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Impact of cytomegalovirus serology on graft survival in living related kidney transplantation: implications for donor selection.

BACKGROUND: The impact of cytomegalovirus in living related kidney transplantation remains controversial. This study considers the implications of donor and recipient cytomegalovirus (CMV) serology for the selection of living related donor. METHODS: Graft survival was estimated by using the bivariate Kaplan-Meier method and multivariate Cox proportional hazards analysis for 7659 living related first transplantations performed in the United States between 1989 and 1994. The effects of donor CMV serology were estimated with respect to recipient CMV serology and compared with human leukocyte antigen (HLA) matching, transplantation, donor, and recipient characteristics. The implications of these estimates for the selection of living related donors were considered. RESULTS: From Kaplan-Meier estimates, donor CMV-seropositive kidneys were associated with significantly reduced graft survival for CMV-seronegative recipients (p = 0.0002) but not CMV-seropositive recipients (p = 0.1623). These findings were verified by use of Cox proportional hazards analysis accounting for covariate factors. The impact of donor CMV-seropositive kidneys on CMV-seronegative recipients was similar to one HLA-DR match, greater than one HLA-B match, and significantly greater than one HLA-A match (p = 0.0331). CONCLUSIONS: Results identify donor CMV serology as an important determinant of transplantation outcome for living related first kidney transplant recipients who are themselves CMV seronegative. Consideration should be given to donor and recipient CMV serology when selecting an appropriate donor for living related kidney transplantation.

Adult↗

Primed CTLs specific for HLA class I may still be present in sensitized patients when anti-HLA antibodies have disappeared: relevance for donor selection.

BACKGROUND: The presence of donor-specific HLA antibodies is generally considered to be a contraindication for transplantation, even when these antibodies are only present in historical sera. Previous studies showed that donor-specific antibodies in current sera were associated with the presence of primed cytotoxic T cells (CTLs) with a high avidity for donor HLA class I antigens. The presence of these CTLs is considered to be a reflection of an activated immune system and a contraindication for transplantation with a donor sharing these particular HLA antigens. METHODS: In the present study we compared the incidence of primed CTLs in patients with anti-HLA antibodies in current sera and in patients with anti-HLA antibodies in historical sera only. Cytotoxic T lymphocyte precursor (CTLp) frequencies and the incidence of primed CTLs directed against HLA class I antigens to which the patient had formed antibodies were studied in 37 sensitized renal patients. As controls, antigens to which a patient has never formed antibodies were tested. RESULTS: In patients with antibodies in current sera mainly primed CTLs were detected, whereas in patients where the antibodies had disappeared mainly naive CTLs were detected. However, in four patients primed CTLs persisted despite the fact that the HLA antibodies had disappeared. CONCLUSION: Considering the previously described association between primed CTLs and graft rejection, these findings may be relevant for the selection of patients who can be transplanted across a positive historical crossmatch. If the antibodies have disappeared and only naive CTLs are present, a successful transplantation should be feasible. A prospective study will reveal whether this is indeed the case.

Antibody Affinity↗

Tissue donor selection and safety.

Authors of recent reports in the medical literature indicate that allograft-associated infection primarily is attributable to violations of proper tissue processing procedures, and illustrate the need for effective quality assurance systems to avoid transplantation of potentially infectious tissue. I describe the experience of the members of the Musculoskeletal Transplant Foundation with the selection, the processing, and the safety of bone and tissue donors for allograft implantation. In 2002, the Musculoskeletal Transplant Foundation screened 10,497 potential donors, but only 4431 (42%) met stringent criteria for recovery. After recovery, another 10% of the donors were rejected, usually because of positive infectious disease tests (45%) or an autopsy finding (31%) that rendered the tissues unsuitable for transplantation. Procedures used by the Musculoskeletal Transplant Foundation for ensuring safety of the tissue and for investigating reports of putative infection are described. The Musculoskeletal Transplant Foundation has had no confirmed cases of allograft-associated infection in over 2 million units transplanted during the past 15 years.

Donor Selection↗

Reliability of HLA-Cw data collected in unrelated bone marrow registry and their usefulness for preliminary donor selection.

