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Donor selection criteria to maximize double platelet products (DPP) by platelet apheresis.

Variant Creutzfeldt-Jakob disease brought us to perform a study to diminish donor exposure from transfusion of platelet concentrates. The current study aimed to develop donor selection criteria that maximize the likelihood of deriving single donor platelets and producing double platelet products (DPP). Donors were recruited among plasmapheresis donors and among other donors when the selected donors did not show up. Donor precount and body weight and haematocrit were examined as determinants of higher split-rates combined with procedure time. When the criterion was set on 225; 82% of the procedures (n=717) with a precount of >225 yielded DPP compared to 54% of the procedures with a precount <225 (p<.01). Body weight >65 kg gave good results in split-rate. Procedure time showed an inverse correlation with the highest correlating precount (r=-.14; p<.001). Eighty one percent of the donors reported a willingness to donate at least seven times a year and 75% accepted the mean procedure time. This confirmed logistical feasibility of the conversion to AP-PC although profits would be reduce 13% compared to platelets from pooled buffy coats.

Blood Donors↗

Approaches to managing volunteer marrow donor registry HLA data. Algorithms for directing donor center-initiated HLA-DR typing of selected donors.

The German bone marrow donor center (DKMS) hasrecruited over 732 500 donors during the first 9 years of its existence. Initially, donors were typed for HLA-A and B, and DR typing was only done on request for a patient-initiated search. In 1994, a project was started which led to the donor center-initiated DR typing (DCI-DRT) of >35,000 donors. These donors were selected by donor-specific criteria (age, sex, height and weight) and according to HLA-A and B phenotypes. The latter was done to avoid unnecessary DR typing of the most common A, B phenotypes With a follow up of >6 years, this strategy has led to a number of confirmatory typings (CT) (n=4588) and stem cell harvests (n=568), which is at least comparable to those ensuing after patient-initiated HLA-DR typing (126 000 DR typings, 8,213 CTs, 888 resulting in stem-cell donation). DCI-DRT seems to be a cost-effective strategy which may help to reduce search times and improve search outcome, and improve the overall efficiency of donor center operations

Adolescent↗

Cytotoxic T lymphocyte precursor frequency analyses in bone marrow transplantation with volunteer unrelated donors. Value in donor selection.

Between May 1989 and February 1994, we performed 48 volunteer unrelated donor BMTs for first chronic phase chronic myeloid leukemia using in vivo T cell depletion for acute graft-versus-host disease (aGvHD) prophylaxis. In 40 cases, adequate material was available to measure the frequency of antirecipient MHC cytotoxic T lymphocyte precursor (CTLp) cells in the blood of potential donors. This supplemented standard serological typing, one-dimensional isoelectric focusing for class I proteins, and allogenotyping for DR and DQ alleles using DNA RFLP analysis in the donor selection process. All recipients were conditioned with cyclophosphamide 120 mg/kg, TBI 1320 cGy, and intravenous Campath 1G. GvHD prophylaxis consisted of CsA, short-course methotrexate, and intravenous Campath 1G. Minimum follow-up in all surviving recipients was 100 days. The development of aGvHD and the probability of leukemia-free survival were compared between the high frequency group (CTLp > 1 in 100,000) (n = 15) and the low frequency group (CTLp < 1 in 100,000) (n = 25). There was a trend for increasing grade of aGvHD, which was statistically significant in the high frequency group when compared with the low frequency group (P = 0.003). Both a high frequency of CTLp (relative risk [RR] = 9.0, P = 0.016) and HLA mismatch (RR = 6.7, P = 0.023) were predictors of severe aGvHD (grade III or IV). Multivariate analysis showed that CTLp group (RR = 3.4, P = 0.015) and CMV status (RR = 3.9, P = 0.008) were predictors of leukemia-free survival. Further investigation showed an interaction between the two, such that CMV seropositive recipients in the high frequency group had a relative risk of 9.4 (P = 0.0001) of treatment failure (death or relapse) when compared with other combinations. We conclude that with our present GvHD prophylaxis regimen, CTLp frequency analysis predicts post-BMT outcome and is a valuable aid in donor selection.

Adolescent↗

A specific assay for anti-HLA antibodies: application to platelet donor selection.

