Overweight and obesity as predictors of early mortality in Mexican children with acute lymphoblastic leukemia: a multicenter cohort study

Juan Carlos Núñez-Enríquez, Ana Elena Gil-Hernández, Elva Jiménez-Hernández, Arturo Fajardo-Gutiérrez, Aurora Medina-Sansón, Janet Flores-Lujano, Laura Eugenia Espinoza-Hernández, David Aldebarán Duarte-Rodríguez, Raquel Amador-Sánchez, José Gabriel Peñaloza-González, José Refugio Torres-Nava, Rosa Martha Espinosa-Elizondo, Luz Victoria Flores-Villegas, Laura Elizabeth Merino-Pasaye, María Luisa Pérez-Saldivar, Elisa María Dorantes-Acosta, Beatriz Cortés-Herrera, Karina Anastacia Solis-Labastida, Nora Nancy Núñez-Villegas, Martha Margarita Velázquez-Aviña, Angélica Rangel-López, Ana Itamar González-Ávila, Jessica Denisse Santillán-Juárez, Alejandra Jimena García-Velázquez, Silvia Jiménez-Morales, Vilma Carolina Bekker-Méndez, Haydee Rosas-Vargas, Minerva Mata-Rocha, Omar Alejandro Sepúlveda-Robles, Jorge Alfonso Martín-Trejo, Juan Manuel Mejía-Aranguré, Juan Carlos Núñez-Enríquez, Ana Elena Gil-Hernández, Elva Jiménez-Hernández, Arturo Fajardo-Gutiérrez, Aurora Medina-Sansón, Janet Flores-Lujano, Laura Eugenia Espinoza-Hernández, David Aldebarán Duarte-Rodríguez, Raquel Amador-Sánchez, José Gabriel Peñaloza-González, José Refugio Torres-Nava, Rosa Martha Espinosa-Elizondo, Luz Victoria Flores-Villegas, Laura Elizabeth Merino-Pasaye, María Luisa Pérez-Saldivar, Elisa María Dorantes-Acosta, Beatriz Cortés-Herrera, Karina Anastacia Solis-Labastida, Nora Nancy Núñez-Villegas, Martha Margarita Velázquez-Aviña, Angélica Rangel-López, Ana Itamar González-Ávila, Jessica Denisse Santillán-Juárez, Alejandra Jimena García-Velázquez, Silvia Jiménez-Morales, Vilma Carolina Bekker-Méndez, Haydee Rosas-Vargas, Minerva Mata-Rocha, Omar Alejandro Sepúlveda-Robles, Jorge Alfonso Martín-Trejo, Juan Manuel Mejía-Aranguré

Abstract

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 was to identify if overweight and obesity are predictors of early mortality and relapse in Mexican children with ALL.

Methods: A multicenter cohort study was conducted. ALL children younger than 15 years old were included and followed-up during the first 24 months after diagnosis. Overweight and obesity were classified according World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) criteria. Early mortality and early relapses were the main outcomes.

Results: A total of 1070 children were analyzed. Overweight/obesity at diagnosis were predictors of early mortality (WHO: HR = 1.4, 95%CI:1.0-2.0; CDC: HR = 1.6, 95%CI:1.1-2.3). However, no associations between overweight (WHO: HR = 1.5, 95%CI:0.9-2.5; CDC: HR = 1.0; 95% CI:0.6-1.6) and obesity (WHO: HR = 1.5, 95%CI:0.7-3.2; CDC: HR = 1.4; 95%CI:0.9-2.3) with early relapse were observed.

Conclusions: Overweight and obese patients embody a subgroup with high risk of dying during leukemia treatment.

