The importance of HLA-DPB1 in unrelated donor hematopoietic cell transplantation

Shaw, Bronwen E.; Gooley, Theodore A.; Malkki, Mari; Madrigal, J. Alejandro; Begovich, Ann B.; Horowitz, Mary M.; Gratwohl, Aloïs; Ringdén, Olle; Marsh, Steven G.E.; Petersdorf, Effie W.

doi:10.1182/blood-2007-06-095265

Cited by 177 publications

(162 citation statements)

References 38 publications

Supporting

Mentioning

140

Contrasting

Unclassified

Order By: Relevance

“…However, we found that the addition of HLA-DPB1 matching to conventional matching algorithms did have practical benefits. We agree with previous publications 410, 12 that matching between host and donor should be performed at 12 loci, including DPB1, in T-cell-depleted PBSC transplantation, when MA conditioning is employed. In acute leukaemia and MDS, as defined in our study population, we see no advantage of mm at DPB1.…”

Section: Discussionsupporting

confidence: 78%

“…[7][8][9] HLA-DPB1 matching is not included in most donor selection algorithms, despite a growing body of evidence reporting a significant impact of disparity at this locus on post transplant complications. 4,[10][11][12][13][14][15][16] HLA-DP molecules present antigenic peptides to T cells, and in the transplant setting allogeneic HLA-DP-specific T cells have been identified in GVHD and GVL reactions. [17][18][19] In T-replete transplants, the effect of mm HLA-DPB1 has been an increase in both GVHD and GVL resulting in a reduced relapse rate (RR), but at the expense of increased nonrelapse mortality (NRM).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In a 12-allele analysis HLA-DPB1 matching is associated with improved OS in leukaemic and myelodysplastic patients receiving myeloablative T-cell-depleted PBSCT from unrelated donors

Burt

Parker

McQuaker

et al. 2014

Bone Marrow Transplant

View full text Add to dashboard Cite

The effect on survival of including HLA-DPB1 in a 12-allele matching strategy was retrospectively evaluated in 130 patients with acute leukaemia and myelodysplasia undergoing T-cell-depleted PBSC transplantation using unrelated donors. Patients received alemtuzumab in vivo T-cell depletion as part of a myeloablative (MA; n ¼ 61) or reduced-intensity conditioning regimen (n ¼ 69). No difference in OS was seen with single-locus mismatching (mm) when 10 conventional alleles (HLA-A, B, C, DRB1 and DQB1) were considered. However, the addition of HLA-DPB1 matching data proved highly discriminatory. Mismatches were identified in 87% of patients previously considered fully matched (1DPmm ¼ 49pts: 2DPmm ¼ 28pts), and in the 9/10 group 22 patients were reclassified as double and 16 as triple mismatches. In 10/10 transplants, there was a distinct trend to poorer OS with double DPB1 mm. If all 12 loci were considered, 98% of single mm were at HLA-DPB1. Furthermore, cumulative mm at two or more loci was associated with significantly poorer 3-year OS (34% vs 48%, P ¼ 0.013: hazard ratio 1.8 (95% confidence interval 1.14-3.06; P ¼ 0.017), although his detrimental effect was only apparent using MA conditioning, in which reduced OS was associated with increased chronic GVHD (61% vs 16%, P ¼ 0.018) and nonrelapse mortality (30% vs 9%, P ¼ 0.039).

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

In a 12-allele analysis HLA-DPB1 matching is associated with improved OS in leukaemic and myelodysplastic patients receiving myeloablative T-cell-depleted PBSCT from unrelated donors

Burt

Parker

McQuaker

et al. 2014

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…DPB1 matches were not identified as a confounding factor in any of the analyses and therefore, did not influence our results. 41 We believe we have dealt with possible confounding from these variables in the appropriate way. The use of the classical D for quantifying LD may constitute a potential weakness in our analysis, because the D calculations are probably only an estimation of the true LD.…”

