- Email: [email protected]
Acute heart transplant rejection associated with late steroid withdrawal
The Journal of Heart and Lung Transplantation Volume 21, Number 1
Abstracts
167
312
313
STEROID WITHDRAWAL IMPROVES LATE SURVIVAL AFTER HEART TRANSPLANTATION: 10 YEAR Results W.S. Ring,1 J.M. DiMaio,1 M.E. Jessen,1 P.A. Kaiser,2 D.M. Meyer,1 C.L. Moncrief,2 M.A. Wait,1 T.T. Hamilton,1 K.A. Hutcheson,1 M. Karandikar,1 B.J. Baldwin,2 J.D. Boehrer,2 V.P. Horn,2 C.W. Yancy,1 1Cardiothoracic Surgery and Cardiology, University of Texas Southwestern Medical Center, Dallas, TX; 2St. Paul Medical Center, Dallas, TX
ACUTE HEART TRANSPLANT REJECTION ASSOCIATED WITH LATE STEROID WITHDRAWAL R. Husa, R. Cecere, M. Cantarovich, N. Giannetti, McGill University Health Cetner, Royal Victoria Hospital, Montreal, Quebec, Canada
Chronic immunosuppression (IMRX) with steroids after heart transplantation (HT) carries significant morbidity. We previously reported increased rejection, improved bone density and exercise tolerance, but no survival benefit at 2 years with steroid withdrawal. From 1988-96, 161 HT’s were performed using initial IMRX of Cyclosporine, Azathioprine, and Prednisone (CAP) without cytolytic induction therapy. A trial of rapid (6 mos) steroid withdrawal was begun in 1990 in patients capable of prolonged follow-up and without renal dysfunction (CAPW, N⫽88, 1990-1996). These were compared to a group without steroid withdrawal (CAP, N⫽66, 1988-1995). 7 patients were excluded due to early (⬍30-day) death unrelated to IMRX. Groups were analyzed by intention to treat with 27/88 (31%) CAPW failing to wean from steroids due to multiple or acute vascular rejections (22), leukopenia (3), pulmonary disease, or renal insufficiency. Groups were comparable with respect to donor and recipient age, size, gender, CMV status, and preop renal function. However, more CAPW patients were UNOS Status 1 (32% CAP vs 64% CAPW, p⬍.0001). With follow-up beyond 10 years, an IMRX intention to treat protocol of CAPW results in improved survival (Fig 1, p⬍.05), in spite of an increased incidence of acute rejection (Fig 2, p⬍.03). Early steroid withdrawal remains our preferred IMRX strategy after HT.
Long-term steroid use is potentially associated with multiple complications. Thus an attempt is usually made for eventual steroid discontinuation. Since long-term post-heart transplant risk of acute rejection is low, many centres do not perform routine endomyocardial biopsies (EMB) in asymptomatic heart transplant recipients beyond one year after surgery. However, the risk of acute rejection after long-term steroid withdrawal in these patients is unknown. We studied 103 patients, two to seventeen years post heart transplantation. Maintenance immunosuppression consisted of azathioprine or mycophenolate mofetil, cyclosporine microemulsion and prednisone. All patients had steroidrelated side-effects (osteoporosis, dyslipidemia, cataracts and/or hyperglycemia). Prednisone was tapered from 5.0 mg to 2.5 mg die., followed by an EMB, which was repeated after prednisone was tapered from 2.5mg to 0mg. EMBs were done within one month of tapering. No additional changes were made to any other immunosuppressive medications at the time of steroid taper or withdrawal. Ten patients (10%) had significant rejection defined as greater than or equal to ISHLT grade 2. Four patients rejected after taper from 5.0 mg to 2.5mg (two grade 2 rejections and two grade 3A), and six patients (one grade 2 and five grade 3A rejections) after discontinuation of prednisone. All rejections were asymptomatic and not associated with abnormal clinical findings. Eight rejections were treated with intravenous steroids and two with high dose oral prednisone. Subsequent biopsies all demonstrated improvement (range: grade 0 to 1A). The majority of patients (70%) had a low risk rejection profile, having no documented rejection prior to steroid tapering. Heart transplant recipients who are on long-term steroid therapy have a risk of important rejection when such therapy is withdrawn. This rejection may be clinically silent. EMB should be performed in patients after long-term steroid withdrawal so that these rejections do not progress untreated. 314 LONG-TERM FOLLOW-UP OF THREE PROSPECTIVE RANDOMIZED TRIALS COMPARING DIFFERENT ANTIBODY INDUCTION PROTOCOLS A. Zuckermann,1 D. Dunkler,1 M. Czerny,1 J. Ankersmit,1 C. Holzinger,2 E. Wolner,1 M. Grimm,1 1Department of Cardiothoracic Surgery, University of Vienna, Vienna, Austria; 2 Department of Cardiac Surgery, KH. St.Po ¨lten, St. Po ¨lten, Austria Purpose: Short-term data from randomised trials have shown significant differences in outcome between various antibody induction therapies. The purpose of this study was to investigate potential long-term influences of different antibody induction treatments. Methods: Patients who underwent three different prospective randomised trials conducted between 1987-1992 were included in this analysis. A total of 222 patients (OKT3 n⫽30, FreseniusATG (F-ATG) n⫽88, thymoglobuline (THG) n⫽77 and BT563 n⫽27) were analysed for survival, incidences of rejection, infection, cancer, graftsclerosis and adverse events. Results were