Keywords: Children; Early mortality; Leukemia; Mexico; Obesity; Overweight.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Disease-free survival (early relapses) according to CDC 2000 nutritional classification (three categories)
Fig. 2
Fig. 2
Disease-free-survival (early relapses) according to CDC 2000 (two categories)
Fig. 3
Fig. 3
Overall survival up to 24 months according to CDC nutritional status
Fig. 4
Fig. 4
Disease free-survival (early relapses) according to WHO nutritional classification
Fig. 5
Fig. 5
Overall survival up to 24 months after diagnosis according to WHO nutritional classification

References

    1. Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang X-S, et al. Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2) Lancet. 2015;385:977–1010. doi: 10.1016/S0140-6736(14)62038-9.
    1. Chatenoud L, Bertuccio P, Bosetti C, Levi F, Negri E, La Vecchia C. Childhood cancer mortality in America, Asia, and Oceania, 1970 through 2007. Cancer. 2010;116:5063–5074. doi: 10.1002/cncr.25406.
    1. Martín-Trejo JA, Núñez-Enríquez JC, Fajardo-Gutiérrez A, Medina-Sansón A, Flores-Lujano J, Jiménez-Hernández E, et al. Early mortality in children with acute lymphoblastic leukemia in a developing country: the role of malnutrition at diagnosis. A multicenter cohort MIGICCL study. Leuk Lymphoma. 2017;58:898–908. doi: 10.1080/10428194.2016.1219904.
    1. Silverman LB, Gelber RD, Dalton VK, Asselin BL, Barr RD, Clavell LA, et al. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber consortium protocol 91-01. Blood. 2001;97:1211–1218. doi: 10.1182/blood.V97.5.1211.
    1. Hargrave DR, Hann II, Richards SM, Hill FG, Lilleyman JS, Kinsey S, et al. Progressive reduction in treatment-related deaths in Medical Research Council childhood lymphoblastic leukaemia trials from 1980 to 1997 (UKALL VIII, X and XI) Br J Haematol. 2001;112:293–299. doi: 10.1046/j.1365-2141.2001.02543.x.
    1. Metzger ML, Howard SC, Fu LC, Peña A, Stefan R, Hancock ML, et al. Outcome of childhood acute lymphoblastic leukaemia in resource-poor countries. Lancet. 2003;362:706–708. doi: 10.1016/S0140-6736(03)14228-6.
    1. Howard SC, Pedrosa M, Lins M, Pedrosa A, Pui C-H, Ribeiro RC, et al. Establishment of a pediatric oncology program and outcomes of childhood acute lymphoblastic leukemia in a resource-poor area. JAMA. 2004;291:2471–2475. doi: 10.1001/jama.291.20.2471.
    1. Advani S, Pai S, Venzon D, Adde M, Kurkure PK, Nair CN, et al. Acute lymphoblastic leukemia in India: an analysis of prognostic factors using a single treatment regimen. 1999;10:167–176. . Accessed 11 Apr 2016.
    1. Rivera-Luna R, Olaya-Vargas A, Velásquez-Aviña M, Frenk S, Cárdenas-Cardós R, Leal-Leal C, et al. Early death in children with acute lymphoblastic leukemia: does malnutrition play a role? Pediatr Hematol Oncol. 2008;25:17–26. doi: 10.1080/08880010701774132.
    1. Jiménez-Hernández E, Jaimes-Reyes EZ, Arellano-Galindo J, García-Jiménez X, Tiznado-García HM, Dueñas-González MT, et al. Survival of Mexican Children with Acute Lymphoblastic Leukaemia under Treatment with the Protocol from the Dana-Farber Cancer Institute 00–01. Biomed Res Int. 2015;2015:9. doi: 10.1155/2015/576950.
    1. Pieters R, de Groot-Kruseman H, Van der Velden V, Fiocco M, van den Berg H, de Bont E, et al. Successful therapy reduction and intensification for childhood acute lymphoblastic leukemia based on minimal residual disease monitoring: study ALL10 from the Dutch childhood oncology group. J Clin Oncol. 2016;34:2591–2601. doi: 10.1200/JCO.2015.64.6364.
