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Predictors and outcomes of acute humoral rejection treated with plasmapheresis in heart transplant recipients
The Journal of Heart and Lung Transplantation Volume 22, Number 1S
Abstracts
20). We analyzed actuarial survival as well as the incidence of the main early and late complications. Main results are shown in the table. Age Group
<60 years 60–70 years 65–70 years p A vs B p A vs C (A) (B) (C)
% ARE ⬎ 3a 70% ARE per patient 2.0 ⫾ 1.8 % Major infection 38% % Malignancy 14% Graft Vessel Disease 10% Diabetes mellitus 13% 1 year survival 77% 5 year survival 68% 10 year survival 60
58% 1.5 ⫾ 1.9 33% 19% 8% 25% 70% 63% 53
47% 1.2 ⫾ 1.6 21% 17% 58% 39%
0.04 0.04 NS NS NS 0.02 0.12 NS NS
0.07 0.05 NS NS 0.10 0.01
ARE, Acute rejection episode.
In conclusion, recipients older than 60 did not show significant differences in long-term survival when compared to younger ones. This group showed a lower incidence of acute rejection, but diabetes mellitus was more frequent among them. On the contrary, the subgroup of patients older than 65 showed a significantly lower survival rate at 5-year follow-up when compared to the other age groups. This results support the policy of admitting selected patients up to 65 years old to HTx waiting lists, but disadvice inclusion of most patients beyond that age. 294 PREDICTORS AND OUTCOMES OF ACUTE HUMORAL REJECTION TREATED WITH PLASMAPHERESIS IN HEART TRANSPLANT RECIPIENTS W.E. Uber,1 S.L. Padgett,1 A.B. VanBakel,2 A.J. Crumbley,3 D.S. Feldman,2 J.S. Ikonomidis,3 K.N. Simpson,1 N.L. Pereira,2 1 Pharmacy, MUSC, Charleston, SC; 2Cardiology, MUSC, Charleston, SC; 3Cardiothoracic Surgery, MUSC, Charleston, SC Purpose: Acute humoral rejection (HR) is characterized by cardiac allograft dysfunction despite a minimal lymphocytic infiltrate on biopsy. Graft loss is high despite augmentation of immunosuppression and therefore identification of predictors of HR is important. The objectives of this study were to identify clinical variables that may be useful in predicting HR in heart transplant (HT) recipients and review our experience of treatment outcome in these patients. Methods: A retrospective review of 182 patients transplanted from 1992-2000 at our institution was performed using archival data from the UNOS database and the patients medical records. There were 20 patients who were diagnosed and treated for HR with plasmapheresis and augmented immunosuppression. This group was compared to 80 HT recipients serving as controls. Data analysis was performed using multivariate logistic regression and chi-square test. Results: There were 35 HT recipient variables examined of which recipient age less than 55 years, female gender, and increased number of cellular rejection episodes were associated with a 6.7 fold (95% CI 1.4, 31.0), 10.5 fold (1.9, 25.7) and 2.5 fold (1.2, 5.4) increased risk of HR respectively. HLA antigen mismatches between the donor and recipient did not predict HR. There were no significant differences in the annual rates of malignancy or infection between the HR group and controls. However the patients with HR had 1.7 times the incidence of graft arteriosclerosis (p ⫽ .003). Five year survival rates by KaplanMeier analysis in patients with HR was 50% compared to 80% in controls. Conclusion: Our results suggest that younger age, female gender and increased frequency of cellular rejection episodes predict HR in HT recipients. The incidence of graft arteriosclerosis is higher in these patients and the outcome despite treatment with plasmapheresis and augmented immunosuppression remains poor.
