Risk factors of major adverse cardiovascular events in patients treated with CART cell during hospitalization
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摘要: 目的:探讨CART细胞治疗患者住院期间发生主要不良心血管事件(MACE)的危险因素。方法:回顾性分析2018年9月—2021年4月于徐州医科大学附属医院接受CART细胞治疗的住院患者155例,其中男90例,女65例。根据MACE发生情况分为事件组34例和非事件组121例。分析两组患者基线资料。使用Cox比例风险回归分析患者发生MACE的影响因素。结果:非MACE组和MACE组在基线治疗使用β受体阻滞剂、血红蛋白(HB)、血小板(PLT)、C反应蛋白(CRP)及白细胞介素(IL-6)水平方面均差异具有统计学意义(均P<0.05),两组在CART细胞治疗后使用类固醇激素、低血压、使用托珠单抗和细胞因子释放综合征(CRS)≥2级方面均差异有统计学意义(均P<0.05)。单因素分析发现基线治疗使用β受体阻滞剂、CART细胞治疗后发生低血压、使用托珠单抗、使用类固醇、CRS≥2级,以及CRP、IL-6、HB、PLT均是MACE发生的影响因素(均P<0.05)。多因素Cox比例风险回归分析CART细胞治疗后发生低血压(HR:3.302,95%CI:1.153~7.971,P<0.05)、CART细胞治疗后CRS≥2级(HR:2.979,95%CI:1.244~7.135,P<0.05)是MACE发生的独立危险因素。χ2检验分析发现,CART细胞治疗后CRS≤1级与CRS≥2级组间MACE发生差异具有统计学意义(13.00%∶64.00%,P<0.05)。Kaplan-Meier生存分析法发现CRS≥2级的患者MACE发生率高于CRS≤1级的患者(P<0.05)。结论:CART细胞治疗后低血压以及CRS≥2级可增加MACE患病风险,在一定程度上可作为CART细胞治疗后患者MACE发生的预测因素。Abstract: Objective: To explore the risk factors of major adverse cardiovascular events(MACE) in patients treated with CART cell therapy during hospitalization.Methods: A total of 155 patients underwent CART cell therapy in the Affiliated Hospital of Xuzhou Medical University from September 2018 to April 2021 were analyzed retrospectively, including 90 males and 65 females. According to the occurrence of MACE, 34 cases were divided into the event group and 121 cases were divided into the non-event group. The clinical baseline data and laboratory indexes of the two groups were analyzed. Cox proportional hazards regression was used to analyze the risk factors of MACE.Results: There were statistical differences in the use of β-blockers, hemoglobin(HB), platelet(PLT), C-reactive protein(CRP), and leukemia interleukin-6(IL-6) levels before the CART cell therapy, as well as the use of steroid hormones and tocilizumab, CRS≥grade 2, and hypotension after CART cell therapy between the two groups(all P<0.05). Univariate Cox proportional hazards regression analysis showed that the use of β-blockers before CART treatment, hypotension, steroid hormones, and tocilizumab after CART cell therapy, CRS≥grade 2, and CRP, IL-6, HB, PLT were the risk factors of MACE(all P<0.05). Multivariate Cox proportional hazards regression analysis showed that hypotension(HR: 3.302, 95%CI: 1.153 to 7.971, P<0.05) and CRS≥grade 2(HR: 2.979, 95%CI: 1.244 to 7.135, P<0.05) after CART cell therapy were independent risk factors for MACE. χ2-test showed that there was a significant difference in MACE between groups with CRS≤grade 1 and CRS≥grade 2 after CART cell therapy(P<0.05). Kaplan-Meier survival analysis estimated that the incidence of MACE in the group with CRS≥grade 2 was higher than that in CRS≤grade1(13.00%∶64.00%, P<0.05).Conclusion: Hypotension and CRS≥grade 2 after CART cell therapy can increase the risk of MACE, which can be used as predictors of MACE after CART cell therapy to a certain extent.
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Key words:
- major adverse cardiovascular events /
- CART cell /
- risk factor
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[1] 花京剩,张剑,陈苏宁,等.CAR-T细胞技术在复发或难治急性淋巴细胞白血病中的临床应用进展[J].临床血液学杂志,2020,33(1):78-82.
[2] 梁爱斌,李萍.CAR-T细胞治疗淋巴瘤的研究进展[J].临床血液学杂志,2020,33(9):599-603.
