Accreditation of histocompatibility and immunogenetics laboratories: Achievements and future prospects from the European Federation for Immunogenetics Accreditation Programme.

The importance of demonstrating adherence to good practice in the provision of clinical services is well recognised, and there are many legislative and regulatory requirements that aim to ensure that services are appropriately reviewed and certified. Therefore, for regulatory purposes, laboratories must provide assurance of the quality of the services they provide. Additionally in the field of transplantation, where donor organs and stem cells are exchanged across national boundaries, adoption of a common set of standards by laboratories across many different countries is an important factor. The European Federation for Immunogenetics (EFI) Accreditation Programme was established to provide assurance that Histocompatibility & Immunogenetics laboratories providing services for transplantation, transfusion, and disease association testing meet the requirements of the specialty specific EFI standards. The first H&I laboratories achieved EFI accreditation in 1995, and currently there are over 260 EFI accredited laboratories in 36 countries. The programme depends on the voluntary participation of the inspectors, who are all experts in the field of H&I, and who, over the last 22 years, have performed over 1400 onsite inspections of laboratories. Inspection findings show the areas that are most frequently found to be deficient in meeting the requirements of the standards, and this can be used to inform educational and other activities with the aim of improving laboratory compliance with the standards. The EFI standards have been regularly updated to reflect the changes in the field with 19 versions over the last 22 years, and the data from the accreditation programme show how laboratories have changed their practices to incorporate new techniques that support patient care.

The conundrum of HLA-DRB1*14:01/*14:54 and HLA-DRB3*02:01/*02:02 mismatches in unrelated hematopoietic SCT.

Uncertainty still exists on the role of polymorphisms outside the HLA-DRB1 binding site or inside the HLA-DRB3 binding groove in unrelated hematopoietic SCT (HSCT). The ideal model to solve the conundrum consists of the transplants mismatched for HLA-DRB1*14:01/*14:54 and/or for HLA-DRB3*02:01/*02:02. A task force was set up in Italy to recruit transplanted pairs defined as HLA-DRB1*14:01 before 2006, the year crucial for the proper definition of the HLA-DRB1*14:54 allele in molecular biology. Out of 2723 unrelated pairs, 189 transplanted in Italy from 1995 to 2006 were HLA-DRB1*14:01 positive; 103/189 pairs with good historical DNA were retyped for HLA-DRB1*14 and HLA-DRB3 at-high resolution level; 31/103 pairs had HLA-DRB1*14 and/or HLA-DRB3 mismatched; 99/103, having complete clinical data, underwent statistical analysis for OS, TRM, disease-free survival and acute and chronic GvHD. No significant involvement of HLA-DRB1*14:01/*14:54 or HLA-DRB3*02:01/*02:02 mismatches was found, either alone or combined. Our findings suggest that disparities at exon 3 of the HLA-DRB1 gene seem unlikely to influence the outcome after HSCT. The same may be envisaged for HLA-DRB3(*)02:01 and (*)02:02 alleles which, although differing in the Ag binding site, seem unable to modulate an appreciable immune response in an HSCT setting.

Distribution of killer cell immunoglobulin-like receptors genes in the Italian Caucasian population.

BACKGROUND: Killer cell immunoglobulin-like receptors (KIRs) are a family of inhibitory and activatory receptors that are expressed by most natural killer (NK) cells. The KIR gene family is polymorphic: genomic diversity is achieved through differences in gene content and allelic polymorphism. The number of KIR loci has been reported to vary among individuals, resulting in different KIR haplotypes. In this study we report the genotypic structure of KIRs in 217 unrelated healthy Italian individuals from 22 immunogenetics laboratories, located in the northern, central and southern regions of Italy. METHODS: Two hundred and seventeen DNA samples were studied by a low resolution PCR-SSP kit designed to identify all KIR genes. RESULTS: All 17 KIR genes were observed in the population with different frequencies than other Caucasian and non-Caucasian populations; framework genes KIR3DL3, KIR3DP1, KIR2DL4 and KIR3DL2 were present in all individuals. Sixty-five different profiles were found in this Italian population study. Haplotype A remains the most prevalent and genotype 1, with a frequency of 28.5%, is the most commonly observed in the Italian population. CONCLUSION: The Italian Caucasian population shows polymorphism of the KIR gene family like other Caucasian and non-Caucasian populations. Although 64 genotypes have been observed, genotype 1 remains the most frequent as already observed in other populations. Such knowledge of the KIR gene distribution in populations is very useful in the study of associations with diseases and in selection of donors for haploidentical bone marrow transplantation.

