Yen‐Michael Sheng Hsu

Background: Plerixafor (P) is a rescue mobilization agent given to improve circulating CD34+ for peripheral blood stem cell (PBSC) collection in donors with inadequate response to granulocyte colony‐stimulating factor (G‐CSF, [G]). In this study, we evaluated the impact of immediate plerixafor administration without leukapheresis interruption for the same‐day PBSC collection in G‐mobilized allogeneic donors with pre‐apheresis peripheral blood CD34+ count ≤30/μL. Study Design: Retrospective analysis of two‐center data from 10/2023 to 11/2025 was conducted. The study group (G + P) received G‐CSF for 5 days and plerixafor without leukapheresis interruption ( n = 12). The control group (G, n = 24) received 5‐day G‐CSF and had similar median apheresis procedure time as study group. Outcomes were evaluated at early procedure (EP) and late procedure (LP) periods, separated by the timing of the interim PBSC product characterization. Results: G + P donors did not experience increased platelet loss or grade 2 or greater adverse reactions in gastrointestinal and immune systems or required day‐2 collection. During the LP period, G + P group had approximately 5.5‐fold increase in median CD34+ cells/L processed/h apheresis ( p < .0001). During the LP period, while G + P group had significant gains in CD34+ yield, there was a significant loss in the control group ( p < .0087). CD34+ collection efficiency was significantly higher in G + P ( p < .0001). All PBSC products from G + P group contained ≥4.5 × 10 ⁶ CD34+/kg recipient while only 63% of controls met this threshold ( p = .016). Conclusions: Same‐day rescue plerixafor without leukapheresis interruption in allogeneic donors suboptimally responding to G‐CSF results in safe and efficient leukapheresis collection while preserving PBSC product quality.

The chimeric antigen receptor (CAR) T cell therapy targeting cluster of differentiation 19 (CD19)‐positive malignancies has shown considerable efficacy in clinical settings. However, the potential genotoxicity of viral‐based CAR‐T therapy, their considerable manufacturing cycle and high costs, prompts questions about its safety and leads to limitations in clinical application. Aiming to explore a safe, efficient, and low‐cost mRNA‐based CAR‐T therapy, we characterize a nonviral, mRNA‐based approach utilizing a current good manufacturing practice (cGMP)‐compatible electroporation (EP) platform to generate anti‐CD19, anti‐CD22, and tandem anti‐CD19/CD22 CAR‐T products with a turn‐around time of less than 48 h. The protocol yields a more than 90% cellular viability with a CAR expression of exceeding 60% within the 24 h of transfection. The mRNA‐based CAR‐T products have a significantly enhanced T cell activation profile with CD69 upregulation, production of tumor necrosis factor‐alpha (TNF‐α), interleukin‐2 (IL‐2), and Granzyme B, and higher Ki67 expression level. Robust in vitro tumor neutralization by the mRNA‐based CAR‐T was observed compared to control. Interestingly, we have observed that the short‐term cell cryopreservation after EP resulted in a 50% reduction of cellular expansion. However, the cryopreservation and thaw did not have an observed negative impact on the in vitro tumor neutralization. Lastly, we have evaluated the metabolic activity of the mRNA‐based CAR‐T products, which has a clearly inducible and significant increase in basal respiration (by 60%) and a 2‐fold spare respiratory capacity (SRC) upon exposure with the antigen positive target cells. We believe this approach holds promise as a viable alternative that addresses the limitations of current CAR‐T therapies, offering a potential solution for future nonviral CAR‐T clinical application.

Immune effector cells (IECs) include a broad range of immune cells capable of modulating several disease states, including malignant and nonmalignant conditions. The growth in the use of IECs as both investigational and commercially available products requires medical institutions to develop workflows/processes to safely implement and deliver transformative therapy. Adding to the complexity of this therapy are the variety of targets, diseases, sources, and unique toxicities that a patient experiences following IEC therapy. For over 25 years, the Foundation for the Accreditation of Cellular Therapy (FACT) has established a standard for the use of cellular therapy, initially with hematopoietic cell transplantation (HCT), and more recently, with the development of standards to encompass IEC products such as chimeric antigen receptor (CAR)-T cells. To date, IEC therapy has challenged the bandwidth and infrastructure of the institutions offering this therapy. To address these challenges, FACT has established a programmatic framework to improve the delivery of IEC therapy. In this study, we outline the current state of IEC program development, accreditation, and solutions to the challenges that programs face as they expand their application to novel IEC therapy.

