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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Leukemia, Lymphoblastic
• Intervention / Treatment: Other: Chemotherapy protocol used

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.

• Study Type: Observational
• Enrollment (Anticipated): 1200

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 02990
    • Centro Médico Nacional Hospital General La Raza, IMSS
  • Mexico City, Mexico, 03103
    • Hospital General Regional Num 1 Carlos McGregor Sánchez Navarro, IMSS
  • Mexico City, Mexico, 06720
    • Hospital de Pediatria "Dr. Silvestre Frenk Freund" CMN Siglo XXI, IMSS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study variables and data will be collected from the clinical files. The information collected by the surveyors will be delivered weekly to our Research Unit, where the field work coordinators will be in charge of assigning them a folio number, reviewing the collection instrument and passing it on to the personnel in charge of capturing the information. In addition, the fieldwork coordinators will supervise the collection of information, the search for files in the archive, the capture of information and will be responsible for keeping the project's database up to date.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Overweight/Obesity; 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 regarding weight and height recorded in clinical files will be used to classify patients' nutritional status in present research has been previously described.

Other: Chemotherapy protocol used; Chemotherapy protocol used in each participating hospital

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	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.	year 5
Disease-free survival	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.).	year 5

Collaborators and Investigators

• Sponsor: Coordinación de Investigación en Salud, Mexico
• Investigators: Principal Investigator: Juan M Mejía-Arangure, PhD, Instituto Mexicano del Seguro Social/Instituto Nacional de Medicina Genomica

Publications and helpful links

General Publications

• Nunez-Enriquez JC, Gil-Hernandez AE, Jimenez-Hernandez E, Fajardo-Gutierrez A, Medina-Sanson A, Flores-Lujano J, Espinoza-Hernandez LE, Duarte-Rodriguez DA, Amador-Sanchez R, Penaloza-Gonzalez JG, Torres-Nava JR, Espinosa-Elizondo RM, Flores-Villegas LV, Merino-Pasaye LE, Perez-Saldivar ML, Dorantes-Acosta EM, Cortes-Herrera B, Solis-Labastida KA, Nunez-Villegas NN, Velazquez-Avina MM, Rangel-Lopez A, Gonzalez-Avila AI, Santillan-Juarez JD, Garcia-Velazquez AJ, Jimenez-Morales S, Bekker-Mendez VC, Rosas-Vargas H, Mata-Rocha M, Sepulveda-Robles OA, Martin-Trejo JA, Mejia-Arangure JM. Overweight and obesity as predictors of early mortality in Mexican children with acute lymphoblastic leukemia: a multicenter cohort study. BMC Cancer. 2019 Jul 18;19(1):708. doi: 10.1186/s12885-019-5878-8.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2010
• Primary Completion (Actual): December 31, 2021
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: February 11, 2020
• First Submitted That Met QC Criteria: February 12, 2020
• First Posted (Actual): February 17, 2020

Study Record Updates

• Last Update Posted (Actual): July 20, 2022
• Last Update Submitted That Met QC Criteria: July 19, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Obesity; Survival; Children; Overweight
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Overnutrition; Nutrition Disorders; Body Weight; Obesity; Leukemia; Overweight; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: R-2015-785-070

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The Ethics Committee asked for not making any individual participant data available

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No