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Risk analysis of cardiovascular toxicity in patients with lymphoma treated with CD19 CAR T cells

Journal of Translational Medicine volume 23, Article number: 8 (2025) Cite this article

Abstract

Background

Anti-CD19 chimeric antigen receptor (CAR) T cell therapy is a common, yet highly efficient, cellular immunotherapy for lymphoma. However, many recent studies have reported on its cardiovascular (CV) toxicity. This study analyzes the cardiotoxicity of CD19 CAR T cell therapy in the treatment of lymphoma for providing a more valuable reference for clinicians.

Methods

The PubMed, Embase, Cochrane library, and Web of Science databases were comprehensively searched from the time of their establishment to May 2024. The ClinicalTrials.gov English database is a comprehensive repository of the original studies of CD19 CAR T cell therapy and associated adverse outcomes, such as arrhythmia, CV events, and hypotension, in patients with lymphoma. The Cochrane Collaboration tool and the Newcastle–Ottawa Scale (NOS) were used to assess the quality of the included original studies. For RCTs, the Cochrane Collaboration tool was used to assess the risk of bias. For non-randomized studies, the risk of bias was assessed using the NOS quality assessment scale.

Results

A risk analysis of two randomized controlled trials and nine cohort studies, totaling 1379 patients with lymphoma receiving CD19 CAR-T, is conducted. The incidences for all-cause mortality, CV events, and hypotension were found to be 17.8%, 17.8%, and 52.8%, respectively. Additionally, the incidences of heart failure (HF), cardiomyopathy, cardiac arrest, and other CV events are 3%, 0.6%, 1.3%, and 2.5%, respectively. In addition to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) as adverse events, patients treated with CD19 CAR T cells are also at risk of CV events. The most common CV events are arrhythmia and HF. Our further analysis showed that the incidence of CV events was 28.7% in the elderly and 13.5% in adults. The incidence of CV events in the elderly was higher than that in adults, and it was statistically significant. Furthermore, the incidence of CV events and hypotension is strongly associated with patients with CRS.

Conclusion

Therefore, clinicians should pay close attention to the occurrence of such CV events and take timely prevention and intervention measures to further improve the safety of CD19 CAR T cell therapy.

Background

Lymphomas are a diverse group of hematologic neoplasms derived from either B cells, T cells, or natural killer cells that usually develop in lymph nodes and other secondary lymphoid organs, although they can also develop in several other tissues and/or involve the blood [1,2,3]. Mature lymphoid malignancies [Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL)] are the most common hematological malignancies, with NHL being the most common malignancy [4]. Chemotherapy is the standard of care for patients with lymphoma. The introduction of monoclonal antibodies targeting surface antigens has dramatically changed the treatment landscape for lymphoma. For example, rituximab, an anti-CD20 antibody that targets CD20 in B-cell NHL, and brentuximab vedotin, which targets CD30 in classical HL and T-cell NHL, significantly improved patient-response rates and clinical outcomes [5, 6]. In addition, a growing understanding of molecular biology and signaling pathways has resulted in the development of many innovative drugs for lymphoma in recent years [7]. The increasing understanding of the crosstalk between malignant lymphocytes and the tumor microenvironment has led to the rapid development of chimeric antigen receptor T cells (CAR T cells) for the treatment of patients with relapsed conditions as well as those with refractory conditions [8, 9].

