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Overweight and Obesity as Prognostic Factors for Survival in Children With Acute Lymphoblastic Leukemia

Conditions
Leukemia, Lymphoblastic
Interventions
Other: Chemotherapy protocol used
Registration Number
NCT04271215
Lead Sponsor
Coordinación de Investigación en Salud, Mexico
Brief Summary

Background: Mexico City has one of the highest incidences and mortality rates of acute lymphoblastic leukemia (ALL) in the world and a high frequency of early relapses (17%) and early mortality (15%). Otherwise, childhood overweight and obesity are reaching epidemic proportions. They have been associated with poor outcomes in children with ALL. The aim of present study is to identify if overweight and obesity are prognostic factors associated with survival rates in Mexican children with ALL. Methods: Multicenter cohort study. ALL children younger than 15 years old are included and followed-up. Overweight and obesity are classified according World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) criteria. Deaths and relapses are the main outcomes.

Detailed Description

Data collection Information regarding sex, age at diagnosis, place of residence, white blood cell (WBC) count, immunophenotype (B or T lineage), weight and height (length when appropriate) at diagnosis, and chemotherapy protocol is collected from the patients' clinical charts by previously standardized staff. Overcrowding was used as a proxy for socioeconomic status (SES) according to the Bronfman's criteria (high SES, up to 1.5 people per room; medium-low SES, more than 1.6 people per room). The risk classification is according to the criteria of the National Cancer Institute (NCI): standard risk \[ages from 1 to 9.99 years; WBC count \< 50 × 109/L\] or as high risk \[age \< 1 or ≥ 10 years or WBC ≥ 50 × 109/L\].

Assessment of nutritional status at diagnosis of ALL BMI at diagnosis will be used.. Using WHO software (version 3.2.2, World Health Organization, Geneva), the BMI-for-age Z-scores were calculated for each patient. According to WHO classification, patients were categorized as normal (- 1.9999 to 0.9999), wasted (- 2 to - 2.9999), severely wasted (≥ - 3), at risk of overweight (1-1.9999), overweight (2 to 2.9999) and obesity (≥3). In addition, the BMI percentiles cutoffs provided by CDC were: normal (p5-84.9999), underweight (\< p5), overweight (p85-94.9999), and obese (≥ p95). The nutritional classification and measurements validation regarding weight and height recorded in clinical files used to classify patients' nutritional status in present research has been previously described. Underweight patients were excluded from the analyses.

Sample size The sample size calculation was performed using Epi-Info version 7 software taking into account a mortality outcome frequency of 10.8% in the unexposed group (normal weight patients) and a death outcome frequency of 24% for the exposed (obese/overweight patients), a statistical power of 80% and a confidence of 95%; resulting in a total "n" of 350 overweight/obese patients to be compared with the rest of the cohort that are not overweight and obese.

Statistical analysis Descriptive statistics and relative risks (RR) calculation with 95% confidence intervals (CI) will be carried out. Kaplan-Meier survival analysis will be conducted. Log-rank test will be calculated. The analyses will be conducted independently for disease-free-survival (DFS) or overall survival (OS), adjusting for variables whose effects on the studied outcomes have been previously documented (age, sex, socioeconomic status, immunophenotype, NCI risk classification, and chemotherapy protocol). A Cox proportional hazard model will be used. Hazard ratios (HR) with 95% CIs will be calculated.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
1200
Inclusion Criteria
  • Patients under 15 years of age
  • Newly diagnosed with acute lymphoblastic leukemia
  • Diagnosis confirmation by bone marrow aspiration and immunophenotype
  • Attended in the participating Hospitals.
Exclusion Criteria
  • Patients with Down Syndrome (for being a population with different disease behavior and cytogenetic alterations than patients without this genetic condition)

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Overweight/ObesityChemotherapy protocol usedBMI at diagnosis will be used. Using WHO software (version 3.2.2, World Health Organization, Geneva), the BMI-for-age Z-scores were calculated for each patient. According to WHO classification, patients were categorized as normal (- 1.9999 to 0.9999), wasted (- 2 to - 2.9999), severely wasted (≥ - 3), at risk of overweight (1-1.9999), overweight (2 to 2.9999) and obesity (≥3). In addition, the BMI percentiles cutoffs provided by CDC were: normal (p5-84.9999), underweight (\< p5), overweight (p85-94.9999), and obese (≥ p95). The nutritional classification and measurements regarding weight and height recorded in clinical files will be used to classify patients' nutritional status in present research has been previously described.
Primary Outcome Measures
NameTimeMethod
Overall survivalyear 5

Deaths of patients occurring during the follow-up period will be collected. The cause of death and the date that this occurred will be also registered. In the case of patients alive at the end of follow-up, the date of the last visit to the hospital will be collected.

Disease-free survivalyear 5

Clinical data and by complementary examinations indicating that there is reappearance of the disease after complete remission has been achieved, presence of blasts \> 5% in bone marrow (bone marrow relapse) or presence of blasts in cerebrospinal fluid fluid (CNS relapse), testicular infiltration by blasts in the biopsy (testicular relapse), combined (bone marrow/CNS) at any time during treatment . In case the patient has relapsed, the site of relapse will be collected (bone marrow, CNS, testicle, ovary, eye, etc.).

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (3)

Hospital General Regional Num 1 Carlos McGregor Sánchez Navarro, IMSS

🇲🇽

Mexico City, Mexico

Centro Médico Nacional Hospital General La Raza, IMSS

🇲🇽

Mexico City, Mexico

Hospital de Pediatria "Dr. Silvestre Frenk Freund" CMN Siglo XXI, IMSS

🇲🇽

Mexico City, Mexico

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