Abstracts
167
312
313
STEROID WITHDRAWAL IMPROVES LATE SURVIVAL AFTER HEART TRANSPLANTATION: 10 YEAR Results W.S. Ring,1 J.M. DiMaio,1 M.E. Jessen,1 P.A. Kaiser,2 D.M. Meyer,1 C.L. Moncrief,2 M.A. Wait,1 T.T. Hamilton,1 K.A. Hutcheson,1 M. Karandikar,1 B.J. Baldwin,2 J.D. Boehrer,2 V.P. Horn,2 C.W. Yancy,1 1Cardiothoracic Surgery and Cardiology, University of Texas Southwestern Medical Center, Dallas, TX; 2St. Paul Medical Center, Dallas, TX
ACUTE HEART TRANSPLANT REJECTION ASSOCIATED WITH LATE STEROID WITHDRAWAL R. Husa, R. Cecere, M. Cantarovich, N. Giannetti, McGill University Health Cetner, Royal Victoria Hospital, Montreal, Quebec, Canada
Chronic immunosuppression (IMRX) with steroids after heart transplantation (HT) carries significant morbidity. We previously reported increased rejection, improved bone density and exercise tolerance, but no survival benefit at 2 years with steroid withdrawal. From 1988-96, 161 HT’s were performed using initial IMRX of Cyclosporine, Azathioprine, and Prednisone (CAP) without cytolytic induction therapy. A trial of rapid (6 mos) steroid withdrawal was begun in 1990 in patients capable of prolonged follow-up and without renal dysfunction (CAPW, N⫽88, 1990-1996). These were compared to a group without steroid withdrawal (CAP, N⫽66, 1988-1995). 7 patients were excluded due to early (⬍30-day) death unrelated to IMRX. Groups were analyzed by intention to treat with 27/88 (31%) CAPW failing to wean from steroids due to multiple or acute vascular rejections (22), leukopenia (3), pulmonary disease, or renal insufficiency. Groups were comparable with respect to donor and recipient age, size, gender, CMV status, and preop renal function. However, more CAPW patients were UNOS Status 1 (32% CAP vs 64% CAPW, p⬍.0001). With follow-up beyond 10 years, an IMRX intention to treat protocol of CAPW results in improved survival (Fig 1, p⬍.05), in spite of an increased incidence of acute rejection (Fig 2, p⬍.03). Early steroid withdrawal remains our preferred IMRX strategy after HT.
Long-term steroid use is potentially associated with multiple complications. Thus an attempt is usually made for eventual steroid discontinuation. Since long-term post-heart transplant risk of acute rejection is low, many centres do not perform routine endomyocardial biopsies (EMB) in asymptomatic heart transplant recipients beyond one year after surgery. However, the risk of acute rejection after long-term steroid withdrawal in these patients is unknown. We studied 103 patients, two to seventeen years post heart transplantation. Maintenance immunosuppression consisted of azathioprine or mycophenolate mofetil, cyclosporine microemulsion and prednisone. All patients had steroidrelated side-effects (osteoporosis, dyslipidemia, cataracts and/or hyperglycemia). Prednisone was tapered from 5.0 mg to 2.5 mg die., followed by an EMB, which was repeated after prednisone was tapered from 2.5mg to 0mg. EMBs were done within one month of tapering. No additional changes were made to any other immunosuppressive medications at the time of steroid taper or withdrawal. Ten patients (10%) had significant rejection defined as greater than or equal to ISHLT grade 2. Four patients rejected after taper from 5.0 mg to 2.5mg (two grade 2 rejections and two grade 3A), and six patients (one grade 2 and five grade 3A rejections) after discontinuation of prednisone. All rejections were asymptomatic and not associated with abnormal clinical findings. Eight rejections were treated with intravenous steroids and two with high dose oral prednisone. Subsequent biopsies all demonstrated improvement (range: grade 0 to 1A). The majority of patients (70%) had a low risk rejection profile, having no documented rejection prior to steroid tapering. Heart transplant recipients who are on long-term steroid therapy have a risk of important rejection when such therapy is withdrawn. This rejection may be clinically silent. EMB should be performed in patients after long-term steroid withdrawal so that these rejections do not progress untreated. 314 LONG-TERM FOLLOW-UP OF THREE PROSPECTIVE RANDOMIZED TRIALS COMPARING DIFFERENT ANTIBODY INDUCTION PROTOCOLS A. Zuckermann,1 D. Dunkler,1 M. Czerny,1 J. Ankersmit,1 C. Holzinger,2 E. Wolner,1 M. Grimm,1 1Department of Cardiothoracic Surgery, University of Vienna, Vienna, Austria; 2 Department of Cardiac Surgery, KH. St.Po ¨lten, St. Po ¨lten, Austria Purpose: Short-term data from randomised trials have shown significant differences in outcome between various antibody induction therapies. The purpose of this study was to investigate potential long-term influences of different antibody induction treatments. Methods: Patients who underwent three different prospective randomised trials conducted between 1987-1992 were included in this analysis. A total of 222 patients (OKT3 n⫽30, FreseniusATG (F-ATG) n⫽88, thymoglobuline (THG) n⫽77 and BT563 n⫽27) were analysed for survival, incidences of rejection, infection, cancer, graftsclerosis and adverse events. Results were