FK-506 RESCUE IMMUNOSUPPRESSION FOR OBLITERATIVE BRONCHIOLITIS AFTER LUNG TRANSPLANTATION

Preliminary experience: Ln a consecutive case series (level V evidence ) involving 10 recipients of unilateral lung transplantation (LT) with bronchiolitis obliterans, in conjunction with Fujisawa protocol 93-0- 003, the physiologic responses to FK 506 (tacrolimus) ''rescue'' immun osuppression were assessed. Recipients were 22+/-18 months post-LT and demonstrated progressive allograft dysfunction that was refractory to pulsed-dose methylprednisolone therapy. All recipients received induc tion immunosuppression with Minnesota antilymphocyte globulin (10 to 1 5 mg/kg/d) for 5 to 10 days, cyclosporine (CsA) (whole-blood Abbott TD X(TM) fluorescence polarization immunoassay (Abbott Inc, Abbott Park, IL)=600 to 800 ng/mL), azathioprine (2 mg/kg/d), and prednisone (taper ed to 0.2 mg/kg/d). The ''rescue'' regimen consisted of oral FK 506 ad justed to maintain a whole-blood Abbott IMX(TM) microparticle enzyme i mmunoassay (Abbott Inc, Abbott Park, IL) of 10 to 15 ng/mL with an ini tial increase in prednisone (1.0 mg/kg/d) during conversion that was s ubsequently tapered to 0.2 mg/kg/d. Spirometry was pet-formed monthly in accordance with accepted American Thoracic Society criteria. Recipi ents were classified in accordance with the International Society for Heart and Lung Transplantation (ISHLT) ''Working Formulation for Stand ardization of Nomenclature and for Clinical Staging of Chronic Dysfunc tion in Lung Allografts'' as stages Ib (n = 2), IIb (n = 4), and IIIb (n=4) upon entry to the protocol. The Delta FEV1/month relationships d uring CsA- and FK 506-based regimens were analyzed by linear regressio n and compared by signed rank test (p<0.05). Results: The Delta FEV1/m onth slopes were -0.0687+/-0.0221 and +0.0300+/-0.033 L/mo (mean+/-SEM ) for CsA and FK 506, respectively (p=0.037). Although no significant spirometric improvement was noted in most recipients, no further decli ne in FEV1 occurred after conversion to FK 506. Recipients with less s evere chronic dysfunction (ie, obliterative bronchiolitis [OB] stages Ib and IIb) stabilized their spirometric indexes at higher levels. Two recipients with OB stage IIIb died of hypercapnic respiratory failure at 6 and 8 months after conversion. Conclusions: The Delta FEV1/mo sl opes stabilized after FK 506 conversion. Earlier conversion may be ben eficial in stabilizing FEV1 at a higher plateau. Significant economic impact may be anticipated with FK 506 compared to alternative cytolyti c strategies for OB. However, multicenter prospective controlled inves tigations are necessary to further address the potential role of FK 50 6 after LT (level I evidence). Furthermore, the ISHLT ''Staging of OB Syndrome'' may have significant clinical implications vis-a-vis progno sis and potential therapies.