Europdonor Foundation

Leiden, Netherlands

Europdonor Foundation

Leiden, Netherlands

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Boo M.,National Marrow Donor Program | Van Walraven S.M.,Europdonor Foundation | Chapman J.,University of Sydney | Lindberg B.,National Marrow Donor Program | And 6 more authors.
Blood | Year: 2011

Hematopoietic stem cell transplantation is a curative procedure for life-threatening hematologic diseases. Donation of hematopoietic stem cells (HSCs) from an unrelated donor, frequently residing in another country, may be the only option for 70% of those in need of unrelated hematopoietic stem cell transplantation. To maximize the opportunity to find the best available donor, individual donor registries collaborate internationally. To provide homogeneity of practice among registries, the World Marrow Donor Association (WMDA) sets standards against which registries are accredited and provides guidance and regulations about unrelated donor safety and care. A basic tenet of the donor registries is that unrelated HSC donation is an altruistic act; nonpayment of donors is entrenched in the WMDA standards and in international practice. In the United States, the prohibition against remuneration of donors has recently been challenged. Here, we describe the reasons that the WMDA continues to believe that HSC donors should not be paid because of ethical concerns raised by remuneration, potential to damage the public will to act altruistically, the potential for coercion and exploitation of donors, increased risk to patients, harm to local transplantation programs and international stem cell exchange, and the possibility of benefiting some patients while disadvantaging others. © 2011 by The American Society of Hematology.


van Halteren A.G.,Immunology Laboratory | Netelenbos T.,Leiden University | Fechter M.,Europdonor Foundation
Chimerism | Year: 2014

Allogeneic hematopoietic stem cell transplantation (HSCT) is a widely applied treatment for disorders mainly involving the hematopoietic system. The success of this treatment depends on many different patient- and donor-specific factors. Based on higher CD34+ yields and superior clinical outcomes associated with the use of male donors, males are generally seen as the preferred HSCT donor. In addition, female donors are notorious for bearing memory type lymphocytes induced by previous pregnancies; such alloimmune cells may provoke unwanted immune reactions such as graft-vs.-host disease in transplant recipients. Consequently, many transplant centers try to avoid parous donors, particularly when searching the best unrelated donor for a male patient. We recently showed that parous women with female offspring have an anti-male directed tolerogenic immune status comparable to that of nulliparous donors. As discussed in this article addendum, the sex of the donor's offspring combined with the presence of HY-specific T regulator cells are possibly better selection criteria than parity status per se.


Hurley C.K.,Georgetown University | Foeken L.,Europdonor Foundation | Horowitz M.,Medical College of Wisconsin | Lindberg B.,National Marrow Donor Program | And 2 more authors.
Bone Marrow Transplantation | Year: 2010

The World Marrow Donor Association (WMDA) is working closely with other international organizations working in cellula therapy such as the Worldwide Network for Blood and Marrow Transplantation (WBMT) to develop and maintain global recommendations and requirements for a standardized practice. WMDA launched its registry accreditation program in September 2003. Since then, 17 of the 71 hematopoietic stem cell donor registries worldwide have been accredited. These accredited registries list over 80% of the hematopoietic stem cell donors and umbilical cord blood units listed in the database of BM Donors Worldwide. The goal of the WMDA Standards and Accreditation process is to protect donors while serving the needs of patients who are urgently seeking histocompatible donors in worldwide searches. These activities address the increasing governmental regulations regarding the quality and safety of stem cells collected internationally for national patients. © 2010 Macmillan Publishers Limited.


Foeken L.M.,World Marrow Donor Association | Green A.,British Bone Marrow Registry | Hurley C.K.,Georgetown University | Marry E.,France Greffe de Moelle Registry | And 3 more authors.
Bone Marrow Transplantation | Year: 2010

The World Marrow Donor Association Annual Reports describe the current status of the use of unrelated hematopoietic cell products worldwide. In 2008, almost 1.7 million individuals were recruited into unrelated stem cell donor registries and almost 78 000 cord blood units were added to the inventory increasing the total number of available stem cell donors worldwide to over 14 million. In 2008, there were 10 481 adult stem cell donations (3221 BM and 7260 PBSC donations) provided from stem cell donor registries in 38 countries. In 2008, 3529 cord blood products were provided from 21 countries. Although the number of BM donations has been stable over the past 10 years, donations of PBSCs and umbilical cord blood are increasing. © 2010 Macmillan Publishers Limited.