CAR-T cell therapy, a remarkable advancement in immunotherapy, marks a paradigm shift in the treatment of lymphoma [10]. Tisagenlecleucel (tisa-cel, Kymriah) is the first CD19-directed CAR-T therapy. It was approved by the US Food and Drug Administration (FDA) in 2017 for use in children and young adults with relapsed or refractory (rr) acute lymphoblastic leukemia [11]. In 2018, tisa-cel was approved by the FDA and the European Medicines Agency for patients with rr large B-cell lymphoma (LBCL) who have not responded even after two or more prior systemic treatment lines [12, 13]. Two other CAR-T products, axicabtagene ciloleucel (axi-cel, Yescarta) and lisocabtagene maraleucel (liso-cel, Breyanzi), have also been approved for rr LBCL [14, 15]. The CD19 CAR-T therapy exhibited impressive objective response rate and complete response (CR) rate in NHL (72% and 52%, respectively) [16]. Although great progress has been achieved in the field of CAR T cell therapy, it is still often associated with significant toxicity. The main adverse events of the CAR T cell therapy include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) [17, 18]. Although cardiovascular toxicity is less common than CRS and neurotoxicity in CAR-T therapy, it remains a potentially serious problem in patients with underlying heart disease or receiving high doses. The symptoms of cardiovascular toxicity may not be obvious and are easily confused with other treatment side effects, leading to their sometimes being overlooked [19]. At present, there is insufficient research on the mechanism of cardiovascular toxicity caused by CAR-T therapy, and there is a lack of clear clinical standards and management guidelines, so its research and attention are low, and clinical trials and patient monitoring mainly focus on CRS and neurotoxicity [20]. When cardiovascular complications may force CAR-T therapy to be interrupted or delayed, affecting treatment effectiveness and compromising cardiac function, treatment plan adjustments may reduce patient survival and tumor control [21]. Although the incidence of cardiovascular toxicity is low in CAR-T therapy, cardiovascular evaluation of lymphoma patients is still very important due to its potential to lead to fatal heart failure and arrhythmia.

In recent years, various cardiovascular (CV) toxic events of the CD19 CAR T cell therapy, used for the treatment of hematological tumors, have been reported. The most common CV toxic events are arrhythmia and heart failure (HF) [22, 23]. However, most of the individual clinical studies on CV toxicity have used relatively small sample sizes, which can compromise the accurate assessment of clinical outcomes and introduce a degree of bias. Although the CD19 CAR T cell therapy is commonly used in patients with lymphoma, its cardiotoxicity in lymphoma has not yet been fully evaluated. This study aims to comprehensively evaluate CV toxic events in patients with lymphoma following CD19 CAR T cell therapy, as doing so may enable the rational use of CD19 CAR T cells in clinical therapy.

Methods

Data sources and search strategy

The literature search strategy follows the requirements of the preferred reporting items for systematic reviews and Meta-Analysis declaration. The PubMed, Embase, Cochrane library, and Web of Science databases were comprehensively searched from the time of their establishment to May 2024. The detailed search strategy takes PubMed database as an example (Supplementary Table S1). The ClinicalTrials.gov English database is a comprehensive repository of the original studies of CD19 CAR T cell therapy and associated adverse outcomes, such as arrhythmia, CV events, and hypotension, in patients with lymphoma. The keywords mainly included “chimeric antigen receptor t-cell and CAR T,” “CAR-T,” “lymphadenoma,” “malignancy,” “cardiovascular,” “cardiotoxicity,” “cardiac,” and “vascular.”

Criteria for including studies

The following inclusion criteria were used for including the studies: (1) Studies should be on the CV effects of CD19 CAR T cell therapy on patients with lymphoma. (2) Studies should be clinical trials, RCTs or non-RCTs, or single-arm studies. (3) The subjects should be patients with lymphoma, regardless of their age and gender. (4) Study articles should be in English. (5) At least one of the following outcome measures must be reported in the study: all-cause mortality, CV events, arrhythmia, HF, cardiac arrest, cardiomyopathy, other CV events, and hypotension.

The following exclusion criteria were used: (1) Studies with fewer than nine patients; (2) reviews, animal experiments, meta-analyses; (3) studies that repeatedly report the same data results; (4) studies for which no research data were available or for which research data were derived from electronic datasets; (5) studies that did not consider the CD19 CAR T cell therapy for lymphoma; and (6) patients with pre-existing cardiovascular disease and those taking other drugs not related to tumor chemotherapy.

Data extraction

Literature search, abstract/manuscript review, inclusion/exclusion, and data collection were conducted independently by the two authors of this analysis and were then cross-reviewed to accurately collect the data. The primary outcome measures were all-cause mortality, CV events [arrhythmias, HF (including decompensated HF and chronic HF), cardiomyopathy, cardiac arrest, and other CV events], and hypotension. In addition, we collected data on authors, year of publication, median age of patients, number of patients, gender, lymphoma type, study type, and outcome of interest.

