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Reconstitution of natural killer cell receptors influences natural killer activity and relapse rate after haploidentical transplantation of T- and B-cell depleted grafts in children

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Reconstitution of natural killer cell receptors influences natural killer activity and relapse rate after haploidentical transplantation of T- and B-cell depleted grafts in children. / Pfeiffer, Matthias M; Feuchtinger, Tobias; Teltschik, Heiko-Manuel; Schumm, Michael; Müller, Ingo; Handgretinger, Rupert; Lang, Peter.

In: HAEMATOLOGICA, Vol. 95, No. 8, 01.08.2010, p. 1381-8.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Transfer › peer-review

Harvard

Pfeiffer, MM, Feuchtinger, T, Teltschik, H-M, Schumm, M, Müller, I, Handgretinger, R & Lang, P 2010, 'Reconstitution of natural killer cell receptors influences natural killer activity and relapse rate after haploidentical transplantation of T- and B-cell depleted grafts in children', HAEMATOLOGICA, vol. 95, no. 8, pp. 1381-8. https://doi.org/10.3324/haematol.2009.021121

APA

Pfeiffer, M. M., Feuchtinger, T., Teltschik, H-M., Schumm, M., Müller, I., Handgretinger, R., & Lang, P. (2010). Reconstitution of natural killer cell receptors influences natural killer activity and relapse rate after haploidentical transplantation of T- and B-cell depleted grafts in children. HAEMATOLOGICA, 95(8), 1381-8. https://doi.org/10.3324/haematol.2009.021121

Vancouver

Pfeiffer MM, Feuchtinger T, Teltschik H-M, Schumm M, Müller I, Handgretinger R et al. Reconstitution of natural killer cell receptors influences natural killer activity and relapse rate after haploidentical transplantation of T- and B-cell depleted grafts in children. HAEMATOLOGICA. 2010 Aug 1;95(8):1381-8. https://doi.org/10.3324/haematol.2009.021121

Bibtex

@article{93429a1f3bff44dbadc4ca4626d7f491,
title = "Reconstitution of natural killer cell receptors influences natural killer activity and relapse rate after haploidentical transplantation of T- and B-cell depleted grafts in children",
abstract = "BACKGROUND: Natural killer cells have been demonstrated to exert remarkable graft-versus-leukemia effects after haploidentical transplantation. Acquisition of both, inhibiting and activating, receptors on developing natural killer cells is an important step in their functional maturation. Here, we report on the reconstitution of natural killer receptors after haploidentical transplantation of T-and B-cell (CD3/CD19) depleted grafts with co-transfusion of natural killer cells in children and its influence on natural killer cell activity and clinical outcome.DESIGN AND METHODS: We analyzed reconstitution patterns of natural killer receptors at different time intervals after haploidentical transplantation by multi-color flow cytometry. Natural killer cell activity and antibody-dependent cellular cytotoxicity was tested against cell lines and leukemic blasts in vitro. Survival was analyzed using Kaplan-Meier estimates.RESULTS: Recovery of CD56(+)/CD16(+) cells was fast with high cytolytic activity against K562 and strong antibody-dependent cellular cytotoxicity activity against neuroblastoma and leukemic blasts as early as day 14 posttransplant. KIR reconstitution showed a predominance of KIR negative natural killer cells early after transplantation and an early reconstitution of CD158b compared to CD158a and CD158e. These differences were independent of presence or absence of the corresponding KIR ligands in donors or recipients. This reconstitution pattern was associated with a higher relapse probability of patients homozygous for HLA-C1-alleles compared to patients homozygous or even heterozygous for HLA-C2-alleles.CONCLUSIONS: Our results indicate a fast recovery of functional and alloreactive natural killer cells with a constant KIR pattern after haploidentical transplantation with T- and B-cell depleted grafts. Moreover, these natural killer cells can mediate antibody-dependent cellular cytotoxicity and therefore may allow for an early use of antibodies against residual malignant cells.",
keywords = "Adolescent, Adult, Alleles, Antigens, CD3, Antigens, CD56, B-Lymphocytes, Child, Child, Preschool, Cytotoxicity, Immunologic, Flow Cytometry, HLA-C Antigens, Hematopoietic Stem Cell Transplantation, Humans, Infant, K562 Cells, Killer Cells, Natural, Receptors, IgG, Receptors, Natural Killer Cell, Recurrence, T-Lymphocytes, Young Adult",
author = "Pfeiffer, {Matthias M} and Tobias Feuchtinger and Heiko-Manuel Teltschik and Michael Schumm and Ingo M{\"u}ller and Rupert Handgretinger and Peter Lang",
year = "2010",
month = aug,
day = "1",
doi = "10.3324/haematol.2009.021121",
language = "English",
volume = "95",
pages = "1381--8",
journal = "HAEMATOLOGICA",
issn = "0390-6078",
publisher = "Ferrata Storti Foundation",
number = "8",

