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Unrelated donors selected prospectively by block-matching have superior bone marrow transplant outcome.

Previous retrospective studies have demonstrated improved outcome in patients whose donors were matched for non-HLA markers in the MHC as well as for HLA genes. Forty patients receiving transplants from unrelated donors were typed prospectively for HLA and non-HLA markers. Non-HLA markers near HLA-B (beta-block markers) and in the DRB1 introns (delta-block markers) were used to assess MHC match between donors and recipient. Patients whose donors were matched at the beta- and delta-blocks had improved event free survival (63%) compared to patients whose donors were mismatched at one or both blocks (25%) (p < 0.05). Patients whose donors were matched at the beta-block had significantly less severe acute graft versus host disease (p < 0.05). In order to investigate the basis for improved outcome block matching was correlated with HLA matching as determined by DNA sequencing. Beta-block matching was highly correlated with matching for exons 2 and 3 of HLA-B but less so for HLA-C. Delta-block matching was highly correlated with matching for exon 2 of HLA DRB1. It is concluded that matching for non-HLA markers in the MHC improves matching for HLA genes. Further studies are required to determine whether matching for non-HLA markers improves outcome to a greater extent than matching for the HLA genes alone.

Adolescent↗

A high resolution HLA class I and class II matching method for bone marrow donor selection.

HLA matching in bone marrow transplantation has an important role in determining successful outcome. However HLA typing of both potential related and unrelated donors can be both time-consuming and laborious, and does not always resolve accurately the true level of histocompatibility. We have utilised a method, reference strand mediated conformation analysis (RSCA), which is technically simple and allows high resolution matching for all HLA loci, for the typing of 48 patients and their potential 120 donors. The results indicate that RSCA can detect many mismatches that are not routinely identified by conventional HLA typing methods. In addition, RSCA can be applied for the simultaneous analysis of multiple potential BM donor samples in order to quickly identify the best match for each patient.

Alleles↗

Topographic matching of selected donor and recipient sites for osteochondral autografting of the articular surface of the femoral condyles.

The purpose of this study was to define the topography of the articular surface of the femoral condyles and to develop a method for computerized topographic matching of donor and recipient sites for osteochondral transplantation. The condyles of seven fresh cadaveric femurs were mounted on the rotating stage of a laser-based coordinate measuring machine. An anatomic coordinate system defining the articular surface of the condyles was created. Customized software was developed to allow selection and topographic matching of osteochondral graft donor and recipient sites from any location on the surface of the condyles. For cartilage defects within the weightbearing portions of the medial or lateral femoral condyles, grafts taken from sites from the most medial or lateral portions of the patellar groove provided a significantly better topographic match than did grafts taken from the central intercondylar notch.

Adult↗

Kidney transplant in children weighing less than 15 kg: donor selection and technical considerations.

BACKGROUND: Small children represent a challenging patient group in kidney transplantation (KTx). The aim of this study was to analyze patient and donor data influencing outcome in children that weighed <15 kg. METHODS: Sixty-eight kidneys were transplanted in 64 children that weighed <15 kg. In 44 cases, kidneys came from cadaveric donors (CAD) and in 24 cases from living-related donors (LRD). Grafts were placed transperitoneally via midline incision (n=16) or extraperitoneally to the iliac fossa (n=52). Vascular anastomoses were routinely performed to the aorta and vena cava even when the extraperitoneal approach was used. RESULTS: Vascular thrombosis was observed in two (3%), urinary leaks in five (7%), and stenosis in four (6%) patients. In six children receiving organs from adults to the iliac fossa, wound closure was performed using an absorbable mesh to avoid organ compression. Initial graft function occurred in 60 cases (88%). Frequency of initial graft function was significantly higher after KTx from LRD (100%) compared with CAD (82%). The 1-, 5-, and 10-year patient survival was 93%, 91%, and 91%, respectively, and the 1-, 5-, and 10-year graft survival was 92%, 85%, and 85%, respectively. There was no significant difference in patient and graft survival when KTx from LRD and CAD were compared. Within the CAD group, graft survival was improved using kidneys from donors >12 years compared with younger donors. CONCLUSION: Despite size discrepancy between recipients and grafts, KTx is feasible in children that weigh <15 kg by using an improved surgical technique even when adult organs are placed to the iliac fossa.

