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Loss of plasmacytoid dendritic cell differentiation is highly predictive for post-induction measurable residual disease and inferior outcomes in acute myeloid leukemia

Measurable residual disease is associated with inferior outcomes in patients with acute myeloid leukemia (AML). Measurable residual disease monitoring enhances risk stratification and may guide therapeutic intervention. The European LeukemiaNet working party recently came to a consensus recommendati...

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Autores principales: Xiao, Wenbin, Goldberg, Aaron D., Famulare, Christopher A., Devlin, Sean M., Nguyen, Nghia T., Sim, Sinnifer, Kabel, Charlene C., Patel, Minal A., McGovern, Erin M., Patel, Akshar, Schulman, Jessica, Dunbar, Andrew J., Epstein-Peterson, Zachary D., Menghrajani, Kamal N., Getta, Bartlomiej M., Cai, Sheng F., Geyer, Mark B., Glass, Jacob L., Taylor, Justin, Viny, Aaron D., Levine, Ross L., Zhang, Yanming, Giralt, Sergio A., Klimek, Virginia, Tallman, Martin S., Roshal, Mikhail
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ferrata Storti Foundation 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601104/
https://www.ncbi.nlm.nih.gov/pubmed/30523054
http://dx.doi.org/10.3324/haematol.2018.203018
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author Xiao, Wenbin
Goldberg, Aaron D.
Famulare, Christopher A.
Devlin, Sean M.
Nguyen, Nghia T.
Sim, Sinnifer
Kabel, Charlene C.
Patel, Minal A.
McGovern, Erin M.
Patel, Akshar
Schulman, Jessica
Dunbar, Andrew J.
Epstein-Peterson, Zachary D.
Menghrajani, Kamal N.
Getta, Bartlomiej M.
Cai, Sheng F.
Geyer, Mark B.
Glass, Jacob L.
Taylor, Justin
Viny, Aaron D.
Levine, Ross L.
Zhang, Yanming
Giralt, Sergio A.
Klimek, Virginia
Tallman, Martin S.
Roshal, Mikhail
author_facet Xiao, Wenbin
Goldberg, Aaron D.
Famulare, Christopher A.
Devlin, Sean M.
Nguyen, Nghia T.
Sim, Sinnifer
Kabel, Charlene C.
Patel, Minal A.
McGovern, Erin M.
Patel, Akshar
Schulman, Jessica
Dunbar, Andrew J.
Epstein-Peterson, Zachary D.
Menghrajani, Kamal N.
Getta, Bartlomiej M.
Cai, Sheng F.
Geyer, Mark B.
Glass, Jacob L.
Taylor, Justin
Viny, Aaron D.
Levine, Ross L.
Zhang, Yanming
Giralt, Sergio A.
Klimek, Virginia
Tallman, Martin S.
Roshal, Mikhail
author_sort Xiao, Wenbin
collection PubMed
description Measurable residual disease is associated with inferior outcomes in patients with acute myeloid leukemia (AML). Measurable residual disease monitoring enhances risk stratification and may guide therapeutic intervention. The European LeukemiaNet working party recently came to a consensus recommendation incorporating leukemia associated immunophenotype-based different from normal approach by multi-color flow cytometry for measurable residual disease evaluation. However, the analytical approach is highly expertise-dependent and difficult to standardize. Here we demonstrate that loss of plasmacytoid dendritic cell differentiation after 7+3 induction in AML is highly specific for measurable residual disease positivity (specificity 97.4%) in a uniformly treated patient cohort. Moreover, loss of plasmacytoid dendritic cell differentiation as determined by a blast-to-plasmacytoid dendritic cell ratio >10 was strongly associated with inferior overall and relapse-free survival (RFS) [Hazard ratio 2.79, 95% confidence interval (95%CI): 0.98-7.97; P=0.077) and 3.83 (95%CI: 1.51-9.74; P=0.007), respectively), which is similar in magnitude to measurable residual disease positivity. Importantly, measurable residual disease positive patients who reconstituted plasmacytoid dendritic cell differentiation (blast/ plasmacytoid dendritic cell ratio <10) showed a higher rate of measurable residual disease clearance at later pre-transplant time points compared to patients with loss of plasmacytoid dendritic cell differentiation (blast/ plasmacytoid dendritic cell ratio <10) (6 of 12, 50% vs. 2 of 18, 11%; P=0.03). Furthermore pre-transplant plasmacytoid dendritic cell recovery was associated with superior outcome in measurable residual disease positive patients. Our study provides a novel, simple, broadly applicable, and quantitative multi-color flow cytometry approach to risk stratification in AML.