Horan J.,Emory University | Wang T.,Medical College of Wisconsin | Haagenson M.,Center for International Blood and Marrow Transplant Research | Spellman S.R.,Center for International Blood and Marrow Transplant Research | And 12 more authors.
Blood | Year: 2012

The importance of human leukocyte antigen (HLA) matching in unrelated donor transplantation for nonmalignant diseases (NMD) has yet to be defined. We analyzed data from 663 unrelated marrow and peripheral blood stem cell transplants performed from 1995 to 2007 for treatment of NMD. Transplantation from a donor mismatched at the HLA-A, -B, -C, or -DRB1, but not -DQB1 or -DPB1, loci was associated with higher mortality in multivariate analyses (P = .002). The hazard ratio for mortality for single (7/8) and double mismatched (6/8) transplants was 1.29 (0.97-1.72; P = .079) and 1.82 (1.30- 2.55; P = .0004), respectively, compared with 8/8 matched transplants. HLA mismatches were not associated with acute or chronic GVHD, but were strongly associated with graft failure. After adjustment for other factors, the odds ratio for graft failure for 7/8 and 6/8 (allele and/or antigen) matched pairs compared with 8/8 matched transplants was 2.81 (1.74-4.54; P < .0001) and 2.22 (1.26-3.97; P = .006), respectively. Patients with NMD should receive transplants from allele matched (8/8) donors if possible. Unlike the case with malignancies, HLAmismatching inNMDis associated with graft failure rather than GVHD. © 2012 by The American Society of Hematology.


Fleischhauer K.,Instituto Of Ricovero E Cura A Carattere Scientifico Irccs H San Raffaele | Shaw B.E.,The Institute of Cancer Research | Shaw B.E.,Royal Free Hospital | Gooley T.,Fred Hutchinson Cancer Research Center | And 14 more authors.
The Lancet Oncology | Year: 2012

