SAN DIEGO—Patients who develop metabolic syndrome (MetS) after hematopoietic stem cell transplant (HSCT) have an increased risk of cardiovascular (CV) events and second malignancies, according to research presented at the 2018 ASH Annual Meeting.

Researchers found that HSCT recipients had a higher prevalence of MetS than the general population, and the incidence of MetS increased with age.

In addition, MetS was a predictor of CV events, and these events were associated with second malignancy.

“Our data support metabolic syndrome being an age-related late effect of transplant that is strongly associated with not only cardiovascular events but also the occurrence of second cancers, and this is a novel finding,” said Diana M. Greenfield, RN, PhD, of Sheffield Teaching Hospitals NHS Foundation Trust in Sheffield, United Kingdom.

Dr. Greenfield presented the data at ASH as abstract 251.

She noted that previous studies have reported rates of MetS after HSCT ranging from 31% to 49%. Intensive chemotherapy and radiation have been associated with MetS, and proposed mechanisms of MetS after HSCT include:

Conditioning regimen-mediated damage to the neuro-hormonal system and vascular endothelium
Immunological and inflammatory effects of allo-grafting, including graft-vs-host disease (GVHD) and treatment.

“Those with metabolic syndrome in the general population are already known to be twice as likely to develop cardiovascular disease as those without metabolic syndrome,” Dr. Greenfield noted. “The risk of cardiovascular hospitalizations and mortality is 3.6-fold higher in transplant patients vs the general population.”

With all this in mind, she and her colleagues set out to determine the prevalence of MetS and associated complications among HSCT recipients treated at 9 European centers in Belgium, France, Germany, Turkey, and the United Kingdom.

The researchers analyzed 462 patients—375 who had received an allogeneic HSCT and 87 who had undergone autologous HSCT. All patients were at least 18 years of age and at least 2 years post-HSCT.

The median age at transplant was 43 (interquartile range, 32-53), and 57.4% of patients were male.

Patients’ diagnoses included acute leukemia (37.9%), lymphoma (27.3%), myelodysplastic syndromes/myeloproliferative neoplasms (13%), chronic leukemia (12.3%), plasma cell disorders (5%), bone marrow failure (4.1%), solid tumors (0.2%), and inherited disorders (0.2%).

Results

The prevalence of MetS in this population was 30.4%. This is higher than the prevalence in the general population in Europe, which is 25%, according to the World Health Organization.

There was no significant difference in MetS prevalence between allogeneic and autologous HSCT recipients—29% and 35.6%, respectively.

However, there was a significant difference in MetS prevalence by age (P<0.001 with increasing age).

Among allogeneic HSCT recipients, there was no relationship between MetS prevalence and the presence or degree of acute or chronic GVHD, current use of immunosuppressive therapy, or conditioning intensity.

There was a significantly higher prevalence of CV events in patients with MetS than in patients without the syndrome—22.6% and 10.7%, respectively (P=0.006).

And logistic regression analysis confirmed that MetS is a predictor of CV events (odds ratio [OR]=4.72; 95% confidence interval [CI], 2.11-10.57).

The researchers also found that increasing age influenced the prevalence of MetS (OR=7.3; 95% CI, 3.2-16.8) and CV events (OR=3; 95% CI, 0.8-11.32) for patients older than 50, compared to patients in the 18-29 age group.

And CV events were associated with second malignancy (OR=7.93; 95% CI, 2.91-21.61).

“Early intervention of reversible features of metabolic syndrome with lifestyle and medical management may reduce the risk of cardiovascular events,” Dr. Greenfield said. “Meanwhile, screening and management should be robustly integrated within routine transplant long-term follow-up care.”

She added that the CIBMTR and EBMT guidelines on MetS and CV disease after HSCT should help in that regard.

Dr. Greenfield reported no conflicts of interest. However, her fellow researchers reported relationships with a range of pharmaceutical companies.

MetS after HSCT linked to CV events, second cancers