Cyclophosphamide rescue therapy for chronic rejection after lung transplantation

Background: Obliterative bronchiolitis remains the leading cause of late mo rtality after heart-lung and lung transplantation. Although several treatme nt options have been advocated, none has proven to be very successful. Cycl ophosphamide is effective in the treatment of idiopathic pulmonary fibrosis , and chronic rejection after lung transplantation is also a fibroprolifera tive 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 prescribe d 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 st age 0, 3 patients in stage 1, and 2 patients in stage 2. Their best postope rative forced expiratory volume in one second (FEV1) was 2.19 +/- 0.75 L. T hree 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 in itiating cyclophosphamide. In 6 of the 7 patients the FEV1 stabilized or in creased after cyclophosphamide had been started (mean FEV1 3 and 6 months a fter 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 transplantatio n.