Hematopoietic stem cell transplants from unrelated donors

Abstract

Transplantation of hematopoietic stem cells is now well established as life-saving therapy for patients with several different genetic and acquired diseases. This has been possible largely because of the identification of HLA as the human major histocompatibility system and the application of new technologies for improving the accuracy of HLA typing and matching. Clinical advances including the development of more effective immune suppression therapy and improvements in supportive care have also been critically important. The lack of HLA-identical sibling donors for most patients and the extensive polymorphism of HLA genes have necessitated establishing very large registries of HLA-typed volunteers. With more than 3 million donors now available worldwide, the number of patients identifying HLA matches has increased substantially. Despite a higher incidence of graft-versus-host disease (GVHD), the results of unrelated donor transplants are favorable when performed under optimal conditions with a well-matched donor. In order to provide transplants for all patients, improved methods for GVHD prophylaxis are needed that will make it possible to safely perform transplants even across limited degrees of HLA disparity.

Bone marrow transplantation with unrelated donors: what is the probability of identifying an HLA-A/B/Cw/DRB1/B3/B5/DQB1-matched donor?

“…3 In the USA over 1200 unrelated BMTs are performed annually through the National Marrow Donor Program. 2 The continuous increase in the numbers of available donors augmented the probability of identifying an HLA-ABDR phenotypically matched donor at the initial search from 10-15% in 1987 to 56% in 1994, 1 70% in 1995 4 to Ͼ90% in 1997. 2 After applying DRB1 high resolution testing an HLA-ABDRB1-matched donor can be found for 40-50% of the patients.…”

“…2 The continuous increase in the numbers of available donors augmented the probability of identifying an HLA-ABDR phenotypically matched donor at the initial search from 10-15% in 1987 to 56% in 1994, 1 70% in 1995 4 to Ͼ90% in 1997. 2 After applying DRB1 high resolution testing an HLA-ABDRB1-matched donor can be found for 40-50% of the patients. 2,[5][6][7] Because of the predominance of Caucasoids in most of the national registries, donor searches are more successful for Caucasoid patients while success rates for patients from other ethnic groups are much lower.…”

“…1,2 As a consequence, in Europe one in four allogeneic transplants is now performed with marrow from an unrelated donor. 3 In the USA over 1200 unrelated BMTs are performed annually through the National Marrow Donor Program.…”

The role of donor-derived veto cells in nonmyeloablative haploidentical HSCT

“…[1][2][3][4] (2) The lengthy process of identifying, typing and harvesting an unrelated donor, with a median time interval between initiation of a search and the donation of marrow of up to 3.5 months, 4,5 which is impracticable for patients in urgent need of transplantation. Hence, transplantation of mismatched HSC as an alternative source is attractive due to its accessibility and its advantage of conferring graft-versusleukemia activity.…”

Successful haematopoietic stem cell transplantation from a matched unrelated donor following three graft failures from HLA-mismatched related donors

“…4 The incidence of graft rejection/failure following HLAmatched unrelated BMT was described to be 10-30%, and is as high as 50-75% among recipients of HLA-nonidentical T cell-depleted marrow. [5][6][7] The outlook is poor for patients with primary graft failure due to infectious complications.…”