Heart transplant recipients in whom high levels of lymphocytotoxic antibodies directed towards a spectrum of histocompatibility antigens develop frequently represent difficult management problems. Recipients of multiple transplants and multiparous females generally form higher levels of panel reactive antibodies, which have been associated with fatal rejection episodes and accelerated graft atherosclerosis. In this study, two multiple transplant patients with preexistent high levels of panel reactive antibodies and two multiparous women who were considered at risk of sensitization were treated with a new form of immunotherapy termed photochemotherapy in addition to conventional immunosuppression. High levels of panel reactive antibodies have been reduced, and patients have suffered few rejection episodes and no infectious complications. This preliminary experience shows that the addition of photochemotherapy to conventional regimens may improve the clinical course of hypersensitized transplant patients without additional immunosuppressive risk.

Adult↗

PubMedDate not supplied

Relation of HLA antibodies and graft atherosclerosis in human cardiac allograft recipients.

Although cyclosporine has helped make heart transplantation a clinical reality, long-term survival remains limited by rejection and graft atherosclerosis. We have previously demonstrated the development of alloreactive lymphocytotoxic antibodies in baboon recipients of heterotopic heart transplants despite cyclosporine administration. The hypothesis of the present study is that cyclosporine-treated human heart transplant recipients are also capable of generating strong humoral immune responses that might adversely affect clinical outcome. Serial serum specimens from 240 heart transplant recipients were tested against a reference panel of 70 cells for anti-HLA lymphocytotoxic antibodies. Patients with serum panel reactive antibody levels greater than 10% were considered antibody producers, whereas those with serum panel reactive antibody levels less than 10% were considered nonproducers. To establish the time course of post-transplantation sensitization, we have tested anti-HLA antibodies in sequential sera at 3-month intervals after transplantation. The 4-year actuarial survival rate of those patients whose panel reactive antibody levels were greater than 10% during the first 6 months after transplantation was 70%, whereas the survival rate of patients whose levels were less than 10% during this time was 93%. The results were significantly different (p less than 0.01). Further heterogeneity among the patients was demonstrated by differential analysis of survival in patients who showed (1) panel reactive antibody levels less than 10% in any of the sera obtained during the first year after transplantation, (2) panel reactive antibody levels greater than 10% in sera obtained during the first 6 months but not thereafter, and (3) panel reactive antibody levels greater than 10% throughout the first year after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

Predictors of survival after repeat heart transplantation. The Registry of the International Society for Heart and Lung Transplantation, and Contributing Investigators.

To examine factors potentially predictive of outcome after repeat heart transplantation, data were analyzed for 449 recipients of second allografts reported to the registry of the International Society for Heart and Lung Transplantation and a matched group of 421 primary transplant recipients. Survival was markedly decreased in repeat transplantation patients (1 year actuarial survival rate, 48% vs 79%; p less than 0.001). Univariate analysis showed no impact on survival of recipient age or gender, ischemic time, or transplant center experience. Accelerated coronary artery disease as the cause of allograft failure, longer interval between transplants, lack of preoperative mechanical assistance, and second transplantation after 1985 were predictive of increased survival after repeat transplantation. An "ideal candidate" defined by these predictive variables had a 1-year survival rate of 64%. In addition to the International Society for Heart and Lung Transplantation registry, a multicenter data base was developed with data for 125 repeat transplant recipients and 1325 primary transplant recipients at 13 transplant centers in the United States. In this group of patients the 1-year survival rate was greater than that in the International Society for Heart and Lung Transplantation registry (60% vs 48%), and the impact of the predictive variables listed previously was decreased. The incidence of rejection, infection, and accelerated coronary artery disease was not different between secondary and primary allograft recipients. Nonskin malignancies occurred more frequently in repeat transplantation patients (8% vs 4%; p less than 0.05). Recipients of second allografts were more likely to have major surgical complications, had a higher level of sensitization to HLA antigens, and were more likely to have a positive donor-specific crossmatch (17% vs 2%). A trend toward improved survival was noted in patients with repetition in the second donor of mismatched HLA antigens present in the first donor (1-year survival rate of 68% vs 47%; p = 0.06). We conclude that longer interval between transplants, accelerated coronary artery disease as cause of allograft loss, and lack of preoperative mechanical assistance are predictive of longer survival after repeat transplantation. Nonetheless, the "ideal candidate" for repeat transplantation has an anticipated survival rate significantly less than that expected for primary transplant recipients.

