FK 506 `Rescue' Immunosuppression for Obliterative Bronchiolitis After Lung Transplantation

¹ From the Division of Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center Lung Transplant Program, UCLA School of Medicine, Los Angeles
² From the Division of Cardiothoracic Surgery, Cedars-Sinai Medical Center Lung Transplant Program, UCLA School of Medicine, Los Angeles
³ From the Division of Pharmacy, Cedars-Sinai Medical Center Lung Transplant Program, UCLA School of Medicine, Los Angeles

Preliminary experience: In 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" immunosuppression 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 induction immunosuppression with Minnesota antilymphocyte globulin (10 to 15 mg/kg/d) for 5 to 10 days, cyclosporine (CsA) (whole-blood Abbott TDX^TM fluorescence polarization immunoassay (Abbott Inc, Abbott Park, IL)=600 to 800 ng/mL), azathioprine (2 mg/kg/d), and prednisone (tapered to 0.2 mg/kg/d). The "rescue" regimen consisted of oral FK 506 adjusted to maintain a whole-blood Abbott IMX^TM microparticle enzyme immunoassay (Abbott Inc, Abbott Park, IL) of 10 to 15 ng/mL with an initial increase in prednisone (1.0 mg/kg/d) during conversion that was subsequently tapered to 0.2 mg/kg/d. Spirometry was performed monthly in accordance with accepted American Thoracic Society criteria. Recipients were classified in accordance with the International Society for Heart and Lung Transplantation (ISHLT) "Working Formulation for Standardization of Nomenclature and for Clinical Staging of Chronic Dysfunction in Lung Allografts" as stages Ib (n=2), IIb (n=4), and IIIb (n=4) upon entry to the protocol. The FEV₁/month relationships during CsA- and FK 506-based regimens were analyzed by linear regression and compared by signed rank test (p<0.05).

Results: The FEV₁/month 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 decline in FEV₁ occurred after conversion to FK 506. Recipients with less severe 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 FEV₁/mo slopes stabilized after FK 506 conversion. Earlier conversion may be beneficial in stabilizing FEV₁ at a higher plateau. Significant economic impact may be anticipated with FK 506 compared to alternative cytolytic strategies for OB. However, multicenter prospective controlled investigations are necessary to further address the potential role of FK 506 after LT (level I evidence). Furthermore, the ISHLT "Staging of OB Syndrome" may have significant clinical implications vis-à-vis prognosis and potential therapies.

This article has been cited by other articles:

				K. Sarahrudi, M. Estenne, P. Corris, J. Niedermayer, C. Knoop, A. Glanville, C. Chaparro, G. Verleden, M. W. Gerbase, F. Venuta, et al. International experience with conversion from cyclosporine to tacrolimus for acute and chronic lung allograft rejection J. Thorac. Cardiovasc. Surg., April 1, 2004; 127(4): 1126 - 1132. [Abstract] [Full Text] [PDF]

				C. Knoop, A. Haverich, and S. Fischer Immunosuppressive therapy after human lung transplantation Eur. Respir. J., January 1, 2004; 23(1): 159 - 171. [Abstract] [Full Text] [PDF]

				B. P. Griffith and R. S. Poston Immunobiology of Heart and Heart-Lung Transplantation Card. Surg. Adult, January 1, 2003; 2(2003): 1403 - 1426. [Full Text]

				J. W. K. van den Berg, P. J. van Enckevort, E. M. TenVergert, D. S. Postma, W. van der Bij, and G. H. Koeter Bronchiolitis Obliterans Syndrome and Additional Costs of Lung Transplantation Chest, December 1, 2000; 118(6): 1648 - 1652. [Abstract] [Full Text] [PDF]

				J W K van den Berg, D S Postma, G H Koëter, and W van der Bij New immunosuppressive drugs and lung transplantation: last or least? Thorax, June 1, 1999; 54(6): 550 - 553. [Full Text]