Increased Relapse Risk of Acute Lymphoid Leukemia in Homozygous HLA-C1 Patients after HLA-Matched Allogeneic Transplantation: A Japanese National Registry Study

Arima, Nobuyoshi; Kanda, Junya; Yabe, Toshikazu; Morishima, Yasuo; Tanaka, Junji; Kako, Shinichi; Sakaguchi, Hirotoshi; Kato, Motohiro; Ohashi, Kazuteru; Ozawa, Yukiyasu; Fukuda, Takahiro; Ota, Shuichi; Tachibana, Takayoshi; Onizuka, Makoto; Ichinohe, Tatsuo; Atsuta, Yoshiko; Kanda, Yoshinobu

doi:10.1016/j.bbmt.2019.10.032

Cited by 5 publications

(4 citation statements)

References 41 publications

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“…Moreover, a survival advantage was also observed in patients with receptor-ligand mismatch compared with receptor-ligand matched pairs ( 59 , 66 , 69 – 71 , 73 , 76 , 79 ). However, several other studies described opposite results ( 63 , 64 , 75 , 77 , 78 ). Of notice, two studies from Japan observed that the lack of the HLA-C2 ligand for donor inhibitory KIR afforded relapse protection in patients with AML and chronic myeloid leukemia, but increased the relapse rate in patients with ALL ( 73 , 75 ).…”

Section: Kir and Transplant Outcomesmentioning

confidence: 87%

“…However, several other studies described opposite results ( 63 , 64 , 75 , 77 , 78 ). Of notice, two studies from Japan observed that the lack of the HLA-C2 ligand for donor inhibitory KIR afforded relapse protection in patients with AML and chronic myeloid leukemia, but increased the relapse rate in patients with ALL ( 73 , 75 ). To date, no plausible explanation has been put forward for this disparity in relapse.…”

Section: Kir and Transplant Outcomesmentioning

confidence: 87%

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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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Section: Kir and Transplant Outcomesmentioning

confidence: 87%

Section: Kir and Transplant Outcomesmentioning

confidence: 87%

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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“…It is noteworthy that patients from their cohort are predominately diagnosed with myeloid disease (AML, CML and MDS) 32,33 . Two relatively large multicenter studies from Japan also reported opposite effects of KIR‐HLA combination on AML and ALL 41,42 . Whether donor aKIR genes play opposite roles in different lineage of diseases still need further confirmation.…”

Section: Discussionmentioning

confidence: 99%

“…32,33 Two relatively large multicenter studies from Japan also reported opposite effects of KIR-HLA combination on AML and ALL. 41,42 Whether donor aKIR genes play opposite roles in different lineage of diseases still need further confirmation.…”

Section: Factors Influencing Os and Grfsmentioning

confidence: 99%

Donor aKIR genes influence the risk of EBV and CMV reactivation after anti‐thymocyte globulin‐based haploidentical hematopoietic stem cell transplantation

Gao,

Shi,

Shi

et al. 2023

HLA

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Hematopoietic stem cell transplantation (HSCT) offers the highest curative potential for patients with hematological malignancies. Complications including infection, graft‐versus‐host disease (GVHD), and relapse reflect delayed or dysregulated immune reconstitution. After transplantation, NK cells rapidly reconstitute and are crucial for immune surveillance and immune tolerance. NK cell function is tightly regulated by killer immunoglobin‐like receptors (KIRs). Previous studies have revealed that donor KIRs, especially some activated KIRs (aKIRs) are closely related to transplant outcomes. Here, we performed a retrospective study, including 323 patients who received haploidentical (haplo) HSCT in our center. In univariate analysis, donor KIR2DS1, KIR2DS3 and KIR3DS1 gene protected patients with lymphoid disease from Epstein–Barr virus (EBV) and cytomegalovirus (CMV) reactivation, while donor KIR2DS1, KIR2DS5 and KIR3DS1 gene conferred a higher risk of CMV reactivation for patients with myeloid disease. Multivariate analysis confirmed that donor telomeric (Tel) B/x and KIR2DS3 gene best protected patients with lymphoid disease from EBV (p = 0.017) and CMV reactivation (p = 0.004). In myeloid disease, grafts lacking Tel B/x and KIR2DS5 gene correlated with the lowest risk of CMV reactivation (p = 0.018). Besides, donor aKIR genes did not influence the rates of GVHD, relapse, non‐relapse mortality (NRM) and overall survival (OS) in this study. The reactivation of EBV and CMV was associated with poor prognosis of haplo‐HSCT. In conclusion, we found that donor aKIR genes might have a synergistic effect on CMV and EBV reactivation after haplo‐HSCT. Whether the influence of donor aKIR genes varies with disease types remained to be studied.

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Dual effects of natural killer cells in transplantation for leukemia

Arima

2021

Critical Reviews in Oncology/Hematology

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Increased Relapse Risk of Acute Lymphoid Leukemia in Homozygous HLA-C1 Patients after HLA-Matched Allogeneic Transplantation: A Japanese National Registry Study

Cited by 5 publications

References 41 publications

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

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

Donor aKIR genes influence the risk of EBV and CMV reactivation after anti‐thymocyte globulin‐based haploidentical hematopoietic stem cell transplantation

Dual effects of natural killer cells in transplantation for leukemia

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