Search PubMed⌕ Search

Biomedical subjects

J Cicciarelli

Publications and source records attributed to J Cicciarelli.

At least 37 records · Page 2Linked to original sources

HLA matching: univariate and multivariate analyses of UNOS Registry data.

1. Black transplant recipients showed little or no matching effect when HLA-A, B, and DR antigens matched. This may have been due in part to differences in serologically defined antigens found in Black populations. 2. There was a statistically significant (p less than 0.001 for best vs worst match) matching effect in White transplant recipients that occurred at 3 months following grafting and continued through 3 years follow-up. These patients had better graft survival for both 5 and 6, compared to 3 and 4, or as compared to 0-, 1-, and 2-match transplants; the corollary groups for mismatched transplants were also significantly different. At 3 years, there was a 20% difference in graft survival from the best- to the worst-matched transplants. Earlier this difference was 7-10% but significantly different. 3. When the HLA Class I parent antigens as defined in the Materials and Methods section were eliminated, there was an increase in graft survival for the best-matched transplants. This was postulated to occur because of better matching obtained by matching the well-defined HLA specificities. 4. With hierarchy matching, possibly there was a stronger effect of matching HLA Class II antigens at 3 months; however, this effect was quickly lost at 1 and 3 years, and data that support early graft survival advantages by matching Class II antigens were inconclusive. Most importantly, there was a threshold matching effect that showed transplant recipients with 4 or more HLA matches or 2 or less mismatches had significantly better short- and long-term outcome than the poorer-matched groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

UNOS Registry data: effect of transfusions.

1. First cadaver White transplant recipients had a 4-5% increase in graft survival associated with transfusions compared with nontransfused recipients (p less than 0.001). The effect, although small, was significant, occurred at 3 months, and was evident at 1 year. This early effect (3 months) was also noted in regraft transplant recipients, living-related recipients, and 1-haplotype match transfused patients. 2. African-American and Hispanic transplant recipients did not show a transfusion effect. Indeed, African-American transplant recipients showed a reverse transfusion effect, which is in contrast to other previously reported UCLA Registry data. 3. The effect of during-transplant transfusions was negligible (ie, a 1% increase in graft survival). Additionally, one-fourth of all recipients had perioperative transfusions. 4. A transfusion effect was not shown within HLA matching for Class I antigens; similarly, little transfusion effect was found within matching groups for Class II antigens. Again, this contrasts with reported UCLA Registry data which indicated that the transfusion effect had a 10-15% difference in graft survival between the non- and transfused individuals in the 2-mismatch HLA Class II antigen group. 5. One of the most important effects on graft survival is donor age, and the preliminary data indicate that transfusions may help graft function in recipients of older donor kidneys. However, there are very few recipients in this older donor category. 6. The incidence of graft rejection was lower in transfused recipients. Additionally, graft rejection episodes remain a very potent indicator of transplant survival. That is, patients having graft rejection at 3 months showed a 20-25% lower 1-year graft survival rate than those without rejection. There were indications that there was less severe graft rejection in transfused patients; however, this could only be shown if graft rejection occurred at discharge and was not evident at 3 months or 6 months posttransplant. 7. SCr was the best indicator of 1-year graft function, even better than the presence or absence of rejection. Lower SCr levels were found in higher frequency in transfused patients. 8. There was a slight increase in graft survival associated with transfusion and PRA in first-transplant recipients, and in the PRA-positive and PRA-negative groups, there was a trend toward lower graft survival for recipients with antibodies. In regrafts, transfused recipients who did not make antibodies had a 5-10% better graft survival than the nontransfused recipients without antibodies. Perhaps this indicates that transplant candidates who did not make cytotoxic antibodies after being transfused were nonresponders.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Clinical kidney transplants, 1988.

1. The one-year graft survival rate of cadaver donor transplants has increased from about 40% in 1965 to almost 80% in 1988. Much of the improvement lies in the reduction of the one-month failure rates, which went down from one quarter in 1965 to 10% in 1988. 2. Kidneys that failed to function in the first month occurred in 5% of first graft patients without cytotoxins and increased to 9% if cytotoxins to more than 50% of the random panel were present. The non-function rate was 9% in regrafted patients without antibodies and double (18%) in those with a PRA of less than 50%. 3. Some indication that the harmful antibodies can be detected by flow cytometry is provided by the fact that low graft survival rates resulted when transplants were done across a positive flow cytometry crossmatch in sensitized patients and in second graft recipients. In non-sensitized patients and in first graft patients, flow cytometry crossmatches against T cells were of no value. 4. The difference between first grafts, second grafts and transplants into sensitized patients disappeared when the grafts that did not function at one month were removed. 5. Cold ischemia time up to 36 hours had no effect on 1-3-year survival rates. Cold ischemia had relatively little effect even on delayed function in first transplants. However, in regrafts and in grafts into patients with preformed cytotoxins, increasing cold ischemia resulted in an increased incidence of delayed function.(ABSTRACT TRUNCATED AT 250 WORDS)

Graft Survival↗

Overview and epitope matching.