}

RIS

TY - JOUR

T1 - Reconstitution of natural killer cell receptors influences natural killer activity and relapse rate after haploidentical transplantation of T- and B-cell depleted grafts in children

AU - Pfeiffer, Matthias M

AU - Feuchtinger, Tobias

AU - Teltschik, Heiko-Manuel

AU - Schumm, Michael

AU - Müller, Ingo

AU - Handgretinger, Rupert

AU - Lang, Peter

PY - 2010/8/1

Y1 - 2010/8/1

N2 - BACKGROUND: Natural killer cells have been demonstrated to exert remarkable graft-versus-leukemia effects after haploidentical transplantation. Acquisition of both, inhibiting and activating, receptors on developing natural killer cells is an important step in their functional maturation. Here, we report on the reconstitution of natural killer receptors after haploidentical transplantation of T-and B-cell (CD3/CD19) depleted grafts with co-transfusion of natural killer cells in children and its influence on natural killer cell activity and clinical outcome.DESIGN AND METHODS: We analyzed reconstitution patterns of natural killer receptors at different time intervals after haploidentical transplantation by multi-color flow cytometry. Natural killer cell activity and antibody-dependent cellular cytotoxicity was tested against cell lines and leukemic blasts in vitro. Survival was analyzed using Kaplan-Meier estimates.RESULTS: Recovery of CD56(+)/CD16(+) cells was fast with high cytolytic activity against K562 and strong antibody-dependent cellular cytotoxicity activity against neuroblastoma and leukemic blasts as early as day 14 posttransplant. KIR reconstitution showed a predominance of KIR negative natural killer cells early after transplantation and an early reconstitution of CD158b compared to CD158a and CD158e. These differences were independent of presence or absence of the corresponding KIR ligands in donors or recipients. This reconstitution pattern was associated with a higher relapse probability of patients homozygous for HLA-C1-alleles compared to patients homozygous or even heterozygous for HLA-C2-alleles.CONCLUSIONS: Our results indicate a fast recovery of functional and alloreactive natural killer cells with a constant KIR pattern after haploidentical transplantation with T- and B-cell depleted grafts. Moreover, these natural killer cells can mediate antibody-dependent cellular cytotoxicity and therefore may allow for an early use of antibodies against residual malignant cells.

AB - BACKGROUND: Natural killer cells have been demonstrated to exert remarkable graft-versus-leukemia effects after haploidentical transplantation. Acquisition of both, inhibiting and activating, receptors on developing natural killer cells is an important step in their functional maturation. Here, we report on the reconstitution of natural killer receptors after haploidentical transplantation of T-and B-cell (CD3/CD19) depleted grafts with co-transfusion of natural killer cells in children and its influence on natural killer cell activity and clinical outcome.DESIGN AND METHODS: We analyzed reconstitution patterns of natural killer receptors at different time intervals after haploidentical transplantation by multi-color flow cytometry. Natural killer cell activity and antibody-dependent cellular cytotoxicity was tested against cell lines and leukemic blasts in vitro. Survival was analyzed using Kaplan-Meier estimates.RESULTS: Recovery of CD56(+)/CD16(+) cells was fast with high cytolytic activity against K562 and strong antibody-dependent cellular cytotoxicity activity against neuroblastoma and leukemic blasts as early as day 14 posttransplant. KIR reconstitution showed a predominance of KIR negative natural killer cells early after transplantation and an early reconstitution of CD158b compared to CD158a and CD158e. These differences were independent of presence or absence of the corresponding KIR ligands in donors or recipients. This reconstitution pattern was associated with a higher relapse probability of patients homozygous for HLA-C1-alleles compared to patients homozygous or even heterozygous for HLA-C2-alleles.CONCLUSIONS: Our results indicate a fast recovery of functional and alloreactive natural killer cells with a constant KIR pattern after haploidentical transplantation with T- and B-cell depleted grafts. Moreover, these natural killer cells can mediate antibody-dependent cellular cytotoxicity and therefore may allow for an early use of antibodies against residual malignant cells.

KW - Adolescent

KW - Adult

KW - Alleles

KW - Antigens, CD3

KW - Antigens, CD56

KW - B-Lymphocytes

KW - Child

KW - Child, Preschool

KW - Cytotoxicity, Immunologic

KW - Flow Cytometry

KW - HLA-C Antigens

KW - Hematopoietic Stem Cell Transplantation

KW - Humans

KW - Infant

KW - K562 Cells

KW - Killer Cells, Natural

KW - Receptors, IgG

KW - Receptors, Natural Killer Cell

KW - Recurrence

KW - T-Lymphocytes

KW - Young Adult

U2 - 10.3324/haematol.2009.021121

DO - 10.3324/haematol.2009.021121

M3 - SCORING: Journal article

C2 - 20145268

VL - 95

SP - 1381

EP - 1388

JO - HAEMATOLOGICA

JF - HAEMATOLOGICA

SN - 0390-6078

IS - 8

ER -