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Biochemical risk factors and outcomes of acute promyelocytic leukemia patients with thrombotic events: a matched pair analysis

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Abstract

Acute promyelocytic leukemia (APL) stands out as a distinctive form of acute leukemia, exhibiting a higher occurrence of thrombotic events when contrasted with other leukemia subtypes. Since thrombosis is a relatively rare but unfavorable condition with poor prognostic implications, it is crucial to determine the risk factors for thrombotic events in APL(thrombosis in large venous or arterial from onset to differentiation therapy in 30d). We performed a retrospective study involving 950 APL patients between January 2000 and October 2022, from which 123 were excluded by younger than 16 years of age, 95 were excluded by incomplete data, and 6 were excluded by thrombosis related to CVC or PICC. A total of 23 APL patients with thrombosis for inclusion in our analysis were performed a 1:5 ratio matching based on sex (perfect match) and age (within 5 years) to patients without thrombosis. These patients were continuously monitored in the outpatient department over a period of 5 years. We meticulously examined clinical and laboratory data to pinpoint the risk factors related to thrombotic events in APL. Our primary clinical endpoints were all-cause mortality and achieving complete remission, while secondary clinical outcomes included APL relapse. Thrombotic events were observed in 2.4% (23/950) of APL patients. Compared to patients without thrombosis, patients with thrombosis had higher lactate dehydrogenase (LDH) [313 (223, 486) vs. 233 (188, 367) U/L, p = 0.020], higher indirect bilirubin [11.2 (7.4, 18.6) vs.8.3 (6.0, 10.7) umol/L, p = 0.004], higher creatinine [72 (62, 85) vs. 63 (54, 74) umol/L, p = 0.026], higher CD2 expression (65.2 vs. 15.2%, p < 0.001), higher CD15 expression (60.9 vs. 24.3%, p = 0.001), and PML/RARαisoforms (p < 0.001). Multivariate-logistic-regression analysis revealed several factors that were markedly related to thrombosis, including LDH (OR≈1.003, CIs≈1.000–1.006, p = 0.021), indirect bilirubin (OR≈1.084, CIs≈1.000–1.188, p = 0.043), CD2 expression positive (OR≈16.629, CIs≈4.001–62.832, p < 0.001), and CD15 expression positive (OR≈7.747, CIs≈2.005–29.941, p = 0.003). The S-type (OR≈0.012, CIs≈0.000–0.310, p = 0.008) and L-type (OR≈0.033, CIs≈0.002–0.609, p = 0.022) PML/RARα isoforms were negatively associated with thrombosis. Kaplan–Meier curves indicated that the survival rates were remarkably varied between APL patients with and without thrombosis (HR:21.34, p < 0.001). LDH and indirect bilirubin are variables significantly associated with thrombosis in APL, S-type and L-type PML/RARαisoforms exhibit a negative association with thrombotic events. The thrombotic events of APL can predict the subsequent survival of thrombosis. The findings of our study have the potential to facilitate early detection of thrombosis and enhance the prognosis for individuals with APL who develop thrombosis. Further validation of our findings will be essential through future prospective or multicenter studies.

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Data Availability

The datasets presented in this article are not openly available because the data are part of an ongoing study at this centre.

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Funding

This work was supported by Peking University People's Hospital Research and Development Funds (RDJ2022-18) and the National Natural Science Foundation of China (grant no. 82270227 & 82070189).

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Author notes

  1. Xiaojing Song and Cheng Chi are contributed equally to this study.

Authors and Affiliations

  1. Department of Emergency, Peking University People’s Hospital, Beijing, 100044, China

    Xiaojing Song, Cheng Chi, Weibo Gao & Jihong Zhu

  2. Department of Hematology, Peking University People’s Hospital, Beijing, 100044, China

    Wei Sun, Yang Liu, Xiaohui Zhang, Xiaojun Huang & Yu Wang

Authors
  1. Xiaojing Song
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Contributions

XS, CC, Ws and YL collectively formulated the study's overarching concept and design. WG, XS, and CC participated in acquiring the data. XS and CC conducted data analysis and interpretation. The initial manuscript draft was prepared by XS and CC. JZ and YW contributed their statistical expertise. All authors collaborated on substantial revisions of the article and contributed intellectually to its content.

Corresponding authors

Correspondence to Jihong Zhu or Yu Wang.

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Ethics

We received ethical approval from the same hospital (2023PHB178-001). Our research strictly adhered to the principles outlined in the Declaration of Helsinki. The funding entity had no influence over the study's implementation. Both patients and hospital personnel were not participants in or aware of the research. Due to our data sharing agreement and the approval of the research ethics board, we are unable to share the original data.

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All authors are obligated to reveal any potential conflicts of interest, including commercial, financial, or other affiliations pertaining to the subject matter of this article. The authors have declared the absence of any such associations.

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Highlights

• First study to explore the prognostic outcomes of acute promyelocytic leukemia patients with thrombotic events.

• APL patients with thrombosis had an elevated mortality rate, while there was no significant difference in relapse rates.

• Lactate dehydrogenase and indirect bilirubin may be risk factors for thrombotic events in APL patients, and hemolysis may be related to the formation of thrombosis in APL.

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Supplementary file1 (XLS 227 KB)

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Song, X., Chi, C., Gao, W. et al. Biochemical risk factors and outcomes of acute promyelocytic leukemia patients with thrombotic events: a matched pair analysis. J Thromb Thrombolysis (2024). https://doi.org/10.1007/s11239-024-02988-x

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  • DOI: https://doi.org/10.1007/s11239-024-02988-x

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