PMID- 36131934 OWN - NLM STAT- MEDLINE DCOM- 20220923 LR - 20220924 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Cytopenia after chimeric antigen receptor T cell immunotherapy in relapsed or refractory lymphoma. PG - 997589 LID - 10.3389/fimmu.2022.997589 [doi] LID - 997589 AB - BACKGROUND: Patients with relapsed or refractory (R/R) lymphomas have benefited from chimeric antigen receptor (CAR)-T-cell therapy. However, this treatment is linked to a high frequency of adverse events (AEs), such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hematologic toxicity. There has been increasing interest in hematological toxicity in recent years, as it can result in additional complications, such as infection or hemorrhage, which remain intractable. METHODS: We conducted a retrospective, single-institution study to evaluate the patterns and outcomes of cytopenia following CAR-T-cell infusion and potential associated factors. RESULTS: Overall, 133 patients with R/R lymphoma who received CAR-T-cell therapy from June, 2017 to April, 2022 were included in this analysis. Severe neutropenia, anemia and thrombocytopenia occurred frequently (71, 30 and 41%, respectively) after CAR-T-cell infusion. A total of 98% of severe neutropenia and all severe thrombocytopenia cases occurred in the early phase. Early severe cytopenia was associated with CRS incidence and severity, as well as peak inflammatory factor (IL-6, C-reactive protein (CRP), and ferritin) levels. In multivariate analysis, prior hematopoietic stem cell transplantation (HSCT), baseline hemoglobin (HB), and lymphodepleting chemotherapy were independent adverse factors associated with early severe cytopenia. In addition, 18% and 35% of patients had late neutrophil- and platelet (PLT)-related toxicity, respectively. In multivariate analysis, lower baseline PLT count was an independent factor associated with late thrombocytopenia. More severe cytopenia was associated with higher infection rates and poorer survival. CONCLUSIONS: This research indicates that improved selection of patients and management of CRS may help to decrease the severity of cytopenias and associated AEs and improve survival following CAR-T-cell therapy. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov/ct2/show/NCT03196830, identifier NCT03196830. CI - Copyright (c) 2022 Zhou, Zhang, Shan, Zong, Geng, Li, Chen, Yu, Xu, Li and Wu. FAU - Zhou, Jin AU - Zhou J AD - National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. AD - Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Suzhou, China. FAU - Zhang, Ying AU - Zhang Y AD - National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. AD - Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Suzhou, China. FAU - Shan, Meng AU - Shan M AD - National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. AD - Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Suzhou, China. FAU - Zong, Xiangping AU - Zong X AD - National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. AD - Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Suzhou, China. FAU - Geng, Hongzhi AU - Geng H AD - National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. AD - Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Suzhou, China. FAU - Li, Jiaqi AU - Li J AD - National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. AD - Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Suzhou, China. FAU - Chen, Guanghua AU - Chen G AD - National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. AD - Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Suzhou, China. FAU - Yu, Lei AU - Yu L AD - Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China. FAU - Xu, Yang AU - Xu Y AD - National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. AD - Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Suzhou, China. FAU - Li, Caixia AU - Li C AD - National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. AD - Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Suzhou, China. FAU - Wu, Depei AU - Wu D AD - National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. AD - Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Suzhou, China. LA - eng SI - ClinicalTrials.gov/NCT03196830 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220905 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Interleukin-6) RN - 0 (Receptors, Chimeric Antigen) RN - 9007-41-4 (C-Reactive Protein) RN - 9007-73-2 (Ferritins) SB - IM MH - *Anemia/etiology MH - C-Reactive Protein/metabolism MH - Cytokine Release Syndrome/etiology MH - Ferritins MH - Humans MH - Immunotherapy, Adoptive/adverse effects MH - Interleukin-6/metabolism MH - *Lymphoma/etiology/therapy MH - *Neutropenia/etiology MH - *Receptors, Chimeric Antigen MH - Retrospective Studies MH - T-Lymphocytes MH - *Thrombocytopenia/etiology PMC - PMC9484486 OTO - NOTNLM OT - Lymphoma OT - chimeric antigen receptor OT - cytokine release syndrome OT - cytopenia OT - hematological toxicity COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/09/23 06:00 MHDA- 2022/09/24 06:00 PMCR- 2022/01/01 CRDT- 2022/09/22 03:29 PHST- 2022/07/19 00:00 [received] PHST- 2022/08/16 00:00 [accepted] PHST- 2022/09/22 03:29 [entrez] PHST- 2022/09/23 06:00 [pubmed] PHST- 2022/09/24 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.997589 [doi] PST - epublish SO - Front Immunol. 2022 Sep 5;13:997589. doi: 10.3389/fimmu.2022.997589. eCollection 2022.