[3] 王祥民,徐开林.多靶点CAR-T细胞治疗在复发难治性多发性骨髓瘤中的应用[J].临床血液学杂志,2020,33(7):446-450.
[4] Ganatra S,Carver JR,Hayek SS,et al.Chimeric antigen receptor T-cell therapy for cancer and heart:JACC council perspectives[J].J Am Coll Cardiol,2019,74(25):3153-3163.
[5] Schubert ML,Schmitt M,Wang L,et al.Side-effect management of chimeric antigen receptor(CAR)T-cell therapy[J].Ann Oncol,2021,32(1):34-48.
[6] Hicks KA,Tcheng JE,Bozkurt B,et al.2014 ACC/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials:A report of the American College of Cardiology/American Heart Association task force on clinical data standards(writing committee to develop cardiovascular endpoints data standards)[J].JAm Coll Cardiol,2015,66(4):403-469.
[7] Lefebvre B,Kang Y,Smith AM,et al.Cardiovascular effects of CAR T Cell therapy:A retrospective study[J].JACC CardioOncol,2020,2(2):193-203.
[8] US Department of Health and Human Services.Common Terminology Criteria for Adverse Events (CT-CAE)version 4.03[National Institutes of Health Wed Site][S/OL].[2010-06-14].http://evs.nci.gov/ftpl/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5X7.PDF
[9] Frey N,Porter D.Cytokine release syndrome with chimeric antigen receptor T cell therapy[j].biology of blood and marrow transplantation[J].Biol Blood Marrow Transpl,2019,25(4):e123-e127.
[10] Gill S,June CH.Going viral:chimeric antigen receptor T-cell therapy for hematological malignancies[J].Immunol Rev,2015,263(1):68-89.
[11] Jacoby E,Shahani SA,Shah NN.Updates on CAR T-cell therapy in B-cell malignancies[J].Immunol Rev,2019,290(1):39-59.
[12] Park JH,Geyer MB,Brentjens RJ.CD19-targeted CAR T-cell therapeutics for hematologic malignancies:interpreting clinical outcomes to date[J].Blood,2016,127(26):3312-3320.
[13] Maude SL,Frey N,Shaw PA,et al.Chimeric antigen receptor T cells for sustained remissions in leukemia[J].N Engl J Med,2014,371(16):1507-1517.
[14] Schuster SJ,Svoboda J,Chong EA,et al.Chimeric antigen receptor T cells in refractory B-cell lymphomas[J].N Engl J Med,2017,377(26):2545-2554.
[15] Ali MT,Yucel E,Bouras S,et al.Myocardial strain is associated with adverse clinical cardiac events in patients treated with anthracyclines[J].J Am Soc Echocardiogr,2016,29(6):522-527.e3
[16] Burstein DS,Maude S,Grupp S,et al.Cardiac profile of chimeric antigen receptor T cell therapy in children:A single-institution experience[J].Biol Blood Marrow Transplant,2018,24(8):1590-1595.
[17] Fitzgerald JC,Weiss SL,Maude SL,et al.Cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukemia[J].Crit Care Med,2017,45(2):e124-e131.
[18] Cordeiro A,Bezerra ED,Hirayama AV,et al.Late events after treatment with CD19-targeted chimeric antigen receptor modified T cells[J].Biol Blood Marrow Transplant,2020,26(1):26-33.
[19] Alvi RM,Frigault MJ,Fradley MG,et al.Cardiovascular events among adults treated with chimeric antigen receptor T-cells(CAR-T)[J].J Am Coll Cardiol,2019,74(25):3099-3108.
[20] Lee DW,Gardner R,Porter DL,et al.Current concepts in the diagnosis and management of cytokine release syndrome[J].Blood,2014,124(2):188-195.
[21] Porter D,Frey N,Wood PA,et al.Correction to:Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel[J].J Hematol Oncol,2018,11(1):81.
[22] Stein-Merlob AF,Rothberg MV,Holman P,et al.Immunotherapy-associated cardiotoxicity of immune checkpoint inhibitors and chimeric antigen receptor Tcell therapy:diagnostic and management challenges and strategies[J].Curr Cardiol Rep,2021,23(3):11.
[23] Oved JH,Barrett DM,Teachey DT.Cellular therapy:Immune-related complications[J].Immunol Rev,2019,290(1):114-126.
[24] Burns EA,Gentille C,Trachtenberg B,et al.Cardiotoxicity associated with anti-CD19 chimeric antigen receptor T-cell(CAR-T)therapy:recognition,risk factors,and management[J].Diseases,2021,9(1).
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