PMID- 37200246
OWN - NLM
STAT- MEDLINE
DCOM- 20230522
LR  - 20230605
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 18
IP  - 5
DP  - 2023
TI  - Calcineurin-inhibitor free immunosuppression after lung transplantation - a 
      single center case-control study in 51 patients converted to Mechanistic Target 
      of Rapamycin (mTOR) inhibitors.
PG  - e0284653
LID - 10.1371/journal.pone.0284653 [doi]
LID - e0284653
AB  - BACKGROUND: Data on calcineurin-inhibitor (CNI) free immunosuppression after lung 
      transplantation (LTx) are limited. Aim of this study was to investigate CNI-free 
      immunosuppression using mechanistic target of rapamycin (mTOR) inhibitors. 
      METHODS: This retrospective analysis was performed at a single center. Adult 
      patients after LTx without CNI during the follow-up period were included. Outcome 
      was compared to those LTx patients with malignancy who continued CNI. RESULTS: 
      Among 2,099 patients in follow-up, fifty-one (2.4%) were converted median 6.2 
      years after LTx to a CNI-free regimen combining mTOR inhibitors with prednisolone 
      and an antimetabolite, two patients were switched to mTOR inhibitors with 
      prednisolone only. In 25 patients, malignancies without curative treatment 
      options were the reason of the conversion, with a 1-year survival of 36%. The 
      remaining patients had a 1-year survival of 100%. Most common non-malignant 
      indication was neurological complications (n = 9). Fifteen patients were 
      re-converted to a CNI-based regimen. The median duration of CNI-free 
      immunosuppression was 338 days. No acute rejections were detected in 7 patients 
      with follow-up biopsies. In multivariate analysis, CNI-free immunosuppression 
      were not associated with improved survival after malignancy. The majority of 
      patients with neurological diseases improved 12 months after conversion. 
      Glomerular filtration rate increased by median 5 (25 and 75% percentiles -6; +18) 
      ml/min/1.73 m2. CONCLUSIONS: mTOR inhibitor based CNI-free immunosuppression may 
      be safely performed in selected patients after LTx. This approach was not 
      associated with improved survival in patients with malignancy. Significant 
      functional improvements were observed in patients with neurological diseases.
CI  - Copyright: (c) 2023 Gottlieb et al. This is an open access article distributed 
      under the terms of the Creative Commons Attribution License, which permits 
      unrestricted use, distribution, and reproduction in any medium, provided the 
      original author and source are credited.
FAU - Gottlieb, Jens
AU  - Gottlieb J
AUID- ORCID: 0000-0002-9540-9022
AD  - Respiratory Medicine, Hannover Medical School, Hannover, Germany.
AD  - German Center for Lung Research (DZL), Hannover, Germany.
FAU - Fischer, Bettina
AU  - Fischer B
AD  - Respiratory Medicine, Hannover Medical School, Hannover, Germany.
FAU - Schupp, Jonas C
AU  - Schupp JC
AD  - Respiratory Medicine, Hannover Medical School, Hannover, Germany.
FAU - Golpon, Heiko
AU  - Golpon H
AD  - Respiratory Medicine, Hannover Medical School, Hannover, Germany.
AD  - German Center for Lung Research (DZL), Hannover, Germany.
LA  - eng
PT  - Journal Article
DEP - 20230518
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - EC 3.1.3.16 (Calcineurin)
RN  - 0 (MTOR Inhibitors)
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (Immunosuppressive Agents)
RN  - W36ZG6FT64 (Sirolimus)
RN  - 9PHQ9Y1OLM (Prednisolone)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *Calcineurin
MH  - Retrospective Studies
MH  - Case-Control Studies
MH  - MTOR Inhibitors
MH  - Calcineurin Inhibitors/therapeutic use
MH  - Immunosuppressive Agents/therapeutic use
MH  - Sirolimus/therapeutic use
MH  - Glomerular Filtration Rate
MH  - Prednisolone
MH  - Immunosuppression Therapy
MH  - TOR Serine-Threonine Kinases
MH  - *Lung Transplantation
MH  - Graft Rejection/prevention & control
PMC - PMC10194991
COIS- Jens Gottlieb: related to this work: Novartis (speaker fees) Jens Gottlieb 
      unrelated to this work: Zambon /Breath Therapeutics (Research grant), Theravance 
      (Advisory), Atheneum (Consultancy), Pierre Fabre (Advisory), Astra Zeneca 
      (Speaker fee), Springer Healthcare (Advisory), Merck (Advisory), European 
      Research Network (Consultancy), Precision (Advisory), German Center of Lung 
      Research (Research grant), Deutsche Forschungsgemeinschaft (Research grant). 
      Heiko Golpon, Bettina Fischer and Jonas Schupp have declared that no competing 
      interests exist.
EDAT- 2023/05/18 19:12
MHDA- 2023/05/22 06:42
PMCR- 2023/05/18
CRDT- 2023/05/18 13:33
PHST- 2022/10/12 00:00 [received]
PHST- 2023/04/05 00:00 [accepted]
PHST- 2023/05/22 06:42 [medline]
PHST- 2023/05/18 19:12 [pubmed]
PHST- 2023/05/18 13:33 [entrez]
PHST- 2023/05/18 00:00 [pmc-release]
AID - PONE-D-22-28204 [pii]
AID - 10.1371/journal.pone.0284653 [doi]
PST - epublish
SO  - PLoS One. 2023 May 18;18(5):e0284653. doi: 10.1371/journal.pone.0284653. 
      eCollection 2023.