Presence of centromeric but absence of telomeric group B KIR haplotypes in stem cell donors improve leukaemia control after HSCT for childhood ALL

Babor, Florian; Peters, Christina; Manser, Angela R.; Glogova, Evgenia; Sauer, Martin; Pötschger, Ulrike; Ahlmann, Martina; Cario, Gunnar; Feuchtinger, Tobias; Gruhn, Bernd; Güngör, Tayfun; Horn, Peter A.; Kremens, Bernhard; Lang, Peter; Mezger, Markus; Müller, Ingo; Mytilineos, Joannis; Oevermann, Lena; Pichler, Herbert; Scherenschlich, Nadine; Schuster, Friedhelm R.; Siepermann, Meinolf; Stachel, Daniel; Strahm, Brigitte; Wößmann, Wilhelm; Escherich, Gabriele; Zimmermann, Martin; Schrappe, Martin; Eckert, Cornelia; Bader, Peter; Uhrberg, Markus; Meisel, Roland

doi:10.1038/s41409-019-0543-z

Cited by 16 publications

(14 citation statements)

References 40 publications

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“…We did not find full-length KIR 2DS4 had significant effect on OS and RFS (P = .13; P = .14). While it is worth noting that although there was no statistical difference between the two groups, we can see 41,42 In this study, KIR genotype had no significant effect on OS (P = .962, HR = 1.021) and RFS (P = .926, HR = 0.96).…”

Section: Impact Of Full-length Kir2ds4 On Relapsecontrasting

confidence: 64%

The impact of donor full‐length KIR2DS4 in the development of acute and chronic GVHD after unrelated allogeneic HSCT

Luo

et al. 2020

Pediatric Transplantation

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Background Killer Ig‐like receptor 2DS4 (KIR2DS4) is the most prevalent activating killer Ig‐like receptor gene. It is divergent and encodes either full‐length or deleted allele variants. The studies of donor killer KIR2DS4 in unrelated allogeneic hematopoietic stem cell transplantations were limited. Methods KIR and HLA genotyping were determined in 75 pairs of Chinese pediatric hematologic malignancy patients. Results Among the 75 donor‐recipient pairs, 77.3% (58/75) of the donors were positive for full‐length KIR2DS4 and 22.7% (17/75) were negative. Patients who had donors positive for full‐length KIR2DS4 had higher cumulative incidence of aGVHD than patients whose donor negative for full‐length KIR2DS4 (86.2% versus 76.5%, P = .038). Multivariate analysis showed full‐length KIR2DS4 was the significant factor for I‐IV aGVHD (HR = 2.166, 95% CI: 1.01‐4.26, P = .025). Subgroup analysis showed that AML and CML patients who received donors negative for full‐length KIR2DS4 have a higher cumulative incidences of cGVHD (75% vs 62%, P = .008). There were no significant effects of full‐length KIR2DS4 on overall survival (P = .13), relapse‐free survival (P = .14), CMV reactivation (P = .52), and relapse (HR = 0.38, 95% CI: 0.09‐1.6, P = .1875). Conclusions Our findings indicated a significant correlation of donor full‐length KIR2DS4 on aGVHD and cGVHD. These results suggested that combining KIR and HLA genotyping may help make a better sense of transplants in these patients.

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Section: Impact Of Full-length Kir2ds4 On Relapsecontrasting

confidence: 64%

The impact of donor full‐length KIR2DS4 in the development of acute and chronic GVHD after unrelated allogeneic HSCT

Luo

et al. 2020

Pediatric Transplantation

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“…In addition to the technique of adoptive transfer, many studies have analyzed the effects of innate donor-recipient NK cell alloreactivity on GVHD in a clinical setting. The majority of studies did not report a significant association between these parameters ( 41 – 44 , 46 , 47 , 50 , 51 , 54 – 56 , 59 , 65 , 66 , 79 , 81 , 83 , 87 – 89 , 91 – 93 , 97 , 98 , 102 , 104 ), while some reported a protective effect ( 70 , 74 , 76 ). Moreover, several studies found that KIR ligand mismatch or receptor-ligand mismatch increased the risk of GVHD ( 45 , 57 , 60 , 64 , 68 , 80 ).…”

