Low incidence of severe acute graft-versus-host disease in children given haematopoietic stem cell transplantation from unrelated donors prospectively matched for HLA class I and II alleles with high-resolution molecular typing

Abstract

Summary:We evaluated the outcome of 63 children given haematopoietic stem cell transplantation from unrelated donors (URD-HSCT) prospectively selected using DNA highresolution typing of both HLA class I and class II loci. Thirty patient/donor pairs (48%) were fully matched. Among the others, HSCT was performed in the presence of one (n ¼ 22), two (n ¼ 9), or three (n ¼ 2) HLA disparities. Patients had either malignant (n ¼ 46) or non-malignant (n ¼ 17) disease. In all cases, graft-versushost disease (GVHD) prophylaxis consisted of cyclosporin A, short-term methotrexate and pretransplant antithymocyte globulin. The probability of haematopoietic recovery at day 100 was 97%. Two patients experienced primary graft failure. The cumulative probability of grades III-IV acute GVHD and of extensive chronic GVHD equalled 8 and 14%, respectively. A total of 12 patients died of transplant-related complications. The probability of transplant-related mortality (TRM) at 100 and 180 days was 10 and 15%, respectively, whereas the cumulative incidence of TRM was 22%. The probability of GVHD-related mortality equalled 6% at 2.5 years. The overall and disease-free survival rates were 67 and 65%, respectively. URD-HSCT with donor selection based on high-resolution HLA typing is associated with low incidence of both severe acute GVHD and graft failure. The observed outcome is comparable to that of children transplanted from HLA-identical siblings.

High-resolution HLA typing by sequencing for HLA-A, -B, -C, -DR, -DQ in 122 unrelated cord blood/patient pair transplants hardly improves long-term clinical outcome

“…In contrast to unrelated bone marrow or adult HSC transplantation, where donor selection on high-resolution DNA typing for both HLA-class I and HLA class II loci has been reported to improve the outcome of unrelated transplantation, [1][2][3]12 the situation in CB transplantation is completely different. The majority of transplant centres search CB only if there is no unrelated matched bone marrow donor available.…”

“…At present the majority of transplant centres/cord blood banks select CB units for a respective patient based on HLA-A, -B low-resolution typing and -DRB1 HR typing. In contrast to bone marrow transplantation, where in the meantime HLA class I (A, B, C) and HLA class II (DRB1 and DQB1) high-resolution typing have been implemented for donor selection to minimize the risk of the two obstacles for successful unrelated stem cell transplantation, GvHD and graft rejection, 2,3,9 no HLA class I and II subtyping data are available for UCBT. Moreover, in contrast to publications concerning unrelated bone marrow donors where mismatches were analysed not only on an overall basis, but also for GvHD or host-versus-graft (HvG), the data are lacking for UCBT.…”

Outcomes of transplantation with partial T-cell depletion of matched or mismatched unrelated or partially matched related donor bone marrow in children and adolescents with leukemias

“…Some studies have shown that in the T-replete setting, more precise characterization and matching of class I alleles may decrease GVHD and graft rejection, and increase survival. 21 Although high-resolution matching of classes I and II may decrease the risk of certain BMT complications with T-replete stem cells, it will also limit donor availability. In contrast to other studies, we found no significant differences in EFS, GVHD or NRM between our URD recipients who were matched vs those who were mismatched.…”

The changing role of stem cell transplantation in childhood

“…16 Support for this conclusion is provided by the recent results obtained using an unrelated donor in children with ALL in second CR, with juvenile myelomonocytic leukemia or with thalassemia. [17][18][19][20] The greatest challenge: transplantation of HSC from an HLA-haploidentical relative…”