Use of daclizumab decreases the frequency of early allograft rejection in de-novo heart transplant recipients

The Journal of Heart and Lung Transplantation Volume 18, Number 1

Abstracts

I I episodes (no 3A) m the Daclizumab group. Four pattents in the control group vs I in the Daclizumab group required OKT3 or ATGAM induction therapy. By Kaplan Meier and log rank analysis, time to first rejection episode was later in the Daclizumab group (p=O.oOl). Daclizumab reduced the frequency of IgM anti-HLA antlbody production from 38% to 0% (p
assessed by measurement of ejection fraction. Plasma BNP levels were measured in the supine position in all patients. RESULTS: There was no signilicant difference between the Iwo groups in terms of age, sex, pre-operative pathology or preoperative lranspulmonary gradient. Doppler-derived diastolic function parameters could be measured in I8 group A and I7 group B patients. Palienls in group A had a signilicanlly lower E:A ralio (1.09+/-0.28 vs 2.23+/-0.22. p2 or E:A ratio l-2 with MDT
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SHOULD ADVANCED RECIPIENT AGE BE CONTRAINDICATED IN CARDIAC TRANSPLANTATION? CONTINUED ANALYSIS OF A SINGLE CENTER EXPERIENCE K Hoercher, JB Young, RC Starling, LL Price, M. Banbury, NS Smedira, PM McCarthy, Cleveland Clinic Foundation. Cleveland, Ohio Purpose: Multicenter registries have demonstrated a statistically signlfnxnt decrease in survival in cardiac transplant (TX) recipients over the age of 65 years and have further suggested that this population is at increased risk for the development of coronary artery disease(CAD)in the allograft. Although advanced reciptent age remains a contraindication toTx at many centers, our institution has excluded age alone as a barrier to TX. This study was done to determine if older recipient age is an independent risk factor for early and late morbidity and mortality following cardiac TX at a single center. Methods280 adult pts underwent primary cardiac TX between January 1, 1995 and June 30. 1998. 32 pts were age 65 years or greater (65-73; mean = 69); the remaining 248 pts were age 64 years or less (I 8-64;mean=5 I). 25% of the older group versus 29% of the younger group were on LVAD support at the tmw of TX. There was a slgniflcant difference in mean donor age m the older reclplent group (43vs35p=.O3). Mean follow up is 18 months.Results:There appears to be little difference in outcomes between the two groups. Post-op length of stay(mean days=l6vsl7)and hospital mortality(3%vs5%) were similar. Actuarial survival calculated by Kaplan-Meier did not demonstrate any significant difference between the two patient groups at 3Odays (96%vs95%); 12months (96%vs88%);or 24 months (90%vs86%).Freedom from CAD was also similar between both groups of pts (84%vs83%) at 24 months of follow-up. Additionally, there was no significant difference in survival among those recipients on LVAD support. In economic terms, there were no cost differences between the two groups from the day ofTx to discharge ($94,000vs$l07,000).Conclusion: Our experience with cardiac transplantation in older recipients has not impacted negatively on morbidity or mortality when compared with the younger population. The favorable results from a single center experience with regard to this issue may be masked in a multicenter study because of inclusion of programs with a wide range of experiences. We believe TX to be a safe and effective therapy for carefully selected older patients with end stage heart fallure and should be considered as an optmn in this population. However, we also reahze that this wll present an ethical dilemma, as this practice will most likely widen the gap between the number of patients awaiting TX and the number of suitable donor hearts More direct shunting of older donors to older reclpxnts may bc advantageous.