Comparative analysis of national regulations concerning blood safety across Europe.

In October 2001, representatives of 17 European countries (Albania, Bosnia-Herzegovina, Bulgaria, Croatia, Czech Republic, Federal Republic of Yugoslavia, Finland, France, Germany, Greece, Italy, Macedonia, Romania, Slovenia, Spain, Turkey and UK) met in Sarajevo at a course organized by the European School of Transfusion Medicine to discuss their countries' regulations concerning different aspects of the safety of blood transfusion. Results are summarized in tables to facilitate comparisons. Most countries (13/17) have specific transfusion laws and 9/17 have hospital-based systems as opposed to national organizations. Quality assurance is common among investigated countries (14/17). Voluntary associations are responsible for donor promotion in the majority of countries (13/17). Exclusively, voluntary non-remunerated donors are found in 5/17 countries, whereas in the remaining ones, incentives, family replacement and remuneration are mechanisms stimulating blood donation. Medical doctors using official selection criteria are checking donor suitability in virtually all countries, which also perform main microbiological testing. Regulations on good clinical use of blood and derivatives are present in most countries but applied only in some. Although the data presented need to be interpreted with some caution, this preliminary analysis shows that, although some significant differences still exist, the majority of countries studied are moving in the same direction to ensure safety of their blood supply.

An immunogenetic map of Lombardy (Northern Italy).

For this study we consulted the Bone Marrow Donors' Registry of Lombardy (Italy) and analyzed 43937 HLA-A,B phenotypes and 13922 HLA-A,B,DR phenotypes. We estimated the HLA-A,B and HLA-A,B,DR haplotype frequencies via the maximum-likelihood method. We analyzed the genetic structure of the 11 provinces of Lombardy by means of Principal Component Analysis and Correspondence Analysis, and estimated the variety of the different haplotypes at provincial level and the percentage of unique phenotypes at village level. We found 11189 different HLA-A,B phenotypes, 661 different HLA-A,B haplotypes and more than 4000 different HLA-A,B,DR haplotypes. We identified 20 villages, in Western Lombardy, very rich in unique/rare phenotypes. Here we report a formula which allows the identification of a putative donor matched for two haplotypes with a recipient. This result may be of great importance for the genetic study of the population of Lombardy and, even more, for bone marrow transplantation programs.

Comparison of plateletpheresis concentrates produced with Spectra LRS version 5.1 and LRS Turbo version 7.0 cell separators.

BACKGROUND: The importance of transfusing WBC-reduced blood components is widely recognized, as it reduces the risk of alloimmunization and transfusion-transmitted CMV infections. The latest generation of cell separators allows the collection of WBC-reduced apheresis platelet concentrates (APCs). MATERIALS AND METHODS: Consecutive APCs (n = 232) were retrospectively evaluated: 163 collected with the Spectra LRS [leukocyte-reduction system] Version 5.1 (Group A) and 69 with the LRS Turbo Version 7.0 (Group B) (both: COBE BCT). Donor peripheral blood count, procedure data, platelet yield, collection efficiency (CE), and residual WBC count in APCs were recorded. RESULTS: The platelet yield was higher in Group B than in Group A: 5.5 +/- 1.4 versus 4.4 +/- 1.1, p<0.0001; residual WBCs were <5 x 10(6) in 99.4 percent of Group A APCs and in 97.1 percent of Group B APCs. CE was higher in Group B than in Group A: 51.4 +/- 8.7 versus 43.6 +/- 6.3, p<0.0001. Moreover, a correlation between predonation platelet count and platelet yield was observed in both groups. A double product (platelet yield >6.0 x 10(11)) was obtained in 28.9 percent of Group B APCs and in 9.2 percent of Group A APCs. CONCLUSIONS: The Spectra LRS Turbo version 7.0 release showed a better CE and resulted in a higher platelet harvest than did the LRS version 5.1. High predonation platelet counts allow a higher platelet yield.