In the present study, we addressed the question of how often HLA-DRB1-matched donors can be found by further typing of AB-matched donors and whether Cw preselection can be helpful. Sixty-eight patients and 174 donors were enrolled in the study. In all donors, confirmatory DNA Cw typing was performed to check reliability of registry Cw data. Among the 129 Cw serologically typed donors, 11 (8.5%) were not confirmed by DNA typing and for 77 (60%) at least one Cw blank antigen was genetically confirmed. In healthy controls, haplotype frequency higher than 1% has been found for 21 (55%) out of 38 Cw-DRB1 haplotypes observed. A subtotal delta made up 67% of subtotal haplotype frequency fraction of 21 haplotypes confirming strong linkage disequilibrium of Cw-DRB1 loci. After Cw preselection 12 (15.4%) out of 78 donors were matched in both DRB1. On the other hand, only two (2.1%) out of 96 AB-matched donors with unknown or incompatible Cw were matched in both DRB1 at low-resolution level (OR = 8.55; P = 0.0060; 95%CI 1.85-39.5). We found at least one DRB1-matched donor for 12 (26.1%) out of 46 patients with Cw-matched donors for which 1-5 (median = 1) of Cw-preselected donors were chosen for further typing. Cw preselection of HLA AB-matched donors for further DRB1 typing may improve the efficacy of stem cell donor search process.

Donor Selection↗

Effect of donor selection on the early outcome of heart transplant recipients.

Recipients receiving heart transplants from 83 donors from 1995 to 2002 were analyzed to evaluate the effect of various donor factors on recipient outcomes. The 83 donors (13 women and 70 men; 2-51 years old) had cold ischemic times ranging between 55 and 287 minutes. Donor age, cause of death, inotropic support, and cold ischemic times of the hearts were compared to 1-year left ventricular ejection fraction, permanent pacemaker dependency, 30-day mortality, and 1-year survival in the recipients. Donors receiving low-dose inotropic support resulted in recipients with permanent pacemaker dependency in 14.8%, and 30-day mortality and 1-year survival rates of 7.4% and 70.3%, respectively. Donors not receiving inotropic support resulted in recipients with permanent pacemaker dependency in 3.5%, and 30-day mortality and 1-year survival of 3.5% and 83.9%, respectively. Cold ischemic times less than or equal to 120 minutes showed 30-day mortality and 1-year survival rates of 0% and 90.9%, respectively. Cold ischemic times equal to or more than 121 minutes showed 30-day mortality and 1-year survival rates of 8% and 76%, respectively. Increased donor age (P=.22) and cold ischemic time showed an increase in mortality without affecting mean ejection fraction in survivors. Use of inotropic support in donors (P=.95) showed an increase in mortality without affecting mean ejection fraction in survivors.

Adolescent↗

Platelet transfusion therapy in an alloimmunized patient. The value of crossmatch procedures for donor selection.

A 51-year-old patient with acute myelogenous leukemia, who was alloimmunized to platelets, failed to show adequate platelet increments after receiving transfusions of HLA grade A-identical platelets. Only platelets from an HLA grade B-matching donor gave high increments. Several crossmatching procedures were used to select platelet donors. A correlation was seen between in vitro tests and in vivo response. HLA typing has limitations in the selection of platelet-compatible donors.

Adult↗

[Donor selection for allogenic bone marrow transplantation from 1991 to 1995. (The Prague Center for Bone Marrow Transplantation)].

BACKGROUND: The prerequisite of successful transplantation of haematopoietic stem cells is to find a suitable, i.e. HLA matched bone marrow donor. In the submitted paper the authors give an account of the strategy of selection of bone marrow donors, as practised by the Prague transplantation group. METHODS AND RESULTS: In 1991 to 1995 (end of first quarter) the authors sought suitable bone marrow donors for 421 patients where an allogenic bone marrow transplantation was indicated. During that period 95 transplantations were performed (22.5% of all indicated cases), incl. 82 from siblings (86.3%) of the implemented allogenic bone marrow transplantations). A HLA matched donor from the wider family circle was selected for 15 donors, transplantation were performed in 6 patients (6.4% of the implemented allogenic bone marrow transplantations). An unrelated bone marrow donor was sought for 41 patients as no donor was found in the wider family. Transplantation was implemented in 7 of these patients (7.3% of the implemented transplantations. CONCLUSIONS: With the increasing experience of our transplantation centre, no doubt, the ratio of other than sibling transplantations of bone marrow will increase. At present it accounts for 13.7%. The task of our HLA group must be selection of donors matched as well as possible with the recipient according to all available tests of tissue compatibility - from the wider family circle as well as from the register of unrelated donors.

