Plethysmographic and Biochemical Markers in the Diagnosis of Endothelial Dysfunction in Pediatric Acute Lymphoblastic Leukemia Survivors – New Applications

MASOPUSTOVA, A.; Jehlička, Petr; Huml, Michal; Votava, Tomáš; Trefil, L.; Kreslová, Marcela; Sýkora, Josef

doi:10.33549/physiolres.933754

Cited by 10 publications

(10 citation statements)

References 32 publications

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“…For example, asymmetric dimethylarginine (ADMA) is a competitive inhibitor of NO synthase and is increased in patients with ALL. ADMA is a product of tumor cell degradation, oxidative stress, manifestation of liver failure and inflammation of the endothelial wall [5,8,9]. It should be noted that there are a number of scientific studies on the levels of nitric oxide in ALL, which have shown the results of increasing total NO [7,14,15].…”

Section: Resultsmentioning

confidence: 99%

“…reached normal values. This is evidently due to the normalization of a number of NO synthetase inhibitors in children in remission [8] and the absence of pathological factors (remission of leukemia, end of treatment). It should be emphasized that children who received anthracycline drugs are at risk of cardiovascular disease even after therapy [6,9,17].…”

Section: Table 3 Correlation Relationships Between Endothelial Dysfunmentioning

confidence: 99%

“…Reduction of biological activity of nitric oxide (NO) leads to stimulation of vasoconstriction, inflammation and thrombosis, damage to tissue structures, plays a crucial role in the pathogenesis of ED [5,8,16]. The role of nitric oxide in disorders of cardiovascular function under conditions of endotoxic shock has been proved [16].…”

Section: Influence Of Nitric Oxide Metabolite Levels On the Developmementioning

confidence: 99%

“…The survival rate of children diagnosed with ALL has been improved due to anthracycline agents, but their use is accompanied by vascular endothelial damage with subsequent development of endothelial dysfunction (ED) [5,6]. Moreover, it has been proved that ED is part of ALL phenotype in children [5,[7][8][9], which also explains the effect of anthracycline agents. Studies have shown that there are functional cross-links between hematologic malignancies and vascular endothelium [10].…”

mentioning

confidence: 99%

“…To date, it has been proven that ED is a common feature of many early complications of chemotherapy, which are a significant cause of morbidity and mortality, despite optimization of treatment protocols [5]. However, there is insufficient data on the role of ED markers in the treatment and remission of ALL in children [8].…”

mentioning

confidence: 99%

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Markers of Endothelial Dysfunction and Their Prognostic Value in Children With Acute Lymphoblastic Leukemia

Odinets¹,

Kondratiuk

Koida³

2020

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Acute lymphoblastic leukemia (ALL) in children is associated with development of a large number of serious complications. Inflammatory and pro-aggregation activation of endothelial cells accompanies the course of leukemia. Endothelial dysfunction (ED) is believed to be an integral part of the pathogenic link of ALL and its complications. Materials and methods. The content of nitric oxide in serum with the concentration of its stable metabolites -NO 2 , NO 3 -was determined in 73 patients with ALL and 19 healthy children. Determination of nitric oxide was performed at different stages of the presentation of ALL: 49 children were examined during the manifestation of leukemia (group 1A), of whom 36 children (group 1B) were re-examined during the first course of treatment -induction of remission. Also 8 children (group 2) were examined during supportive therapy and 16 children (group 3) who underwent complete chemotherapy treatment. Results. The study showed that nitrite increase and nitrate reduction secondary to reduced total nitric oxide content during all treatment periods in children with ALL. In addition, signs of endothelial dysfunction were recorded in patients after treatment. ROC analysis showed that reduction in NO 2 content lower than 12.31 µmol/l and the sum of NO 2 + NO 3 lower than 32.99 µmol/l significantly had a negative effect on the survival of children with ALL. Conclusions. ED accompanies the course of ALL in children. Determination of nitric oxide is of diagnostic and prognostic importance in patients with leukemia. The critical fall in the concentration of NO and NO 2 accompanies development of multiple organ failure with fatal outcome in children with ALL. Preservation of signs of ED after the end of the treatment of leukemia indicates the need for cardiac monitoring of patients with ALL in history.

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Section: Resultsmentioning

confidence: 99%

Section: Table 3 Correlation Relationships Between Endothelial Dysfunmentioning

confidence: 99%

Section: Influence Of Nitric Oxide Metabolite Levels On the Developmementioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Markers of Endothelial Dysfunction and Their Prognostic Value in Children With Acute Lymphoblastic Leukemia

Odinets¹,

Kondratiuk

Koida³

2020

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Biomarkers of cardiometabolic complications in survivors of childhood acute lymphoblastic leukemia

Morel

Léveillé

Samoilenko

et al. 2020

Sci Rep

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Survivors of childhood acute lymphoblastic leukemia (cALL) are at higher risk of developing cardiometabolic complications. We aimed at exploring the associations between biomarkers of inflammation, oxidative stress, endothelial function, endotoxemia and cardiometabolic risk factors. We conducted a cross-sectional analysis in 246 cALL survivors (mean age, 22.1 ± 6.3 years; mean time since diagnosis, 15.5 ± 5.2 years) and evaluated the associations using a series of logistic regressions. Using structural equation models, we also tested if the relationship between endotoxemia and cardiometabolic complications was mediated by the latent (unobserved) variable inflammation inferred from the observed biomarkers CRP, TNF-α and IL-6. High leptin-adiponectin ratio was associated with obesity [adjusted OR = 15.7; 95% CI (6.2–39.7)], insulin resistance [20.6 (5.2–82.1)] and the metabolic syndrome [11.2 (2.6–48.7)]. Higher levels of plasminogen activator inhibitor-1 and tumor necrosis factor-α were associated with obesity [3.37 (1.6–7.1) and 2.34 (1.3–4.2), respectively] whereas high C-reactive protein levels were associated with insulin resistance [3.3 (1.6–6.8)], dyslipidemia [2.6 (1.4–4.9)] and MetS [6.5 (2.4–17.9)]. Our analyses provided evidence for a directional relationship between lipopolysaccharide binding protein, related to metabolic endotoxemia, inflammation and cardiometabolic outcomes. Identification of biomarkers and biological mechanisms could open new avenues for prevention strategies to minimize the long-term sequelae, improve follow-up and optimize the quality of life of this high-risk population.

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Changes in vascular function and correlation with cardiotoxicity in women with newly diagnosed breast cancer undergoing HER2-directed therapy with and without anthracycline/cyclophosphamide

Hazim,

Nhola,

Kailash

et al. 2023

European Heart Journal Open

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Aims The objective of this study was to assess the effect of HER2-directed therapy (HER2-Tx) on peripheral vasoreactivity and its correlation with cardiac function changes and the additive effects of anthracycline/cyclophosphamide (AC) therapy and baseline cardiovascular risk. Methods and Results Single-center, prospective cohort study of women with newly diagnosed stage 1-3 HER2-positive breast cancer undergoing HER2-Tx +/- AC. All participants underwent baseline and three-monthly evaluations with Endo-Peripheral Arterial Tonometry (Endo-PAT), vascular biomarkers (C-type natriuretic peptide (CNP) and neuregulin-1 beta (NRG-1β)), and echocardiography. Cardiotoxicity was defined as a decrease in the left ventricular ejection fraction (LVEF) of >10% to a value <53%. Of the 47 patients enrolled, 20 (43%) received AC in addition to HER2-Tx. Deterioration of reactive hyperemia index (RHI) on Endo-PAT by ≥20% was more common in patients receiving HER-Tx plus AC than HER2-Tx alone (65% vs 22%; p=0.003). A decrease in CNP and log NRG-1β levels by 1 standard deviation did not differ significantly between the AC and non-AC groups (CNP: 20.0% vs 7.4%; p=0.20 and NRG-1β: 15% vs 11%; p=0.69) nor did GLS (35% vs 37%; p=0.89). Patients treated with AC had a significantly lower 3D GE LVEF than non-AC recipients as early as 3 months after exposure (mean 59.3 % (SD 3) vs. 63.8 (SD 4); p=0.02). RHI and GLS were the only parameters correlating with LVEF change. Conclusion Combination therapy with AC, but not HER2-Tx alone, leads to a decline in peripheral vascular and cardiac function. Larger studies will need to define more precisely the causal correlation between vascular and cardiac function changes in cancer patients.

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Plethysmographic and Biochemical Markers in the Diagnosis of Endothelial Dysfunction in Pediatric Acute Lymphoblastic Leukemia Survivors – New Applications

Cited by 10 publications

References 32 publications

Markers of Endothelial Dysfunction and Their Prognostic Value in Children With Acute Lymphoblastic Leukemia

Markers of Endothelial Dysfunction and Their Prognostic Value in Children With Acute Lymphoblastic Leukemia

Biomarkers of cardiometabolic complications in survivors of childhood acute lymphoblastic leukemia

Changes in vascular function and correlation with cardiotoxicity in women with newly diagnosed breast cancer undergoing HER2-directed therapy with and without anthracycline/cyclophosphamide

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