Background: The risks after unrelated-donor haemopoietic-cell transplantation with matched HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 alleles between donor and recipient (10/10 matched) can be decreased by selection of unrelated donors who also match for HLA-DPB1; however, such donors are difficult to find. Classification of HLA-DPB1 mismatches based on T-cell-epitope groups could identify mismatches that might be tolerated (permissive) and those that would increase risks (non-permissive) after transplantation. We did a retrospective study to compare outcomes between permissive and non-permissive HLA-DPB1 mismatches in unrelated-donor haemopoietic-cell transplantation. Methods: HLA and clinical data for related-donor transplantations submitted to the International Histocompatibility Working Group in haemopoietic-cell transplantation were analysed retrospectively. HLA-DPB1 T-cell-epitope groups were assigned according to a functional algorithm based on alloreactive T-cell crossreactivity patterns. Recipients and unrelated donors matching status were classified as HLA-DPB1 match, non-permissive HLA-DPB1 mismatch (those with mismatched T-cell-epitope groups), or permissive HLA-DPB1 mismatch (those with matched T-cell-epitope groups). The clinical outcomes assessed were overall mortality, non-relapse mortality, relapse, and severe (grade 3-4) acute graft-versus-host disease (aGvHD). Findings: Of 8539 transplantations, 5428 (64%) were matched for ten of ten HLA alleles (HLA 10/10 matched) and 3111 (36%) for nine of ten alleles (HLA 9/10 matched). Of the group overall, 1719 (20%) were HLA-DPB1 matches, 2670 (31%) non-permissive HLA-DPB1 mismatches, and 4150 (49%) permissive HLA-DPB1 mismatches. In HLA 10/10-matched transplantations, non-permissive mismatches were associated with a significantly increased risk of overall mortality (hazard ratio [HR] 1·15, 95% CI 1·05-1·25; p=0·002), non-relapse mortality (1·28, 1·14-1·42; p<0·0001), and severe aGvHD (odds ratio [OR] 1·31, 95% CI 1·11-1·54; p=0·001), but not relapse (HR 0·89, 95% CI 0·77-1·02; p=0·10), compared with permissive mismatches. There were significant differences between permissive HLA-DPB1 mismatches and HLA-DPB1 matches in terms of non-relapse mortality (0·86, 0·75-0·98; p=0·03) and relapse (1·34, 1·17-1·54; p<0·0001), but not for overall mortality (0·96, 0·87-1·06; p=0·40) or aGvHD (OR 0·84, 95% CI 0·69-1·03; p=0·09). In the HLA 9/10 matched population, non-permissive HLA-DPB1 mismatches also increased the risk of overall mortality (HR 1·10, 95% CI 1·00-1·22; p=0·06), non-relapse mortality (1·19, 1·05-1·36; p=0·007), and severe aGvHD (OR 1·37, 95% CI 1·13-1·66; p=0·002) compared with permissive mismatches, but the risk of relapse was the same in both groups (HR 0·93, 95% CI 0·78-1·11; p=0·44). Outcomes for HLA 10/10-matched transplantations with non-permissive HLA-DPB1 mismatches did not differ substantially from those for HLA 9/10-matched transplantations with permissive HLA-DPB1 mismatches or HLA-DPB1 matches. Interpretation: T-cell-epitope matching defines permissive and non-permissive HLA-DPB1 mismatches. Avoidance of an unrelated donor with a non-permissive T-cell-epitope mismatch at HLA-DPB1 might provide a practical clinical strategy for lowering the risks of mortality after unrelated-donor haemopoietic-cell transplantation. Funding: National Institutes of Health; Associazione Italiana per la Ricerca sul Cancro; Telethon Foundation; Italian Ministry of Health; Cariplo Foundation; National Cancer Institute; National Heart, Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; Office of Naval Research; IRGHET Paris; Swedish Cancer Society; Children's Cancer Foundation; Swedish Research Council; Cancer Society in Stockholm; Karolinska Institutet; and Leukemia and Lymphoma Society. © 2012 Elsevier Ltd.


Welte K.,National Marrow Donor Program | Foeken L.,Europdonor Foundation | Gluckman E.,Hopital St Louis | Navarrete C.,NHS Blood and Transplant
Bone Marrow Transplantation | Year: 2010

The international exchange of cord blood units (CBUs) for transplantation has brought new challenges to the stem cell donor registries involved in the exchange of BM and PBSCs. The unique properties of cord blood cells and differences in the search processes between CBUs and adult unrelated donors has required registries responsible for cord blood bank (CBB) networks to review their current practices and to develop new processes to accommodate for the provision of CBUs. This paper describes the aims and activities of the World Marrow Donor Association (WMDA) Cord Blood Working Group (CBWG) which was established in 2007 to gather and exchange information about cord blood registry needs and activities, and to develop guidelines to support and promote safe effective international exchange of unrelated CBUs for transplantation. © 2010 Macmillan Publishers Limited.


Brand A.,Europdonor Foundation | Brand A.,Leiden University | Doxiadis I.N.,Leiden University | Roelen D.L.,Leiden University
Tissue Antigens | Year: 2013

While the role of donor-specific antibodies (DSA) in solid organ transplantation is well established, their importance in hematopoietic stem cell transplantation (HSCT) is only now becoming clear. A review of the literature reporting on HLA immunization in HSCT provides ample circumstantial evidence that donor-specific HLA antibodies (DSA) are associated with a 2- to 10-fold increase of graft failure of HLA mismatched HSCT, irrespective the type of the graft, or the patient conditioning. Nevertheless, this is not a condition 'sine qua non', and engraftment has been documented despite the presence of DSA. However, prediction of graft failure based on serology is cumbersome. Although sensitivity and specificity of current solid-phase assays (SPAs) for HLA antibody detection are high, correlation with graft failure remains elusive. When lacking an alternative donor, reduction of strong reacting DSA must be attempted. Unfortunately, results of DSA reduction treatments in HSCT are scarcely reported. Case reports show that persisting DSA after plasma-exchange and immunosuppressive treatment can become negative after a 'last rescue' in vivo absorption with antigen-bearing platelets or donor lymphocyte transfusions. The destruction of engrafting hematopoietic cells by antibodies appears to be an immediate event. Blocking antibody mediated effector functions, e.g. with intravenous immunoglobulin (IvIg), may have additional value, despite IvIg often not reducing the antibody titre. An even less explored aspect of HLA-immunization is the presence of non-DSA antibodies in the host or HLA antibodies emerging post-transplantation. Such antibodies, either causally or as confounders, may be associated with negative transplant outcome. We conclude that HLA antibody assessment should be at the forefront in the treatment handbook of HSCT. © 2012 John Wiley & Sons A/S.