Risk of bias and quality evaluation of the included literature

This study included two types of literature: RCTs and non-randomized studies. The Cochrane Collaboration tool and the Newcastle–Ottawa Scale (NOS) were used to assess the quality of the included original studies. For RCTs, the Cochrane Collaboration tool was used to assess the risk of bias, including sequence generation, assignment sequence hiding, blinding, missing outcome data, and other biases [24]. For non-randomized studies, the risk of bias was assessed using the NOS quality assessment scale, taking into account study group selectivity, intergroup comparability, and certainty of outcome [25]. The scale is scored from 0 to 9. Studies having a score above 5 were considered high quality, and those with a score below 5 were considered low quality.

Statistical analysis

The proportional outcomes of the studies were summarized using the Freeman–Tukey double arcsine transform. The results were reported as a ratio with a 95% confidence interval (CI). Heterogeneity of the included studies was assessed using Q tests and II tests. When I2 > 50%, the random effect model was used for the analysis; otherwise, the fixed effect model was used (I2 ≤ 50%). The I2 statistic describes the percentage of studied variation resulting from heterogeneity rather than chance. To explore the source of heterogeneity and the stability of the results, a sensitivity analysis was performed by excluding each study in turn. In addition, the Begg’s funnel plot and Egger’s test were used to evaluate the publication bias. All analyses were performed using R (version 4.3.2). P < 0.05 denoted statistical significance.

Results

Search results

The flow chart of the literature search process is shown in Fig. 1. This search led to the identification of 1240 abstracts, clinical studies, case studies, and other publications. Of these, 11 publications were finally selected [26,27,28,29,30,31,32,33,34,35,36]. Two of these studies were randomized controlled trials (RCTs) and nine were cohort studies, with a total of 1379 patients. The quality of these two RCTs was independently assessed using the Cochrane Collaboration tool [31, 33]. The nine cohort studies were independently assessed using the NOS (Cohort study) system (Supplementary Table S2). The main limitations of the included RCTs are the possible lack of random sequence generation and the lack of assigned sequence hiding (Supplementary Figure S1).

Fig. 1
figure 1

Search strategy and study selection

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Characteristics of the included studies and NOS grade

Detailed characteristics of the included studies are listed in Table 1. These studies considered clinical data published between 2017 and 2024. The sample size varied from 47 to 345 cases. The overall cohort study quality was rated medium to high.

Table 1 Characteristics of the included studies and participants
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Overall incidence of all-cause mortality

Six studies evaluated the overall incidence of all-cause mortality in lymphoma patients after treatment with the CD19 CAR T cell therapy, as shown in Fig. 2A, with a combined all-cause mortality rate of 17.8% (95% CI 0.057–0.299). Subgroup analysis by age showed that the incidence of all-cause mortality was 16.2% (95% CI 0.073–0.251) in the elderly and 19.1% (95% CI 0.002–0.380) in adults, the results were not statistically significant (P = 0.79) (Fig. 2B). Because of significant heterogeneity (I2 = 94.56%, P < 0.01), a random effects model was used. In addition, sensitivity analysis was performed by sequentially excluding each study. The sensitivity analysis did not show any study with a large impact on the results (Fig. 2C), suggesting that the current results are stable.

Fig. 2
figure 2

All-cause mortality. A Forest plot of the overall incidence of all-cause mortality. B Subgroup analysis of all-cause mortality by age. C Sensitivity analysis of all-cause mortality

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Overall incidence of CV events

Ten studies evaluated the overall incidence of CV events after CD19 CAR T cell therapy in patients with lymphoma. The incidence rate of CV events for all patients undergoing CD19 CAR T cell therapy was calculated as 17.8% (95% CI 0.116–0.240). A random effects model was used (I2 = 95.57%, P < 0.01) (Fig. 3A). Subgroup analysis by age showed that the incidence of CV events was 28.7% (95% CI 0.204–0.371) in the elderly and 13.5% (95% CI 0.079–0.191) in adults. The incidence of CV events in the elderly was higher than that in adults, and it was statistically significant (P < 0.01) (Fig. 3B). Sensitivity analysis demonstrated that no studies had a large impact on the results (Fig. 3C), indicating that the current results were stable. In addition, we assessed the risk of CV events in patients with or without CRS, the risk ratio (RR) is 1.196 (95% CI 0.350–4.085) (Supplementary Figure S2). In a subgroup analysis of different CD19 CAR T products, the results showed that product differences had little effect on the incidence of CV events (Supplementary Figure S3).

