Efficacy of tacrolimus rescue therapy in refractory acute rejection after lung transplantation.
BACKGROUND
Encouraging results in transplantation of other solid organs led to investigation of the use of tacrolimus in lung transplantation as a salvage immunosuppressant in persistent acute rejection.


METHODS
The incidence and severity of acute rejection and the number of steroid pulses were analyzed in 20 lung recipients who were converted from a cyclosporine- to a tacrolimus-based immunosuppressive regimen because of refractory biopsy-proven acute rejection.


RESULTS
Tacrolimus was started 12.0 +/- 13.0 months after transplantation, and the mean follow-up was 25.0 +/- 13.7 months. After shifting to tacrolimus, a significant decline was observed in both the number of acute rejections per patient (3.0 +/- 1.56 to 0.85 +/- 1.14, p < 0.0001), and the incidence of acute rejection per 100 patient-days (1.52 +/- 0.99 to 0.14 +/- 0.21, p < 0.0001). Furthermore, the average histologic grade of rejection decreased from 1.9 +/- 0.8 to 0.4 +/- 0.5 (p < 0.0001). Methylprednisolone pulses similarly decreased from 1.9 +/- 1.3/patient to 0.3 +/- 0.7/patient (p < 0.0001). During cyclosporine immunosuppression, the mean forced expiratory volume in 1 second decreased to 84.4% +/- 13.3% of individual best value. The average lung function parameters were stable 3 months after the change of medication, and then began to improve. After an average follow-up of 36.5 +/- 19.2 months, 2 patients have developed bronchiolitis obliterans syndrome (one has Stage 1 and one has Stage 3).


CONCLUSIONS
Conversion to a tacrolimus-based immunosuppressive regimen for refractory acute lung rejection is associated with reduced incidence and severity of acute rejection episodes, steroid sparing, and stabilization or improvement of pulmonary function.
Vitulo
Patrizio
P
Division of Pulmonary Medicine, IRCCS Policlinico S. Matteo, Pavia, Italy. vitulop@smatteo.pv.it
Oggionni
Tiberio
T
Cascina
Alessandro
A
Arbustini
Eloisa
E
D'Armini
Andrea M
AM
Rinaldi
Mauro
M
Meloni
Federica
F
Rossi
Albino
A
Viganò
Mario
M
D000208:Acute Disease; D000328:Adult; D023381:Endpoint Determination; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006084:Graft Rejection / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016559:Tacrolimus / Q000627:therapeutic use*; D013995:Time; D013997:Time Factors; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016559:Tacrolimus