Alloimmunization to donor class I HLA antigens represents a major obstacle to successful platelet transfusion therapy. It is desirable to distinguish alloimmunization from nonimmunologic causes of poor platelet survival to assess the need for HLA-matched, single-donor platelets. We describe a new in vitro assay for anti-HLA antibodies and report its application to the problem of platelet crossmatching. In contrast to previously described crossmatch techniques, the immunobead assay is specific for anti-HLA antibodies. The assay was used to evaluate 51 single-donor platelet transfusions given to seven patients from 35 different donors. Recipient plasma was assayed for antibodies directed against HLA antigens present on donor platelets. A one-hour posttransfusion corrected count increment of greater than or equal to 7,500 was considered a successful outcome. Twenty-nine of 33 (87.9%) transfusion episodes associated with a negative immunobead assay had successful outcomes. The four unsuccessful transfusions were associated with potential nonimmunologic causes of poor platelet survival. Only two of 18 (11.1%) episodes associated with a positive assay had successful outcomes. Only one unsuccessful transfusion episode was associated with a negative immunobead assay and a positive radiolabeled antiglobulin test result, which suggested that isolated alloantibodies to antigens other than class I HLA antigens are not a common cause of platelet refractoriness. Platelets stored in suspension at 4 degrees C or frozen in liquid nitrogen were found suitable for crossmatch testing.

Adult↗

Lung transplantation. Donor selection.

The demand for donor lungs currently exceeds the supply of suitable grafts by a significant margin. Legal backgrounds and organizational and logistic issues are of major impact on the available donor pool. Re-evaluation of the donor criteria currently in use and new, innovative approaches such as living donor lung transplantation and non-heart-beating donation will hopefully contribute to improve this situation and reduce waiting time and waiting list mortality.

Brain Death↗

Transfusion-transmitted malaria: current donor selection guidelines are not sufficient.

A case of transfusion-transmitted malaria was identified in a 50-year-old male patient with sickle cell disease. The donor was Ghanaian, but had migrated to the UK some years previously and had not left the UK for 8 years. The donor met all of the extant donor selection guidelines [1] and a donation was consequently collected. However, on subsequent investigation of the case, the donor was found to be parasitaemic and have high titre malarial antibodies. As a result of this case, changes to the United Kingdom donor selection guidelines have been proposed. These changes will prevent any such further transmissions.

Animals↗

Influence of HLA-DPB1 mismatches on MLR responses: the role of high resolution HLA class II typing and MLC in unrelated donor selection for BMT.

Twenty eight Hungarian patients lacking a compatible related donor and their 61 HLA-A,B,DR serologically identical potential unrelated donors (selected from BMDW) were investigated in this study. Out of the 61 donor-recipient pairs only 7 (11,5%) proved to be HLA-identical at DNA level. Thirty one pairs (50,8%) differed in DP alleles, 1 pair (1,6%) has a DQ mismatch only and 22 (36,1%) pairs differed in more alleles. More than one potential donor was found for 26 patients and 5 of them have several donors with DP mismatches only. Among the 31 donor-recipient pairs differing only in DP alleles, 0, 1 and 2 mismatches were observed in GvH direction in 7, 10 and 14 cases, respectively. In the MLC assay no proliferative response was observed when no DP mismatch has been found. Among the 1 and 2 DP mismatched cases 11 (35,5%) gave negative and 13 (41,9%) gave positive MLR results. We have found a large scatter in RR values. On the basis of the DNA typing and MLR results we have found that HLA-DPB1*0101-0201 stimulator-responder combination always gave negative MLR in both direction. HLA-DPB1*0201-0301 and DPB1*0301-0401 allele combinations were reactive in all cases. In conclusion MLC assay might indicate the low immunogeneicity in certain DP allele combinations as well as the avoidable positive combinations, which may help to select the best fitting donor for BMT.

Bone Marrow Transplantation↗

Optimizing donor selection in a cord blood bank.

OBJECTIVES: The main limitation factor for the wide use of umbilical cord blood (UCB) as a source of hematopoietic progenitor for transplantation is cell dose. One of the specific areas identified by some studies for improvement of UCB collection is donor selection. METHODS: Over a 3-mth period, 391 consecutive maternal-neonatal pairs were evaluated during the pre-partum period in the maternity ward at La Fe University Hospital (Valencia) by the Cord Blood Bank staff. Reasons for discarding umbilical cord blood donors and collected UCB units at the Cord Blood Bank in Valencia have been analysed. Obstetric factors influencing TNC content of 1300 collected UCB units have been determined, in order to establish obstetric criteria for cord blood donors selection in our geographic area. RESULTS: Only 32.5% of potential cord blood donors were refused. Among 1300 UCB collected, 506 (38.9%) were discarded before cryopreservation, mainly due to low cell counts. Multivariate analyses showed that the main significant factors influencing nucleated cell count were the weight of the placenta, sex of newborn and mode of collection. CONCLUSIONS: Our study shows that maternal medical histories must be completely reviewed by medical staff before collection of the UCB. Obstetrical factors influence cell content of UCB and could be added to standard cord blood donor criteria in order to improve the bank efficiency.

Antigens, CD↗

Analysis of Minnesota Multiphasic Personality Inventory-2 profiles of prospective anonymous oocyte donors in relation to the outcome of the donor selection process.

OBJECTIVE: To examine the scores of prospective anonymous oocyte donors on the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) in four outcome groups. DESIGN: Chart review. SETTING: Academic medical center. PATIENT(S): One hundred fifty prospective anonymous oocyte donors who underwent a preliminary screening and a 1-hour structured psychological interview and who completed the MMPI-2. INTERVENTION(S): Psychological evaluation prior to donation. MAIN OUTCOME MEASURE(S): Scores on the MMPI-2 and outcomes of the donor selection process. RESULT(S): Seventy (47%) women were accepted as donors and completed one donation cycle; 30 (20%) were accepted as donors but did not donate because of medical reasons or relocation; 18 (12%) were accepted as donors but were noncompliant; and 32 (21%) were rejected as donors because of psychological concerns. Statistically significant differences were found between outcome groups on scales F, K, 1, 2, 7, 8, and 0. Although these differences were statistically significant, all group subscale mean scores were in the average to low-average range and differences between group means were small. CONCLUSION(S): The MMPI-2 differentiates between prospective donor outcome groups, but psychologists need to interpret the results of the MMPI-2 carefully in the context of clinical interview information.

Female↗

Donor selection--securing a safe blood supply.

A survey of blood donors conducted at the Red Cross Blood Bank, Melbourne, Victoria in May 1989 identified deficits in the knowledge of some donor groups. As a result a new medical form for potential donors was designed and trialled. While there were few differences in responses to questions relating to interviewing, general health, medication or transfusion therapy, responses to questions regarding the eligibility of AIDS/high risk groups to donate showed several statistically significant differences. Although improvements in donor awareness have been demonstrated in some areas, further action is necessary to ensure that effective donor selection contributes to quality control and safety of transfusion products.

Acquired Immunodeficiency Syndrome↗

Analysis of donor selection procedure in 139 living-related kidney donors and follow-up results for donors and recipients.

In 1981 an active programme was started in our centre for living-related kidney donation (LRD). The structure of this LRD programme is described in this paper. Retrospectively the results of this LRD programme were studied. Between 1981 and 1988 139 potential living donors were evaluated. Of all potential donors 47 (34%) actually donated a kidney, including 24 HLA non-identical combinations. Follow-up was obtained until 1990. An acceptable incidence of morbidity and mortality for donors and recipients was observed. A high number of potential donors was excluded during the selection procedure (66%). They were often refused for medical reasons (29%), with a high incidence of renal dysfunction (16%). No long-term adverse effects of nephrectomy regarding decreased renal function, hypertension, or proteinuria were seen. Of all actual donors 23% experienced minor complications after donation. Living-related kidney transplants showed better graft function than cadaveric grafts.

Adolescent↗

Lung donors selection criteria: a review.

Lung transplantation has had increasing success worldwide and it became an acceptable treatment modality in end-stage pulmonary diseases. The insufficient supply of donor lungs, resulting in prolonged waiting time, and the significant rise of patients on the waiting list, have forced the most experienced transplantation centers to redefine the acceptable lung donor criteria including marginal allografts. Existing standard lung donor criteria have been established in the first period of lung transplantation activity, based mainly on opinions and individual experiences rather than on existing evidences: the paucity of donors may be also explained by the rigid application of these criteria. The quality of donor organs has a significant impact on early and long-term recipient outcome. Recent studies have demonstrated that the use of marginal donors did not affect early and late recipient outcome, and significantly increased the number of transplants performed. The aim of this paper is to review how the main lung donor selection criteria have been changed and how they influence the recipient outcome.