Bone Marrow Transplantation↗

Selecting donors of platelets for refractory patients on the basis of HLA antibody specificity.

BACKGROUND: Patients who are refractory to platelet transfusion as a result of HLA alloimmunization are generally given HLA-matched or crossmatched platelets. However, HLA-matched platelets that are matched at HLA-A and -B loci (A-matched) or those without any mismatched or cross-reactive antigens (BU-matched) are frequently unavailable. A disadvantage of crossmatching is that crossmatched platelets have a shelf life of only 5 days, so that crossmatch tests must be performed frequently for patients requiring long-term platelet transfusions. An alternative method is the selection of platelets according to the patient's HLA antibody specificity, called the antibody specificity prediction (ASP) method. STUDY DESIGN AND METHODS: An anti-human globulin-enhanced microlymphocytotoxicity test modified by a double addition of serum and a computer program were used to determine the specificity of patients' HLA antibodies. Platelet crossmatching was performed with a solid-phase adherence assay. The percentage of platelet recovery (PPR) was determined in 1621 platelet transfusions in an observational study in 114 patients, and the PPR of platelets selected by the ASP method was compared with the PPR of those that were HLA-matched, crossmatched, or randomly selected. The numbers of potential donors in files of HLA-typed donors as identified by HLA matching vs. the ASP method were determined. RESULTS: After adjustments for covariates, the mean +/- SEM PPR was similar for HLA-matched (21 +/-4%), cross-matched (23+/-4%), and ASP-selected (24+/-3%) platelets and was significantly lower for randomly selected (15+/-1.4%) platelets. For 29 alloimmunized HLA-typed patients, the mean number of potential donors found in a file of 7247 HLA-typed donors was 6 who were an HLA-A match (median = 1), 33 who were an HLA-BU match (median = 20), and 1426 who were identified by the ASP method (median = 1365). CONCLUSION: The ASP method of donor selection for refractory alloimmunized patients appears as effective as HLA matching or crossmatching. Far more donors are identified in a file of HLA-typed donors by the ASP method than by HLA matching, and this indicates that the ASP method provides important advantages regarding the availability of compatible platelet components.

Analysis of Variance↗

Rapid DNA crossmatch analysis of HLA class II genotypic polymorphisms by temperature gradient gel electrophoresis in unrelated bone marrow donor selection.

The present paper demonstrates the usefulness of the temperature gradient gel electrophoresis (TGGE) as a precise method for the rapid identification of HLA-DR full matched donors by molecular crossmatch analysis. The resulting TGGE fingerprints are highly diverse for different HLA-DR genotypes and identical for samples with identical HLA-DR type, as shown for a panel of 25 randomly selected PCR-SSO pretyped DNA samples. In addition, TGGE analysis of a panel of homozygous typing cell lines (HTCs) established, that even subtle differences in the DR4 subtypes are detectable by TGGE crossmatch analysis. Furthermore, TGGE crossmatch analysis of unrelated donor/patient pairs demonstrated, that only HLA-DR identical patient/donor combinations showed identical TGGE patterns. Thus crossmatch analysis by TGGE presents a novel basis for a rapid and safe unrelated bone marrow donor selection strategy. Only HLA class I identical donors which also show HLA-DR identity in the TGGE crossmatch test are selected for the final confirmation of the HLA class II genes by a suitable DNA subtyping method.

Alleles↗

Impact of multidetector CT on donor selection and surgical planning before living adult right lobe liver transplantation.