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spelling pubmed-66011042019-07-08 Loss of plasmacytoid dendritic cell differentiation is highly predictive for post-induction measurable residual disease and inferior outcomes in acute myeloid leukemia Xiao, Wenbin Goldberg, Aaron D. Famulare, Christopher A. Devlin, Sean M. Nguyen, Nghia T. Sim, Sinnifer Kabel, Charlene C. Patel, Minal A. McGovern, Erin M. Patel, Akshar Schulman, Jessica Dunbar, Andrew J. Epstein-Peterson, Zachary D. Menghrajani, Kamal N. Getta, Bartlomiej M. Cai, Sheng F. Geyer, Mark B. Glass, Jacob L. Taylor, Justin Viny, Aaron D. Levine, Ross L. Zhang, Yanming Giralt, Sergio A. Klimek, Virginia Tallman, Martin S. Roshal, Mikhail Haematologica Article Measurable residual disease is associated with inferior outcomes in patients with acute myeloid leukemia (AML). Measurable residual disease monitoring enhances risk stratification and may guide therapeutic intervention. The European LeukemiaNet working party recently came to a consensus recommendation incorporating leukemia associated immunophenotype-based different from normal approach by multi-color flow cytometry for measurable residual disease evaluation. However, the analytical approach is highly expertise-dependent and difficult to standardize. Here we demonstrate that loss of plasmacytoid dendritic cell differentiation after 7+3 induction in AML is highly specific for measurable residual disease positivity (specificity 97.4%) in a uniformly treated patient cohort. Moreover, loss of plasmacytoid dendritic cell differentiation as determined by a blast-to-plasmacytoid dendritic cell ratio >10 was strongly associated with inferior overall and relapse-free survival (RFS) [Hazard ratio 2.79, 95% confidence interval (95%CI): 0.98-7.97; P=0.077) and 3.83 (95%CI: 1.51-9.74; P=0.007), respectively), which is similar in magnitude to measurable residual disease positivity. Importantly, measurable residual disease positive patients who reconstituted plasmacytoid dendritic cell differentiation (blast/ plasmacytoid dendritic cell ratio <10) showed a higher rate of measurable residual disease clearance at later pre-transplant time points compared to patients with loss of plasmacytoid dendritic cell differentiation (blast/ plasmacytoid dendritic cell ratio <10) (6 of 12, 50% vs. 2 of 18, 11%; P=0.03). Furthermore pre-transplant plasmacytoid dendritic cell recovery was associated with superior outcome in measurable residual disease positive patients. Our study provides a novel, simple, broadly applicable, and quantitative multi-color flow cytometry approach to risk stratification in AML. Ferrata Storti Foundation 2019-07 /pmc/articles/PMC6601104/ /pubmed/30523054 http://dx.doi.org/10.3324/haematol.2018.203018 Text en Copyright© 2019 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.
spellingShingle Article
Xiao, Wenbin
Goldberg, Aaron D.
Famulare, Christopher A.
Devlin, Sean M.
Nguyen, Nghia T.
Sim, Sinnifer
Kabel, Charlene C.
Patel, Minal A.
McGovern, Erin M.
Patel, Akshar
Schulman, Jessica
Dunbar, Andrew J.
Epstein-Peterson, Zachary D.
Menghrajani, Kamal N.
Getta, Bartlomiej M.
Cai, Sheng F.
Geyer, Mark B.
Glass, Jacob L.
Taylor, Justin
Viny, Aaron D.
Levine, Ross L.
Zhang, Yanming
Giralt, Sergio A.
Klimek, Virginia
Tallman, Martin S.
Roshal, Mikhail
Loss of plasmacytoid dendritic cell differentiation is highly predictive for post-induction measurable residual disease and inferior outcomes in acute myeloid leukemia
title Loss of plasmacytoid dendritic cell differentiation is highly predictive for post-induction measurable residual disease and inferior outcomes in acute myeloid leukemia
title_full Loss of plasmacytoid dendritic cell differentiation is highly predictive for post-induction measurable residual disease and inferior outcomes in acute myeloid leukemia
title_fullStr Loss of plasmacytoid dendritic cell differentiation is highly predictive for post-induction measurable residual disease and inferior outcomes in acute myeloid leukemia
title_full_unstemmed Loss of plasmacytoid dendritic cell differentiation is highly predictive for post-induction measurable residual disease and inferior outcomes in acute myeloid leukemia
title_short Loss of plasmacytoid dendritic cell differentiation is highly predictive for post-induction measurable residual disease and inferior outcomes in acute myeloid leukemia
title_sort loss of plasmacytoid dendritic cell differentiation is highly predictive for post-induction measurable residual disease and inferior outcomes in acute myeloid leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601104/
https://www.ncbi.nlm.nih.gov/pubmed/30523054
http://dx.doi.org/10.3324/haematol.2018.203018
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