Association of red blood cell 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 has transformed the treatment paradigm for relapsed or refractory non-Hodgkin's lymphoma (NHL), acute lymphoblastic leukemia (ALL), and multiple myeloma (MM). However, its clinical application is often complicated by prolonged cytopenias and coagulopathy, resulting from lymphodepleting chemotherapy and immune-mediated marrow suppression, frequently necessitating blood transfusions. Notably, more than half of patients require red blood cell or platelet transfusions within the first month following infusion. Early red blood cell transfusion has been correlated with inferior progression-free and overall survival. Additionally, transfusion-related immunomodulation may impair antitumor immune responses and elevate the risk of infectious complications. This study utilizes six years of nationwide data to evaluate the prognostic significance of red blood cell transfusion in CAR T-cell recipients. Methods Using data from the National Inpatient Sample (NIS) from 2017 to 2022, we identified adult patients with NHL, MM, or ALL who underwent CAR T-cell therapy. Patients were stratified based on receipt of red blood cell transfusion. Weighted analyses ensured national representation, and multivariate logistic regression was used to evaluate associations between transfusion status and clinical outcomes. Statistical significance was set at p < 0.05. Results Among 5,705 adults who underwent CAR T-cell therapy (78.7% with NHL, 15.6% with MM, and 5.7% with ALL), 715 patients (12.5%) received red blood cell transfusion. A significantly higher proportion of Hispanic patients required transfusion (16.1% vs. 9.8%, p < 0.05). Transfusion was independently associated with increased all-cause in-hospital mortality (6.3% vs. 2.1%, p < 0.05; adjusted odds ratio [aOR] 3.3, 95% confidence interval [CI] 1.5–7.3). Transfused patients also had higher odds of acute kidney injury (aOR 2.4, 95% CI 1.6–3.6), respiratory failure (aOR 2.3, 95% CI 1.2–4.2), all-cause shock (aOR 3.1, 95% CI 1.6–5.8), and intracranial hemorrhage (aOR 3.9, 95% CI 1.4–11.3). Additionally, transfusion was associated with greater use of mechanical ventilation (aOR 2.5, 95% CI 1.2–5.1) and vasopressor support (aOR 2.9, 95% CI 1.5–5.6). No significant associations were observed with gastrointestinal hemorrhage (aOR 0.3, 95% CI 0.0–3.0) or disseminated intravascular coagulation (aOR 2.3, 95% CI 0.9–6.1). Transfusion was also linked to prolonged hospitalization, with an adjusted increase of 4.4 days (p < 0.05). The mean hospitalization charge for CAR T-cell therapy was $1,321,248.00, with no significant difference between transfused and non-transfused cohorts. Conclusion In this large, nationally representative cohort, red blood cell transfusion during CAR T-cell therapy was independently associated with significantly worse clinical outcomes, including higher in-hospital mortality, increased risk of organ dysfunction, greater utilization of critical care resources, and prolonged hospitalization. The consistent link between transfusion and multiple adverse outcomes suggests that transfusion may serve as a surrogate marker of clinical deterioration and underlying disease severity in this high-risk population. Further studies are warranted to elucidate the pathophysiologic mechanisms underlying poor outcomes, particularly the roles of systemic inflammation, immune dysregulation, marrow suppression, and transfusion-associated coagulopathy. Early identification and targeted management of these factors may help mitigate complications and improve overall outcomes in patients receiving CAR T-cell therapy.