Bone marrow transplantation for childhood hematological disorders: a global pediatric approach in a twelve year single center experience.

One hundred and 43 consecutive pediatric patients (June 1985-December 1996) with at least 18 months of follow-up, were considered: most of the patients (111/143, 77.6%) underwent allogeneic BMT. The median follow-up was 5.7 years. Overall survival and 5 years EFS were 48.6% and 46.9%, respectively. For patients who underwent allogeneic BMT from HLA-identical siblings, the 5 years EFS for ALL was 75% in 1st CR, 60.4% in 2nd CR, 22.3% in > 2nd CR and 86.7% for AML in 1st CR. The EFS for Allo-BMT in "good" and "poor" prognosis patients was 68.6% and 21.8%, respectively (p value = 0.001). Early mortality in Allo-BMT patients was 17.7% between 1985-1990 and 10.3% between 1991-1996. Early treatment-related organ complications occurred mostly in patients who underwent BMT from an unrelated or a mismatched family donor. Late toxicity was evaluated in 57 patients (median follow-up of 82 months): none of the patients complained of significant late cardiac or respiratory dysfunction. With regards to growth, 18/57 patients (31.6%) lost more than two height centile channels. Three cases of thyroid neoplasms were observed. Evaluation of psychosocial functioning, studied in 39 patients who had at least 2 years of follow-up in CR, did not reveal any evident quality of life impairment. The possibility of curing childhood hematological malignancies is based on a global pediatric and multidisciplinary approach. A continuous need to improve results in terms of EFS and quality of life suggests that further multicenter prospective studies should be carried out.

[Comparative analysis of PAC-I and PAC-II]. / Análise comparativa entre PAC-I e PAC-II.

Comparison between the results of students' evaluation of the University of São Paulo Medical School with the results of the coordinators' evaluation of their own program is presented; 32 programs during 1996 were studied. In 50% of the cases, the students and professors evaluation were identical. In 28.1% of the cases, the evaluations made by students were higher than the professors' evaluation, mainly in clerkship. In 21.8% of the cases, the contrary took place mainly in the first to fourth year programs.

[Teacher's opinions regarding graduation programs at the University of São Paulo Medical School--PAC-II]. / A opinião dos professores sobre seus programas na graduação médica da FMUSP-O PAC-II.

The authors show the results of the "Curricular Evaluation Program" of University of São Paulo Medical School pertaining to the year of 1996. This program (PAC-II) is based on teachers' opinions regarding the subjects taught (1st to 4th grades) and hospital intern courses. The opinions collected concerning such programs were definitely favorable. Most of the teachers considered the programs to be either good or very good. It was also identified that the hospital intern courses were a little more valued than the other courses taught in the first four grades.

[Program evaluation Curriculum of the University of São Paulo Medical School. For the year 1994 and the period 1989-1994]. / Programa de avaliação curricular da FMUSP--o ano de 1994 e o período de 1989-1994.

The authors present the results of the Program of Curriculum Evaluation of the University of São Paulo Medical School for the year of 1994, as well as the 1989-1994 period. The academic year of 1994 wasn't a good year to the medical graduation regarding disciplines from the first to the fourth year; only 14.3% of the disciplines achieved 90% or more of "excellent" + "good". The disciplines held at internship continued, on the most, doing well. The analysis of the 1989-1994 period outstands different sequential evaluation.

Donor organ procurement in the North Italy Transplant program (NITp) in 1994: the beginning of a promising trend?

Donor organ procurement is a world-wide problem. In Italy it is particularly so and the reasons for this are investigated. An overall increase in the number of donors has been noted in 1994 and the first 8 months of 1995, and ways of continuing this encouraging trend should be pursued by improvements in education, legislation, and hospital organization.

