Daphna Hutt1, Bella Bielorai2, Bella Baturov1, Inna Z'orbinski1, Natalia Ilin1, Etai Adam1, Orit Itzhaki3, Michal J Besser4, Amos Toren2, Elad Jacoby5. 1. Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel. 2. 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. 3. Ella Institute of Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel. 4. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Ella Institute of Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel. 5. 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.
Abstract
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: 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: 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 × 106 CAR + cells/kg) and the other in failure of CAR T-cell production. 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.
BACKGROUND: Autologous CD19chimeric-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: 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: 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 × 106 CAR + cells/kg) and the other in failure of CAR T-cell production. 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.
Authors: Michael P Gustafson; Courtney M Wheatley-Guy; Allison C Rosenthal; Dennis A Gastineau; Emmanuel Katsanis; Bruce D Johnson; Richard J Simpson Journal: J Immunother Cancer Date: 2021-07 Impact factor: 13.751