Fig. 3
figure 3

Cardiovascular (CV) events. A Forest plot of the overall incidence of CV events. B Subgroup analysis of CV events by age. C Sensitivity analysis of CV events

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Incidence of arrhythmias

Six studies reported arrhythmias, with a combined incidence of 11.5% (95% CI 0.089–0.142). The common effect model was used (I2 = 37.70%, P = 0.15) (Fig. 4A). Subgroup analysis by age showed that the incidence of arrhythmia was 20.6% (95% CI 0.115–0.327) in the elderly and 10.8% (95% CI 0.081–0.136) in adults, the results were not statistically significant (P = 0.06) (Fig. 4B). Sensitivity analysis showed that none of the studies significantly interfered with the results of the present investigation (Fig. 4C).

Fig. 4
figure 4

Arrhythmias. A Forest plot of the overall incidence of arrhythmias. B Subgroup analysis of arrhythmias by age. C Sensitivity analysis of arrhythmias

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Incidence of HF

Six studies evaluated the incidence of HF after the CD19 CAR T cell therapy in patients with lymphoma. The combined rate of HF for all patients was 3% (95% CI 0.012–0.048). The included studies exhibited heterogeneity (I2 = 62.17%, P = 0.02). A random effects model was used (Fig. 5A). A sensitivity analysis was conducted, which showed that none of the studies had any effect on the current results (Fig. 5B).

Fig. 5
figure 5

Heart failure (HF). A Forest plot of the overall incidence of HF. B Sensitivity analysis of HF

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Incidence of hypotension

Hypotension is considered another important outcome beyond traditional CV events. Therefore, we further assessed the incidence of hypotension. Six studies reported on the overall incidence of hypotension in patients with lymphoma after CD19 CAR T cell infusion. We reported the overall incidence of hypotension as 52.8% (95% CI 0.239–0.816). A significant heterogeneity was noted among studies (I2 = 99.45%, P < 0.01). Therefore, a random effects model was adopted (Fig. 6A). Subgroup analysis of CRS showed that patients with CRS had a higher incidence of hypotension than those without CRS, the risk ratio is 1.147 (95% CI 0.862–1.527) (Fig. 6B). Sensitivity analysis, performed by sequentially excluding each study one by one, showed that the results did not change much (Fig. 6C). Hence, our results were robust and credible.

Fig. 6
figure 6

Hypotension. A Forest plot of the overall incidence of hypotension. B Subgroup analysis of hypotension by presence or absence of CRS. C Sensitivity analysis of hypotension

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Incidence of cardiomyopathy, cardiac arrest, and other CV events

For the incidence of cardiomyopathy, cardiac arrest and other CV events, three reported cardiomyopathy and other three reported cardiac arrest and other CV toxic events (Fig. 7A–C). The overall incidence of cardiomyopathy was 0.6% (95% CI 0.000–0.012), that of cardiac arrest was 1.3% (95% CI 0.003–0.024), and that of other CV events was 2.5% (95% CI 0.004–0.047). Sensitivity analysis, performed by sequentially excluding each study one by one, showed that the results did not change much. Hence, the results of this analysis were stable (Fig. 7D–f).

Fig. 7
figure 7

Incidence of cardiomyopathy, cardiac arrest, and other cardiovascular (CV) events. A Forest plot of the overall incidence of cardiomyopathy. B Forest plot of cardiac arrest. C Forest plot of other CV events. D Sensitivity analysis of the overall incidence of cardiomyopathy. E Sensitivity analysis of cardiac arrest. F Sensitivity analysis of other CV events

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Publication bias analysis

The risk of publication bias was assessed based on the funnel plot and Egger’s test (Table 2). Egger’s test did not find any evidence of a potential publication bias in the reporting of arrhythmias, HF, cardiomyopathy, cardiac arrest, other CV events, hypotension, and other outcomes (P > 0.05). However, Egger’s test (P < 0.05) identified a publication bias in the outcomes of all-cause mortality and CV events.