[Curriculum evaluation program of the University of São Paulo Medical School--results for 1993 and a 5-year analysis]. / Programa de avaliação curricular da Faculdade de Medicina da Universidade de São Paulo--resultados de 1993 e análise quinqüenal.

The following report contains the results of the "Curricular Evaluation Program" of University of São Paulo Medical School pertaining to the year of 1993 and to the five-year period between 1989 and 1993. This evaluation of all undergraduate courses was made by students, responding to questionnaires supplied at the end of each program. In 1993, 60.6% of programs were considered as very good programs. In relation to 1989-1993 period, are presented the results of a disciplines group of the 4th year and a internship stages of the 5th year.

[Opinion of the people in charge of the medical graduation disciplines at the São Paulo University Medical School on the 'curriculum evaluation program']. / Opinião dos responsáveis pelas Disciplinas da Graduação Médica da FMUSP sobre o "Programa de Avaliação Curricular".

Results of "Curricular Evaluation Program" (CEP) of Medical School of S. Paulo University (FMUSP) are presented. CEP numbers are obtained form students answers offered to a padronized questionnaire which included theoretical and practical aspects of curricular process. Authors asked for the opinion of curricular disciplines coordinators of FMUSP about CEP and concluded: 1. CEP has large or reasonable profitability for 95.3% of coordinators; 2. CEP questionnaire was considered adequate by 85.7% of respondents, but 42.8% mentioned deficiencies in questionnaire revitance to them; 3. CEP presents excellent performance at FMUSP departments level.

HLA-DRB1 compatibility in cadaver kidney transplantation: correlation with graft survival and function.

The introduction of genomic HLA-DR typing has stimulated a re-evaluation of the role of HLA-DR compatibility on cadaver kidney transplantation. We retrospectively studied the influence of HLA-DRB1 matching on the survival of 416 patients using univariate and Cox regression analysis as well as its influence on the occurrence of rejection episodes and on creatinine level at the 3rd month in the 198 recipients for whom these data were available. The following parameters were also considered: HLA-A,B compatibility, donor and recipient age, graft number, pre-transplant blood transfusions and panel reactive antibodies (PRA). Twenty-four month graft survival was 100% for transplants with zero mismatches (n = 47), 87.9% for those with one mismatch (n = 191) and 81.3% for those with two mismatches (n = 178). In the Cox model, HLA-DRB1 matching was the most significant variable influencing graft survival (47% of chi 2 P = 0.001), followed by HLA-A,B matching (23%, P = 0.02) and donor age (19%, P = 0.04). Ninety-two percent of the patients with zero mismatches experienced no rejection episodes in the first 3 posttransplant months compared with 62% and 41% of patients with one and two mismatches, respectively. Mean creatinine level (mg/dl) was 1.2, 1.4, and 1.5 in patients with zero, one, and two mismatches, respectively. Should these results be confirmed by prospective studies, HLA-DRB1 compatibility will have to be considered as an organ allocation criterion.

Cadaver kidney transplantation in the north Italy transplant program in the nineties.

The most relevant changes which have taken place in the NITp in the nineties include the introduction of HLA-DRB1 matching, the extension of both recipient and donor selection criteria, and an increase in donor procurement and consequently, in transplantation activity. Some of the changes in policy resulted from extensive analysis of our previous experience. For the future years, the NITp has set the following priorities: Consolidate the increase of donor procurement activity registered in the past 15 months by educational campaigns for health workers and the public, and organizational measures aimed at strengthening ICUs, nominating transplant coordinators and introducing a system of reimbursement for organs procured. Improve the quality of results in terms of patient rehabilitation and cost-benefit through: continued evaluation of protocols for patient admission on the waiting lists and careful selection of donors; and prospective use of genomic HLA Class II matching and also consider genomic typing for HLA Class I which is almost a reality. Establish a single pool of patients on the waiting list evaluated according to common protocols with the possibility of performing the transplant in each of the authorized centers in turn, respecting the best HLA match and the local use of organs. Finally, standards for donor treatment, organ procurement, histocompatibility testing and transplantation must be established. For this purpose, accreditation programs which have begun to be applied in Europe seem to be the adequate tool.