Dr. Onsager et al., Efficacy of tacrolimus in the treatment of refractory rejection in heart and lung transplant recipients, J HEART LUN, 18(5), 1999, pp. 448-455
Background: Refractory acute cellular rejection may occur despite triple-dr
ug immunosuppression (cyclosporine A, steroids, azathioprine/mycophenolate
mofetil). The purpose of this study was to determine the efficacy of tacrol
imus rescue therapy in patients maintained on cyclosporine-based immunosupp
ression (CBI).
Methods: Between December 1993 and October 1996, 208 patients underwent tho
racic organ transplantation at the Hospital of the University of Wisconsin
at Madison. One hundred forty-nine patients underwent heart replacement; 59
underwent lung transplantation. One hundred thirty-nine of the heart trans
plant cohort received CBI preceded by induction therapy with OKT3. Forty-si
x of the lung transplant cohort received CBI without induction cytolytic th
erapy. Refractory rejection was defined as failure to respond to high-dose
steroids (500 mg to 1 g IV methylprednisolone for 3 days) and/or nionoclona
l antibody therapy (OKT3, 5 to 10 mg IV/day for 7 to 14 days). In patients
with refractory rejection, cyclosporine was replaced with tacrolimus.
Results: Overall, 16% (30/185) of patients receiving CBI experienced refrac
tory rejection. Thirty-one episodes of grade IIIa or greater rejection occu
rred in 11% (15/139) of heart transplant recipients. Twenty episodes of gra
de II to IV rejection occurred in 33%(15/46) of lung transplant recipients.
After tacrolimus rescue therapy, 93% (14/15) of patients in the heart tran
splant group converted to grade II or less rejection. Refractory rejection
was reversed in 73% (11/15) of the lung transplant group. Reversal was docu
mented at biopsy in all (8/8) lung recipients in whom it had been histologi
cally identified. FEV, values of 3 additional patients stabilized.
Conclusions: The incidence of refractory rejection in thoracic organ transp
lant recipients on CBI is significant. Reversal of refractory rejection fol
lows rescue immunotherapy with tacrolimus.