Dendritic Cell Recovery Impacts Outcomes after Umbilical Cord Blood and Sibling Donor Transplantation for Hematologic Malignancies

Waseem Touma; Claudio G. Brunstein; Qing Cao; Jeffrey S. Miller; Julie Curtsinger; Michael R. Verneris; Veronika Bachanova

doi:10.1016/j.bbmt.2017.07.008

Dendritic Cell Recovery Impacts Outcomes after Umbilical Cord Blood and Sibling Donor Transplantation for Hematologic Malignancies

Waseem Touma, Claudio G. Brunstein, Qing Cao, Jeffrey S. Miller, Julie Curtsinger, Michael R. Verneris, Veronika Bachanova

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Dendritic cells (DCs) orchestrate immune responses after allogeneic hematopoietic cell transplantation (HCT). We studied the association of donor myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) recovery in the landmark analysis of umbilical cord blood (UCB) and matched related donor (RD) HCT. Eighty patients (42 UCB and 38 RD recipients) with a day 100 blood sample were included in the analysis. Median age was 51 years (range, 20 to 71). Most patients had acute leukemia (50%) or lymphoma (23%) and received reduced-intensity conditioning (75%). After transplantation, UCB recipients had higher DC counts than RD recipients reaching normal levels at day 100 after transplantation (UCB median 4.7 cells/µL versus RD median 1.7 cells/µL). UCB recipients with high day 100 pDCs levels (≥ median) had 2-fold lower risk of relapse compared with those with pDC^low (14% versus 28%, P =.29) and a trend to improved 1-year survival in multivariate analysis with hazard ratio of.22 (95% confidence interval,.04 to 1.05; P =.057). Cytomegalovirus (CMV) reactivation had adverse impact on DC reconstitution at day 100 in both UCB and RD groups and almost exclusively affected the mDC subset (CMV reactivation: mDC 3.2 cells/µL versus no CMV reactivation: 7.8 cells/µL; P =.004). Collectively, these data suggest that high levels of circulating pDCs at day 100 after UCB transplantation confer a survival advantage at 1 year.

Original language	English (US)
Pages (from-to)	1925-1931
Number of pages	7
Journal	Biology of Blood and Marrow Transplantation
Volume	23
Issue number	11
DOIs	https://doi.org/10.1016/j.bbmt.2017.07.008
State	Published - Nov 2017

Bibliographical note

Funding Information:
Research reported in this publication was supported by National Institutes of Health grant P30 CA77598 utilizing the Biostatistics and Bioinformatics Core, Oncology Medical Informatics Services and the Translational Therapy Laboratory, all Shared Resources of the Masonic Cancer Center, University of Minnesota and by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114 . This work was supported in part by a grant from the National Cancer Institute CA65493 (J.S.M., M.R.V., C.G.B.) and National Center for Advancing Translational Sciences KL2 TR000113 and the National Institutes of Health Award Number UL1TR000114 (V.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2017 The American Society for Blood and Marrow Transplantation

Keywords

Dendritic cells
Related donor transplantation
Umbilical cord blood transplantation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbmt.2017.07.008

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083873

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title = "Dendritic Cell Recovery Impacts Outcomes after Umbilical Cord Blood and Sibling Donor Transplantation for Hematologic Malignancies",

abstract = "Dendritic cells (DCs) orchestrate immune responses after allogeneic hematopoietic cell transplantation (HCT). We studied the association of donor myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) recovery in the landmark analysis of umbilical cord blood (UCB) and matched related donor (RD) HCT. Eighty patients (42 UCB and 38 RD recipients) with a day 100 blood sample were included in the analysis. Median age was 51 years (range, 20 to 71). Most patients had acute leukemia (50%) or lymphoma (23%) and received reduced-intensity conditioning (75%). After transplantation, UCB recipients had higher DC counts than RD recipients reaching normal levels at day 100 after transplantation (UCB median 4.7 cells/µL versus RD median 1.7 cells/µL). UCB recipients with high day 100 pDCs levels (≥ median) had 2-fold lower risk of relapse compared with those with pDClow (14% versus 28%, P =.29) and a trend to improved 1-year survival in multivariate analysis with hazard ratio of.22 (95% confidence interval,.04 to 1.05; P =.057). Cytomegalovirus (CMV) reactivation had adverse impact on DC reconstitution at day 100 in both UCB and RD groups and almost exclusively affected the mDC subset (CMV reactivation: mDC 3.2 cells/µL versus no CMV reactivation: 7.8 cells/µL; P =.004). Collectively, these data suggest that high levels of circulating pDCs at day 100 after UCB transplantation confer a survival advantage at 1 year.",

keywords = "Dendritic cells, Related donor transplantation, Umbilical cord blood transplantation",

