its prompt detection and treatment. This patient also had severe metabolic acidosis, likely secondary to hypoglycemia, creating a serious clinical picture despite a well-appearing child. This example of incongruity between laboratory tests and clinical appearance adds nuance to the existing literature. Moreover, although 6MP-associated hypoglycemia is rare, it may be more prevalent than the literature suggests, as symptoms of hypoglycemia—nausea, vomiting, and somnolence—mirror common chemotherapy side effects. 6MP-induced hypoglycemia can be ameliorated with the addition of allopurinol to shunt metabolism in favor of the production of therapeutic metabolites over hepatotoxic metabolites. Additionally, a morning administration of 6MP and frequent snacks may also help to prevent hypoglycemia. Overall, this case adds to the literature of unusual reactions to 6MP including hypoglycemia in an older child without traditional risk factors.

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.

Post-transplant lymphoproliferative disorder (PTLD) is a complication of immunosuppressive therapy following solid organ or hematopoietic cell transplantation. Initial treatment typically includes a reduction of immunosuppression with or without rituximab. However, the optimal therapy for PTLD with plasmacytic differentiation is unclear. We present 3 cases of pediatric patients with plasmacytic PTLD. Two patients received a standard rituximab-based approach and relapsed, prompting additional chemotherapy. The third patient was treated with a novel regimen of bortezomib, dexamethasone, and daratumumab. This regimen was safe, well-tolerated, and resulted in a 2-year remission. Larger studies are needed to further explore this regimen.