Body Weight↗

Evaluation of serological screening of cadaveric sera for donor selection for cornea transplantation.

Human corneas are explanted for grafting as late as 72 h after death, for example, from medical examiner cases. Currently, infection of the donor with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) is excluded in most cornea banks by serological testing of the cadaveric serum only. The reliability of this strategy was investigated by testing paired cadaveric and premortem sera of 33 potential donors. Results were discordant in 17 of 33 donors by at least one assay. Most frequently, HBsAg enzyme-linked immunosorbent assay (ELISA) yielded false-positive results with the cadaveric serum (16 of 33 serum pairs). Virus safety of the graft was affected in a single case, which was HCV antibody negative in the cadaveric serum, but positive in the premortem serum (confirmed by HCV-RIBA strip immunoassay). Forensic DNA profiling by polymerase chain reaction (PCR) of both serum samples confirmed that these were derived from the same individual. In conclusion, the results indicate that serological testing of cadaveric sera is not a reliable method for screening of potential cornea donors, and may not be sufficient for the virus safety of cornea grafts. Therefore, other screening strategies such as detection of viral nucleic acids by PCR should be evaluated.

Adult↗

Sperm and oocyte donor selection and management: experience of a 10 year follow-up of more than 2100 candidates.

BACKGROUND: The main concerns for couples undergoing assisted reproduction treatment using donor gametes are the possibilities of acquiring infectious diseases and of transmitting genetic disorders to the progeny. They are also frequently concerned and interested in the cultural and psychological background of the donors. Our aim was to examine the current prevalence of genetic alterations and infectious diseases in our sperm and oocyte donor population, and to review our experience in the management of donors and candidates during the last 10 years. METHODS AND RESULTS: Routine blood analyses, semen and vaginal cultures together with complete medical, psychological and genetic histories were examined retrospectively. Our results clearly show that the frequency of sexually transmitted diseases and genetic disorders is comparable with both the frequency present in the population requiring infertility treatments and the general population. CONCLUSIONS: The screening procedure applied to all the candidates sufficiently minimizes any risk to the gamete receiver and the offspring.

Adolescent↗

[New possibilities of donor selection for bone marrow and organ transplantation by HLA typing and genomic DNA].

For one year we determined HLA class II antigens from all patients with renal and haematological disorders and their healthy family members both by using serological methods and DNA typing (SSO, SSP). The rate of discrepancies between the results of serological DR typing and DRB1 typing was 10.8% (13/120). We were able to demonstrate that DNA typing for class II antigens leads to definite results even for patients with a poor cell quality or with lymphocytopenia where serological typing is often impossible. Furthermore, DNA typing from patients with haematological disorders is very important, especially if a bone marrow transplantation is considered. In addition to MLC testing, DRB1, DQB1 and DPB1 typing should be carried out for the patient and the potential donor. DNA typing is also recommended for patients waiting for a kidney transplantation particularly if they were serologically typed as 'homozygous', as the chance to receive an HLA-compatible organ is much higher for a heterozygous individual.

Bone Marrow Transplantation↗

Reassessment of blood donor selection criteria for United States travelers to malarious areas.

In the United States (US), travelers who have had malaria or who have taken antimalarial chemoprophylaxis are deferred as blood donors for 3 years to prevent transfusion-transmitted malaria. To assess the impact of shortening this 3-year exclusion period, national malaria surveillance data from 1972 to 1988 were reviewed. The average annual rate of transfusion-transmitted malaria is 0.25 cases per million units of blood collected. Of 45 reported cases, 38 percent were caused by Plasmodium malariae, 29 percent by P. falciparum, 24 percent by P. vivax, and 9 percent by P. ovale. Thirty-two donors were implicated in 34 cases of transfusion-transmitted malaria. Of 30 implicated donors whose native country was identified, 23 (77%) were foreign nationals and 7 (23%) were from the US. In a review of all imported malaria cases by species and by interval between date of entry and onset of illness, 98 percent of P. falciparum, 86 percent of P. malariae, 76 percent of P. vivax, and 74 percent of P. ovale infections became symptomatic within 6 months of the patient's arrival in the US, regardless of the use of prophylaxis. Shortening to 6 months the donor exclusion period for US travelers to malarious areas would result in a minimum of 70,000 additional blood donors' being made available, with a maximum annual increase of 0.03 additional cases of transfusion-transmitted malaria. The potential benefit of bringing healthy travelers back into the donor pool after a shorter period of exclusion merits consideration by the blood banking industry.

