Metabolic Syndrome Post Allogeneic STEM CELL Transplantation in Adult Patients Is NOT an Uncommon Complication. a Single Center Experience

Background: The significant advances which have been achieved in the field of allogeneic transplantation (alloHCT) have resulted in better post-transplant outcome and prolonged survival. Therefore, complications other than the Graft vs. Host disease (GvHD) or disease recurrence have become increasingly important. The post-transplant metabolic syndrome (PT-MS), caused by several factors (i.e. immunosuppressive agents, chemo-radiotherapy, anti-viral, and biologic therapies) is a well known post-transplant complication in pediatric allografted long-term survivors however, only a few studies have evaluated the prevalence of the PT-MS in adults. In this retrospective study, we sought to evaluate the incidence, risk factors and impact of the PT-MS on alloSCT outcome.

Methods: From 1/2011 to 12/2018, 54 patients (34 males and 20 females) with adequate clinical and laboratory data and a minimum follow-up of 6 months were included in the study. Median age was 35.6 years (range, 16-67) and following a myeloablative (n=34) or reduced intensity (n=20) regimen patients received either a mobilized peripheral blood stem cell (n=45) or marrow (n=9) graft originating from full-matched siblings (n=46) or haploidentical (n=8) donors. Calcineurin inhibitors plus either short-term Methotrexate or Mycophenolate Mofetil were given as GvHD prophylaxis. Diagnosis of PT-MS was based on NCEP-ATPIII criteria; for patients with unknown data for abdominal circumference, a modified criterion of body mass index (BMI) ≥25kg/m² was utilized instead. The independent t-test, logistic regression analysis and log-rank tests were used for statistical analysis.

Results: Twenty-four (44%) patients (14 males, 10 females) fulfilled the criteria for PT-MS. Twenty had been diagnosed after the 1^st trimester, 3 patients after the 2^nd and in addition 1 after the 3^rd trimester post alloSCT. Twenty out of 24 (83%) patients had elevated glucose, 19/24 (80%) had BMI>25kg/m², 18/24 (75%) elevated triglycerides levels, 14/24 (60%) low HDL levels and 13/24 (55%) hypertension. Six (25%) had a known history of MS before alloSCT (10 patients had no available data to assess for MS diagnosis prior to alloSCT). Interestingly, in 8/24 (33%) patients who had PT-MS diagnosed early, either in the 1^st or 2^nd trimester, the syndrome was completely reversible beyond the 6-month post alloSCT follow-up period. In the aforementioned statistical models, patients' gender, age, BMI, type of conditioning regimen and GvHD co-existence were evaluated as potential predisposing factors for the PT-MS. In univariate and multivariate analysis only BMI>25kg/m² and age>35 years were detected as significant risk factors (p< 0.01) for development of PT-MS. The PT-MS did not adversely impact survival or the NRM incidence post alloSCT.

Conclusions: In our study, in agreement with other publications, we demonstrate that the PT-MS is not an uncommon complication in the early post-transplant period however, for approximately 1/3 of patients the syndrome was reversible. For patients with high risk features (BMI>25kg/m², age> 35 years, known history of diabetes-mellitus, dyslipidemia, hypertension) apart of close monitoring, specific diet and encouragement for exercise might help reduce the incidence and severity of PT-MS. Nevertheless, prospective and well design trials are warranted to determine the incidence, severity and impact of PT-MS on alloSCT outcome for adult patients.