Sirolimus-Based Immunosuppression Is Associated with Decreased Incidence of Post-Transplant Lymphoproliferative Disorder after Heart Transplantation: A Double-Center Study

被引:4
|
作者
Asleh, Rabea [1 ,2 ,3 ]
Vucicevic, Darko [4 ]
Petterson, Tanya M. [5 ]
Kremers, Walter K. [1 ,2 ,5 ]
Pereira, Naveen L. [1 ,2 ]
Daly, Richard C. [1 ,2 ]
Edwards, Brooks S. [1 ,2 ]
Steidley, D. Eric [6 ]
Scott, Robert L. [6 ]
Kushwaha, Sudhir S. [1 ,2 ]
机构
[1] Mayo Clin, Dept Cardiovasc Dis & Hlth Sci Res, Rochester, MN 55905 USA
[2] Mayo Clin, William J von Liebig Ctr Transplantat & Clin Rege, Rochester, MN 55905 USA
[3] Hebrew Univ Jerusalem, Hadassah Univ Med Ctr, Heart Inst, Fac Med, IL-9112001 Jerusalem, Israel
[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Cardiol, Los Angeles, CA 90095 USA
[5] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA
[6] Mayo Clin Arizona, Dept Cardiovasc Dis, Phoenix, AZ 85054 USA
关键词
mTOR inhibitors; sirolimus; post-transplant lymphoproliferative disorder; heart transplantation; immunosuppression; SOLID-ORGAN TRANSPLANTATION; CARDIAC TRANSPLANTATION; SIGNAL-TRANSDUCTION; ADULT HEART; RAPAMYCIN; RISK; PROLIFERATION; MALIGNANCY; CONVERSION; SURVIVAL;
D O I
10.3390/jcm11020322
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Mammalian target of rapamycin (mTOR) inhibitors have been shown to reduce proliferation of lymphoid cells; thus, their use for immunosuppression after heart transplantation (HT) may reduce post-transplant lymphoproliferative disorder (PTLD) risk. This study sought to investigate whether the sirolimus (SRL)-based immunosuppression regimen is associated with a decreased risk of PTLD compared with the calcineurin inhibitor (CNI)-based regimen in HT recipients. We retrospectively analyzed 590 patients who received HTs at two large institutions between 1 June 1988 and 31 December 2014. Cox proportional-hazard modeling was used to examine the association between type of primary immunosuppression and PTLD after adjustment for potential confounders, including Epstein-Barr virus (EBV) status, type of induction therapy, and rejection. Conversion from CNI to SRL as primary immunosuppression occurred in 249 patients (42.2%). During a median follow-up of 6.3 years, 30 patients developed PTLD (5.1%). In a univariate analysis, EBV mismatch was strongly associated with increased risk of PTLD (HR 10.0, 95% CI: 3.8-26.6; p < 0.001), and conversion to SRL was found to be protective against development of PTLD (HR 0.19, 95% CI: 0.04-0.80; p = 0.02). In a multivariable model and after adjusting for EBV mismatch, conversion to SRL remained protective against risk of PTLD compared with continued CNI use (HR 0.12, 95% CI: 0.03-0.55; p = 0.006). In conclusion, SRL-based immunosuppression is associated with lower incidence of PTLD after HT. These findings provide evidence of a benefit from conversion to SRL as maintenance therapy for mitigating the risk of PTLD, particularly among patients at high PTLD risk.
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页数:12
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