OBJECTIVE: This study was performed to document the impact of multidetector multiphase CT in facilitating patient selection and surgical planning in potential donors being evaluated for living adult right lobe liver transplantation. SUBJECTS AND METHODS: Forty consecutive potential donors were included in the study. There were 26 men and 14 women, (age range, 18-57 years; mean, 37 years) We performed CT using a multidetector scanner, after IV injection of 180 mL of contrast material at 5 mL/sec. Arterial phase images were acquired at 18 sec (collimation, 1.25 mm; table speed, 7.5) and portal phase images, at 60 sec (collimation, 2.5 mm; table speed, 15). Postprocessing was performed on a commercially available workstation. CT data included dual-energy assessment of liver parenchyma for fatty infiltration; depiction of arterial, portal venous, and hepatic venous anatomy and identification of important vascular variants; and determination of total and lobar liver volume. RESULTS: Of the 40 potential liver donors evaluated, 15 patients (37.5%) were excluded on the basis of CT findings, with most exclusions a result of portal vein anomalies (n = 8). Fatty infiltration resulted in four exclusions (10%), and small liver volume resulted in three exclusions (7.5%). CONCLUSION: Multidetector multiphase CT provided comprehensive parenchymal, vascular, and volumetric preoperative evaluation of potential donors undergoing living adult right lobe liver transplantation. This information had a major impact on patient selection because it was used to stratify patients. It allowed the surgeons to plan their surgical approach, and this planning may reduce postoperative complications.

Adolescent↗

Donor selection for unrelated cord blood transplants.

The number of unrelated cord blood transplants is increasing, with more than 8000 patients reported worldwide. Criteria of donor choice have been identified. Cell dose measured by number of nucleated cells is the most important factor, thus increases in cell dose can partially overcome the presence of HLA incompatibilities. Overall, increasing the number of HLA incompatibilities is associated with non-engraftment, but it also decreases the risk of relapse in patients with malignant disease, resulting in an absence of effect of HLA incompatibilities on event-free survival (survival without relapse or complications related to the transplant). However, in patients with non-malignant disorders, increasing the number of HLA incompatibilities decreases the overall survival. These results show that criteria of donor choice based on number of infused cells, number of HLA incompatibilities and diagnosis improve outcomes of unrelated cord blood transplants. Currently, owing to the possibility of using a non HLA identical donor, most patients can find a donor, increasing the need for the development of the inventory of cord blood banks. Methods of improving engraftment are currently under investigation.

Cord Blood Stem Cell Transplantation↗

Oocyte donor selection from 554 candidates.

Oocyte donation is a technique in full expansion in the field of human reproduction. The main problem with this technique is the shortage of oocytes. In our programme, prospective donors are selected from anonymous, well-informed university students over 18 years of age, who give their informed consent in writing. Before being accepted as donors, the candidates' personal and family medical histories were taken and they were given a gynaecological examination, genital ultrasonography, and analysed for syphilis, acquired immune deficiency syndrome, hepatitis B and C, coagulation factor VIII, fetal haemoglobin and karyotype. The donors received economic compensation of about 750 euros. Over the last 6 years, 554 medical histories have been taken. Fifty-eight candidates (10.5%) were rejected because of previous family or personal pathologies. Only 243 out of 496 (49%) continued the study. Sixteen candidates (7%) were rejected as a result of gynaecological problems and ultrasonographic results; and 12 (4.9%) as a result of their blood test results; 215 donors were accepted (38.8% of the original population). Other options for recruiting oocyte donors are commented on and we argue that the methodology described here is the most suitable one.

Adult↗

INH-A21: a donor-selected Staphylococcal human immune globulin for the prevention of late-onset neonatal Staphylococcal infection.

INH-A21 is an experimental human immune globulin for intravenous infusion (IGIV) derived from donors specifically selected for elevated levels of antibodies against the Staphylococcal fibrinogen-binding proteins, serine aspartate dipeptide repeat G and clumping factor A. Phase II results demonstrated that infusions of INH-A21 were well tolerated and there were no trends for increasing adverse events, or the common morbidities associated with prematurity. Enrollment has been completed in (but no results have been released from) a Phase III human trial testing INH-A21 as a prophylactic agent against staphylococcal infection in very low birth weight infants (500-1250 g).

Adhesins, Bacterial↗