Association of platelet transfusion and clinical outcomes in chimeric antigen receptor T-cell therapy: Insights from a six-year nationwide analysis

Abstract Background Chimeric Antigen Receptor (CAR) T-cell therapy is an established treatment for relapsed or refractory non-Hodgkin's lymphoma (NHL), acute lymphoblastic leukemia (ALL), and multiple myeloma (MM). Despite its efficacy, CAR T-cell therapy is frequently complicated by hematologic toxicities, particularly thrombocytopenia and coagulopathy, which increase bleeding risk. Early thrombocytopenia occurs in up to 43% of CAR T-cell therapy patients. Moreover, bleeding is reported in as many as 33% of CAR T-cell therapy patients and is often associated with prolonged prothrombin time, elevated IL-6 and IL-10 levels, and low baseline platelet counts. Over half of CAR T-cell recipients require platelet or red blood cell transfusions within the first month after therapy. Importantly, transfusion requirements have been independently linked to increased mortality, suggesting a potential prognostic role. Moreover, platelet transfusion refractoriness is more common in CAR T-cell recipients compared to those receiving chemotherapy and is associated with severe cytokine release syndrome (CRS) and bleeding. Using a U.S. national cohort, this study examines the association between platelet transfusion and clinical outcomes following CAR T-cell therapy and explores its prognostic implications. Methods We analyzed data from the National Inpatient Sample (NIS) from 2017 to 2022, identifying adult patients with NHL, MM, or ALL who underwent CAR T-cell therapy. Patients were stratified by whether they received platelet transfusions. Weighted analyses ensured national representativeness, and multivariate regression models assessed associations between transfusion status and clinical outcomes. Statistical significance was defined as p < 0.05. Results Among 5,705 adults who underwent CAR T-cell therapy (78.7% NHL, 15.6% MM, 5.7% ALL), 375 (6.6%) received platelet transfusions. A significantly higher proportion of Hispanic patients (18.7% vs. 10.0%, p < 0.05) and patients with atrial fibrillation (22.7% vs. 11.3%, p < 0.05) required transfusion. Platelet transfusion was independently associated with increased all-cause in-hospital mortality (10.7% vs. 2.1%, p < 0.001; adjusted odds ratio [aOR] 6.3, 95% CI 2.6–15.6). Transfused patients also had significantly higher odds of acute kidney injury (aOR 3.2, 95% CI 1.9–5.4), respiratory failure (aOR 3.3, 95% CI 1.7–6.5), shock (aOR 6.6, 95% CI 3.3–13.2), venous thromboembolism (aOR 3.5, 95% CI 1.1–11.9), intracranial hemorrhage (aOR 14.5, 95% CI 5.7–37.3), and disseminated intravascular coagulation (aOR 4.6, 95% CI 1.5–14.2). Additionally, platelet transfusion was linked to increased use of renal replacement therapy (aOR 6.2, 95% CI 1.5–26.2), mechanical ventilation (aOR 4.8, 95% CI 2.1–11.1), and vasopressor support (aOR 5.9, 95% CI 2.4–14.3). Transfused patients demonstrated greater utilization of blood transfusions (aOR 149.6, 95% CI 62.9–355.8), cryoprecipitate, and fresh frozen plasma (aOR 35.4, 95% CI 13.4–93.0). There was no significant association with gastrointestinal hemorrhage (aOR 0.6, 95% CI 0.1–4.5). Platelet transfusion was also strongly associated with prolonged hospitalization (+11.3 days, p < 0.001) and increased total hospital costs (+$441,207.50, p < 0.05), after adjusting for relevant covariates. Conclusion Among patients receiving CAR T-cell therapy for NHL, MM, or ALL, platelet transfusion was independently associated with increased in-hospital mortality, critical complications, and greater healthcare utilization. These findings suggest that platelet transfusion may serve as a prognostic marker to identify patients at higher risk of adverse outcomes. Further research is needed to elucidate the underlying mechanisms linking platelet transfusion to clinical outcomes, including the roles of severe CRS, consumptive coagulopathy, and bone marrow suppression. This knowledge could enhance risk stratification and optimize supportive care strategies in this population.