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USE OF DACLIZUMAB DECREASES THE FREQUENCY OF EARLY ALLOGRAFT REJECTION IN DE-NOVO HEART TRANSPLANT RECIPIENTS Ainnt Beniaminovitz, Silviu Itescu, Mary Donovan, Elirabeth Burke, Julie Webb, Katherine Leitz. Niloo Edwards, Donna Man&i, Columbia Umversity, NY, NY Induction therapy using a monoclonal antibody to the IL2 receptor (Daclizumab) has been shown to decrease acute rejection episodes following renal transplantion. To investigate if a similar effect exists in cardiac allograft recipients, 42 de-nova non-sensitzed patients were randomly assigned to induction therapy with Daclizumab. Twenty-one patients received Dachzumab intravenously at 3 dose of I mg/kg withm 24 hours of transplant and every 2 weeks for a total of 5 doses. All patients received cyclosporme, prednisone and mycophenolate mofetil. Clinical endpoints followed were: survival, duration of ionotropic support, length of stay post-transplant, Incidence of InfectIon, time to first rejection, rejection frequency and severity, production of anti-HLA antibodies, and the presence of IL-2 receptor expressing T cell? in the allograft. Recipient age. gender, tschemlc time, number of donor-reclplent HLA-DR matches and CMV mismatches were similar I” both groups. There were 4 deaths in the control group vs I in the Daclizumab group (p
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THE EFFECT OF INHALED STEROIDS ON EXHALED NITRIC OXIDE IN LUNG TRANSPLANT RECIPIENTS WITH LYMPHOCYTIC BRONCHITIS. A De Sovza. T Small. A J Fisher, PA Corris. Department of Respiratory Medicine, Freeman Hospital, Newcastle-upon-Tyne, United Kingdom. We have previously validated exhaled nitric oxide (eN0) as a marker of lower respiratory tract NO production indicating its potential as a useful surrogate marker of airway inflammation. We have also demonstrated that in lung transplant recipients eN0 is raised in lymphocytic bronchitis (LB), a risk factor for obliterative bronchiolitis (OB), but not in acute vascular rejection alone. Previous studies have shown that in clinically stable recipients that eN0 levels are stable but there is a wide inter-patient variability. We hypothesized that inhaled steroids may reduce airway inflammation in recipients with LB who were receiving systemic immunosuppression including oral steroids and that eN0 may be a useful non-invasive measure of inflammation. In a prospective study II lung allografi recipients (6 male, 5 female) who developed biopsy proven LB and had no evidence of infection were treated with 800 mcg bd of inhaled budesonide via a torbohaler. Nitric Oxide levels pre diagnosis were available with at least 2 readings separated by more than one week in 9 patients and a single reading in the other 2 patients. Nitric oxide levels (mean -t SEM) prior to the diagnosis of LB were 6.65ppm (? I .2) and the FEVI was 2.581( * 0.31). At the time of biopsy when the diagnosis of LB was made, eN0 had risen to 14.1 lppm (+ 2.58) and FEVI had fallen to 2.341 (+ 0.37). Afier at least 1 months treahnent with inhaled steroid the eN0 levels fell to 7.65ppm (i 1.65) and FEVI rose to 2.51 ( f 0.37). Significant differences in eN0 levels from baseline compared to those at time of diagnosis of LB were noted (p =0.03 paired T-test) and were associated with significant fall in FEVI (p=O.O3). There was no significant difference in either eN0 or FEVI comparing pre-diagnosis and post treatment (p= 0.35 and 0.52 respectively). Three patients were identified retrospectively who had biopsy proven LB and who did not receive inhaled steroid. In these recipients eN0 levels remained elevated over the observation period (mean NO =10.7ppm). We conclude that eN0 is raised in patients with isolated lymphocytic bronchitis and this is associated with a fall in FEVI. The fall in FEVl and the rise in eN0 can be reversed with inhaled steroids. The strategy of adding inhaled steroids may reduce their risk of OB. Funded by the British Lung Foundation.

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PROSPECTIVE RANDOMIZED TWO-CENTER TRIAL COMPARING CYCLOSPORINE A (CSA) VS. TACROLIMUS (TAC), IN COMBINATION WITH MYCOPHENOLATE MOFETIL (MMF) AND STEROIDS AFTER LUNG TRANSPLANTATION (LTX). W. Klepetko’, H. Reichenspurne?, A. Zuckermann’, B. Meise?, T. Birsan’, H. Treede’. N. Kupilik’, F. Ku?, W. Wisser’, ’ University of Vienna, Vienna, Austria, and ‘Ludwig-Maximilian University, Munich, Germany Background: CsA and Tat have been used mostly rn combination with Azathioprine (Aza) as primary immunosuppression after LTX. Benefit or risk deriving from the combination of these drugs with MMF are yet unknown. Methods: In a prospective P-center open randomized trial, CsA+MMF+steroids were compared to Tac+MMF+steroids after primary LTX. All patients underwent induction therapy with rabbit-ATG. The two groups were compared with regard to patient survival, acute allcgraft rejection (AAR), infectious episodes and side effects. Results: Between 9/97 and 7/98. 42 LTX recipients were randomized to receive either CsA (n=20) or Tat (n=22). Groups were comparable with regard to age, gender, transplant procedure, and CMV match. Mean follow-up was 1521t84 and 205&l 01 days, respectively (PNS). Three- and B-months survival was similar in the two groups (0.95 vs. 0.94, and 0.85 vs. 0.81, respectively; P=NS). Two patients from the CsA group were retransplanted for early grafi failure on days 22 and 50, respectively. Freedom from AAR at 3 and 6 months was 0.60 vs. 0.64 and 0.36 vs. 0.58, respectively (PNS). Mean number of treated AAR episodes/l00 patient-days was 0.42+0.60 in the CsA group vs. 0.28iO.38 in the Tat group (P=NS). One patient from the CsA group required switch to Tat to control ongomg rejection, while no