Brain Death↗

Role of the mixed lymphocyte culture (MLC) reaction in marrow donor selection: matching for transplants from related haploidentical donors.

The utility of the MLC assay as a test of HLA-D region matching and predictor of acute graft-versus-host disease (GvHD) was evaluated in 157 patients receiving marrow grafts from HLA-A, B identical related haploidentical donors. All donors and recipients were tested by HLA-DR serology, by Dw phenotyping with homozygous typing cells (HTC) and by standard MLC. Ninety-nine of the donor-recipient pairs were mismatched for a serologically defined HLA-DR antigen while 109 pairs were mismatched for the HLA-DR region by HTC typing. Donor antirecipient relative responses (RR) in MLC, corresponding to the GvHD vector in marrow transplantation, ranged from -4% to 100%, with a median of 25%. A comparison of reactivity in MLC with presence or absence of matching by Dw phenotyping, however, showed a significant overlap in the distribution of RRs from HLA-Dw matched versus Dw mismatched pairs, suggesting that the MLC was not a reliable predictor of HLA-Dw matching. Using an optimally-defined cutoff of 3% RR, the MLC was correlated with risk of developing clinically significant grades II-IV acute GvHD (p = 0.03) but not with risk of developing severe grades III-IV GvHD (p = 0.18). In contrast, matching by Dw phenotype was a significant predictor of GvHD, with Dw-compatible transplant recipients less likely to develop either grades II-IV (p = 0.004) or III-IV (p = 0.036) GvHD than Dw-incompatible transplant recipients. Overall, these results underscore the difficulty in using the MLC to measure HLA-D region compatibility and predict the risk of severe graft-versus-host disease among patients receiving related haploidentical marrow grafts. HLA-D (HTC) typing results correlate primarily with DRB compatibility, and with the advent of DRB1 allele matching by sequence-specific oligonucleotide probes (SSOP) or by direct sequencing, the precision in donor matching achievable with these methods is far greater than with either HLA-D typing or direct MLC testing.

Adolescent↗

Blood donor selection and screening: strategies to reduce recipient risk.

Various measures are taken to ensure the safety of the blood supply. Donor selection begins with education of the public about transfusion-transmissible diseases. Potential donors must answer a questionnaire designed to identify specific risk factors for these infections. The questionnaire is the only line of protection against certain infections for which no testing is performed, such as malaria, babesiosis, leishmaniasis, and Chagas disease. All donations are tested for the presence of antibodies to HIV-1 and -2, HCV, HTLV and syphilis, the hepatitis B surface antigen (HbsAg), the p24 antigen (HIV), and also for HIV and HCV nucleic acids. The introduction of new and improved screening tests for transfusion-transmissible diseases has led to remarkable improvement in the safety of the blood supply, with substantial shortening of the window period for HIV, HCV, and HBV infections. The current challenge of the industry is to reduce even further the small but significant risk of bacterial contamination of platelet components. Finally, some safety measures are purely precautionary, such as the deferral of donors who have traveled to certain countries affected by the bovine spongiform encephalopathy (BSE).

Antibodies, Viral↗

Increased fecundity resulting from semen donor selection based upon in vitro sperm motility.

