Francesco Ceppi1,2, Julie Rivers1,3, Colleen Annesley1,3, Navin Pinto1,3, Julie R Park1,3, Catherine Lindgren4, Stephanie Mgebroff4, Naomi Linn5, Meghan Delaney6,7, Rebecca A Gardner1,3. 1. Center for Clinical and Translational Research, Seattle Children's Hospital and Research Institute, Seattle, Washington. 2. Pediatric Hematology-Oncology Research Laboratory & Pediatric Hematology-Oncology Unit, Division of Pediatrics, Department Woman-Mother-Child, University Hospital of Lausanne, Lausanne, Switzerland. 3. Department of Pediatrics, University of Washington, Bloodworks NW, Seattle, Washington. 4. Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Bloodworks NW, Seattle, Washington. 5. Apheresis Department, Bloodworks NW, Seattle, Washington. 6. Children's National Health System, Washington, DC. 7. Department of Pathology, Seattle Children's Hospital, Seattle, Washington.
Abstract
BACKGROUND: The first step in the production of chimeric antigen receptor T cells is the collection of autologous T cells using apheresis technology. The procedure is technically challenging, because patients often have low leukocyte counts and are heavily pretreated with multiple lines of chemotherapy, marrow transplantation, and/or radiotherapy. Here, we report our experience of collecting T lymphocytes for chimeric antigen receptor T-cell manufacturing in pediatric and young adult patients with leukemia, non-Hodgkin lymphoma, or neuroblastoma. STUDY DESIGN AND METHODS: Apheresis procedures were performed on a COBE Spectra machine using the mononuclear cell program, with a collection target of 1 × 109 total mononuclear cells per kilogram. Data were collected regarding preapheresis and postapheresis blood counts, apheresis parameters, products, and adverse events. RESULTS: Ninety-nine patients (ages 1.3-25.7 years) and 102 apheresis events were available for analysis. Patients underwent apheresis at a variety of absolute lymphocyte cell counts, with a median absolute lymphocyte count of 944 cells/μL (range, 142-6944 cells/μL). Twenty-two patients (21.6%) had absolute lymphocyte counts less than 500 cells/μL. The mononuclear cell target was obtained in 100% of all apheresis harvests, and chimeric antigen receptor T-cell production was possible from the majority of collections (94%). Mononuclear cell collection efficiency was 65.4%, and T-lymphocyte collection efficiency was 83.4%. Ten patients (9.8%) presented with minor adverse events during the 102 apheresis procedures, with one exception of a severe allergy. CONCLUSIONS: Mononuclear cell apheresis for chimeric antigen receptor T-cell therapy is well tolerated and safe, and it is possible to obtain an adequate quantity of CD3+ lymphocytes for chimeric antigen receptor T-cell manufacturing in heavily pretreated patients who have low lymphocyte counts.
BACKGROUND: The first step in the production of chimeric antigen receptor T cells is the collection of autologous T cells using apheresis technology. The procedure is technically challenging, because patients often have low leukocyte counts and are heavily pretreated with multiple lines of chemotherapy, marrow transplantation, and/or radiotherapy. Here, we report our experience of collecting T lymphocytes for chimeric antigen receptor T-cell manufacturing in pediatric and young adult patients with leukemia, non-Hodgkin lymphoma, or neuroblastoma. STUDY DESIGN AND METHODS: Apheresis procedures were performed on a COBE Spectra machine using the mononuclear cell program, with a collection target of 1 × 109 total mononuclear cells per kilogram. Data were collected regarding preapheresis and postapheresis blood counts, apheresis parameters, products, and adverse events. RESULTS: Ninety-nine patients (ages 1.3-25.7 years) and 102 apheresis events were available for analysis. Patients underwent apheresis at a variety of absolute lymphocyte cell counts, with a median absolute lymphocyte count of 944 cells/μL (range, 142-6944 cells/μL). Twenty-two patients (21.6%) had absolute lymphocyte counts less than 500 cells/μL. The mononuclear cell target was obtained in 100% of all apheresis harvests, and chimeric antigen receptor T-cell production was possible from the majority of collections (94%). Mononuclear cell collection efficiency was 65.4%, and T-lymphocyte collection efficiency was 83.4%. Ten patients (9.8%) presented with minor adverse events during the 102 apheresis procedures, with one exception of a severe allergy. CONCLUSIONS: Mononuclear cell apheresis for chimeric antigen receptor T-cell therapy is well tolerated and safe, and it is possible to obtain an adequate quantity of CD3+ lymphocytes for chimeric antigen receptor T-cell manufacturing in heavily pretreated patients who have low lymphocyte counts.
Authors: Sherilyn A Tuazon; Ang Li; Theodore Gooley; Thomas W Eunson; David G Maloney; Cameron J Turtle; Michael L Linenberger; Laura S Connelly-Smith Journal: Transfusion Date: 2019-02-06 Impact factor: 3.157