S169
295 THE IMPACT OF INDUCTION THERAPY AND THE DONOR SPECIFIC CROSSMATCH ON OUTCOME AFTER HEART TRANSPLANTATION E. Devyatko,1 A. Zuckermann,1 D. Dunkler,1 M. Ruzicka,1 A. Bohdjalian,1 G. Wieselthaler,1 M. Grimm,1 1Department of CardioThoracic Surgery, University Clinic of Vienna, Vienna, Austria HLA matching is associated with better graft survival in renal transplantation. Its role in cardiac transplantation (Tx) is still unclear. Nothing is known about the potential impact of induction therapy on outcome of well vs. poorly HLA matched cardiac recipients. The combined effect of histocompatibility and type of induction was analysed to determine their influence on graft survival, incidence of rejection and severe graft sclerosis in cardiac recipients. Donor HLA crossmatching was performed for 849 cardiac Tx. Completed data for HLA-A,-B and -DR mismatches exist for 623 patients. Postoperative management consists of induction and triple immunosupression with calcineurin inhibitors, azathioprine or MMF and corticosteroids. 593 patients, collected in Group 1, were treated with thymoglobuline and other 256 recipients (Group 2) with different poly- (ATG Fresenius, ATGAM) or monoclonal (OKT-3, BT563) antibodies. The cohort had a mean number of 5.03⫾0.93 (5) HLA mismatches. The distribution of mismaches (MM) to different HLA loci was as follow: (1). HLA-A: 0 MM-7%, 1 MM-35%, 2 MM-58%; (2). HLA-B: 0 MM-1%, 1 MM-16%, 2 MM-83%; (3). HLA-DR: 0 MM-3%, 1 MM-23%, 2 MM-74%. Statistical analysis demonstrates significantly better results for the Group 1 in : overall survival for HLA-A zero-MM (p ⫽ 0.0011) , HLA-A 2-MM (p ⫽ 0.02), HLA-B 2-MM (p ⫽ 0.002), HLA-DR 2-MM (p ⫽ 0.03) ; freedom from severe graft sclerosis for HLA-B 2-MM (p ⫽ 0.04); freedom from clinical rejection for HLA-A 1-MM (p⫽0.03), HLA-A 2-MM (p ⫽ 0.0001), HLA-B 1-MM (p ⫽ 0.037), HLA-B 2-MM (p ⬍ 0.0001), HLA-DR 1-MM (p ⫽ 0.0005), HLA-DR 2-MM (p ⬍ 0.0001). Our experience demonstrates considerable positive impact of induction therapy with thymoglobuline compared with another types of induction on outcome, degree of acute and chronic rejection after heart transplantation despite of HLA-mismatch. 296 ELEVATED CXCR4 LEVELS ON PERIPHERAL BLOOD T-CELLS IN HEART TRANSPLANTATION PATIENTS P. Athanassopoulos,1 L.M.B. Vaessen,2 W. Weimar,2 A.H.M.M. Balk,3 A.P.W.M. Maat,1 A.J.J.C. Bogers,1 1Cardiothoracic Surgery, Erasmus M.C., Rotterdam; 2Internal Medicine, Erasmus M.C., Rotterdam; 3 Cardiology, Erasmus M.C., Rotterdam, Netherlands We examined chemokine receptor (CKR) expression in fresh peripheral whole blood of congestive heart failure patients before and after heart transplantation (HTx). CKR expression on T-cells and monocytes plays a key role in initiating immune responses. CXCR4, a constitutive CKR involved in naive T-cell homing to lymphoid organs may prove interesting in this context. Six patients (mean age: 53 years, range 39-62) with cardiomyopathy were compared to 6 healthy controls (mean age: 48.8 years, range 31-60). All patients received induction and triple therapy. Heparinized peripheral blood of patients was collected preHTx, and at 10, 20 and 30 days post-HTx. Control blood samples were collected at corresponding time-points. Levels of CCR-1, -2, -3, -5, -6 and CXCR-1,-2,-3,-4 were measured by flow cytometry. Data were expressed as median MESF units (molecules of equivalent soluble
Abstracts
20). We analyzed actuarial survival as well as the incidence of the main early and late complications. Main results are shown in the table. Age Group
<60 years 60–70 years 65–70 years p A vs B p A vs C (A) (B) (C)
% ARE ⬎ 3a 70% ARE per patient 2.0 ⫾ 1.8 % Major infection 38% % Malignancy 14% Graft Vessel Disease 10% Diabetes mellitus 13% 1 year survival 77% 5 year survival 68% 10 year survival 60
58% 1.5 ⫾ 1.9 33% 19% 8% 25% 70% 63% 53
47% 1.2 ⫾ 1.6 21% 17% 58% 39%
0.04 0.04 NS NS NS 0.02 0.12 NS NS
0.07 0.05 NS NS 0.10 0.01
ARE, Acute rejection episode.
In conclusion, recipients older than 60 did not show significant differences in long-term survival when compared to younger ones. This group showed a lower incidence of acute rejection, but diabetes mellitus was more frequent among them. On the contrary, the subgroup of patients older than 65 showed a significantly lower survival rate at 5-year follow-up when compared to the other age groups. This results support the policy of admitting selected patients up to 65 years old to HTx waiting lists, but disadvice inclusion of most patients beyond that age. 294 PREDICTORS AND OUTCOMES OF ACUTE HUMORAL REJECTION TREATED WITH PLASMAPHERESIS IN HEART TRANSPLANT RECIPIENTS W.E. Uber,1 S.L. Padgett,1 A.B. VanBakel,2 A.J. Crumbley,3 D.S. Feldman,2 J.S. Ikonomidis,3 K.N. Simpson,1 N.L. Pereira,2 1 Pharmacy, MUSC, Charleston, SC; 2Cardiology, MUSC, Charleston, SC; 3Cardiothoracic Surgery, MUSC, Charleston, SC Purpose: Acute humoral rejection (HR) is characterized by cardiac allograft dysfunction despite a minimal lymphocytic infiltrate on biopsy. Graft loss is high despite augmentation of immunosuppression and therefore identification of predictors of HR is important. The objectives of this study were to identify clinical variables that may be useful in predicting HR in heart transplant (HT) recipients and review our experience of treatment outcome in these patients. Methods: A retrospective review of 182 patients transplanted from 1992-2000 at our institution was performed using archival data from the UNOS database and the patients medical records. There were 20 patients who were diagnosed and treated for HR with plasmapheresis and augmented immunosuppression. This group was compared to 80 HT recipients serving as controls. Data analysis was performed using multivariate logistic regression and chi-square test. Results: There were 35 HT recipient variables examined of which recipient age less than 55 years, female gender, and increased number of cellular rejection episodes were associated with a 6.7 fold (95% CI 1.4, 31.0), 10.5 fold (1.9, 25.7) and 2.5 fold (1.2, 5.4) increased risk of HR respectively. HLA antigen mismatches between the donor and recipient did not predict HR. There were no significant differences in the annual rates of malignancy or infection between the HR group and controls. However the patients with HR had 1.7 times the incidence of graft arteriosclerosis (p ⫽ .003). Five year survival rates by KaplanMeier analysis in patients with HR was 50% compared to 80% in controls. Conclusion: Our results suggest that younger age, female gender and increased frequency of cellular rejection episodes predict HR in HT recipients. The incidence of graft arteriosclerosis is higher in these patients and the outcome despite treatment with plasmapheresis and augmented immunosuppression remains poor.
