Brief Communication
Cyclophosphamide rescue therapy for chronic rejection after lung transplantation

https://doi.org/10.1016/S1053-2498(99)00072-8Get rights and content

Abstract

Background: Obliterative bronchiolitis remains the leading cause of late mortality after heart–lung and lung transplantation. Although several treatment options have been advocated, none has proven to be very successful. Cyclophosphamide is effective in the treatment of idiopathic pulmonary fibrosis, and chronic rejection after lung transplantation is also a fibroproliferative process. We therefore conducted an open, uncontrolled study to look at the effect of cyclophosphamide rescue therapy in the treatment of chronic rejection in lung transplant recipients.

Methods

Between October 1996 and March 1998 cyclophosphamide was prescribed to 7 patients with chronic and persistent rejection who failed to respond to conventional therapy (pulse steroids or antilymphocyte products or both).

Results

Cyclophosphamide therapy was initiated on postoperative day 478 ± 366. At that time 2 patients were in bronchiolitis obliterans syndrome stage 0, 3 patients in stage 1, and 2 patients in stage 2. Their best postoperative forced expiratory volume in one second (FEV1) was 2.19 ± 0.75 L. Three months before the start of cyclophosphamide the FEV1 had declined to 1.90 ± 0.83 L, with a further decline to 1.63 ± 0.64 L at the time of initiating cyclophosphamide. In 6 of the 7 patients the FEV1 stabilized or increased after cyclophosphamide had been started (mean FEV1 3 and 6 months after cyclophosphamide of 1.77 ± 0.58 L and 1.79 ± 0.48 L, respectively). One patient died 18 months after the introduction of cyclophosphamide due to progressive obliterative bronchiolitis. In one patient cyclophosphamide had to be stopped because of persistent leucopenia.

Conclusions

Cyclophosphamide might be a promising therapeutic alternative for the treatment of chronic persistent rejection after lung transplantation.

Section snippets

Patients and methods

In an open, uncontrolled study, we have analyzed the effect of rescue treatment with cyclophosphamide in 7 patients with chronic rejection, not responding to conventional therapy with high doses of intravenous steroids, antilymphocyte products, or both. They had all been treated with rATG induction therapy and triple immunosuppression, consisting of cyclosporine, azathioprine, and steroids. In one patient cyclosporine has been switched to FK506 because of recurrent acute rejection episodes. The

Results

For the whole patient group, the best FEV1 after transplantation, was 2.19 ± 0.75 L (range, 0.94 to 2.9 L). Three months before starting cyclophosphamide, the FEV1 had significantly declined to 1.90 ± 0.83 L (range, 0.83 to 2.56 L; p = 0.03). At the time of initiating cyclophosphamide, the FEV1 had further declined to 1.63 ± 0.64 L (range, 0.54 to 2.4 L; p = 0.0003 vs the best post-operative FEV1). This represents a mean decline in FEV1 of 0.13 ± 0.11 L per month over the last 3 months. The

Discussion

Since it has been demonstrated that augmentation of the immunosuppressive therapy can stop the progression of OB/BOS in a number of patients,7 many therapeutic regimens have been used to tackle this problem. Amongst them, changing of cyclosporine to FK506 or azathioprine to MMF were quite successful. The role of cyclophosphamide in the treatment of chronic rejection after (H)LTx remains unknown. After an initial success with this therapy in one patient,8 we have now presented the results in 7

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