What is the clinical evidence from this study?

Study design: Observational. Population: Acute Lymphoblastic Leukemia (ALL) Survivors (n=40). Intervention: History of acute lymphoblastic leukemia and its treatment vs. Healthy subjects. Primary outcome: Reactive hyperemia index (RHI) (p=<0.05).

What does this research mean for the field?

Pediatric survivors of acute lymphoblastic leukemia demonstrate premature endothelial dysfunction, indicated by a significantly lower reactive hyperemia index and elevated hsCRP compared to healthy controls. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

December 9, 2018Open Access

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

Q: What are the key findings of this study?

Pediatric survivors of acute lymphoblastic leukemia demonstrated a significantly lower reactive hyperemia index (median 1.5 vs 1.8, p<0.05) and elevated hsCRP compared to healthy controls, suggesting premature endothelial dysfunction.

Q: What does this research mean for the field?

Pediatric survivors of acute lymphoblastic leukemia demonstrate premature endothelial dysfunction, indicated by a significantly lower reactive hyperemia index and elevated hsCRP compared to healthy controls. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

Key Result

Pediatric survivors of acute lymphoblastic leukemia demonstrated a significantly lower reactive hyperemia index (median 1.5 vs 1.8, p<0.05) and elevated hsCRP compared to healthy controls, suggesting premature endothelial dysfunction.

Study Design

Type

Observational (n=40)

Multicenter

Structured PICO

Does a history of acute lymphoblastic leukemia treatment increase surrogate markers of endothelial dysfunction in pediatric survivors?

Population

40 children and adolescents, including 22 acute lymphoblastic leukemia survivors at least two years post-treatment and 18 healthy controls, evaluated for endothelial dysfunction.

Exposure

History of successful treatment for acute lymphoblastic leukemia (ALL) with cytostatic therapy including anthracyclines (cumulative dose 240-360 mg/m2) and cyclophosphamide (3,000 mg/m2)

Comparator

Healthy subjects without a history of inflammatory, metabolic or neoplastic diseases

Outcome

Endothelial dysfunction assessed by plethysmographic reactive hyperemia index (RHI) and biomarkers (ADMA, hsCRP, E-selectin, VCAM)surrogate

Pediatric survivors of acute lymphoblastic leukemia exhibit signs of premature endothelial dysfunction, as evidenced by decreased reactive hyperemia index and elevated inflammatory biomarkers.

Main Result

Absolute Event Rate: 1.5% vs 1.8%

p-value: p=<0.05

Limitations

Lack of a precise cut-off limit for RHI in children
Sensors are unified and the minimum finger thickness is not defined, limiting use in younger children
Small sample size

Abstract

Acute lymphoblastic leukemia (ALL) and its treatment are associated with endothelial dysfunction (ED) and increased cardiovascular risk in adulthood. There are no data on ED in children after successful treatment of ALL. We aimed to assess new ED in these children using the plethysmographic reactive hyperemia index (RHI) and biomarkers that are known to be related to ED. In all, 22 children (mean 15.6 years), after successful treatment of ALL, and 18 healthy subjects were included in this prospective study. RHI, plasma concentrations of asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP) and E-selectin were measured in all children. RHI values were significantly lower in ALL patients when compared with healthy controls (p<0.05). hsCRP was significantly increased in ALL patients compared with the control group (p<0.001). E-selectin plasma levels were higher in ALL patients as compared to healthy controls (p=0.05). This is the first study that combines both plethysmographic and biochemical methods to assess ED in ALL survivors. Significantly decreased RHI with elevated plasma concentrations of biochemical markers imply a possible association with premature ED in ALL patients. The combined diagnostic approach seems to be a valuable tool for more accurate detection of ED and preventive cardiovascular management in these patients.

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