    1. Maldonado-Alcázar A, Núñez-Enríquez JC, García-Ruiz CA, Fajardo-Gutiérrez A, Mejía-Aranguré JM. Alterations of nutritional status in childhood acute leukemia. In: Mejía-Aranguré JM, editor. Clinical epidemiology of acute lymphoblastic leukemia - from the molecules to the clinic. Rijeka: InTech; 2013. pp. 277–296.
    1. Orgel E, Genkinger JM, Aggarwal D, Sung L, Nieder M, Ladas EJ. Association of body mass index and survival in pediatric leukemia: a meta-analysis. Am J Clin Nutr. 2016;103:808–817. doi: 10.3945/ajcn.115.124586.
    1. Gelelete CB, Pereira SH, Azevedo AMB, Thiago LS, Mundim M, Land MGP, et al. Overweight as a prognostic factor in children with acute lymphoblastic leukemia. Obesity. 2011;19:1908–1911. doi: 10.1038/oby.2011.195.
    1. Pramanik R, Sheng X, Ichihara B, Heisterkamp N, Mittelman SD. Adipose tissue attracts and protects acute lymphoblastic leukemia cells from chemotherapy. Leuk Res. 2013;37:503–509. doi: 10.1016/j.leukres.2012.12.013.
    1. Aldhafiri FK, McColl JH, Reilly JJ. Prognostic significance of being overweight and obese at diagnosis in children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2014;36:234–236. doi: 10.1097/MPH.0000000000000056.
    1. Baillargeon J, Langevin A-M, Lewis M, Estrada J, Mullins J, Pitney A, et al. Obesity and survival in a cohort of predominantly Hispanic children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2006;28:575–578. doi: 10.1097/01.mph.0000212985.33941.d8.
    1. Ethier M-C, Alexander S, Abla O, Green G, Lam R, Sung L. Association between obesity at diagnosis and weight change during induction and survival in pediatric acute lymphoblastic leukemia. Leuk Lymphoma. 2012;53:1677–1681. doi: 10.3109/10428194.2012.664843.
    1. Orgel E, Sposto R, Malvar J, Seibel NL, Ladas E, Gaynon PS, et al. Impact on survival and toxicity by duration of weight extremes during treatment for pediatric acute lymphoblastic leukemia: a report from the Children’s oncology group. J Clin Oncol. 2014;32:1331–1337. doi: 10.1200/JCO.2013.52.6962.
    1. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from Cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348:1625–1638. doi: 10.1056/NEJMoa021423.
    1. Hijiya N, Panetta JC, Zhou Y, Kyzer EP, Howard SC, Jeha S, et al. Body mass index does not influence pharmacokinetics or outcome of treatment in children with acute lymphoblastic leukemia. Blood. 2006;108:3997–4002. doi: 10.1182/blood-2006-05-024414.
    1. Bhurosy T, Jeewon R. Overweight and obesity epidemic in developing countries: a problem with diet, physical activity, or socioeconomic status? Sci World J. 2014;2014:964236. doi: 10.1155/2014/964236.
    1. Güngör NK. Overweight and obesity in children and adolescents. J Clin Res Pediatr Endocrinol. 2014;6:129–143. doi: 10.4274/Jcrpe.1471.
    1. Wang Y, Lim H. The global childhood obesity epidemic and the association between socio-economic status and childhood obesity. Int Rev Psychiatry. 2012;24:176–188. doi: 10.3109/09540261.2012.688195.
    1. Popkin BM. The nutrition transition: an overview of world patterns of change. Nutr Rev. 2004;62(7 Pt 2):S140–S143. doi: 10.1111/j.1753-4887.2004.tb00084.x.
    1. Bronfman M, Guiscafré H, Castro V, Castro R, Gutiérrez G. Strategies for improving the therapeutic patterns used in acute diarrhea in primary medical care units. II. The measurement of inequality: a methodologic strategy, analysis of the socioeconomic features of the sample. Arch Invest Med (Mex) 1988;19:351–360.
    1. World Health Organization . Investigating causes of undernutrition and of overweight [job aid]. Training Course on Child Growth Assessment. 2006.
