Page 102 - Haematologica-April 2018

C. Oudin et al. Introduction
The number of long-term survivors of childhood acute leukemia (AL) has dramatically increased over the past decades. Improvements in treatment and supportive care have resulted in 5-year survival rates exceeding 85% in children with acute lymphoblastic leukemia (ALL)1-3 and approximately 55-60% among children with acute myeloid leukemia (AML).4-6 Therefore, the long-term chronic health condition of such patients has become a major public health concern.7 Several authors have shown that long-term survivors of childhood cancer are at risk of metabolic syndrome, a well-known marker of cardiovas- cular morbidity and mortality.8-12
Overall, previous studies in this field showed that long- term survivors of childhood AL are at risk of developing a metabolic syndrome, as compared with controls, but sev- eral issues need to be addressed. Firstly, our team and oth- ers have previously shown that hematopoietic stem cell transplantation (HSCT) and cranial irradiation11,13-18 are clearly associated with a higher risk of metabolic syn- drome, while the risk of metabolic syndrome for patients who received chemotherapy only has not been specifical- ly assessed in large comparative studies.
Secondly, prevalence of the metabolic syndrome varies greatly from one country to another.19-21 Many metabolic syndrome studies were carried out in the USA,11,17,22 where metabolic syndrome occurs more frequently among the general population than in France19,23-25 or other European countries. Consequently, extrapolating US-based results to understand metabolic syndrome in a non-US country may not be appropriate. Furthermore, the incidence of meta- bolic syndrome increases with age and is influenced by sex, country of origin, socio-economic status24 and aca- demic level.26 Thus, the real risk of developing metabolic syndrome among survivors of childhood AL cannot be accurately evaluated without considering all these param- eters.
This study is based on data from the LEA (French acronym for “leukemia in children and adolescents”) cohort, a French prospective multicenter cohort designed to evaluate the long-term health status of childhood AL survivors.
The primary objective of the present study was to eval- uate the prevalence of metabolic syndrome and its com- ponents in adults from the LEA cohort, and to compare it with that found in controls from a French volunteer cohort. More than 1000 patients from the LEA cohort (60% of them treated with chemotherapy only), were compared with age- and sex-matched controls from the Investigation and Clinical Prevention (IPC) cohort, in which volunteer patients were recruited from one of the largest preventive healthcare centers in France.
We also aimed to determine the potential effects of dif- ferent therapeutic modalities used during leukemia treat- ment on metabolic syndrome occurrence, and to assess the risk of metabolic syndrome among patients who received only chemotherapy [without HSCT and without central nervous system (CNS) irradiation]. Lastly, we aimed to investigate whether the metabolic syndrome profile (i.e. the cluster of components that constitute metabolic syndrome) varied between the IPC cohort and the LEA cohort, which would suggest divergent mecha- nisms concerning metabolic syndrome development between these two groups.
Methods
This study is based on a comparison between the LEA cohort and a control group from the IPC cohort.
The LEA group
The LEA program was implemented in 2004 to prospectively evaluate the long-term health status, Quality of Life and socio- economic status of childhood AL survivors enrolled in treatment programs from 1980 to the present, in 16 cancer centers in France. The details of the program have been previously described.27,28 Data regarding different long-term complications were collected during specific medical visits at pre-defined dates (Online Supplementary Appendix). Since 2007, assessment of metabolic syn- drome has been systematically proposed to all adults participating in the LEA program. The study was approved by the French National Program for Clinical Research, the National Cancer Institute, and by the review boards of the institutions involved. All patients provided written informed consent for participation in the study.
The inclusion criteria for the current study were: 1) participation in the LEA program between 2007 and 2014; 2) older than 18 years of age at last LEA evaluation; and 3) at least one complete evalua- tion for metabolic syndrome.
Comparison cohort: IPC group
The IPC centers are dedicated to the evaluation of the general health status of French patients living in the Paris area (France). These medical centers, funded by the French National Social Security, offer a free medical examination every five years to working and retired employees and their families. During each examination, patients benefit from a medical check-up including medical examination and biological tests. A self-administered questionnaire provides information concerning higher education, medical history, current health status and medication. During these medical check-ups all patients were screened for metabolic syndrome. Selected controls were age- (2-year categories) and sex- matched 3:1 to the LEA patients.
Outcome measurements
Metabolic syndrome was defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP- ATPIII) revised in 200523 as the combination of at least three of the following criteria: 1) increased waist circumference (≥102 cm in men and ≥88 cm in women); 2) increased blood pressure (systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg) or treatment for hypertension; 3) reduced HDL-choles- terol [<40 mg/dL (1.03 mmol/L) in men, <50 mg/dl (1.3 mmol/l) in women]; 4) elevated fasting glucose levels (≥5.5 mmol/L) or treat- ment for hyperglycemia; and 5) increased triglycerides (≥1.7 mmol/L) or treatment for hypertriglyceridemia. For further details, see the Online Supplementary Appendix.
Statistical analysis
Statistical analysis was performed using SPSS 20.0 (SPSS Inc., Chicago, IL, USA) and Intercooled Stata 9.0 for Windows. Qualitative data are expressed as percentages. Quantitative data are shown as mean±Standard Error of Mean (SEM). χ2 and Fischer exact tests were used to compare qualitative variables. Quantitative variables were compared using the Student test or the Mann-Whitney test. Logistical regression, adjusted for sex and age, was used to evaluate the probability of developing metabolic syndrome in the LEA subgroups and the IPC group. Odds Ratios (ORs) were estimated with 95% confidence interval (CI). P<0.05 was considered significant.
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haematologica | 2018; 103(4)