Table 2 The pooled proportions of outcomes for lymphoma with CD19 CAR-T cell therapy
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Discussion

CD19 CAR T cell therapy has gained wide acceptance in recent years for the treatment of lymphoma. However, the CD19 CAR T cell therapy causes certain serious adverse events too, such as neurotoxicity and cytokine syndrome [37]. Notably, the damaging effect of CART on cardiac function has been neglected in clinics. We aim to evaluate CV toxicity-related adverse events and provide relevant references for managing the clinical treatment of lymphoma. To our knowledge, this is the largest and most comprehensive analysis of associated CV toxicity resulting from CD19 CAR T cell therapy in patients with lymphoma. The results showed that the CD19 CAR T cell therapy increases risk of cardiovascular toxicity in patients with lymphoma. In addition to hypotension, arrhythmias and HF were the most common CV adverse events, followed by cardiac arrest. Our findings further systematically confirm recent individual findings on the CV adverse effects of the CD19 CAR T cell therapy and may contribute to the development of new CAR technologies with reduced CV toxicity.

As the use of CAR-T cells increases, understanding the mechanisms behind CV injury becomes critical, as it can aid in early intervention and prevention of cardiotoxicity. However, the precise mechanism of CV adverse reactions in CAR-T therapy has not yet been established. The CAR-T therapy gives rise to CV adverse reactions by causing severe CRS, which leads to hemodynamic instability, capillary leakage, and disseminated intravascular coagulation. In addition, it increases the serum concentrations of the Von Willebrand factor and angiopoietin-2 [38]. IL-6 (interleukin-6) is a key cytokine that causes CAR-T treatment-related CRS. A significant increase in IL-6 levels is closely related to adverse CV reactions. Pathan et al. found that IL-6 (serum endothelium-activating cytokine) inhibits myocardial contractile function through the p38MAPK signaling pathway [39]. Increased TNF-α (tumor necrosis factor-α) release leads to severe heart disease by causing endothelial damage and is highly associated with other cardiovascular events such as hypotension, heart failure, and cardiovascular dysfunction [40]. TNF-α and IL-6 and their downstream effector molecules lead to endothelial cell activation, increased vascular permeability, loss of vascular tone, activation of the complement system, coagulation cascade and subsequent disseminated intravascular coagulation (DIC) and myocardial dysfunction [41]. We further assessed the risk of patients with CRS and found that patients with CRS had a higher probability of developing hypotension than those without CRS (RR: 1.147). The incidence of CV toxicity was higher in patients with CRS than in patients without CRS (RR: 1.196), further suggesting a strong association between CRS and CV toxicity. We delved into whether these mechanisms manifest differently in different types of patients. We performed a subgroup analysis of older adults and adults and found that the incidence of CV toxicity was higher in older adults than in adults (28.7 vs 13.5).

Our study found that CD19 CAR T treatment for lymphoma resulted in CV events (incidence rate: 17.8%) and arrhythmias (incidence rate: 11.5%). These values are higher than the previously reported rates of CV events (16.7%) and arrhythmias (6.5%) for hematologic disorders treated with CAR T cell therapy [42, 43]. Therefore, when using the CAR T cell therapy, patients with lymphoma need more CV attention compared to patients with other blood disorders. In the studies of Lefebvre et al. [44] and Mahmood et al. [45], patients experienced cardiac events at a median time of 11 (6–151) and 12 (7–99) days after CAR-T cell infusion, respectively. Therefore, the close temporal association between CAR-T cell infusion and the occurrence of cardiac events supports a potential causal relationship. Early intervention is very important. Some related treatment strategies have been widely used in clinical practice by many centers. For example, tocilizumab is commonly used as first-line therapy for cardiovascular toxicity, but corticosteroids are also used when patients do not respond to an initial dose of tocilizumab within 24 h [46], which is considered part of first-line therapy for patients with acute life-threatening toxic effects (such as malignant arrhythmias) [47]. Before and during CD19 CAR T cell therapy in lymphoma patients, it is necessary for clinical staff to develop a specific cardiovascular screening regimen. In addition, oncologists and cardiologists are recommended to collaborate across disciplines in the management of these patients to work together to safeguard patients’ heart health and make anti-tumor treatments safer and more effective.

