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Amyotrophic lateral sclerosis (ALS) is an orphan neurodegenerative disease. Immune system dysregulation plays an essential role in ALS onset and progression. Our preclinical studies have shown that the administration of exogenous allogeneic B cells improves outcomes in murine models of skin and brain injury through a process termed pligodraxis, in which B cells adopt an immunoregulatory and neuroprotective phenotype in an injured environment. Here, we investigated the effects of B‐cell therapy in the SOD1G93A mouse preclinical model of ALS and in a person living with ALS. Purified splenic mature naïve B cells from haploidentical donor mice were administered intravenously in SOD1G93A mice for a total of 10 weekly doses. For the clinical study in a person with advanced ALS, IgA gammopathy of unclear significance, and B lymphopenia, CD19+ B cells were positively selected from a healthy haploidentical donor and infused intravenously twice, at a 60‐day interval. Repeated intravenous B‐cell administration was safe and significantly delayed disease onset, extended survival, reduced cellular apoptosis, and decreased astrogliosis in SOD1G93A mice. Repeated B‐cell infusion in a person with ALS was safe and did not appear to generate a clinically evident inflammatory response. An improvement of 5 points on the ALSFRS‐R scale was observed after the first infusion. Levels of inflammatory markers showed persistent reduction post‐infusion. This represents a first demonstration of the efficacy of haploidentical B‐cell infusion in the SOD1G93A mouse and the safety and feasibility of using purified haploidentical B lymphocytes as a cell‐based therapeutic strategy for a person with ALS. [ABSTRACT FROM AUTHOR]

Great strides have been made in computerization of ordering processes for general medications and chemotherapy agents. However, systems for ordering, processing, and administration of cellular therapies continue to be largely paper-based, without the safety features of computerized order entry. To address this deficit, Partners Healthcare System Information Services (PHSIS; Boston, MA) has worked with oncologists and staff in the cell processing laboratory at the Dana-Farber Cancer Institute (Boston, MA) to develop and implement a novel, comprehensive computerized system for physician ordering and management of cellular products. A multidisciplinary team was formed to accomplish the task of developing a cellular product management system. This team identified the unique characteristics of cellular therapies and sought to develop a comprehensive computerized system that addressed these needs. The biotherapy order entry system developed and implemented by PHS-IS includes a suite of three interrelated applications that addresses all requirements of a traditional computerized provider order entry system, as well as features unique to cellular therapies. The biotherapy suite of applications has addressed patient safety concerns, streamlined the ordering of cellular therapy products, and has reduced opportunities for error and delay in product administration. [ABSTRACT FROM AUTHOR]

Introduction With rapidly increasing demand, resources at cellular therapy centers may be stretched thin. Apheresis and processing lab facilities must meet increased collection, processing, and storage requests, necessitating efficiency. We queried the field's practice of collecting autologous stem cells for 2 transplants in adult multiple myeloma (MM) patients under 65 for efficiency and clinical relevance as MM collections consume significant cell therapy resources. Methods Data points from 2012, 2014, and 2016 for MM patients at DFCI were reviewed: percentage of patients who received first and second transplants after autologous collection, days of collection, and excess hematopoietic progenitor cell HPC(A) bags in cryostorage. MM clinician leadership discussed existing guidelines and clinical rationale for HPC(A) collection targets. After changes implemented in Feb. 2018, collection and storage data was compiled to assess impact. Apheresis & Cell Storage Data Prior to Change From Jul. to Dec. 2017, MM patients <65 (n=65) utilized mean bed-days per collection event of 2.13 (range 1-8 days, SE 0.13) with 31% completing collection in 1 day. For all of 2017, 141 MM patients <65 yielded 453 excess HPC(A) bags in cryostorage for at least 9 months without infusion: 66% of all bags initially frozen and 3.2 excess bags/patient. Clinical Practice Patterns & Change in Guidelines Before Feb. 2018, autologous MM collection target for patients <65 years old was 8 × 10e6 CD34+cells/kg, allowing for 2 potential transplants. Data reviewed for 2012, 2014, and 2016 (n=385 MM patients collected) showed that overall only 75% of patients (range per year, 63 - 87%) received a first transplant/reinfusion. Only 0.7% of those initially transplanted in those years received a second transplant. As a result, collection targets for MM autologous patients <65 were lowered to 4 × 10e6 CD34+cells/kg. Apheresis & Cell Storage Results Following Change Between Feb. – Jul. 2018, the total collection days for adult autologous MM patients <65 (n=44) decreased to mean 1.45 (range 1-4, SE 0.11, p < 0.01). Patients finishing collection in one day increased to 66% (see Figure 1, p < 0.0001). Additionally, excess HPC(A) bags in storage for at least 1 month was only 2.5/patient, a decrease of 22.7% (p = 0.003) from prior time period. In that same 6-month period, the collection facility increased general collections outside of autologous stem cells by 43%, (p < 0.0001) and specifically CAR-T MNC collections by 240% (p < 0.0001) without increasing bed numbers or nursing hours. Conclusion Reducing autologous collection targets for MM patients <65 improved resource utilization across the entire apheresis and cell processing system at DFCI with significant reductions in collection days and storage requirements. Such optimization of clinical efficiency is necessary to set the stage for ongoing rapid growth in cellular therapies. [ABSTRACT FROM AUTHOR]