Metabolic Syndrome Is Common Following Haematopoietic Cell Transplantation (HCT) and Is Associated with Increased Cardiovascular Disease and Second Cancers: An EBMT Cross-Sectional Non-Interventional Study
Authors: Greenfield Diana M , Salooja Nina , Peczynski Christophe , van der Werf Steffie , Schoemans Helene , Hill Kate , Cortelezzi Agostino , Lupo Stanghellini Maria Teresa , Ozkurt Zubeyde Nur , Arat Mutlu , Metzner Bernd , Turlure Pascal , Rovo Alicia , Socié Gérard , Mohty Mohamad , Nagler Arnon , Kroeger Nicolaus , Luft Thomas , Labopin Myriam , Han Thang , Tichelli André , Duarte Rafael F , Basak Grzegorz W , Snowden John A 
Published: October 2019

Abstract
Metabolic syndrome (MetS) is defined as a clustering of five factors including (1) fasting hyperglycaemia (2) hypertriglyceridaemia (3) low HDL cholesterol (4) hypertension (5) obesity (high waist circumference). According to the International Diabetes Federation harmonised definition, a large waist circumference plus any other two features meet criteria for diagnosis of MetS. It is associated with raised risk of cardiovascular disease (CVD) by 3-fold and is increasingly recognised in patients after HCT. Recent guidelines for long-term HCT survivors recommend screening for MetS. We performed a large cross-sectional service evaluation of HCT survivors in centres working in accordance with international screening guidelines. We have previously presented interim results regarding the prevalence of MetS and associated risk factors and now present the final results.
This was an EBMT approved cross-sectional, non-interventional study of consecutive HCT patients (allo and auto) aged 18+ years and a minimum of 2 year post-transplant attending routine follow-up HCT and/or late effects clinics in 9 centres. Centres completed proformas incorporating routine recording of the MetS parameters (given above) as well as performance status (ECOG); evidence of cardiovascular events; family history of premature CVD; and relevant drug history. Univariate comparison of patients and HCT characteristics between the 2 groups (MetS vs no MetS) was performed using non-parametric Mann-Witney U test for continuous variables and Chi-square test or Fisher test for categorical variables. All tests were two-sided. Multivariate logistic regression analyses were performed to predict MetS and cardiovascular events. Variables with a p-value <0.2 in univariate analysis were included.
Table 1 gives the population demographic, age, primary disease and transplant details. The prevalence of MetS was 30.4% (allo 29%, auto 35.6% ns). There was a significant difference in prevalence by age at follow-up (p<0.001 with increasing age) with 39% having MetS in those aged 50+. ECOG status was not significantly different between those with or without MetS. No relationship between presence or degree of acute or chronic GvHD was observed and no difference in current use of immunosuppressant therapy. Notably, there was a significantly higher prevalence of cardiovascular events in those with MetS than those without (22.6.vs 10.7%, P=0.006). Logistic regression analysis confirmed that MetS is a predictor of cardiovascular events (OR 4.72, 95%CI 2.11-10.57). CVE were also associated with occurrence of a second malignancy (OR 7.93, 95%CI 2.91-21.61). There was an influence of increasing age both in the prevalence of metabolic syndrome (OR 7.3, 95% CI 3.2,16.8) and CVE (OR 3, 95%CI 0.8-11.32) for the over 50s compared with those aged 18-29.
This large study in HCT survivors confirms high prevalence of metabolic syndrome following both allogeneic and autologous HCT of 30.4% overall rising to 39% in those aged over 50 years at follow-up. The data support MetS being an age-related late effect of HCT that is strongly associated with not only cardiovascular events but also the occurrence of second cancers. Further analysis examining the relationship between intensity of treatment and prevalence of MetS and CVE is needed. The data supports routine screening for MetS of both allo and auto HCT patients. Early intervention of reversible features of MetS with lifestyle and medical management may reduce the risk of cardiovascular events, but this needs be tested in a randomised controlled trial setting. Meanwhile, screening and management should be robustly integrated within routine HCT long-term follow-up care.
Table 1. Table 1.

Disclosures
Cortelezzi: janssen: Consultancy; novartis: Consultancy; roche: Consultancy; abbvie: Consultancy. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding, Speakers Bureau; Servier: Consultancy; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; MaaT Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Speakers Bureau; Bristol Myers: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Molmed: Consultancy; Janssen: Honoraria, Research Funding, Speakers Bureau. Kroeger:Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; JAZZ: Honoraria; Sanofi: Honoraria; Neovii: Honoraria, Research Funding. Snowden:Jazz & Sanofi: Other: Speaker fees at ASH; Jannssen/J&J: Other: Speaker fees.