Azathioprine withdrawal in stable lung and heart/lung recipients receiving cyclosporine-based immunosuppression.
BACKGROUND
Chronic rejection is the leading cause of graft failure after (heart-) lung transplantation. Therefore, many centers maintain a triple immunosuppressive cyclosporine-based regimen including azathioprine (AZA) during the long-term course after lung transplantation. However, an increased risk of malignancies has been attributed to prolonged immunosuppression, and there is evidence that less intensive immunosuppressive regimens are feasible in the long-term course after other solid organ transplantation. Therefore, we investigated the effects of AZA withdrawal in stable lung transplant recipients.


METHODS
A prospective study was performed to assess the effects of AZA withdrawal in patients who received a lung transplant more than 4 years ago with stable graft function defined by absence of rejection episodes for at least 2 years and no evidence of bronchiolitis obliterans.


RESULTS
A total of 24 patients qualified for the study and 7 discontinued AZA. Despite the small number of patients, termination of the study became necessary after 12 months because significantly more grafts showed deteriorating function after withdrawing AZA (4 of 7) compared to recipients continuing a triple therapy (1 of 17; P<0.05). In recipients with deteriorating graft function conventional treatment with high-dose corticosteroids and reinstitution of AZA failed to stop the development of obliterative bronchiolitis.


CONCLUSIONS
Our data reinforce the importance of a potent immunosuppressive regimen for the maintenance of stable graft function after lung transplantation.
Hoffmeyer
F
F
Department of Respiratory Medicine, Medizinische Hochschule Hannover, Germany.
Hoeper
M M
MM
Spiekerkötter
E
E
Harringer
W
W
Haverich
A
A
Fabel
H
H
Niedermeyer
J
J
D000208:Acute Disease; D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage* / Q000009:adverse effects; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000517:prevention & control; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000517:prevention & control; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control; D016041:Heart-Lung Transplantation / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016040:Lung Transplantation / Q000276:immunology* / Q000502:physiology; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012129:Respiratory Function Tests; D012449:Safety
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine