Impact of highly conserved HLA haplotype on acute graft-versus-host disease

Morishima, Satoko; Ogawa, Seishi; Matsubara, Aiko; Kawase, Takakazu; Nannya, Yasuhito; Kashiwase, Koichi; Satake, Masahiro; Saji, Hiroo; Inoko, Hidetoshi; Kato, Shingo; Kodera, Yoshihisa; Sasazuki, Takehiko; Morishima, Yasuo

doi:10.1182/blood-2009-10-251157

Cited by 80 publications

(89 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our transplantation results are in concordance with results from Petersdorf et al 4 and the Japanese study, 5 showing less Xgrade II aGVHD in the patients with FH. Although there are genetic differences between our population and the Japanese population, the principle appears to be similar.…”

Section: Discussionsupporting

confidence: 82%

“…Immunogenetic profiles for successfully transplanted individuals including parameters as HLA haplotypes and cytokine gene polymorphism may contribute to a better understanding of the underlying mechanisms leading to aGVHD. 9 Morishima et al 5 demonstrated that the HLA haplotype itself affects incidence of aGVHD. These findings suggest that the genetic factor of specific haplotypes would contribute to reducing or increasing the risk of aGVHD.…”

Section: Discussionmentioning

confidence: 99%

“…It appeared that the genetic factor of specific haplotypes is associated with either increased or decreased risk of aGVHD. 5 The role of some of these non-HLA genes have been studied (reviewed [6][7][8][9][10] ): single nucleotide polymorphisms and/or microsatellites within cytokine (-receptor) genes and other non-HLA encoded genes, including those of the innate immune system, may indeed influence HSCT outcome. [11][12][13][14][15][16][17] Genes in the TNF block, MICA/MICB and microsatellite markers are of specific interest because they are in linkage disequilibrium (LD) with the classical HLA genes and could be inherited together as one genetic unit.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

show abstract

“…This difference from our results may be partly explained by the fact that, in the Valcarcel study, the MUD group included a significantly smaller number of ALL patients with low-risk cytogenetics. Alternatively, it can be explained by less severe GVHD and a possibly lower rate of GVHD-associated mortality in 8/8 MUD transplantation in the JMDP cohorts due to genetic homogeneity, and potential matching of HLA haplotypes, some of which are highly conserved [17].…”

Section: Hla 1-antigen Mismatched Related Transplantationmentioning

confidence: 99%

Effect of HLA mismatch on acute graft-versus-host disease

Kanda

2013

Int J Hematol

View full text Add to dashboard Cite

HLA matching between donors and recipients is the most important factor associated with acute graftversus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation. With improvements in GVHD prophylaxis and supportive care, transplantations from HLA mismatched donors are performed increasingly frequently, drawing greater attention to the effects of HLA mismatch. In related transplantation, HLA 1-antigen mismatch at the HLA-A, HLA-B, and HLA-DR loci is considered acceptable, but the incidence of severe acute GVHD under standard prophylaxis is higher than that for matched related and unrelated transplantation, highlighting the need for a modification of GVHD prophylaxis. Development of new GVHD prophylaxes has now made HLA 2-3-antigen mismatched related transplantation feasible, and has almost overcome the HLA barrier. In unrelated bone marrow or peripheral blood stem cell transplantation, donors matched for HLA-A, HLA-B, HLA-C, and HLA-DRB1 alleles are the most preferable. The impact of allele or antigen mismatch has been evaluated in a number of studies, but the results of these have not been consistent, partly due to differences in race and HLA distribution. The effects of HLA mismatch may differ depending on the year of transplantation and the form of GVHD prophylaxis administered. In cord blood transplantation, successful transplantation can be achieved with up to two HLA mismatches. In children, compared to the use of HLA mismatched units, the use of HLA-matched units is associated with a lower risk of acute GVHD and mortality, while in adults HLA mismatches may have a lower impact on outcome. Thus, the effect of HLA matching should be evaluated separately for different stem cell sources.

show abstract

“…34 Recent studies from the Japan Marrow Donor Registry have demonstrated that highly conserved common HLA haplotypes, ranging from the centromeric HLA-DPB1 to the telomeric HLA-A, display a strong correlation with reduced incidences of aGVHD. 35 It is possible that our patient groups share certain low-GVHD haplotypes that are characteristic of the southern Han Chinese people, although obtaining confirmation of this conjecture would require further analysis.…”

Section: Discussionmentioning

confidence: 99%

A novel conditioning regimen improves outcomes in β-thalassemia major patients using unrelated donor peripheral blood stem cell transplantation

Li¹,

Wang²,

Feng³

et al. 2012

Blood

111

View full text Add to dashboard Cite

We used a novel NF-08-TM transplant protocol based on intravenous busulfan, cyclophosphamide, fludarabine, and thiotepa in 82 consecutive patients with ␤-thalassemia major (TM), including 52 with allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated donors (UDs) with well-matched human leukocyte antigens and 30 with hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSDs). The median age at transplantation was 6.0 years (range, 0.6-15.0 years), and the ratio of male-to-female patients was 56:26. The median follow-up time was 24 months (range, 12-39 months). The estimated 3-year overall survival and TMfree survival were 92.3% and 90.4% in the UD-PBSCT group and 90.0% and 83.3% in the MSD-HSCT group. The cumulative incidences of graft rejection and grades III-IV acute graft-versus-host disease were 1.9% and 9.6%, respectively, in the UD-PBSCT group and 6.9% and 3.6%, respectively, in the MSD-HSCT group. The cumulative incidence of transplant-related mortality was 7.7% in the UD-PBSCT group and 10.0% in the MSD-HSCT group. In conclusion, UD-PBSCTs using the welltolerated NF-08-TM protocol show similar results to MSD-HSCTs and can be used to treat ␤-thalassemia patients in the absence of MSDs. (Blood. 2012;120(19): 3875-3881)

show abstract

Impact of highly conserved HLA haplotype on acute graft-versus-host disease

Cited by 80 publications

References 28 publications

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

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

Effect of HLA mismatch on acute graft-versus-host disease

A novel conditioning regimen improves outcomes in β-thalassemia major patients using unrelated donor peripheral blood stem cell transplantation

Contact Info

Product

Resources

About