1. Kidney graft survival rates have stabilized over the past 4 years, suggesting that gains achieved with CsA have plateaued. The overall 1-year graft survival is 77% for first cadaver donor transplants, 90% for parental donors, and 93% for HLA-identical sibling donors. Patient survival for all categories is now over 95%. 2. The UNOS 6-antigen match program has resulted in outstanding graft survivals. Of 88 kidneys which were transplanted into first graft recipients, the 6-antigen match kidney had a 1-year graft survival of 91% compared to 74% for the contralateral kidney transplanted locally (p less than 0.008). 3. In highly sensitized patients with more than 80% PRA the shipped 6-antigen matched kidney had a 91% 1-year graft survival rate compared to 72% survival in comparable control patients from the registry (p less than 0.005). In patients with less than 80% PRA, 6-antigen matched kidneys had 90% 1-year graft survival compared to 80% in controls (p less than 0.00001). 4. The spread of 1-year graft survival rates at 68 centers that performed more than 100 transplants was 63-94%. The cumulative graft survival of 6-antigen matches performed at 129 different centers was 90%. Thus, the strong center effect was neutralized by the use of matched transplants. 5. In contrast to the 1% of patients who would receive O-B,DR mismatched transplants on a random basis, if kidneys were shared in the national pool, 74% could receive such a transplant. We therefore propose that a keep one-share one policy be adopted for all kidneys harvested in the United States. If no 0-B,DR mismatched patient is available, both kidneys will be kept by the harvesting center. Since 63% of kidneys are currently being shared with other centers for various reasons, the 75% sharing suggested by the new system should not impose a hardship on transplant centers. The UNOS payback agreement will be replaced by this agreement by which shipping will be done only to achieve excellent matches. 6. In order to achieve a better method of excluding the worst mismatches, an attempt was made to develop a new method of mismatching using amino acid sequences of the HLA specificities. Donor and recipient types can be converted to amino acid sequences and the mismatching done on the basis of amino acids of mismatch at each residue or position. For each residue, specific combinations of amino acid substitutions were examined individually to determine their effect on graft survival. From these studies, a list of "immunogenic" amino acids was prepared, and graft survival was then computed for increasing numbers of amino acids of mismatch.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Living-related donor kidney transplants.

1. Black kidney graft recipients do poorly when compared to Caucasians and Asians. This effect is significant for both Black 2-haplotype identical and 1-haplotype identical sibling transplants. Since 1984 graft survival in Caucasian siblings was 90% at 3 years for 2-haplotype matches and 80% at 3 years for 1-haplotype matches. 2. CsA has had a 10% effect in 1-haplotype sibling transplants comparing the results from 1984 through 1989 to 1978 through 1983. The CsA effect is about a 5% difference in HLA-identical transplants. 3. Diabetic patients transplanted after 1984 had a significantly poor graft survival which was ameliorated when treatment was equivalent to ESRD patients with glomerulonephritis and pyelonephritis use of CsA in more recent times. 4. The transfusion effect was significant in 2-haplotype and 1-haplotype transplants in the 1978 to 1983 period and is now not significant in any LRD transplant categories. 5. HLA panel-reactive antibody did not effect graft survival of LRD transplants. 6. CsA has a significant effect on 1-haplotype transplants but no effect on 2-haplotype transplants.

Blood Transfusion↗

Long-term survival of kidney grafts.

1. In the long-term period, the half-life effectively measured loss rate. For HLA-identical sib donors the half-life was 25 years; for parental donors, 13 years; and for cadaver donors, 8 years (now possibly 11 years). 2. HLA-A,B,DR matching exerted the greatest effect on half-life, for a half-life of 17 years was achieved for cadaver donors. This rate was not quite as high as that for A,B,DR matched siblings but was higher than the one haplotype mismatched parental donor transplants. 3. Caucasian recipients had a half-life of 8 years compared to 5 years for black recipients. 4. Excellent centers had a 10-year half-life compared to 5 years for fair centers. 5. Cold ischemia time over 24 hours, recipient age over 55, and donor age of 50-60 had a small effect on the half-life in the order of 1 to 3 years. 6. Among the short-term factors that affect the 1-year graft survival, there was a 12% difference between excellent and fair centers. An 11% difference between A,B,DR matched transplants and 6 A,B,DR mismatched grafts was noted. First-cadaver donor grafts had a 10% higher graft survival at 1-year than second grafts. Other factors together with the difference in 1-year graft survival between the extremes were as follows: sensitization 9%, race 8%, transfusion 6%, donor age 6%, diabetic 3%, recipient age 3% and cold ischemia 1%. Thus more factors affect short-term survival than long-term survival.

