Platelet decrease and efficacy of platelet-rich plasma return for CAR-T lymphocyte apheresis in low-weight patients

Abstract Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a transformative treatment for relapsed or refractory acute lymphoblastic leukemia (ALL) and malignant lymphoma; however, the safety of lymphocyte apheresis, which is an essential preparatory step in CAR-T cell manufacturing, remains under-investigated, particularly in pediatric patients with low body weight. In such individuals, limited circulating blood volume renders them vulnerable to procedural complications, including thrombocytopenia, due to disproportionately high extracorporeal volumes and increased processed blood volume per kilogram. Although current guidelines acknowledge the risks of hemodynamic instability in small patients due to circuit priming, few studies have specifically addressed this population. Notably, tisagenlecleucel (Tisa-cel) requires the collection of a defined absolute number of CD3-positive T cells rather than a fixed processed volume, which often necessitates larger blood processing volumes in lower-weight patients and may further increase the risk of platelet loss. In prior work, we reported the utility of platelet-rich plasma (PRP) return to mitigate thrombocytopenia following peripheral blood stem cell apheresis, a procedure sharing similar technical elements (PMID: 34133767). In this study, we investigated the extent of thrombocytopenia and the effect of PRP return in pediatric ALL patients weighing less than 25 kg who underwent lymphocyte apheresis for Tisa-cel manufacturing. Among 144 total lymphocyte apheresis sessions conducted between 2019 and 2024 at our institution, 42 (29.1%) were for pediatric relapsed/refractory ALL, of which 19 patients (45.2%) weighed less than 25 kg. In this subgroup, platelet counts decreased by a median of 77 × 10⁹/L (range: 6–420 × 10⁹/L), corresponding to a median percentage drop of 52% (range: 10.9–86.7%). We next examined the impact of PRP return on post-apheresis thrombocytopenia. Platelet counts significantly declined from a pre-apheresis median of 156 × 10⁹/L (range: 55–561 × 10⁹/L) to a post-apheresis median of 79 × 10⁹/L (range: 19–165 × 10⁹/L) with significance (p = 0.00014). PRP return led to a statistically significant improvement, raising the platelet count to a median of 122 × 10⁹/L (range: 44–324× 10⁹/L; p = 0.00016). However, none of the patients regained their pre-apheresis baseline platelet levels. Finally, we analyzed the correlation between clinical characteristics and the degree of platelet decrease. The percentage reduction in platelet count was significantly associated with age (r = –0.494, p = 0.0310), height (r = –0.594, p = 0.0073), weight (r = –0.712, p = 0.0006), processed blood volume per kilogram (r = 0.765, p < 0.0001), pre-apheresis white blood cell count (r = 0.612, p = 0.0050), hemoglobin reduction (r = 0.599, p = 0.0067), and post-apheresis platelet count (r = –0.482, p = 0.0370). Collectively, our data suggest that CAR-T lymphocyte apheresis in low-weight patients can cause substantial thrombocytopenia, and that PRP return may serve as a beneficial strategy to attenuate this effect, though it does not fully restore pre-apheresis platelet levels. Furthermore, body weight and processed blood volume per kilogram emerged as key risk factors, underscoring the need for individualized blood volume estimation and standardized apheresis protocols tailored to this vulnerable population.