Successful autologous T cell apheresis in pediatric patients with hematologic malignancies, solid tumors, and brain tumors.
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BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy is being used to target a range of pediatric cancers. Starting materials are critical for successful CAR T cell manufacturing, most often obtained via autologous mononuclear cell (auto-MNC) apheresis. While apheresis strategies are established for patients with B cell acute lymphoblastic leukemia (B-ALL), these approaches are not standardized and there are limited data on how these practices apply across other disease groups. Here, we report our experience with apheresis for CAR T cell production across various pediatric cancer diagnoses. METHODS: We performed a single-center retrospective analysis of auto-MNC apheresis events. Parameters for apheresis suitability included peripheral blood absolute lymphocyte count (ALC) ≥300 cells/µL and CD3+ ≥150 cells/µL. Meeting apheresis goal was defined as postprocessing yield within 90% of target (2 × 109 total nucleated cells [TNC] and 1 × 109 CD3+ cells). Multi-day collections were considered single apheresis events. Baseline and collection characteristics were compared across disease groups, and univariable and multivariable logistic regression models were applied to explore the associations between baseline factors and successful apheresis collection, adjusting for baseline covariates. RESULTS: We evaluated 151 auto-MNC apheresis collections from 138 unique patients diagnosed with ALL (n = 80), AML (n = 23), lymphoma (n = 2), solid tumor (n = 16), or brain tumor (n = 17). The median age at time of apheresis collection was 11.7 years (range 1.4-23.5), and the median amount of blood processed was 1.9 (range 0.8-8.2) total blood volumes (TBV), with no statistically significant difference in TBV processed between disease groups (P = 0.218). Overall, 87% of patients met both total nucleated cell (TNC) and CD3+ goals, with no statistically significant differences across disease groups in univariate or multivariate analyses. Collection efficiency was not impacted by burden of peripheral blasts among patients with leukemia. In multivariate analysis, increasing age was associated with increased odds of successful apheresis (OR: 1.17, 95% CI: 1.06-1.32), while odds of successful collection decreased with increasing baseline white blood cell count (OR: 0.92, 95% CI: 0.81-0.99). Subsequent CAR T cell manufacturing was successful in 127 of 129 procedures (98.4%). CONCLUSIONS: We report that auto-MNC apheresis collection criteria can be applied across an array of pediatric oncologic indications, resulting in highly successful apheresis and subsequent manufacturing campaigns without significant differences between disease groups. Age and baseline WBC count may influence successful apheresis, but overall low failure rates limit current risk factor analysis.