PMID- 30711744
OWN - NLM
STAT- MEDLINE
DCOM- 20190718
LR  - 20211204
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 69
DP  - 2019 Apr
TI  - The change of immunosuppressive regimen from calcineurin inhibitors to mammalian 
      target of rapamycin (mTOR) inhibitors and its effect on malignancy following 
      heart transplantation.
PG  - 150-158
LID - S1567-5769(18)31097-X [pii]
LID - 10.1016/j.intimp.2019.01.035 [doi]
AB  - Malignancy is a significant cause of mortality after organ transplantation. There 
      is an increased rate of malignancy following heart transplantation (HTx) compared 
      to the general population and other organ transplant recipients. Post-HTx 
      patients with a history of malignancy are also at a higher risk of developing new 
      malignancies or exacerbation of their existing malignancies. Mammalian target of 
      Rapamycin inhibitors (mTORIs) are newly introduced immunosuppressive drugs with a 
      unique mechanism of action. By changing the immunosuppressive regimen from 
      classic drugs, especially calcineurin inhibitors (CNIs) to mTORIs, the rate of 
      developing de novo malignancies and the relapse of former malignancies is 
      significantly reduced. However, issues like allograft function, total 
      surveillance of patients, and post-transplantation complications should be 
      considered during the conversion of drug regimens utilizing CNIs to drug regimens 
      employing mTORIs. We reviewed different post-heart transplant maintenance 
      immunosuppressive regimens and their effect on post-HTx malignancies with a focus 
      on mTORIs, compared safety against effectiveness, and gathered conclusions based 
      on our review of the literature, which may lead clinicians to make a better 
      evidence-based decision regarding post-HTx maintenance immunosuppressive drug 
      regimens. Overall, CNI to mTORI conversion in post-HTx maintenance 
      immunosuppressive drug regimens was associated with a reduced rate of developing 
      malignancy in post-HTx patients. Furthermore, nephrotoxicity decreased 
      significantly while using mTORIs in combination with lower doses of CNIs and the 
      rejection rate was equivalent to CNI-only regimens. In conclusion, mTORI-based 
      maintenance immunosuppressive drug regimens seem to be safe and beneficial when 
      considering efficacy vs. adverse effects, and all-cause mortality rates are 
      significantly lower in patients switched to mTORIs when compared to CNI 
      recipients.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Saber-Moghaddam, Niloufar
AU  - Saber-Moghaddam N
AD  - School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
FAU - Nomani, Homa
AU  - Nomani H
AD  - School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
FAU - Sahebkar, Amirhossein
AU  - Sahebkar A
AD  - Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, 
      Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology 
      Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
FAU - Johnston, Thomas P
AU  - Johnston TP
AD  - Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, 
      University of Missouri-Kansas City, Kansas City, MO, USA.
FAU - Mohammadpour, Amir Hooshang
AU  - Mohammadpour AH
AD  - Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of 
      Medical Sciences, Mashhad, Iran; Pharmaceutical Research Center, Pharmaceutical 
      Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. 
      Electronic address: Mohamadpoorah@mums.ac.ir.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20190131
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Calcineurin Inhibitors/*therapeutic use
MH  - Drug Substitution
MH  - *Heart Transplantation
MH  - Humans
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Neoplasms/etiology/*prevention & control
MH  - Postoperative Complications/*prevention & control
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
OTO - NOTNLM
OT  - Calcineurin inhibitors
OT  - Heart transplantation
OT  - Immunosuppressive
OT  - mTOR inhibitors
EDAT- 2019/02/04 06:00
MHDA- 2019/07/19 06:00
CRDT- 2019/02/04 06:00
PHST- 2018/11/09 00:00 [received]
PHST- 2019/01/24 00:00 [revised]
PHST- 2019/01/25 00:00 [accepted]
PHST- 2019/02/04 06:00 [pubmed]
PHST- 2019/07/19 06:00 [medline]
PHST- 2019/02/04 06:00 [entrez]
AID - S1567-5769(18)31097-X [pii]
AID - 10.1016/j.intimp.2019.01.035 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2019 Apr;69:150-158. doi: 10.1016/j.intimp.2019.01.035. Epub 
      2019 Jan 31.