    1. Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Nikšić M, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. 2018;391:1023–1075. doi: 10.1016/S0140-6736(17)33326-3.
    1. Núñez-Enríquez JC, Bárcenas-López DA, Hidalgo-Miranda A, Jiménez-Hernández E, Bekker-Méndez VC, Flores-Lujano J, et al. Gene expression profiling of acute lymphoblastic leukemia in children with very early relapse. Arch Med Res. 2016;47(8):644–655. doi: 10.1016/j.arcmed.2016.12.005.
    1. Inaba H, Greaves M, Mullighan CG. Acute lymphoblastic leukaemia. Lancet. 2013;381(9881):1943–1955. doi: 10.1016/S0140-6736(12)62187-4.
    1. Belle Fabiën N., Wenke-Zobler Juliane, Cignacco Eva, Spycher Ben D., Ammann Roland A., Kuehni Claudia E., Zimmermann Karin. Overweight in childhood cancer patients at diagnosis and throughout therapy: A multicentre cohort study. Clinical Nutrition. 2019;38(2):835–841. doi: 10.1016/j.clnu.2018.02.022.
    1. Brown AL, Lupo PJ, Danysh HE, Okcu MF, Scheurer ME, Kamdar KY. Prevalence and predictors of overweight and obesity among a multiethnic population of pediatric acute lymphoblastic leukemia survivors: a cross-sectional assessment. J Pediatr Hematol Oncol. 2016;38:429–436. doi: 10.1097/MPH.0000000000000555.
    1. Amankwah EK, Saenz AM, Hale GA, Brown PA. Association between body mass index at diagnosis and pediatric leukemia mortality and relapse: a systematic review and meta-analysis. Leuk Lymphoma. 2016;57:1140–1148. doi: 10.3109/10428194.2015.1076815.
    1. Barlow Sarah E. Expert Committee Recommendations Regarding the Prevention, Assessment, and Treatment of Child and Adolescent Overweight and Obesity: Summary Report. Pediatrics. 2007;120(Supplement 4):S164–S192. doi: 10.1542/peds.2007-2329C.
    1. Aldhafiri FK, McColl JH, Reilly JJ. Prevalence of being underweight and overweight and obesity at diagnosis in UK patients with childhood acute lymphoblastic leukaemia 1985-2002. J Hum Nutr Diet. 2014;27:76–79. doi: 10.1111/jhn.12112.
    1. Tan SY, Poh BK, Nadrah MH, Jannah NA, Rahman J, Ismail MN. Nutritional status and dietary intake of children with acute leukaemia during induction or consolidation chemotherapy. J Hum Nutr Diet. 2013;26:23–33. doi: 10.1111/jhn.12074.
    1. Antillón FG, Blanco JG, Valverde PD, Castellanos M, Garrido CP, Girón V, et al. The treatment of childhood acute lymphoblastic leukemia in Guatemala: biologic features, treatment hurdles, and results. Cancer. 2017;123:436–448. doi: 10.1002/cncr.30257.
    1. Stary J, Zimmermann M, Campbell M, Castillo L, Dibar E, Donska S, et al. Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002. J Clin Oncol. 2014;32:174–184. doi: 10.1200/JCO.2013.48.6522.
    1. Aplenc R, Zhang M-J, Sung L, Zhu X, Ho VT, Cooke K, et al. Effect of body mass in children with hematologic malignancies undergoing allogeneic bone marrow transplantation. Blood. 2014;123:3504–3511. doi: 10.1182/blood-2013-03-490334.
    1. Han PY, Duffull SB, Kirkpatrick CMJ, Green B. Dosing in obesity: a simple solution to a big problem. Clin Pharmacol Ther. 2007;82:505–508. doi: 10.1038/sj.clpt.6100381.
    1. Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children’s oncology group. J Clin Oncol. 2012;30:1663–1669. doi: 10.1200/JCO.2011.37.8018.
    1. Cui L, Li Z-G, Chai Y-H, Yu J, Gao J, Zhu X-F, et al. Outcome of children with newly diagnosed acute lymphoblastic leukemia treated with CCLG-ALL 2008: the first nation-wide prospective multicenter study in China. Am J Hematol. 2018;93:913–920. doi: 10.1002/ajh.25124.

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