Background: Unproven cellular therapies are being offered to patients for a variety of conditions and diseases for which other treatments have failed. The use of untested cellular therapies is a worldwide problem. Practitioners (e.g., physicians, scientists, QA/QI facility managers, and policy advocates) are perhaps unaware of the risks involved with such therapies. Therefore, a critical need exists to bring attention to the potential limitations and adverse effects of these therapies to inform and limit misinformation.Study Design and Methods: We describe the extent of the unproven cellular therapy problem through a search of scientific literature and social media coverage. We also describe the regulatory framework that can be used by the practitioner to review and evaluate both proven and unproven cellular therapies.Results: We report on the current state of unproven cellular therapies across the globe. A workflow to facilitate an understanding of the regulatory processes involved in the approval of cellular therapies is provided as well as a list of warnings required by regulatory agencies on various products. It is hoped that this article will serve as a tool kit to educate the practitioner on navigating the field of unproven cellular therapy products.Discussion: Increasing awareness of the issues associated with unproven therapies through education is important to help in reducing misinformation and risks to patients.

Background: Thawed Plasma (TP), plasma thawed and refrigerated for up to 5 days, is a commonly transfused plasma product. This pilot study was conducted to determine whether Thawed Solvent/Detergent‐treated Plasma stored refrigerated for up to 5‐days post‐thaw (T‐S/D) was as efficacious as TP.Study Design and Methods: This single institution retrospective cohort analysis evaluated the efficacy of T‐S/D in reversing coagulopathies in comparison to TP. Utilizing the institution's electronic medical records, transfusion data were collected in adult patients who received either TP or T‐S/D. The primary outcome was the incidence of subsequent transfusions within 24 hours after first dose of either type of plasma. Secondary outcomes included the number of blood products transfused within 24 hours of first‐dose plasma, correction of pre‐transfusion coagulation laboratory values, volume transfused, and clinical outcomes.Results: TP was received by 301 patients and 137 received T‐S/D during the first 32 months post‐implementation of T‐S/D. There was no difference in incidence of subsequent transfusions or number of blood products given. The median pre‐INR of both the TP and T‐S/D cohorts was 1.9, with a similar decrease in INR of 0.2 and 0.3 (p = 0.36), respectively, post plasma transfusion. There was no difference in correction of PT/aPTT, mortality, transfusion reactions, readmission rates, length of stay, or inpatient deep venous thrombosis. The median volume of T‐S/D plasma transfused for the first dose was 126 mL less than TP (p = .0001).Conclusion: T‐S/D was as efficacious as TP for the treatment of coagulopathies and the reversal of coagulation laboratory values.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Alternative donor transplantation with the haplo-cord platform allows the use of a lower-dose single umbilical cord blood unit (CBU) by co-infusion of third-party CD34⁺-selected cells from a haploidentical relative, which provides early transient engraftment while awaiting durable CBU engraftment. In our experience, ~15% of patients lack a suitable haploidentical donor. Here we report 26 patients who underwent haplo-cord transplant using CD34⁺-selected partially matched unrelated donor grafts. Twenty-four were conditioned with fludarabine/melphalan +/− low-dose TBI (n = 16). Twenty-five received ATG and all received posttransplant tacrolimus and mycophenolate mofetil. Median time to neutrophil and platelet recovery was 11 and 18 days. CBU engraftment, with CD33 and CD3 >5% cord chimerism in the myeloid/lymphoid compartment by day +60, occurred in 20 of 24 patients (83%). Incidence of grade 2–4 acute graft-versus-host disease (GVHD) was 27% at day +100, and chronic GVHD was 4% at 1 year. Overall survival at 1 year was 54%. For patients in need of an alternative transplant who lack a haploidentical donor, haplo-cord transplantation using CD34⁺-selected partially matched unrelated donor grafts results in rapid engraftment with no increased rate of cord graft failure or GVHD.