AUTHOR=Liu Yadan , Liang Bin , Liu Yan , Wei Guoqing , Wu Wenjun , Yang Luxin , Yang Li , Huang He , Xie Jue , Hu Yongxian 

TITLE=Cytokine Release Syndrome Is an Independent Risk Factor Associated With Platelet Transfusion Refractoriness After CAR-T Therapy for Relapsed/Refractory Acute Lymphoblastic Leukemia

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.702152

DOI=10.3389/fphar.2021.702152

ISSN=1663-9812

ABSTRACT=BACKGROUND Chimeric antigen receptor T cell (CAR-T) therapy is successful in improving treatment outcomes for relapsed/refractory acute lymphoblastic leukemia (R/R ALL). However, toxicities associated with CAR-T therapy are being increasingly identified. Pancytopenia is one of the most common complications after CAR-T therapy, and platelet transfusions are an essential part of its supportive care. STUDY DESIGN AND METHODS This study aimed to assess the effectiveness of platelet transfusions for R/R ALL patients at our single center and identify associated risk factors. Overall, 44 R/R ALL patients were enrolled in this study, of whom 26 received CAR-T therapy and 18 received salvage chemotherapy. RESULTS Patients in the CAR-T group had a higher incidence of platelet transfusion refractoriness (PTR) (15/26, 57.7%) than those in the chemotherapy group (3/18, 16.7%) (p=0.007). For patients receiving CAR-T therapy, multivariate analysis showed that cytokine release syndrome (CRS) was the only independent risk factor associated with PTR (p=0.020). Moreover, higher peak serum IL-6 and IFN-γ levels suggested a higher risk of PTR (p=0.024 and 0.009, respectively). Patients with PTR received more platelet infusion doses than those without PTR (p=0.0426). Patients with PTR had more grade 3–4 bleeding events than those without PTR (21.4% vs. 0%, p=0.023). CONCLUSION We found for the first time that PTR is associated with the CRS grade. Improved knowledge on the mechanisms of PTR after CAR-T therapy is needed to design a rational therapeutic strategy that aims to improve the efficiency of transfusions.