author = "Waseem Touma and Brunstein, {Claudio G.} and Qing Cao and Miller, {Jeffrey S.} and Julie Curtsinger and Verneris, {Michael R.} and Veronika Bachanova",

note = "Funding Information: Research reported in this publication was supported by National Institutes of Health grant P30 CA77598 utilizing the Biostatistics and Bioinformatics Core, Oncology Medical Informatics Services and the Translational Therapy Laboratory, all Shared Resources of the Masonic Cancer Center, University of Minnesota and by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114 . This work was supported in part by a grant from the National Cancer Institute CA65493 (J.S.M., M.R.V., C.G.B.) and National Center for Advancing Translational Sciences KL2 TR000113 and the National Institutes of Health Award Number UL1TR000114 (V.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2017 The American Society for Blood and Marrow Transplantation",

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AU - Touma, Waseem

AU - Brunstein, Claudio G.

AU - Cao, Qing

AU - Miller, Jeffrey S.

AU - Curtsinger, Julie

AU - Verneris, Michael R.

AU - Bachanova, Veronika

N1 - Funding Information: Research reported in this publication was supported by National Institutes of Health grant P30 CA77598 utilizing the Biostatistics and Bioinformatics Core, Oncology Medical Informatics Services and the Translational Therapy Laboratory, all Shared Resources of the Masonic Cancer Center, University of Minnesota and by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114 . This work was supported in part by a grant from the National Cancer Institute CA65493 (J.S.M., M.R.V., C.G.B.) and National Center for Advancing Translational Sciences KL2 TR000113 and the National Institutes of Health Award Number UL1TR000114 (V.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: © 2017 The American Society for Blood and Marrow Transplantation

PY - 2017/11

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N2 - Dendritic cells (DCs) orchestrate immune responses after allogeneic hematopoietic cell transplantation (HCT). We studied the association of donor myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) recovery in the landmark analysis of umbilical cord blood (UCB) and matched related donor (RD) HCT. Eighty patients (42 UCB and 38 RD recipients) with a day 100 blood sample were included in the analysis. Median age was 51 years (range, 20 to 71). Most patients had acute leukemia (50%) or lymphoma (23%) and received reduced-intensity conditioning (75%). After transplantation, UCB recipients had higher DC counts than RD recipients reaching normal levels at day 100 after transplantation (UCB median 4.7 cells/µL versus RD median 1.7 cells/µL). UCB recipients with high day 100 pDCs levels (≥ median) had 2-fold lower risk of relapse compared with those with pDClow (14% versus 28%, P =.29) and a trend to improved 1-year survival in multivariate analysis with hazard ratio of.22 (95% confidence interval,.04 to 1.05; P =.057). Cytomegalovirus (CMV) reactivation had adverse impact on DC reconstitution at day 100 in both UCB and RD groups and almost exclusively affected the mDC subset (CMV reactivation: mDC 3.2 cells/µL versus no CMV reactivation: 7.8 cells/µL; P =.004). Collectively, these data suggest that high levels of circulating pDCs at day 100 after UCB transplantation confer a survival advantage at 1 year.

AB - Dendritic cells (DCs) orchestrate immune responses after allogeneic hematopoietic cell transplantation (HCT). We studied the association of donor myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) recovery in the landmark analysis of umbilical cord blood (UCB) and matched related donor (RD) HCT. Eighty patients (42 UCB and 38 RD recipients) with a day 100 blood sample were included in the analysis. Median age was 51 years (range, 20 to 71). Most patients had acute leukemia (50%) or lymphoma (23%) and received reduced-intensity conditioning (75%). After transplantation, UCB recipients had higher DC counts than RD recipients reaching normal levels at day 100 after transplantation (UCB median 4.7 cells/µL versus RD median 1.7 cells/µL). UCB recipients with high day 100 pDCs levels (≥ median) had 2-fold lower risk of relapse compared with those with pDClow (14% versus 28%, P =.29) and a trend to improved 1-year survival in multivariate analysis with hazard ratio of.22 (95% confidence interval,.04 to 1.05; P =.057). Cytomegalovirus (CMV) reactivation had adverse impact on DC reconstitution at day 100 in both UCB and RD groups and almost exclusively affected the mDC subset (CMV reactivation: mDC 3.2 cells/µL versus no CMV reactivation: 7.8 cells/µL; P =.004). Collectively, these data suggest that high levels of circulating pDCs at day 100 after UCB transplantation confer a survival advantage at 1 year.

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Dendritic Cell Recovery Impacts Outcomes after Umbilical Cord Blood and Sibling Donor Transplantation for Hematologic Malignancies

Abstract

Bibliographical note

Keywords

UN SDGs

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