Multidimensional assessment of patient condition and mutational analysis in peripheral blood, as tools to improve outcome prediction in myelodysplastic syndromes: A prospective study of the Spanish MDS group

Ramos, Fernando; Robledo, Cristina; Pereira, Arturo; Pedro Olive, Carme; Benito, Rocío; De Paz, Raquel; Rey, Mónica del; Insunza, Andrés; Tormo, Mar; Díez-Campelo, María; Xicoy, Blanca; Salido, Eduardo; Sánchez-del-Real, Javier; Arenillas Rocha, Leonor; Florensa Brichs, Lourdes; Luño, Elisa; Cañizo, Consuelo del; Sanz, Guillermo F.; Hernández-Rivas, Jesús María; Spanish Group for Myelodysplastic Syndromes (GESMD)

Multidimensional assessment of patient condition and mutational analysis in peripheral blood, as tools to improve outcome prediction in myelodysplastic syndromes: A prospective study of the Spanish MDS group

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dc.contributor.author Ramos, Fernandoca
dc.contributor.author Robledo, Cristinaca
dc.contributor.author Pereira, Arturoca
dc.contributor.author Pedro Olive, Carmeca
dc.contributor.author Benito, Rocíoca
dc.contributor.author De Paz, Raquelca
dc.contributor.author Rey, Mónica delca
dc.contributor.author Insunza, Andrésca
dc.contributor.author Tormo, Marca
dc.contributor.author Díez-Campelo, Maríaca
dc.contributor.author Xicoy, Blancaca
dc.contributor.author Salido, Eduardoca
dc.contributor.author Sánchez-del-Real, Javierca
dc.contributor.author Arenillas Rocha, Leonorca
dc.contributor.author Florensa Brichs, Lourdesca
dc.contributor.author Luño, Elisaca
dc.contributor.author Cañizo, Consuelo delca
dc.contributor.author Sanz, Guillermo F.ca
dc.contributor.author Hernández-Rivas, Jesús Maríaca
dc.contributor.author Spanish Group for Myelodysplastic Syndromes (GESMD)ca
dc.date.accessioned 2018-03-21T08:02:14Z
dc.date.issued 2017
dc.description.abstract The International Prognostic Scoring System and its revised form (IPSS-R) are the most widely used indices for prognostic assessment of patients with myelodysplastic syndromes (MDS), but can only partially account for the observed variation in patient outcomes. This study aimed to evaluate the relative contribution of patient condition and mutational status in peripheral blood when added to the IPSS-R, for estimating overall survival and the risk of leukemic transformation in patients with MDS. A prospective cohort (2006-2015) of 200 consecutive patients with MDS were included in the study series and categorized according to the IPSS-R. Patients were further stratified according to patient condition (assessed using the multidimensional Lee index for older adults) and genetic mutations (peripheral blood samples screened using next-generation sequencing). The change in likelihood-ratio was tested in Cox models after adding individual covariates. The addition of the Lee index to the IPSS-R significantly improved prediction of overall survival [hazard ratio (HR) 3.02, 95% confidence interval (CI) 1.96-4.66, P < 0.001), and mutational analysis significantly improved prediction of leukemic evolution (HR 2.64, 1.56-4.46, P < 0.001). Non-leukemic death was strongly linked to patient condition (HR 2.71, 1.72-4.25, P < 0.001), but not to IPSS-R score (P = 0.35) or mutational status (P = 0.75). Adjustment for exposure to disease-modifying therapy, evaluated as a time-dependent covariate, had no effect on the proposed model's predictive ability. In conclusion, patient condition, assessed by the multidimensional Lee index and patient mutational status can improve the prediction of clinical outcomes of patients with MDS already stratified by IPSS-R.
dc.description.sponsorship Celgene S.L., Madrid, Spain; Fundación Española de Hematología y Hemoterapia (FEHH); Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund(ERDF) “Una manera de hacer Europa”,Grant numbers: RD12/0036/0069, RD1 2/0036/0044; Junta de Castilla y Leon, Grantnumbers: BIO/SA47/13, GRS 994/A/14,GRS 1033/A/14, GRS 1043/A/16; European Union Seventh Framework Programme [FP7/2007-2013], Grant number: 306242-NGS-PTL; PETHEMA Foundation
dc.format.mimetype application/pdf
dc.identifier.citation Ramos F, Robledo C, Pereira A, Pedro C, Benito R, de Paz R. et al. Multidimensional assessment of patient condition and mutational analysis in peripheral blood, as tools to improve outcome prediction in myelodysplastic syndromes: A prospective study of the Spanish MDS group. Am J Hematol. 2017 Sep;92(9):E534-E541. DOI: 10.1002/ajh.24813
dc.identifier.doi http://dx.doi.org/10.1002/ajh.24813
dc.identifier.issn 0361-8609
dc.identifier.uri http://hdl.handle.net/10230/34218
dc.language.iso eng
dc.publisher Wileyca
dc.relation.ispartof American Journal of Hematology. 2017 Sep;92(9):E534-E541
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/306242
dc.rights This is the peer reviewed version of the following article: Ramos F, Robledo C, Pereira A, Pedro C, Benito R, de Paz R. et al. Multidimensional assessment of patient condition and mutational analysis in peripheral blood, as tools to improve outcome prediction in myelodysplastic syndromes: A prospective study of the Spanish MDS group. Am J Hematol. 2017 Sep;92(9):E534-E541, which has been published in final form at http://dx.doi.org/10.1002/ajh.24813. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.other Hematologia
dc.subject.other Síndromes mielodisplàsiques
dc.title Multidimensional assessment of patient condition and mutational analysis in peripheral blood, as tools to improve outcome prediction in myelodysplastic syndromes: A prospective study of the Spanish MDS groupca
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/acceptedVersion

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