Somers J.A.E.,van Rood Center for Clinical Transfusion Research Sanquin Blood Supply | Somers J.A.E.,Erasmus University Rotterdam | Brand A.,van Rood Center for Clinical Transfusion Research Sanquin Blood Supply | Brand A.,Europdonor Foundation | And 9 more authors.
Biology of Blood and Marrow Transplantation | Year: 2013

Single cord blood unit (CBU) predominance is usually established within the first month after double umbilical cord blood transplantation (UCBT). However, the kinetics of engraftment of the different leukocyte subsets and the mechanism of graft predominance is largely unknown. To investigate whether a differential engraftment might reveal a specific subset that could play a key role in the mechanism of graft predominance, we studied early engraftment kinetics of different leukocyte subpopulations by flow cytometry using human monoclonal antigen-specific human leukocyte antigen antibodies, directed against mismatched human leukocyte antigen-A or -B antigens between recipient and CBUs. Twenty-two patients, who had received a double UCBT preceded by a reduced-intensity conditioning regimen, were evaluated at days +11, +18, +25, and +32 posttransplantation. Single CBU predominance in the various leukocyte subsets was established within 18 days posttransplantation. CD4+ T cells of the dominant CBU showed early peripheral blood expansion. Moreover, chimerism in CD4+ and CD8+ T cell and natural killer cell subsets at day +11 was predictive of ultimate graft predominance. These findings show that engraftment kinetics of the various leukocyte subsets vary considerably after double UCBT and may suggest an important role for CD4+ T cells in a presumed alloreactive graft-versus-graft rejection. © 2013 American Society for Blood and Marrow Transplantation.


Rutten C.E.,Leiden University | van Luxemburg-Heijs S.A.P.,Leiden University | Halkes C.J.M.,Leiden University | van Bergen C.A.M.,Leiden University | And 5 more authors.
Biology of Blood and Marrow Transplantation | Year: 2013

Clinical studies have demonstrated that HLA-DPB1-mismatched allogeneic stem cell transplantation (allo-SCT) is associated with a decreased risk of disease relapse and an increased risk of graft-versus-host disease (GVHD) compared with HLA-DPB1-matched SCT. In T cell-depleted allo-SCT, mismatching of HLA-DPB1 was not associated with an increased risk of severe GVHD, but a significant decreased risk of disease relapse was still observed. To investigate whether patient HLA-DP-specific CD4+ T cell responses were frequently induced after T cell-depleted HLA-DPB1-mismatched allo-SCT and donor lymphocyte infusion (DLI), we developed a method to screen for the presence of HLA-DP-specific CD4+ T cells using CD137 as an activation marker and analyzed 24 patient-donor combinations. The patients suffered from various B cell malignancies, multiple myeloma, and myeloid leukemias. Patient HLA-DP-specific CD4+ T cells were detected after DLI in 13 of 18 patients who exhibited a clinical response to DLI, compared with only 1 of 6 patients without a clinical response to DLI. Eight patients developed significant GVHD. These data show that patient HLA-DP-specific CD4+ T cells frequently occur after HLA-DPB1-mismatched T cell-depleted allo-SCT and DLI, and are associated with graft-versus-leukemia reactivity both in the presence and absence of GVHD. © 2013 American Society for Blood and Marrow Transplantation.

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