S169
295 THE IMPACT OF INDUCTION THERAPY AND THE DONOR SPECIFIC CROSSMATCH ON OUTCOME AFTER HEART TRANSPLANTATION E. Devyatko,1 A. Zuckermann,1 D. Dunkler,1 M. Ruzicka,1 A. Bohdjalian,1 G. Wieselthaler,1 M. Grimm,1 1Department of CardioThoracic Surgery, University Clinic of Vienna, Vienna, Austria HLA matching is associated with better graft survival in renal transplantation. Its role in cardiac transplantation (Tx) is still unclear. Nothing is known about the potential impact of induction therapy on outcome of well vs. poorly HLA matched cardiac recipients. The combined effect of histocompatibility and type of induction was analysed to determine their influence on graft survival, incidence of rejection and severe graft sclerosis in cardiac recipients. Donor HLA crossmatching was performed for 849 cardiac Tx. Completed data for HLA-A,-B and -DR mismatches exist for 623 patients. Postoperative management consists of induction and triple immunosupression with calcineurin inhibitors, azathioprine or MMF and corticosteroids. 593 patients, collected in Group 1, were treated with thymoglobuline and other 256 recipients (Group 2) with different poly- (ATG Fresenius, ATGAM) or monoclonal (OKT-3, BT563) antibodies. The cohort had a mean number of 5.03⫾0.93 (5) HLA mismatches. The distribution of mismaches (MM) to different HLA loci was as follow: (1). HLA-A: 0 MM-7%, 1 MM-35%, 2 MM-58%; (2). HLA-B: 0 MM-1%, 1 MM-16%, 2 MM-83%; (3). HLA-DR: 0 MM-3%, 1 MM-23%, 2 MM-74%. Statistical analysis demonstrates significantly better results for the Group 1 in : overall survival for HLA-A zero-MM (p ⫽ 0.0011) , HLA-A 2-MM (p ⫽ 0.02), HLA-B 2-MM (p ⫽ 0.002), HLA-DR 2-MM (p ⫽ 0.03) ; freedom from severe graft sclerosis for HLA-B 2-MM (p ⫽ 0.04); freedom from clinical rejection for HLA-A 1-MM (p⫽0.03), HLA-A 2-MM (p ⫽ 0.0001), HLA-B 1-MM (p ⫽ 0.037), HLA-B 2-MM (p ⬍ 0.0001), HLA-DR 1-MM (p ⫽ 0.0005), HLA-DR 2-MM (p ⬍ 0.0001). Our experience demonstrates considerable positive impact of induction therapy with thymoglobuline compared with another types of induction on outcome, degree of acute and chronic rejection after heart transplantation despite of HLA-mismatch. 296 ELEVATED CXCR4 LEVELS ON PERIPHERAL BLOOD T-CELLS IN HEART TRANSPLANTATION PATIENTS P. Athanassopoulos,1 L.M.B. Vaessen,2 W. Weimar,2 A.H.M.M. Balk,3 A.P.W.M. Maat,1 A.J.J.C. Bogers,1 1Cardiothoracic Surgery, Erasmus M.C., Rotterdam; 2Internal Medicine, Erasmus M.C., Rotterdam; 3 Cardiology, Erasmus M.C., Rotterdam, Netherlands We examined chemokine receptor (CKR) expression in fresh peripheral whole blood of congestive heart failure patients before and after heart transplantation (HTx). CKR expression on T-cells and monocytes plays a key role in initiating immune responses. CXCR4, a constitutive CKR involved in naive T-cell homing to lymphoid organs may prove interesting in this context. Six patients (mean age: 53 years, range 39-62) with cardiomyopathy were compared to 6 healthy controls (mean age: 48.8 years, range 31-60). All patients received induction and triple therapy. Heparinized peripheral blood of patients was collected preHTx, and at 10, 20 and 30 days post-HTx. Control blood samples were collected at corresponding time-points. Levels of CCR-1, -2, -3, -5, -6 and CXCR-1,-2,-3,-4 were measured by flow cytometry. Data were expressed as median MESF units (molecules of equivalent soluble