Adult↗

PubMedDate not supplied

Influence of HLA mismatch on rejection after heart transplantation: a multiinstitutional study. The Cardiac Transplant Research Database Group.

HLA mismatch has been shown to influence survival after heart transplantation. No large multicenter study has examined the effect of HLA mismatch on cardiac allograft rejection. HLA mismatch and other potential risk factors for rejection were analyzed in data from 27 institutions (1719 patients) participating in the Cardiac Transplant Research Database between January 1, 1990, and June 30, 1992. Complete HLA information on the A, B, and DR loci was available for both donor and recipient in 1190 patients. Of these, 619 (52%) had five or six mismatches; 68 (6%) had zero, one, or two mismatches. The mean number of mismatches was 4.4 and did not differ, regardless of donor-recipient race match (4.3 versus 4.8, p = 0.19). According to multivariate analysis, risk factors for time to first rejection included younger recipient age (p < 0.0001), female gender of both donor and recipient (p < 0.0006), number of HLA mismatches (p = 0.013) and black recipient race (p < 0.004). Patients with zero, one, or two mismatches (n = 67) had a 54% freedom from rejection at 1 year versus 36% for patients with three or more mismatches (n = 1005, p = 0.02). HLA mismatch number did not affect time to first rejection or rejection frequency among black patients. Risk factors (by multivariate analysis) for death or retransplantation because of rejection included female recipient gender (p = 0.008) and black recipient race (p = 0.006). The probability of rejection-related death or retransplantation by 2 years was 0% with zero, one, or two HLA mismatches versus 5% for three to six mismatches (p = 0.14). These findings should stimulate further investigation of methods to clarify the HLA effect in heart transplantation and eventually the use of HLA typing in donor-recipient selection.

Actuarial Analysis↗

PubMedDate not supplied

Myocardial perfusion scintigraphy in heart transplant recipients with and without allograft atherosclerosis: a comparison of thallium-201 and technetium 99m sestamibi.

Our objectives were to assess the comparative value of thallium-201 and technetium 99m sestamibi for the detection of cardiac allograft atherosclerosis and the left ventricular ejection fraction response to exercise in heart transplant recipients with and without allograft atherosclerosis. Allograft atherosclerosis is the critical factor limiting long-term survival in heart transplant recipients. Annual coronary angiography is invasive and expensive. A noninvasive test to detect allograft atherosclerosis would be clinically useful. Treadmill exercise testing followed by myocardial perfusion single-photon computed tomographic imaging was performed in 25 heart transplant recipients. All patients underwent coronary angiography. Group 1 (13 patients) had angiographic coronary artery disease; group 2 (12 patients) did not. Eighteen patients underwent two exercise tests to equivalent work loads with thallium-201 and technetium 99m sestamibi; seven patients underwent only thallium-201 imaging. First-pass left ventricular ejection fraction was measured during injection of technetium 99m sestamibi. In group 1, 10 of 13 patients had abnormal thallium-201 scans. There was no significant difference in the number of patients who had abnormal thallium-201 (7/10) and technetium 99m sestamibi scans (6/10). Fifty-two percent (12/23) of discordantly scored segments were reversible on thallium-201 and fixed on technetium 99m sestamibi imaging compared with the opposite (0%; 0/23) (p < 0.01). All patients in group 2 had normal perfusion scans. There were no false-positive scans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