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Conversion to sirolimus and mycophenolate can attenuate the progression of bronchiolitis obliterans syndrome and improves renal function after lung transplantation.
Transplantation 2006; 81(3):355-60T

Abstract

BACKGROUND

Bronchiolitis obliterans syndrome (BOS) is the major problem after lung and heart-lung transplantation (LTx/HLTx). Sirolimus (Sir) and Mycophenolate (MMF) showed a promising efficacy in the treatment of BOS in animal models. The first clinical experience in converting LTx/HLTx-recipients with BOS from calcineurin inhibitor-(CNI)-based immunosuppression to a Sir-MMF based immunosuppression is reported herein.

METHODS

Six LTx- and five HLTx-recipients (eight men; 0.9 to 8 years after transplantation) with CNI-based immunosuppression (plus MMF) in whom BOS was diagnosed were included in the study. Mean patient age was 37+/-13 years (range 17-62 years). Sir was started with 6 mg and continued adjusted to according target trough levels (8-14 ng/ml). Subsequently, the CNIs were tapered down and finally stopped. Follow up included self determined pulmonary function tests, microbiological screening, chest radiographs, and laboratory studies

RESULTS

Two acute rejection episodes occurred during the study period. The incidence of infection was 2.2+/-1.3 infections/patient-year after conversion. Mean FEV1 decreased after a mean follow up of 14.8+/-1.4 months: from 2.1+/-0.7 l prior conversion to 1.3+/-0.6l after conversion (P=0.03). However, graft function remained stable in three patients and progression of BOS slowed down in three patients. Overall, 2 of 10 patients died due to ongoing BOS while awaiting retransplantation

CONCLUSIONS

After BOS was diagnosed, conversion to MMF and Sir stabilized graft function only in some of the converted patients. Therefore, earlier administration of Sir-based immunosuppression might be a more promising approach. Whether conversion to CNI-free immunosuppression can actually ameliorate the extent or progression of BOS has to be investigated in randomized trials.

Authors+Show Affiliations

Department of Cardiothoracic and Vascular Surgery, Friedrich Schiller University Hospital, Jena, Germany. jgroetzner@t-online.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

16477220

Citation

Groetzner, Jan, et al. "Conversion to Sirolimus and Mycophenolate Can Attenuate the Progression of Bronchiolitis Obliterans Syndrome and Improves Renal Function After Lung Transplantation." Transplantation, vol. 81, no. 3, 2006, pp. 355-60.
Groetzner J, Wittwer T, Kaczmarek I, et al. Conversion to sirolimus and mycophenolate can attenuate the progression of bronchiolitis obliterans syndrome and improves renal function after lung transplantation. Transplantation. 2006;81(3):355-60.
Groetzner, J., Wittwer, T., Kaczmarek, I., Ueberfuhr, P., Strauch, J., Nagib, R., ... Wahlers, T. (2006). Conversion to sirolimus and mycophenolate can attenuate the progression of bronchiolitis obliterans syndrome and improves renal function after lung transplantation. Transplantation, 81(3), pp. 355-60.
Groetzner J, et al. Conversion to Sirolimus and Mycophenolate Can Attenuate the Progression of Bronchiolitis Obliterans Syndrome and Improves Renal Function After Lung Transplantation. Transplantation. 2006 Feb 15;81(3):355-60. PubMed PMID: 16477220.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Conversion to sirolimus and mycophenolate can attenuate the progression of bronchiolitis obliterans syndrome and improves renal function after lung transplantation. AU - Groetzner,Jan, AU - Wittwer,Thorsten, AU - Kaczmarek,Ingo, AU - Ueberfuhr,Peter, AU - Strauch,Justus, AU - Nagib,Ragi, AU - Meiser,Bruno, AU - Franke,Ulrich, AU - Reichart,Bruno, AU - Wahlers,Thorsten, PY - 2006/2/16/pubmed PY - 2006/4/7/medline PY - 2006/2/16/entrez SP - 355 EP - 60 JF - Transplantation JO - Transplantation VL - 81 IS - 3 N2 - BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the major problem after lung and heart-lung transplantation (LTx/HLTx). Sirolimus (Sir) and Mycophenolate (MMF) showed a promising efficacy in the treatment of BOS in animal models. The first clinical experience in converting LTx/HLTx-recipients with BOS from calcineurin inhibitor-(CNI)-based immunosuppression to a Sir-MMF based immunosuppression is reported herein. METHODS: Six LTx- and five HLTx-recipients (eight men; 0.9 to 8 years after transplantation) with CNI-based immunosuppression (plus MMF) in whom BOS was diagnosed were included in the study. Mean patient age was 37+/-13 years (range 17-62 years). Sir was started with 6 mg and continued adjusted to according target trough levels (8-14 ng/ml). Subsequently, the CNIs were tapered down and finally stopped. Follow up included self determined pulmonary function tests, microbiological screening, chest radiographs, and laboratory studies RESULTS: Two acute rejection episodes occurred during the study period. The incidence of infection was 2.2+/-1.3 infections/patient-year after conversion. Mean FEV1 decreased after a mean follow up of 14.8+/-1.4 months: from 2.1+/-0.7 l prior conversion to 1.3+/-0.6l after conversion (P=0.03). However, graft function remained stable in three patients and progression of BOS slowed down in three patients. Overall, 2 of 10 patients died due to ongoing BOS while awaiting retransplantation CONCLUSIONS: After BOS was diagnosed, conversion to MMF and Sir stabilized graft function only in some of the converted patients. Therefore, earlier administration of Sir-based immunosuppression might be a more promising approach. Whether conversion to CNI-free immunosuppression can actually ameliorate the extent or progression of BOS has to be investigated in randomized trials. SN - 0041-1337 UR - https://www.unboundmedicine.com/medline/citation/16477220/Conversion_to_sirolimus_and_mycophenolate_can_attenuate_the_progression_of_bronchiolitis_obliterans_syndrome_and_improves_renal_function_after_lung_transplantation_ L2 - http://dx.doi.org/10.1097/01.tp.0000195781.02268.5e DB - PRIME DP - Unbound Medicine ER -