Semen donors were selected from a population of 100 roosters based upon the extent to which sperm penetrated 6% (wt/vol) Accudenz from an overlay of extended semen. Semen donors categorized by average or high sperm motility (n = 5 per phenotype) were ejaculated weekly, their ejaculates pooled by phenotype, and pooled semen extended. A subsample of each sperm suspension was overlaid on 6% (wt/vol) Accudenz in a cuvette, the cuvette was placed in a 41 C water bath, and the absorbance of the Accudenz layer was measured after a 5-min incubation. The remainder of the sperm suspension was inseminated (n = 55 hens per phenotype). Each hen was inseminated weekly with 50 x 10(6) sperm for 14 wk. The hatchability of eggs laid by hens inseminated with sperm from the high motility phenotype was 10% greater (P < or = 0.001) than that of hens inseminated with sperm from the average phenotype. The difference in fecundity was explicable in terms of fertility (P < or = 0.001). A replicate experiment tested the effect of sperm motility as well as insemination dose on fertility. Roosters were treated as above, and hens (n = 41 to 45 per phenotype) were inseminated weekly with 25, 50, or 100 x 10(6) sperm per hen for 3 wk. Two-way ANOVA detected a sperm motility effect (P < or = 0.0001) but did not detect a dose effect (P > or = 0.05) or a motility by dose interaction (P > or = 0.05). A posteriori comparison among means revealed that the maximal fertility obtained with sperm from average roosters was 9% less (P < or = 0.05) than that obtained with only 25% as many sperm from the high motility phenotype. These experiments demonstrated that the fecundity of artificially inseminated hens can be increased when sperm penetration of Accudenz is used as a selection criterion for semen donors.

Analysis of Variance↗

HLA antibody enhancement by double addition of serum: use in platelet donor selection.

The identification of HLA class I alloantibodies is important for organ transplantation and platelet transfusion in alloimmunized patients. Because microcytotoxicity testing against frozen trays of lymphocyte panels is rapid and efficient for determining specificities of unknown antibodies, a simple method was devised to increase test sensitivity to weak antibodies. Standard anti-human globulin (AHG)-facilitated microcytotoxicity was modified by the insertion of a double addition-of-serum (DAS) step, and reagent and patient's sera were evaluated by both methods. DAS modification increased antibody titers and, more significantly, made the identification of weak specificities easier because of the twofold to threefold increase in reactivity rates (29-42% for AHG vs. 75-82% for DAS) of panel cells that were expected to be positive, while low (approx. 1%) "extra" reaction rates were maintained for cells that were expected to be negative. DAS was relatively unaffected by variations in serum volumes or target cell preparation, and its use did not significantly increase test time or costs. In a program of platelet donor selection driven by donor antibody rather than donor-recipient antigen matching, DAS greatly facilitated platelet transfusion support for alloimmunized patients.

Antibody Specificity↗

Prevention of transmission of HIV by organ and tissue transplantation. HIV testing protocol and a proposal for recommendations concerning donor selection.

Human immunodeficiency virus (HIV) can be transmitted by solid organ and some forms of tissue transplantation. Although routine screening of organ and tissue donors for anti-HIV antibodies was implemented in most Western European countries and North America in 1985, several recent case reports indicate that a definite, albeit very small, risk of HIV transmission still remains. The screening tests that are currently used cannot rule out a false-negative test result occurring during the window period. Moreover, massive transfusion of the donor during the donor procedure may result in an undetectable anti-HIV antibody titer (by dilution of donor blood) that consequently leads to a false-negative test result. These risks of HIV transmission via transplantation and important issues in HIV testing are discussed in detail. Furthermore, several recommendations for the prevention of transmission and a protocol for HIV testing for both organ and tissue donation are presented. These may serve as intermediary guidelines until official ones, such as already exist for blood donation, are defined by the transplantation communities. The exclusion of donors whose behavior may place potential recipients at risk for HIV infection is essential. A thorough heteroanamnesis of the donor's next of kin during the donor procedure should provide sufficient information about donor history to enable a decision to be made in this respect. Special attention is given to the question of whether the existing donor selection criteria for blood donation should be applied in a similar way to organ donation since the strict application of selection criteria may limit the number of available donor organs.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Serodiagnosis↗

[Transplantation of the cornea from the donor selected on the basis of HLA compatibility in high risk leukoma].

Fifteen corneal grafts were performed in 15 men with high risk leukoma (5+) in the period October 1988--November 1990. The age of the patients oscillated between 11 and 76 years. In 5 patients the grafting was done in only eye. The period of observation after surgery amounted 4-29 months. The favourable results (transparent and ++semi-transparent grafts) were obtained in 9 eyes (60 p.c.) and partly opacified grafts in 6 (40 p.c.). Neither of the grafts opacified. In the preceding years--without taking into account the antigenic selection of the donor--favourable results in similar leukoma cases were achieved in ca. 42 p.c. of cases.

Adolescent↗