Cohort Studies↗

An update on HLA matching, including HLA "epitope" matching: a new approach.

1. HLA mismatching for -A, -B, and DR loci was updated from the UCLA Transplant Registry and showed a strong effect at 1, 2, and 3 years posttransplant. The effect of mismatching was most prominent in the zero-mismatched groups compared to 1 or more mismatched for HLA-A, -B, and -DR. 2. Patient survival was analyzed as a function of HLA matching and shown to be significantly improved in comparison to those groups of patients that were more poorly matched. The better patient survival is postulated to be a function of fewer rejection episodes and decreased amount of immunosuppression necessary for transplant function in better-matched groups of patients. 3. HLA-A, -B, and -DR epitope matching was considered on the basis of serological crossreactivity for the A and B loci and oligonucleotide homologies for the DR locus. Epitope matching showed that there was a 15% difference between the zero mismatched and the over 25 mismatched recipient groups, thus increasing range and resolution of the analysis of the zero versus very highly mismatched recipient combinations. HLA epitope matching is an important first step in determining the immunogenicity of the homologies and disparities among the HLA-A, -B, and -DR antigens.

Actuarial Analysis↗

Living donor kidney transplants.

1. Whites showed an increase in graft survival in the 2-haplotype matched transplant recipients compared to black recipients at 1-, 2-, and 3-years posttransplant. The difference was not found in the Asian population. Comparing 1-versus 2-haplotype matched transplants showed an increasing statistical significance at yearly intervals, indicating that there was increased HLA chromosome matching effect at 2 and 3 years. Additionally, 2-haplotype matched transplant regrafts showed similar results to first grafts; however, 1-haplotype matched regrafts did poorly relative to 1-haplotype matched first grafts. 2. Living nonrelated transplants and 0-haplotype matched transplants did well initially at 1-year graft survival but there was a decrease in graft survival in these transplant groups at 2 and 3 years. 3. Sensitized patients who received transplants from their mother or father showed an increase in transplant survival in the former and decreased transplant survival in the latter. This may be associated with the exposure in utero of the recipient to the noninherited maternal antigens, thus allowing the better graft survival with the mother as the donor. 4. Cyclosporine showed little effect on graft survival with the exception of a statistically significant difference only in 1-year graft survival for 1-HLA haplotype matched transplant recipients. However, an inverse effect was noted for mother-to-child transplants where CsA treatment showed statistically significant poorer transplant survival a 1 and 2 years. 5. In 1-haplotype matched transplants, neither random transfusion nor donor-specific transfusion exerted much effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Clinical transplants 1988. Overview.

1. The 3-month actual graft survival of 6-antigen matched transplants in the UNOS program was 96% compared to 85% in control kidneys which were not shipped (p = 0.004). Actuarial graft survival at 1 year was 89% for the 6-antigen matched kidneys and 78% for the controls (p = 0.02). 2. Several individual centers reported 1-year graft survival rates of 85-95% (in the first half of this volume). Various immunosuppressive protocols and attention to patient care resulted in high 10-year survival of 53% in 1 instance (Leuven). 3. The 1-year graft survival peaked at about 77% for transplants performed in 1985, 1986, and 1987. 4. Among transplants performed since 1984, HLA matching of cadaver donor transplants showed a 13% difference at 1 year between the best and worst A,B,DR matches, which expanded in 3 years to an 18% difference. 5. The center effect, which produces about a 13% difference in 1-year graft survival for cadaver donors, decreased to 0 in HLA-identical transplants. Thus, when the donor and recipient were histocompatible, all centers were able to achieve superior results. The results of the 6-antigen Match Study appear to validate this conclusion. 6. Preformed antibody is associated with a 9% decrease in graft survival for greater than 50% PRA in first grafts and 4% in second grafts. For peak antibodies, the difference was 7% for first grafts and 11% for second grafts. 7. Platelet flow cytometry in 23 patients with a positive flow cytometry crossmatch to T cells furnished a further refinement in grouping the patients. All 11 patients with a negative platelet crossmatch had functioning grafts at 1 month whereas only 5 of 12 patients with a positive platelet crossmatch had a functional graft at 1 month (p = 0.003). 8. The duration of first graft effect on the second graft has diminished considerably as immunosuppression improved. Patients whose first graft survived more than a year and who had a high 1-year graft survival of the second graft lost their second graft at an accelerated rate after the first year. At the end of 4 years, their survival was the same as that of the responder patients who had rejected their first grafts within 3 months. 9. False positive crossmatches, especially in "highly" sensitized patients were identified by the use of DTT. Transplants into 69 patients who were positive by the standard test but negative after DTT had a 94% 1-month function rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Cadaver↗

Blood transfusions and HLA matching--an either/or situation in cadaveric renal transplantation.