Adult↗

Brain-dead kidney donor: selection, care, and administration.

Over four and a half years a district general hospital provided 34 cadaveric kidneys for transplantation. All brain-dead patients were regarded as potential donors, flow charts being used to maintain circulation and urine formation and facilitate administration. With this system the time lapse between diagnosis of brain death and removal of kidneys ranged from three to six hours and ischaemia was minimised. It is concluded that adoption of the system by other hospitals of comparable size would result in enough good-quality kidneys to satisfy present needs, thus reducing the initial high failure rate and enabling more patients to be accepted for dialysis.

Brain↗

Infectious disease transmission through cell, tissue, and organ transplantation: reducing the risk through donor selection.

The incidence of cell transplant-transmitted infection is unknown and can only be inferred from prospective studies--that have not yet been performed and reported. The possibility of donor-to-recipient disease transmission through cell transplant therapy can be considered by reviewing the risk associated with other transplanted tissues and organs. Viral, bacterial, and fungal infections have been transmitted via transplantation of organs, tissue allografts such as bone, skin, cornea, and heart valves, and cell such as islets, hematopoietic stem cells, and semen. Several types of protozoan and worm parasites have been transferred via organ transplants. Bone allografts have transmitted hepatitis, tuberculosis, and human immunodeficiency virus (HIV-1). Corneas have transmitted rabies, Creutzfeldt-Jakob disease (CJD), hepatitis B (HBV), cytomegalovirus (CMV), herpes simplex virus (HSV), bacteria, and fungi. Heart valves have been implicated in transmitting tuberculosis and hepatitis B. HIV-1 and CMV seroconversion has been reported in patients receiving skin from seropositive donors. CJD has been transmitted by dura and pericardium transplants. Over the past several years, improvements in donor screening criteria, such as excluding potential donors with infection and those with behaviors risky for HIV-1 and hepatitis infection, and introduction of new donor blood tests have greatly reduced the risk of HIV-1 and hepatitis and may have nearly eliminated the risk of tuberculosis and CJD. Prior to use, many tissues are exposed to antibiotics, disinfectants, and sterilants, which further reduce or remove the risk of transmitted disease. Because organs, cells, and some tissue grafts cannot be subjected to sterilization steps, the risk of infectious disease transmission remains and thorough donor screening and testing is especially important.

Communicable Disease Control↗

Canine platelet alloimmunization: the role of donor selection.

Five different platelet transfusion programmes were evaluated in a canine model to determine the most effective method of providing long-term platelet support. When a weekly transfusion from a single unrelated donor was used, alloimmune platelet refractoriness developed in 95% of recipients after an average of 3.1 +/- 0.7 transfusions, and donor platelets circulated for a total of 8.2 +/- 2.3 d. When multiple unrelated donors were used, the percentage of refractory recipients was similar (60% versus 77%) whether platelets came from six single donors given sequentially or from a pool of the same six donors given repeatedly. There was, however, a significant difference in the number of transfusions given prior to immunization (14 +/- 5 transfusions lasting 32 +/- 12 d for sequential single donors as compared to 5.5 +/- 1.0 transfusions lasting 13 +/- 2 d for the pooled donors). When littermates were used as platelet donors, the frequency of refractory recipients, the number of transfusions required to immunize, and the circulation time of donor platelets before refractoriness was not better than when multiple unrelated single donors were used. Furthermore, there was no significant difference in effectiveness between DLA-identical and DLA-nonidentical littermate platelet donors. In recipients previously immunized by a pool of six unrelated donors, the same percentage of recipients was refractory to DLA-identical littermate donors as had been observed following only DLA-identical platelet transfusions. This suggests that non-DLA immunizing platelet antigens, not shared between approximately 30% of DLA-identical littermates, are well represented in a random canine population. However, prior random transfusions did not compromise long-term platelet support from 'truly' platelet compatible DLA-identical littermate donors. These studies indicate that single donor transfusions either from littermates or sequential unrelated donors are the most effective method of providing long-term platelet support. However, the use of pooled unrelated donor transfusions, followed by DLA-identical donors in immunized recipients is an equally acceptable alternative.

Animals↗