This study is the first to analyze the cardiotoxicity caused by CAR-T in lymphoma. The study results have important clinical implications. However, our study has certain limitations too. First, there is a certain degree of heterogeneity among the studies considered herein, possibly because of the small number of RCTs on CD19 CAR-T cell immunotherapy in patients with lymphoma. Second, the overall study sample size is relatively small, which may have hindered the accurate estimation of clinical outcomes. Therefore, it is necessary to conduct large-sample, multicenter RCTs to further confirm the effect of the CD19 CAR-T cell therapy on CV toxicity in patients with lymphoma, improve the safety of CD19 CAR-T cell therapy, and help clinicians better understand and manage the adverse effects of the treatment to maximize patient efficacy and safety.

Conclusions

This study showed that lymphoma patients treated with CD19 CAR T cell therapy may be at an increased risk for CV toxicity, especially arrhythmia, and HF. Therefore, clinicians should closely monitor the occurrence of such CV events and take timely preventive and intervention measures to improve the safety of the CD19 CAR T cell therapy (Fig. 8). In addition, a deeper understanding of cardiotoxicity will help drive the development of new trial protocols to reduce CD19 CAR T cell treatment-associated toxicity and improve patient outcomes. This study is not only critical for improving the clinical efficacy of CD19 CAR T cell therapy for lymphoma, but also for improving the understanding of and managing the adverse effects of the therapy to maximize patient efficacy and safety.

Fig. 8
figure 8

Risk analysis of cardiovascular toxicity in patients with lymphoma treated with CD19 CAR T cells

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Availability of data and materials

Not applicable.

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Acknowledgements

Not applicable.

Funding

This work was supported by the Natural Science Foundation of Guizhou Province (Nos. QianKeHe Basics—ZK[2023] Key 042, Qiankehe Cooperation Platform Talents [2021] Postdoctoral Station 007); the Research Project of Education Department of Guizhou Province (No. QianJiaoJi [2023] 037); the Science and Technology Innovation Talent Team Project (grant number GZYTD [2024] 003); and the Subject Excellent Reserve Talent Project (No. gyfyxkrc-2023-14). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

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Author notes

  1. Yang Liu and Xiaoshuang Yuan contributed equally to this work.

Authors and Affiliations

  1. Clinical Medical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No. 71 Bao Shan North Road, Yunyan District, Guiyang, 550001, Guizhou, China

    Yang Liu, Xu Yang, Bo Yang, Guangyang Liu & Feiqing Wang

  2. Department of Hematology Oncology, Affiliated Hospital of Guizhou Medical University, No. 4 Bei Jing Road, Yunyan District, Guiyang, 550004, Guizhou, China

    Xiaoshuang Yuan & Yanju Li

  3. Fourth Medical Center, General Hospital of People’s Liberation Army: Chinese PLA General Hospital, Beijing, 100089, China

    Xiao Xu

  4. People’s Liberation Army Joint Logistic Support Force 920, Hospital, Kunming, Yunnan, China

    Sanbin Wang

  5. Center of Tissue Engineering and Stem Cell Research, Guizhou Medical University, Guiyang, Guizhou, China

    Zhixu He

  6. Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China

    Feiqing Wang

Authors
  1. Yang Liu
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  2. Xiaoshuang Yuan
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  3. Xu Yang
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  4. Bo Yang
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  5. Guangyang Liu
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  8. Zhixu He
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  9. Feiqing Wang
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  10. Yanju Li
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Contributions

LY, WFQ, LYJ, and YXS conceived and designed the study. They had full access to all the data in the study and are responsible for the integrity of the data, the accuracy of the data analysis, and the writing of the report. HZX, WSB, and XX critically revised the report. LGY, YX, and YB performed the statistical analyses. All authors contributed to data acquisition and analysis. All authors have reviewed and approved the final version of the manuscript.

Corresponding authors

Correspondence to Feiqing Wang or Yanju Li.

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All the authors contributed to the data acquisition and analyses. All the authors have reviewed and approved of the final version of the manuscript and consent to publish.

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Liu, Y., Yuan, X., Yang, X. et al. Risk analysis of cardiovascular toxicity in patients with lymphoma treated with CD19 CAR T cells. J Transl Med 23, 8 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12967-024-06035-4

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Journal of Translational Medicine

ISSN: 1479-5876

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