Cyclosporine-treated recipients of primary cadaver donor renal transplants had a one-year graft survival rate of 79% if they received pretransplant blood transfusions (n = 5308). The one-year survival rate for nontransfused recipients (n = 709) was significantly lower at 69% (P less than 0.001). The transfusion effect was larger in black recipients (a 17% difference) than in white recipients (5%). The effect was also larger in recipients of grafts poorly matched for HLA-A, B, -B, DR, or -DR antigens than in recipients of well-matched grafts. Transfusions did not significantly improve graft survival in recipients with zero or one HLA-A, B or -B, DR, or zero -DR-mismatched grafts. However, transfusions accounted for increases of 10%, 14%, and 17% in patients receiving grafts mismatched at 2, 3, or 4 HLA-B, DR antigens, respectively. Several factors including cyclosporine and HLA matching have contributed to improving graft survival rates in nontransfused recipients. Sensitization was noted in 20% of transfused patients awaiting primary renal transplants in Southern California, as compared with 10% in transplanted patients, suggesting a tendency to transplant nonsensitized patients. Of the sensitized patients, 75% were female. Based on these data, we suggest that high survival of primary kidney allografts in the cyclosporine era can best be maintained by the continued use of pretransplant transfusions for the majority of recipients--or, alternatively, by HLA matching for patients who are at higher risk of becoming sensitized.

Blood Transfusion↗

The effect of zero HLA class I and II mismatching in cyclosporine-treated kidney transplant patients.

The effect of HLA matching on one-year first cadaver donor graft survival rates between best and worst matches was 6% (P less than 0.001) for A, B; 7% (P less than 0.001) for DR; 9% (P less than 0.001) for A, DR; 15% (P less than 0.001) for B, DR; and 17% (P less than 0.001) for A, B, DR. For second cadaver donor grafts, the differences were comparable. Analysis of the cyclosporine-treated patients separately yielded similar results: 5% (NS) for A, B; 7% (P less than 0.001) for DR; 13% (P less than 0.001) for A, DR; 16% (P less than 0.001) for B, DR; and 18% (P less than 0.001) for A, B, DR. The most significant effect of matching was achieved by zero mismatching B and DR antigens. The one-year graft survival for patients with zero A, B, DR mismatch was 88% with cyclosporine. Without cyclosporine, zero mismatched A, B, DR grafts survive at 84%; this difference is not statistically significant. Zero mismatching for class I and II antigens (that is, A, DR or B, DR with cyclosporine) gives one-year graft survivals of 84% and 87%, respectively. The zero mismatching HLA class I and II antigen effect is lost when even one antigen is mismatched. Transfusions improved the one-year graft survival 10% in cyclosporine-treated patients, but not in those who were not treated with cyclosporine. Seventy-one patients transfused with more than 4 units of blood, zero B, DR mismatched, and treated with cyclosporine had a 91% one-year graft survival. Recipient pool sizes for obtaining zero A, B, DR or B, DR mismatched donors are calculated. Zero A, B, DR mismatched patients can be transplanted at a 19% frequency with a 10,000 recipient pool. The success rate for zero mismatching of class I and class II antigens indicates that kidney sharing and large recipient pool sizes are a reasonable policy.

Azathioprine↗

The center effect.

1. Transplant centers were grouped according to one-year graft survival rates of first cadaver transplant recipients treated with CsA. Not surprisingly, the major differences among center groups were associated with the success achieved with CsA in both patient and graft survival. Centers with the poorest survival rates were those with the least improvement over azathioprine and prednisone immunosuppression. 2. There was a definite "learning curve" associated with improvements using CsA immunosuppression for excellent and good centers. Fair centers have yet to see a significant improvement in graft survival overall with CsA. 3. Survival rates for living-related transplants varied little among the center groups, suggesting that most centers do equally well with low-risk transplants. 4. Pretransplant risk factors such as HLA matching, sensitization status, age, sex, and race of the recipients, and ischemia times varied little among the center groups. The center effect cannot be explained by recipient demographic risk factors.

Adolescent↗