Get Off on the Right Foot: How to Plan an Efficient Leukocytapheresis to Collect T Cells for CAR T-Cell Manufacturing

Background: The major drug regulatory agencies have approved chimeric antigen receptor (CAR) T cells for the treatment of some B-cell lymphoproliferative diseases. Their use is expanding, and new indications will be approved. Efficient mononuclear cell collection by apheresis providing enough T cells is a critical step in further CAR T-cell manufacturing process. It is important that apheresis units are prepared for the collection of the required T cells for manufacturing with the highest efficiency and safety for the patient. Summary: Several series have studied different characteristics that could influence the collection efficiency of T cells for CAR T-cell manufacturing. Also, an effort has been made to identify predictors of the total number of target cells collected. Despite these publications and the large number of ongoing clinical trials, consensus protocols in apheresis are scarce. Key Messages: The aim of this review was to summarize the set of measures described to optimize apheresis and ensure patient safety. Moreover, we also propose, in a practical approach, a way to apply this knowledge to the daily routine in the apheresis unit.

[1]  H. Vrielink,et al.  Mathematics of apheresis. , 2023, Transfusion and Apheresis Science.

[2]  R. Burkhardt,et al.  Apheresis for chimeric antigen receptor T‐cell production in adult lymphoma patients , 2022, Transfusion.

[3]  L. Vercellino,et al.  Real-world characteristics of T-cell apheresis and clinical response to tisagenlecleucel in B-cell lymphoma , 2022, Blood advances.

[4]  M. Qayed,et al.  Leukapheresis guidance and best practices for optimal chimeric antigen receptor T-cell manufacturing. , 2022, Cytotherapy.

[5]  Suzanne R. Thibodeaux,et al.  Considerations for immune effector cell therapy collections: a white paper from the American Society for Apheresis. , 2022, Cytotherapy.

[6]  Suzanne R. Thibodeaux,et al.  Lack of defined apheresis collection criteria in publicly available CAR‐T cell clinical trial descriptions: Comprehensive review of over 600 studies , 2022, Journal of clinical apheresis.

[7]  R. Saccardi,et al.  How Can Accreditation Bodies, Such as JACIE or FACT, Support Centres in Getting Qualified? , 2022, The EBMT/EHA CAR-T Cell Handbook.

[8]  C. Chabannon,et al.  Providing the Starting Material to the Manufacturer of an Approved and Commercially Available Autologous CAR-T Cell Treatment , 2022, The EBMT/EHA CAR-T Cell Handbook.

[9]  E. Mcgrath,et al.  The Regulatory Framework for CAR-T Cells in Europe: Current Status and Foreseeable Changes AND Centre Qualification by Competent Authorities and Manufacturers , 2022, The EBMT/EHA CAR-T Cell Handbook.

[10]  The EBMT/EHA CAR-T Cell Handbook , 2022 .

[11]  M. Kersten,et al.  Management of Adults and Children receiving CAR T-cell therapy: 2021 Best Practice Recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA). , 2021, Annals of oncology : official journal of the European Society for Medical Oncology.

[12]  K. Akashi,et al.  Optimization of lymphapheresis for manufacturing autologous CAR-T cells , 2021, International Journal of Hematology.

[13]  I. Yakoub-Agha,et al.  [How to perform leukapheresis for procurement of the staring material used for commercial CAR T-cell manufacturing: A consensus from experts convened by the SFGM-TC]. , 2021, Bulletin du cancer.

[14]  P. Shi.  Optimizing leukapheresis product yield and purity for blood cell-based gene and immune effector cell therapy , 2020, Current opinion in hematology.

[15]  E. Seifried,et al.  Unstimulated apheresis for chimeric antigen receptor manufacturing in pediatric/adolescent acute lymphoblastic leukemia patients , 2020, Journal of clinical apheresis.

[16]  P. Dreger,et al.  Current Challenges in Providing Good Leukapheresis Products for Manufacturing of CAR-T Cells for Patients with Relapsed/Refractory NHL or ALL , 2020, Cells.

[17]  A. Toren,et al.  Feasibility of leukapheresis for CAR T-cell production in heavily pre-treated pediatric patients. , 2020, Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis.

[18]  M. Lozano,et al.  Peripheral venous access devices for apheresis: 16‐gauge is not always needed , 2020, Transfusion.

