Joanne Kurtzberg

Background and aims: Cord blood infusion is an emerging treatment for cerebral palsy (CP) currently offered in the United States through clinical trials and an expanded access pathway. This study aimed to understand the barriers and facilitators influencing implementation of cord blood treatment for CP, to help inform future implementation efforts. Methods: Semi-structured interviews were conducted with US professionals involved in the cord blood treatment program for CP at Duke University and a collaborator site. Data were analyzed using reflexive thematic analysis. Results: From 16 interviews, 5 themes were identified capturing patterned barriers and enablers. Key facilitators included boundary-spanning clinical leadership, interprofessional coordination, dedicated resourcing, responsiveness to community demand, an established safety profile, and a strong research culture. Barriers included the need for cross-disciplinary expertise, uncertainty regarding efficacy evidence, funding and regulatory constraints, and system-level challenges. Participants described that many barriers were overcome to establish the program, while acknowledging that others may persist and are context dependent. Conclusions: Findings highlight that implementation of cord blood treatment for CP is feasible within specialized settings but contingent on local infrastructure, governance, and workforce capacity. Identified facilitators align with established implementation strategies and offer transferable insights, while underscoring the need for regulatory approval, ethical oversight, and system-level supports to enable equitable and sustainable access to emerging regenerative therapies for CP.

Infantile Krabbe disease (IKD) is a rapidly progressive leukodystrophy for which hematopoietic stem cell transplantation (HCT) offers the only disease-modifying treatment. HCT must occur presymptomatically, ideally by 30 days of life, to optimize survival and neurodevelopmental outcomes. With the expansion of newborn screening for Krabbe disease (KD), pediatric neurologists and geneticists will be responsible for obtaining urgent diagnostic testing and connecting families to experts for information and treatment. Given the variability in state-specific screening protocols, clinicians must be familiar with their local algorithms to act quickly on receiving abnormal results and refer to nearby, specialty treatment centers. Informed consent discussions must clearly outline the natural history of untreated IKD, the requirement for rapid, presymptomatic treatment, and provide a realistic view of the benefits and limitations of HCT. Supportive and palliative care should be prioritized regardless of treatment choice. This publication provides expert guidance on interpreting newborn screening results, conducting rapid confirmatory testing, and referring to and/or establishing treatment centers ready to care for IKD. With anticipatory planning and interdisciplinary collaboration, pediatric specialists can provide accurate diagnosis, compassionate counseling, and expedited evaluation to meet the narrow window for effective HCT.

Juvenile systemic sclerosis (jSSc) is a rare, chronic, autoimmune disease in children/adolescents and is associated with significant morbidity, skin thickening/hardening (scleroderma), organ toxicity and sub-optimal therapeutic options. In this report, autologous stem cell transplantation is associated with clinical improvement in a 17-year-old with refractory jSSc.

Ceroid lipofuscinosis neuronal (CLN) encompasses rare inherited neurodegenerative disorders that present in childhood with clinical features including epilepsy, psychomotor delay, progressive vision loss, and premature death. Published experience utilizing umbilical cord blood transplant (UCBT) for these disorders is limited. This retrospective analysis includes patients with CLN (2, 3, and 5) who underwent UCBT from 2012 to 2020. All subjects (n = 8) received standard-of-care myeloablative conditioning. Four also enrolled in clinical trial NCT02254863 and received intrathecal DUOC-01 cells posttransplant. Median age at UCBT was 5.9 years. All subjects achieved neutrophil engraftment with >95% donor chimerism at a median of 28.5 days. Sinusoidal obstructive syndrome was not observed. Severe acute graft-versus-host disease occurred in 12.5%. Other complications included autoimmune hemolytic anemia (25%) and viral reactivation/infection (62.5%). No transplant-related mortality was observed. Two CLN2 patients died, 1 from progressive disease and 1 from unknown cause at days +362 and +937, respectively. With median follow-up of 8 years, overall survival at 100 days and 24 months was 100% and 88%, respectively. Three of 4 CLN3 subjects stabilized Hamburg motor and language scores. While UCBT appears safe and feasible in these patients, given the variable expression and natural history, extended follow-up and further studies are needed to elucidate the potential impact of UCBT on clinical outcomes.

Cellular therapies rely on highly specialized supply chains that often depend on single source providers. Public cord blood banks (CBB) manufacturing the first cell therapy to be highly regulated by the FDA and related international agencies are a prime example of being subject to this phenomenon. In addition to banking unrelated donor cord blood units for transplantation, CBBs also source and characterize starting materials for supply to allogeneic cell therapy developers that often employ customized technologies offered by just a small number of manufacturers. As such, these supply chains are especially sensitive to even minor changes which often result in potential major impacts. Regulations can shape supply chain efficiencies, both directly via the definition of restricted technology and process requirements and indirectly by steering strategic business decisions of critical supply or service providers. We present 3 current supply chain issues with different root causes that are swaying efficiencies in cord blood banking and beyond. Specifically, the shortage of Hespan, a common supplement used in cord blood processing, the decision by the provider to stop supporting medical device marking of the Sepax system broadly used in cord blood banking, and a new European ruling on phasing out plasticizers that are critical for providing flexibility to cord blood collection bags, are all threatening downstream supply chain issues for the biologics field. We discuss overcoming these hurdles through the prism of unified mitigation strategies, defined, and implemented by multi-factorial teams and stakeholders, to negotiate resolutions with providers and regulators alike.

Cord blood units (CBUs) that are ineligible for licensure due to incomplete compliance with FDA recommendations may be used for hematopoietic stem cell transplantation under urgent medical need and an Investigational Drug Application. The largest reason for CBU donor ineligibility is Zika virus (ZIKV) risk. The study’s objective was to analyze the impact of current FDA recommendations for ZIKA risk on a large public cord blood bank and propose updated recommendations. We performed a retrospective analysis of Carolinas Cord Blood Bank (CCBB), an FDA licensed public CBB, using data from January 1, 2016 to November 21, 2023 and compared FDA recommendations for transfusion transmitted infections (TTI) for blood products and relevant communicable disease agents or diseases for human cell, tissue, or cellular or tissue-based products (HCT/Ps). CCBB: 9057 (84.3% licensed) CBUs were banked. 984/1682 (58.5%) of unlicensed CBUs had ZIKV risk. 22.0% of CBUs with ZIKV risk were from Hispanic parents, compared to 16.1% of all units. 31 of IND CBUs (11 due to ZIKV risk without reported ZIKV transmission) were safely infused. FDA Guidance: HCT/P ZIKV, HIV, and vCJD recommendations have not been updated since 2018 in contrast to FDA removal of ZIKV as a relevant TTI in 2021 and updating HIV and vCJD guidance related to TTI in 2023 and 2022, respectively. The FDA should consider new data to revise the HCT/P donor eligibility recommendations, which will increase the number of eligible HCT/P donors, and potentially improve access to therapies for a more diverse patient population.