A major goal of the World Marrow Donor Association (WMDA) is to foster international transplants of hematopoietic stem cells through the establishment of guidelines and recommendations in this field. In this tradition, this study defines a comprehensive framework for HLA matching programs, which use intricate algorithms to rapidly select potential donors for a patient from a database and to present these donors in a prioritized list. Starting with the comparison of single HLA markers of the donor and the patient possibly obtained using different testing methodologies at different resolutions, the more complex matching of loci and phenotypes is inductively built up. The consensus of this international collaborative group describes the state of the art in the field and points out many important design options compatible with the best practice. This should help existing registries to review and validate the most critical part of their IT systems and newly created donor registries around the world to tackle one of their real challenges.
Cord blood unit (CBU) transplantations to patients mismatched for only 1 HLA antigen, which is identical to the CBU noninherited maternal antigen (NIMA), are designated as having a 6/6 "virtual" NIMA-matched phenotype and have a prognosis similar to 6/6 inherited HLA-matched CBUs. Such virtual HLA phenotypes of CBUs can be created by replacing the inherited alleles with 1 or more NIMAs. Phenotypes of Dutch patients (n = 2020) were matched against the inherited and virtual HLA phenotypes of the National Cord Blood Program CBU file (with known NIMA, n = 6827). Inherited 6/6 matches were found for 11% of the patients. Including virtual phenotypes resulted in, overall, 19-fold more different phenotypes than were inherited, conferring 6/6 virtual matches for an additional 20% of the patients, whereas another 17% might benefit from CBUs with a 4/6 HLA match and 1 NIMA match (4/6 + 1NIMA or 5/6 virtual match). The elucidation of donors' maternal HLA phenotypes can provide significant numbers of 6/6 and 5/6 virtually matched CBUs to patients and is potentially cost effective.
© Ferrata Storti Foundation IntroductionAllogeneic hematopoietic progenitor cell transplantation plays an important role in treatment of hematooncological diseases. For patients lacking a matched related donor, an unrelated donor (UD) or cord blood unit (CBU) may provide a valuable alternative. Alternative donors are identified through registries of volunteer unrelated donors or public cord blood banks. In the past decade, the identification and availability of UD and UCB have improved. Bone Marrow Donors Worldwide (BMDW), the file of registered unrelated donors, almost tripled (from 7.4 million donors in 2001 to over 21 million in December 2012), while the inventory of unrelated CBU grew from 87,000 in 2001 to over 500,000.1 To date (2016) the number of registered donors has increased to over 27 million, and currently over 650.000 CBU are registered. Increased knowledge of the HLA system, more well-typed donors, and the availability of several search-related software tools 2-5 have facilitated and speeded up the efficiency of the search process. [6][7][8] Simultaneously searching for a back-up donor can minimize the delay if a donor is unexpectedly not fit or unavailable to donate.9 Given these recent improvements, we set out to address the questions of whether a higher percentage of patients in need of an UD/CBU may actually reach transplantation nowadays, whether the time needed to identify an UD/CBU has decreased, and whether possible factors can be identified for potential improvement. We addressed the questions in a large cohort of 3,365 consecutive UD searches performed between 2001-2012 in the Netherlands, including searches for Dutch patients of Northwestern European (NWE) and non-Northwestern European (non-NWE) descent. Methods The patients and donor searchesEuropdonor Foundation, the Dutch Stem cell donor registry, coordinates the UD searches in the Netherlands, serving a population of 16.8 million inhabitants. There were eight adult and two pediatric stem cell transplantation units in 2012 in the Netherlands, and the number of new searches increased to approximately 500 annually. All UD and CBU searches performed from 2001 until 2012 for the patients of all Dutch transplantation centers were included (n=3,365, Figure 1) for the initial 'donor found' analysis, and divided into two periods: cohort I, 2001-2006 (n=1,093) and cohort II, 2007II, -2012. Patients for whom a search was cancelled in less time than the median search time for the given year, and for whom no donor was yet identified were excluded for the 'donor found' analysis (cohort I, n=75; cohort II, n=131), leaving 3,124 evaluable search cases. Each cohort was split according to NWE and non-NWE descent. Patients were assigned to NWE or non-NWE background based upon self-identified descent.10 Descendants from the Netherlands, Germany, Belgium, Luxembourg, Great Britain, Ireland, and Scandinavia were considered NWE. The non-NWE group consisted of patients with self-reported genetic ancestry in Northern Africa (n=51), Sub-Saharan A...
For more than two decades, international cooperation and information technology have been playing key roles in the identification of suitable unrelated donors and cord blood units for hematopoietic SCT. To ensure consistent coding and interpretation of HLA data among the linked computer systems, the World Marrow Donor Association has standardized the extensions of the World Health Organization (WHO) Nomenclature for factors of the HLA system applied in practice. The first version of this report published in 2007 has become the reference for the technical validation of HLA information on donors and patients in the context of search and matching and is used by registries of volunteer unrelated hematopoietic stem cell donors and umbilical cord blood banks throughout the world. The present update became necessary after the major revision of the WHO HLA nomenclature in April 2010. It now covers issues arising when alleles are withdrawn or renamed because of the continuous updating of the WHO HLA nomenclature. In addition, formal validation and interpretation rules for the so-called 'multiple allele codes' have been added.
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