[19]  J. Ludden,et al.  Principles and Practice , 1998, Community-based Learning and Social Movements.

[20]  M. Lozano,et al.  Leukocytapheresis in nonmobilized donors for cellular therapy protocols: Evaluation of factors affecting collection efficiency of cells , 2019, Journal of clinical apheresis.

[21]  D. Stroncek,et al.  Effects of starting cellular material composition on chimeric antigen receptor T‐cell expansion and characteristics , 2019, Transfusion.

[22]  Eileen M. Walsh,et al.  Evaluation of peripheral blood mononuclear cell collection by leukapheresis , 2019, Transfusion.

[23]  D. Maloney,et al.  Factors affecting lymphocyte collection efficiency for the manufacture of chimeric antigen receptor T cells in adults with B‐cell malignancies , 2019, Transfusion.

[24]  A. Lodge,et al.  EU Regulatory Pathways for ATMPs: Standard, Accelerated and Adaptive Pathways to Marketing Authorisation , 2019, Molecular therapy. Methods & clinical development.

[25]  S. Hetjens,et al.  Low-Volume Leukapheresis in Non-Cytokine-Stimulated Donors for the Collection of Mononuclear Cells , 2018, Transfusion Medicine and Hemotherapy.

[26]  Michel Sadelain,et al.  Chimeric Antigen Receptor Therapy. , 2018, The New England journal of medicine.

[27]  L. Pilcher,et al.  Comparison of the CMNC and MNC apheresis protocol for the collection of T‐cells showed comparable outcome: An observational study in a single centre , 2018, Journal of clinical apheresis.

[28]  J. Cid,et al.  The Barcelona Hospital Clínic therapeutic apheresis database , 2018, Journal of clinical apheresis.

[29]  Francesco Ceppi,et al.  Lymphocyte apheresis for chimeric antigen receptor T‐cell manufacturing in children and young adults with leukemia and neuroblastoma , 2018, Transfusion.

[30]  A. Padmanabhan.  Cellular collection by apheresis , 2018, Transfusion.

[31]  C. Leveque,et al.  Ultrasound‐guided peripheral venous access for therapeutic apheresis procedures reduces need for central venous catheters , 2017, Journal of clinical apheresis.

[32]  A. Schmidt,et al.  Evolution of MNC and lymphocyte collection settings employing different Spectra Optia® Leukapheresis systems , 2017, Vox sanguinis.

[33]  J. Whitlock,et al.  Optimizing autologous nonmobilized mononuclear cell collections for cellular therapy in pediatric patients with high‐risk leukemia , 2017, Transfusion.

[34]  D. Stroncek,et al.  Autologous lymphapheresis for the production of chimeric antigen receptor T cells , 2017, Transfusion.

[35]  L. Castagna,et al.  Donor lymphocyte infusion after allogeneic stem cell transplantation. , 2016, Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis.

[36]  H. Vrielink,et al.  Calculations in apheresis , 2015, Journal of clinical apheresis.

[37]  J. Cid,et al.  Efficacy and safety of plasma exchange: ann 11-year single-center experience of 2730 procedures in 317 patients. , 2014, Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis.

[38]  R. Zimmermann,et al.  First comparative evaluation of a new leukapheresis technology in non‐cytokine‐stimulated donors , 2014, Vox sanguinis.

[39]  L. Ferrucci,et al.  Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. , 2004, The journals of gerontology. Series A, Biological sciences and medical sciences.

[40]  K. Ikeda,et al.  Collection of MNCs and progenitor cells by two separators for PBPC transplantation: a randomized crossover trial , 2003, Transfusion.

[41]  A. Remaley,et al.  Controlled study of citrate effects and response to IV calcium administration during allogeneic peripheral blood progenitor cell donation , 2002, Transfusion.

[42]  D. Printz,et al.  Collection efficiencies of MNC subpopulations during autologous CD34+ peripheral blood progenitor cell (PBPC) harvests in small children and adolescents , 2001, Journal of clinical apheresis.

[43]  Jean-Pierre Harrison,et al.  Apheresis ‐ Principles and Practice , 1998 .

[44]  Napier.  Guide to the Preparation, Use and Quality Assurance of Blood Components. , 1998 .

[45]  M. Brecher,et al.  Atypical reactions associated with use of angiotensin‐converting enzyme inhibitors and apheresis , 1994, Transfusion.