The recent work by O'Reilly et al. [
] provides an elegant tool for chimeric antigen receptor (CAR)–T-cell apheresis planning by generating a formula that predicts the process volume required to achieve a certain target dose of T cells. The formula is mathematically much more sophisticated than the referenced one that we had previously proposed. Our “formula” is solely the estimate that at least 40% of T cells presented at the connector will be collected into the product bag [
- O'Reilly MA
- Malhi A
- Cheok KPL
- Ings S
- Balsa C
- Keane H
- et al.
A novel predictive algorithm to personalize autologous T-cell harvest for chimeric antigen receptor T-cell manufacture.
Cytotherapy. 2023; 25: 323-329
]. O'Reilly et al. comment that the process volumes suggested by the “40% formula” regularly result in the collection of more than the required dose. Indeed, the 40% formula underpromises by design, as it is based on worst-case estimates of collection efficiency (CE). Past experience teaches that, although the mean CE for lymphocytes of 60% or so is achieved with current apheresis technology, CE is quite variable [
- Yakoub-Agha I
- Chabannon C
- Bader P
- Basak GW
- Bonig H
- Ciceri F
- et al.
Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE).
Haematologica. 2020; 105: 297-316
]. A CE of 40%, and, accordingly, the targeted cell dose, will be exceeded by 90% of aphereses if the proposed volume can be processed. Although overcollection may be economically undesirable, from the patient's perspective, the meaningful risk is undercollection. Moreover, the formula by O'Reilly et al. is mathematically unable to predict small process volumes: where high T-cell concentrations are present in blood or modest T-cell doses are targeted, the formula predicts negative process volumes. Therefore, the minimum recommended process volume is 7 L. Experience teaches, however, that the mean CAR-T apheresis process volume in adults is less than 5 L [
- Schulz M
- Bialleck H
- Thorausch K
- Bug G
- Dunzinger U
- Seifried E
- et al.
Unstimulated leukapheresis in patients and donors: comparison of two apheresis systems.
Transfusion. 2014; 54: 1622-1629
] and that 7 L is not reasonably achievable in most children. Targeting a T-cell dose of 109, the dose required for manufacturing of Liso-cel, the formula by O'Reilly et al. proposes a process volume of 7 L for all patients with a T-cell concentration in the peripheral blood of at least 200/µL, i.e., the sometimes-mentioned lower threshold for CAR-apheresis eligibility.
- Pineyroa JA
- Cid J
- Vlagea A
- Carbasse G
- Henao P
- Bailo N
- et al.
Evaluation of cell collection efficiency in non-mobilized adult donors for autologous chimeric antigen receptor T-cell manufacturing.
Vox Sang. 2022; 118: 217-222
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Cytotherapy
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- A novel predictive algorithm to personalize autologous T-cell harvest for chimeric antigen receptor T-cell manufacture.Cytotherapy. 2023; 25: 323-329
- Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE).Haematologica. 2020; 105: 297-316
- Unstimulated leukapheresis in patients and donors: comparison of two apheresis systems.Transfusion. 2014; 54: 1622-1629
- Evaluation of cell collection efficiency in non-mobilized adult donors for autologous chimeric antigen receptor T-cell manufacturing.Vox Sang. 2022; 118: 217-222
Published online: May 06, 2023
Accepted: April 12, 2023
Received: March 6, 2023
Publication stageIn Press Corrected Proof
© 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.