Section: Kir and Transplant Outcomesmentioning

confidence: 96%

“…Five of these studies reported that the protection effects mainly existed in the KIR Cen-B locus ( 67 , 88 , 91 , 92 , 96 ). Babor et al further suggested that the presence of Cen-B with absence of Tel-B improved leukemia control in pediatric patients with ALL ( 97 ). At the genetic level, the KIR2DS2 gene, which is located on the Cen-B motif ( 72 , 76 , 79 , 90 , 92 , 96 ), and the KIR2DS1 gene, located on the Tel-B motif ( 51 , 72 , 82 , 98 ), were found to be related to a decreased relapse rate or an improved survival.…”

Section: Kir and Transplant Outcomesmentioning

confidence: 99%

Influence of KIR and NK Cell Reconstitution in the Outcomes of Hematopoietic Stem Cell Transplantation

Gao

et al. 2020

Front. Immunol.

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Natural killer (NK) cells play a significant role in immune tolerance and immune surveillance. Killer immunoglobin-like receptors (KIRs), which recognize human leukocyte antigen (HLA) class I molecules, are particularly important for NK cell functions. Previous studies have suggested that, in the setting of hematopoietic stem cell transplantation (HSCT), alloreactive NK cells from the donor could efficiently eliminate recipient tumor cells and the residual immune cells. Subsequently, several clinical models were established to determine the optimal donors who would exhibit a graft-vs. -leukemia (GVL) effect without developing graft-vs. -host disease (GVHD). In addition, hypotheses about specific beneficial receptor-ligand pairs and KIR genes have been raised and the favorable effects of alloreactive NK cells are being investigated. Moreover, with a deeper understanding of the process of NK cell reconstitution post-HSCT, new factors involved in this process and the defects of previous models have been observed. In this review, we summarize the most relevant literatures about the impact of NK cell alloreactivity on transplant outcomes and the factors affecting NK cell reconstitution.

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“…Notably, comparing the outcome of ALL and AML patients, a different role of donor centromeric regions was reported. Indeed, Cen B/x Tel A/A donor KIR repertoire was associated with a very low relapse rate in ALL patients, whereas a fully A/A donor genotype significantly reduced relapse risk for AML patients. The relevance of this novel algorithm for donor selection was discussed.…”

Section: Kir and Transplantationmentioning

confidence: 99%

Report from the Eleventh Killer Immunoglobulin‐like Receptor (KIR) Workshop: Novel insights on KIR polymorphism, ligand recognition, expression and function

Falco

Sivori

Meazza

et al. 2019

HLA

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The Eleventh Killer Immunoglobulin‐like Receptor (KIR) Workshop was held in Camogli (Genoa, Italy) in October 2018. This congress brought together 113 participants working on KIR field. Fifty‐eight studies have been presented, the majority of which included unpublished data. Thus, KIR workshop, allowing the meeting of people sharing their knowledge and experience in a friendly atmosphere, still represents a special event of fruitful discussion and exchange of novel breakthrough, results, and ideas. In this report, we summarize all the scientific contributions highlighting the most recent advances in KIR field. Forty abstracts presented at the KIR Workshop are published in this issue.

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Presence of centromeric but absence of telomeric group B KIR haplotypes in stem cell donors improve leukaemia control after HSCT for childhood ALL

Cited by 16 publications

References 40 publications

The impact of donor full‐length KIR2DS4 in the development of acute and chronic GVHD after unrelated allogeneic HSCT

The impact of donor full‐length KIR2DS4 in the development of acute and chronic GVHD after unrelated allogeneic HSCT

Influence of KIR and NK Cell Reconstitution in the Outcomes of Hematopoietic Stem Cell Transplantation

Report from the Eleventh Killer Immunoglobulin‐like Receptor (KIR) Workshop: Novel insights on KIR polymorphism, ligand recognition, expression and function

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