Feasibility of leukapheresis for CAR T-cell production in heavily pre-treated pediatric patients.


Journal

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis
ISSN: 1473-0502
Titre abrégé: Transfus Apher Sci
Pays: England
ID NLM: 101095653

Informations de publication

Date de publication:
Aug 2020
Historique:
received: 10 02 2020
revised: 26 03 2020
accepted: 26 03 2020
pubmed: 18 5 2020
medline: 9 6 2021
entrez: 17 5 2020
Statut: ppublish

Résumé

Autologous CD19 chimeric-antigen receptor (CAR) T-cells are an effective salvage therapy for patients with relapsed or refractory B cell malignancies. The essential first step in the production is the collection of mature lymphocytes through leukapheresis. It is a challenging procedure given the fact patients are heavily pretreated and the special considerations of pediatric apheresis. We analyzed the data of leukapheresis outcome for CAR T production in a phase 1b/2 clinical trial enrolling 34 children, adolescents and young adults with relapsed or refractory B-cell malignancies. All patients underwent a single leukapheresis. Given a short production time for CAR T-cells, most patients received bridging therapy prior to apheresis. Leukapheresis was performed using peripheral venous access in the majority (82%) of patients, and the remainder required arterial line or central venous access. T-cell collection efficiency (CE) was variable with a median of 18%. No apheresis-related adverse events were noted, and all procedures were successful but two: one resulting in lower than target dose (1 × 10 Collection of sufficient T-cells in heavily pretreated pediatric patients via a single apheresis procedure is feasible even with relatively low T-cell CE.

Sections du résumé

BACKGROUND BACKGROUND
Autologous CD19 chimeric-antigen receptor (CAR) T-cells are an effective salvage therapy for patients with relapsed or refractory B cell malignancies. The essential first step in the production is the collection of mature lymphocytes through leukapheresis. It is a challenging procedure given the fact patients are heavily pretreated and the special considerations of pediatric apheresis.
METHODS METHODS
We analyzed the data of leukapheresis outcome for CAR T production in a phase 1b/2 clinical trial enrolling 34 children, adolescents and young adults with relapsed or refractory B-cell malignancies.
RESULTS RESULTS
All patients underwent a single leukapheresis. Given a short production time for CAR T-cells, most patients received bridging therapy prior to apheresis. Leukapheresis was performed using peripheral venous access in the majority (82%) of patients, and the remainder required arterial line or central venous access. T-cell collection efficiency (CE) was variable with a median of 18%. No apheresis-related adverse events were noted, and all procedures were successful but two: one resulting in lower than target dose (1 × 10
CONCLUSIONS CONCLUSIONS
Collection of sufficient T-cells in heavily pretreated pediatric patients via a single apheresis procedure is feasible even with relatively low T-cell CE.

Identifiants

pubmed: 32414613
pii: S1473-0502(20)30059-8
doi: 10.1016/j.transci.2020.102769
pii:
doi:

Substances chimiques

Receptors, Chimeric Antigen 0

Types de publication

Journal Article

Langues

eng

Pagination

102769

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest DH and EJ received honoraria from Novartis. All other authors have no conflicts of interest.

Auteurs

Daphna Hutt (D)

Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.

Bella Bielorai (B)

Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Bella Baturov (B)

Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.

Inna Z'orbinski (I)

Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.

Natalia Ilin (N)

Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.

Etai Adam (E)

Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.

Orit Itzhaki (O)

Ella Institute of Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel.

Michal J Besser (MJ)

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Ella Institute of Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel.

Amos Toren (A)

Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Elad Jacoby (E)

Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: elad.jacoby@sheba.gov.il.

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Classifications MeSH