Cardiovascular Risk: Analysis of Known Factors in Patients After Treosulfan-Based Conditioning for Haploidentical and HLA-Identical Stem Cell Transplantation
Authors: Forcina Alessandra , Lupo Stanghellini Maria Teresa , Greco Raffaella , Lorusso Alessandro , Clerici Daniela , Peccatori Jacopo , Bernardi Massimo , Lunghi Francesca , Marcatti Magda , Camba Lionello , Guggiari Elena , Assanelli Andrea , Bondanza Attilio , Carrabba Matteo , Marktel Sarah , Corti Consuelo , Ciceri Fabio 
Published: October 2019

Abstract
Abstract 4471
Allogeneic stem cell transplantation (HSCT) is an emerging risk factor for cardiovascular disease. Long-term survivors seem to be at higher risk for premature arterial vascular disease compared with sex- and age-matched population. In HSCT, pre-transplant treatments and the conditioning regimen play a key role in endothelial and organ damage. The use of immunosuppressant drugs to prevent graft-versus-host disease (GvHD) influences as well the development of cardiac disease. To better understand the impact of treosulfan-based conditioning regimens in leading to the emergence of cardiovascular disease, we retrospectively evaluated 94 consecutive patients who had survived longer than 1 year, transplanted at Our Institution between 2002 and 2010 (62 males – median age 46, range 14–69). For 48 patients an HLA-identical sibling was available, 6 patients found an unrelated donor while 40 patients underwent haploidentical HSCT from family donors. Forty-six patients received in vivo T-cell depletion and 72 B-cell depletion. GvHD prophylaxis was based upon cyclosporine + methotrexate for the HLA-identical transplants (48 – median EBMT risk score 3) whereas rapamycin + MMF were used for patients undergoing transplantation from HLA-haploidentical donors (35 – median EBMT risk score 4); 9 did not receive any immunosuppression because of application of suicide gene strategy as tool to prevent GvHD (median EBMT risk score 3). We compared clinical variables (i.e. GvHD, OS, TRM, major cardiac events and comorbidities) with biochemical and functional tests (i.e. cardiac function, lipid profile and ferritin levels) both before and 1 year after transplantation. After a median follow-up of 29 months, only 3 patients experienced a major cardiovascular event; no one experienced a late congestive heart failure. In all series, we found that ferritin levels significantly decrease after 1 year of follow-up, compared to pre-transplant values (P <0.0001); viceversa, the lipid profile (total cholesterol, HDL and LDL fractions) remarkably increased (p <0.05). Interestingly, the linear regression analysis for the overall survival showed no difference for both ferritin level and cholesterol level. Moreover, no significant variations were detected comparing cyclosporine versus rapamycin-treated patients, nor comparing patients with or without GvHD. Increased rates of cardiovascular disease are commonly associated to HSCT. In our experience, no differences were found in the incidence of cardiovascular events comparing different donor source or immunosuppressants. This suggests that haploidentical transplants are feasible and have similar cardiac toxicity than standard HLA-identical ones. Our analysis was surely limited by the short time of observation. In future, the evaluation of dynamic biomarkers on a greater series and on a longer follow-up will help us to identify a tailored schedule of cardiac monitoring after HSCT to prevent major lethal events in our patients.

Disclosures:
No relevant conflicts of interest to declare.