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An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies

Since its reclassification as a distinct disease entity, clinical research efforts have attempted to establish baseline characteristics and prognostic scoring systems for chronic myelomonocytic leukemia (CMML). Although existing data for baseline characteristics and CMML prognostication have been ro...

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Autores principales: Padron, E, Garcia-Manero, G, Patnaik, M M, Itzykson, R, Lasho, T, Nazha, A, Rampal, R K, Sanchez, M E, Jabbour, E, Al Ali, N H, Thompson, Z, Colla, S, Fenaux, P, Kantarjian, H M, Killick, S, Sekeres, M A, List, A F, Onida, F, Komrokji, R S, Tefferi, A, Solary, E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526779/
https://www.ncbi.nlm.nih.gov/pubmed/26230957
http://dx.doi.org/10.1038/bcj.2015.53
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author Padron, E
Garcia-Manero, G
Patnaik, M M
Itzykson, R
Lasho, T
Nazha, A
Rampal, R K
Sanchez, M E
Jabbour, E
Al Ali, N H
Thompson, Z
Colla, S
Fenaux, P
Kantarjian, H M
Killick, S
Sekeres, M A
List, A F
Onida, F
Komrokji, R S
Tefferi, A
Solary, E
author_facet Padron, E
Garcia-Manero, G
Patnaik, M M
Itzykson, R
Lasho, T
Nazha, A
Rampal, R K
Sanchez, M E
Jabbour, E
Al Ali, N H
Thompson, Z
Colla, S
Fenaux, P
Kantarjian, H M
Killick, S
Sekeres, M A
List, A F
Onida, F
Komrokji, R S
Tefferi, A
Solary, E
author_sort Padron, E
collection PubMed
description Since its reclassification as a distinct disease entity, clinical research efforts have attempted to establish baseline characteristics and prognostic scoring systems for chronic myelomonocytic leukemia (CMML). Although existing data for baseline characteristics and CMML prognostication have been robustly developed and externally validated, these results have been limited by the small size of single-institution cohorts. We developed an international CMML data set that included 1832 cases across eight centers to establish the frequency of key clinical characteristics. Of note, we found that the majority of CMML patients were classified as World Health Organization CMML-1 and that a 7.5% bone marrow blast cut-point may discriminate prognosis with higher resolution in comparison with the existing 10%. We additionally interrogated existing CMML prognostic models and found that they are all valid and have comparable performance but are vulnerable to upstaging. Using random forest survival analysis for variable discovery, we demonstrated that the prognostic power of clinical variables alone is limited. Last, we confirmed the independent prognostic relevance of ASXL1 gene mutations and identified the novel adverse prognostic impact imparted by CBL mutations. Our data suggest that combinations of clinical and molecular information may be required to improve the accuracy of current CMML prognostication.
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spelling pubmed-45267792015-08-06 An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies Padron, E Garcia-Manero, G Patnaik, M M Itzykson, R Lasho, T Nazha, A Rampal, R K Sanchez, M E Jabbour, E Al Ali, N H Thompson, Z Colla, S Fenaux, P Kantarjian, H M Killick, S Sekeres, M A List, A F Onida, F Komrokji, R S Tefferi, A Solary, E Blood Cancer J Original Article Since its reclassification as a distinct disease entity, clinical research efforts have attempted to establish baseline characteristics and prognostic scoring systems for chronic myelomonocytic leukemia (CMML). Although existing data for baseline characteristics and CMML prognostication have been robustly developed and externally validated, these results have been limited by the small size of single-institution cohorts. We developed an international CMML data set that included 1832 cases across eight centers to establish the frequency of key clinical characteristics. Of note, we found that the majority of CMML patients were classified as World Health Organization CMML-1 and that a 7.5% bone marrow blast cut-point may discriminate prognosis with higher resolution in comparison with the existing 10%. We additionally interrogated existing CMML prognostic models and found that they are all valid and have comparable performance but are vulnerable to upstaging. Using random forest survival analysis for variable discovery, we demonstrated that the prognostic power of clinical variables alone is limited. Last, we confirmed the independent prognostic relevance of ASXL1 gene mutations and identified the novel adverse prognostic impact imparted by CBL mutations. Our data suggest that combinations of clinical and molecular information may be required to improve the accuracy of current CMML prognostication. Nature Publishing Group 2015-07 2015-07-31 /pmc/articles/PMC4526779/ /pubmed/26230957 http://dx.doi.org/10.1038/bcj.2015.53 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Padron, E
Garcia-Manero, G
Patnaik, M M
Itzykson, R
Lasho, T
Nazha, A
Rampal, R K
Sanchez, M E
Jabbour, E
Al Ali, N H
Thompson, Z
Colla, S
Fenaux, P
Kantarjian, H M
Killick, S
Sekeres, M A
List, A F
Onida, F
Komrokji, R S
Tefferi, A
Solary, E
An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies
title An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies
title_full An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies
title_fullStr An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies
title_full_unstemmed An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies
title_short An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies
title_sort international data set for cmml validates prognostic scoring systems and demonstrates a need for novel prognostication strategies
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526779/
https://www.ncbi.nlm.nih.gov/pubmed/26230957
http://dx.doi.org/10.1038/bcj.2015.53
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