Considerations for immune effector cell therapy collections: a white paper from the American Society for Apheresis.

BACKGROUND AIMS: This white paper was developed to provide leukapheresis guidance for the collection of mononuclear cells from adult and pediatric patients who are destined for immune effector cell (IEC) therapies for commercial and research applications. Currently, there is considerable variability in leukapheresis processes and limited published information regarding best practices relevant to new cellular therapies, especially IECs. Herein the authors address critical leukapheresis questions in five domains to help guide consistent collection processes and ensure high-quality products. The first four domains are onboarding, pre-collection, collection and post-collection, with protocol feasibility, preparation, care and follow-up of the patient/donor at each step, respectively, and technical considerations during collection. The fifth domain of quality assurance focuses on ensuring product potency, purity, safety and auditing. METHODS: The American Society for Apheresis (ASFA) Clinical Applications Committee (IEC Therapy Subcommittee) was charged by the society's board of directors with working collaboratively with other ASFA committees and organizations, including the Foundation for the Accreditation of Cellular Therapy, Association for the Advancement of Blood and Biotherapies, American Society for Transplantation and Cellular Therapy, National Marrow Donor Program and International Society for Cell & Gene Therapy, to develop guidelines regarding leukapheresis collection of cells destined for the manufacture of IEC therapies. After a review of the literature and discussion with members of the involved committees and various institutions, a draft guidance was created and circulated for comment and revision. RESULTS: Critical aspects of apheresis that could affect the quality and quantity of the leukapheresis product were identified. These areas were then discussed and reviewed. After consensus, the best practice guidelines were proposed and accepted. CONCLUSIONS: In the current era of rapid growth of IEC therapies, it is important to address critical leukapheresis steps to provide high-quality products and more consistent practices and to eliminate redundant efforts.

Therapeutic plasma exchange is a safe and effective bridge therapy in patients with alcohol-associated ACLF not having immediate prospects for liver transplantation-A case-control, pilot study.

BACKGROUND: Therapeutic plasma exchange (TPE) is a well-established treatment modality in acute liver failure patients, but its efficacy in treating acute on chronic liver failure (ACLF) patients is yet to be established. AIM: To assess the efficacy and safety of TPE in patients with alcohol-associated ACLF who were nonresponders to standard medical treatment (SMT) and without immediate prospects for liver transplantation. METHODS: Twenty-eight alcohol-related ACLF (grade II) patients (14 cases and 14 controls) were enrolled in the study. Cases underwent standard volume TPE along with SMT while the controls were on SMT alone. The change (baseline to day 10) in laboratory parameters, cytokine concentrations, clinical severity scores along with 30 and 90 day mortality rates were noted and compared between the two groups. The adverse events (AEs) were noted in the groups and analyzed. RESULTS: A total of 51 TPE procedures were performed in 14 patients (average of 3.62 procedures/patient). TPE was effective in reduction of serum bilirubin, ammonia, activated partial thromboplastin time, prothrombin time, international normalized ratio, and severity scores (ACLF Research Consortium, Maddrey's discriminant function, and model for end-stage liver disease) (P < .05). There was no significant difference in the reduction of serum interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α concentrations among cases. Among the cases who received the complete TPE interventions, 30- and 90-day mortality rates were lower in the cases as compared to controls albeit only the 90-day mortality was significantly different. Procedure-related AEs was observed in 2% of procedures. CONCLUSION: TPE is an effective and well-tolerated bridge therapy in patients with alcohol-associated ACLF of moderate severity not improving on SMT and without immediate prospects for liver transplantation.

Interesting rare case of polyarteritis nodosa related to hepatitis B virus and plasma exchange role? - A case report and review of the literature.

Immune-mediated diseases wherein immune complex-mediated injury is predominant; plasma exchange remains a therapeutic option for vasculitis. Hepatitis B virus-associated polyarteritis nodosa (HBV-PAN) wherein immunosuppressants can be contraindicated, plasma exchanges have a proven role when combined with antiviral therapy. Plasma exchange by hastening the clearance of immune complexes is beneficial in acute organ dysfunction. A 25-year-old male presented with complaints of generalized weakness, tingling numbness and weakness of extremities, joint pain, weight loss, and rashes over arms and legs for 2 months. Hepatitis B workup showed high viral loads of HBV (34 million IU/ml) and hepatitis e antigen positivity (1129.06 U/ml). Cardiac workup showed elevated cardiac enzymes and decreased ejection fraction (40%-45%). The finding of contrast-enhanced computed tomography (CECT) chest and abdomen with CT angiogram abdomen was steady with medium vessel vasculitis. A diagnosis of vasculitis with probable etiology of HBV-related PAN with mononeuritis multiplex and myocarditis was made. He was treated with steroids, tablet tenofovir, and 12 sessions of plasma exchanges. On average, 2078 ml of plasma was exchanged during each session with 4% albumin as a replacement fluid using central femoral line dialysis catheter as vascular access on automated cell separator Optia ®Spectra (Terumo BCT, Lakewood, Co). He was discharged with the resolution of symptoms, including myocarditis and increase in power strength and still in follow-up. The present index case indicates that antiviral combined with plasma exchange after short-term corticosteroids is an effective therapy for HBV-PAN. TPE can be used as adjuvant therapy along with antiviral therapy in a rare disease like HBV-related PAN.

Should we adopt an automated de-centralized model of chimeric antigen receptor- T cells manufacturing for low-and middle-income countries? A real world perspective.

Autologous chimeric antigen receptor-T (CAR-T) cell therapy has proven itself as an effective therapeutic modality for cancers, especially hematological malignancies and is emerging as a potential candidate for solid organ cancers as well. However, the accessibility to treatment has been limited due to complexities and costs associated with manufacturing a genetically modified autologous product. The centralized model of CAR-T manufacturing which has emerged as the dominant model in developed nations does not seem well-suited to the needs and realities of the developing economies. In this context, we explore the relative advantages and disadvantages of the two models from a developing nation's perspective.

Predictors of outcomes in children with Central Nervous System tuberculosis.

BACKGROUND: Central Nervous system tuberculosis (CNS-Tb) is the most lethal form of extra-pulmonary tuberculosis in children. The lack of markers of outcome provides little information on the efficacy of the current treatment protocols for CNS-Tb and thus results in a higher mortality rate than other extrapulmonary manifestations of tuberculosis. This study aims to identify significant factors that will reliably predict the outcomes at discharge in children admitted with CNS-Tb. METHODS AND MATERIAL: This is a prospective observational study in children with neurotuberculosis admitted at a tertiary care hospital. Clinical presentations at the time of admission were studied. Outcomes at the end of in-patient care (completely cured, survival with some/severe disability or death) were correlated with clinical, laboratory, microbiological, and radiological parameters. Univariate and multivariate analyses were applied to study the parameters and a p-value ≤ 0.05 with a confidence interval (CI) of 95% was considered as statistically significant. FINDINGS: The study included 100 children between 4 months and 12 years of age with a mean of 5.84 (±3.5) years. At discharge, 55% of children recovered completely, 20% had some or severe disability and 25% died. On multivariate analysis, high CSF protein (p = 0.050) and drug resistance (p = 0.034) were highly associated with fatality. Meningeal enhancements with basal exudates (p = 0.021) and CSF lymphocyte count >90% were highly associated with survival with disability. Stage I disease at presentation (p < 0.0001) was the only variable associated with complete recovery. INTERPRETATION: Reliable prognostic markers for CNS-Tb can aid in predicting the efficacy of the current treatment and the anticipated outcome in the children with this disease. FUNDING: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.