Section: Discussionmentioning

confidence: 99%

The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT

Jöris

Lankester

Borne

et al. 2012

Bone Marrow Transplant

View full text Add to dashboard Cite

The MHC region on chromosome 6 contains a large number of non-HLA genes next to the HLA genes. Matching for HLA in unrelated hematopoietic SCT (HSCT) does not necessarily mean that these non-HLA genes are also matched. We selected 348 Northwest European patients transplanted with an HLA-A-, -B-, -C-, -DRB1-, -DQB1-matched unrelated donor (MUD) between 1987 and 2008. Patients' haplotypes were identified via descend. We were unable to determine the haplotypes of the donor; therefore we used frequent haplotypes (FH) in high linkage disequilibrium (LD) as a proxy for haplotype matching. Presence of a FH in a patient positively affected the probability and speed of identifying a matched unrelated donor. Competing risk survival analysis showed that patients with one or two FH have a statistically significantly decreased probability of developing Xgrade II acute GVDH (aGVHD) without increased risk of relapse compared to patients without FH (HR (95% CI): 0.53 (0.31-0.91)). This association was strongest for those FH with the highest LD between both HLA-A and -C or -B, and HLA-C or -B and -DRB1 (HR (95% CI): 0.49 (0.26-0.92)). These results extend evidence that non-HLA allele coding regions have a significant impact on development of Xgrade II aGVHD. We conclude that there is more to successful HSCT than matching for HLA genes.

show abstract

“…Later, Shaw et al once again analyzed the clinical importance of HLA-DPB1 in unrelated ASCT. [16][17][18] In this study HLA-DPB1 mismatch predicted an increased risk of aGVHD and the effect of HLA-DPB1 on relapse was significant only in patients matched for 10/10 alleles. There was an increased risk of mortality in the patients who were mismatched for HLA-DPB1, however this did not remain significant in multivariate analysis.…”

Section: Discussionmentioning

confidence: 98%

“…[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] For instance, in the study by Loiseau et al reported increased frequency of severe aGVHD and poorer survival in two HLA-DP incompatibilities in a group of unrelated ASCT patients. 10 In this study they were not able show a significant relationship between HLA-DP mismatches and disease relapse.…”

Section: Discussionmentioning

confidence: 99%

Impact of HLA-DPB1 Matching in Unrelated Allogeneic Stem Cell Transplantation: Results of Two Centers From Turkey

Kantarcıoğlu¹

2017

UHOD

View full text Add to dashboard Cite

In this study, we retrospectively examined 34 donor/recipient transplant pairs fully tested for the alleles HLA-A, B, C, DRB1, DQB1 and DPB1 in two different centers in Istanbul, Turkey. HLA-DPB1 disparity in at least one antigen level was 79.6% and only 20.6% of transplant pairs were fully identical for HLA-DPB1, in our study group. Neutrophil and thrombocyte engraftment successfully occurred in the entire study group. When the occurrence of severe (Grade III-IV) aGVHD was taken into account, we have observed that, non-permissive HLA-DPB1 mismatches were a significant factor for development of severe aGVHD (p= 0.019). There was a trend of increasing significance for the gut (p= 0.006) and liver (p: 0.054) aGVHD but not for skin aGVHD in non-permissive HLA-DPB1 mismatched transplantations. In multivariate analysis, non-permissive HLA-DPB1 mismatches remained as an independent factor for severe aGVHD. Our results did not show a significant impact of HLA-DPB1 mismatches on relapse. In survival analysis, both HLA-DPB1 disparities and non-permissive mismatches showed a decreasing trend of event free and overall survival times. Considering these results during donor selection may improve transplant outcomes in the setting of unrelated ASCT.

show abstract

The importance of HLA-DPB1 in unrelated donor hematopoietic cell transplantation

Cited by 177 publications

References 38 publications

In a 12-allele analysis HLA-DPB1 matching is associated with improved OS in leukaemic and myelodysplastic patients receiving myeloablative T-cell-depleted PBSCT from unrelated donors

In a 12-allele analysis HLA-DPB1 matching is associated with improved OS in leukaemic and myelodysplastic patients receiving myeloablative T-cell-depleted PBSCT from unrelated donors

The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT

Impact of HLA-DPB1 Matching in Unrelated Allogeneic Stem Cell Transplantation: Results of Two Centers From Turkey

Contact Info

Product

Resources

About