Impact of body mass index on relapse in children with acute lymphoblastic leukemia treated according to Nordic treatment protocols

Christina Egnell, Susanna Ranta, Joanna Banerjee, Andrea Merker, Riitta Niinimäki, Bendik Lund, Pernille Rudebeck Mogensen, Ólafur G Jonsson, Goda Vaitkeviciene, Kristi Lepik, Anders Forslund, Mats Heyman, Arja Harila-Saari, Christina Egnell, Susanna Ranta, Joanna Banerjee, Andrea Merker, Riitta Niinimäki, Bendik Lund, Pernille Rudebeck Mogensen, Ólafur G Jonsson, Goda Vaitkeviciene, Kristi Lepik, Anders Forslund, Mats Heyman, Arja Harila-Saari

Abstract

Objectives: High body mass index (BMI) is associated with poorer survival in childhood acute lymphoblastic leukemia (ALL), but the actual impact on the risk of relapse still needs to be clarified. We evaluated the impact of BMI at diagnosis on the risk of relapse in children with ALL treated according to Nordic Society of Paediatric Haematology and Oncology (NOPHO) protocols.

Method: In a multicenter study, we collected data on BMI at diagnosis and outcome of 2558 children aged 2.0-17.9 years diagnosed between 1992 and 2016. Patients were divided into four groups according to International Obesity Task Force (IOTF) childhood BMI cut-offs: underweight, <17; healthy weight, 17-25; overweight, 25-30; and obese, ≥30 kg/m2 .

Results: In Cox multivariate regression analyses, an increased risk of relapse was observed in children aged 10-17.9 years with unhealthy BMI at diagnosis (underweight hazard ratio HR: 2.90 [95% confidence interval: 1.24-6.78], P = .01; overweight, HR: 1.95 [1.11-3.43], P = .02, and obese HR: 4.32 [95% 2.08-8.97], P < .001), compared to children with healthy weight. BMI had no impact on relapse in children under 10 years of age.

Conclusion: High BMI, and especially obesity at diagnosis, is an independent adverse prognostic factor for relapse in older children with ALL.

Keywords: acute lymphoblastic leukemia; body mass index; children; obesity; survival.

Conflict of interest statement

There are no conflicts of interest to declare.

© 2020 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Kaplan‐Meier curves illustrating the effect of BMI classification on overall survival (A and B) and cumulative incidence of relapse (C and D) in younger children (age 2.0‐9.9 y) (A and C), and older children (age 10.0‐17.9 y) (B and D). For the assessment of cumulative incidence of relapse, death and secondary malignant neoplasm (SMN) were treated as competing risks
Figure 2
Figure 2
Estimated association between BMI standard deviation score (BMI SDS) as a continuous variable in a Cox proportional hazards model with restricted cubic splines, in children aged 10.0‐17.9 y at diagnosis and the log HR for time to relapse. The U‐shaped association between BMI SDS and log HR of relapse show that the risk appears to increase below and above a BMI SDS of around zero.

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