Clinical significance of chromatin-spliceosome acute myeloid leukemia: a report from the Northern Italy Leukemia Group (NILG) randomized trial 02/06.

Autor:	Caprioli C; ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy., Lussana F; ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy., Salmoiraghi S; ASST Ospedale Papa Giovanni XXIII and FROM Research Foundation, Bergamo, Italy., Cavagna R; ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy., Buklijas K; ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy., Elidi L; ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy., Zanghi' P; ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy., Michelato A; ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy., Delaini F; ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy., Oldani E; ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy., Intermesoli T; ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy., Grassi A; ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy., Gianfaldoni G; AOU Careggi, Firenze, Italy., Mannelli F; AOU Careggi, Firenze, Italy., Ferrero D; AOU Città della Salute e della Scienza, Torino, Italy., Audisio E; AOU Città della Salute e della Scienza, Torino, Italy., Terruzzi E; Azienda Ospedaliera San Gerardo, Monza, Italy., De Paoli L; Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy., Cattaneo C; Spedali Civili, Brescia, Italy., Borlenghi E; Spedali Civili, Brescia, Italy., Cavattoni I; Ospedale San Maurizio, Bolzano, Italy., Tajana M; ASST Ospedale di Cremona, Cremona, Italy., Scattolin AM; Ospedale dell'Angelo e SS. Giovanni e Paolo, Venezia Mestre, Italy., Mattei D; Azienda Ospedaliera S. Croce e Carle, Cuneo, Italy., Corradini P; Fondazione IRCCS Istituto Nazionale dei Tumori., Campiotti L; Università dell'Insubria, Varese, Italy., Ciceri F; IRCCS Ospedale San Raffaele, Milano, Italy., Bernardi M; IRCCS Ospedale San Raffaele, Milano, Italy., Todisco E; IRCCS Istituto Clinico Humanitas di Rozzano, Rozzano, Italy., Cortelezzi A; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy., Falini B; Università di Perugia, Perugia, Italy., Pavoni C; ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy., Bassan R; Ospedale dell'Angelo e SS. Giovanni e Paolo, Venezia Mestre, Italy., Spinelli O; ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy., Rambaldi A; ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy.
Jazyk:	angličtina
Zdroj:	Haematologica [Haematologica] 2021 Oct 01; Vol. 106 (10), pp. 2578-2587. Date of Electronic Publication: 2021 Oct 01.
DOI:	10.3324/haematol.2020.252825
Abstrakt:	Secondary acute myeloid leukemia (sAML) after myelodysplastic or myeloproliferative disorders is a high-risk category currently identified by clinical history or specific morphological and cytogenetic abnormalities. However, in the absence of these features, uncertainties remain to identify the secondary nature of some cases otherwise defined as de novo AML. To test whether a chromatin-spliceosome (CS) mutational signature might better inform the definition of the de novo AML group, we analyzed a prospective cohort of 413 newly diagnosed AML patients enrolled into a randomized clinical trial (NILG AML 02/06) and provided with accurate cytogenetic and molecular characterization. Among clinically defined de novo AML, 17.6% carried CS mutations (CS-AML) and showed clinical characteristics closer to sAML (older age, lower white blood cell counts and higher rate of multilineage dysplasia). Outcomes in this group were adverse, more similar to those of sAML as compared to de novo AML (overall survival, 30% in CS-AML and 17% in sAML vs 61% in de novo AML, P<0.0001; disease free survival, 26% in CS-AML and 22% in sAML vs 54% of de novo AML, P<0.001) and independently confirmed by multivariable analysis. Allogeneic transplant in first complete remission improved survival in both sAML and CS-AML patients. In conclusion, these findings highlight the clinical significance of identifying CS-AML for improved prognostic prediction and potential therapeutic implications. (NILG AML 02/06: ClinicalTrials.gov Identifier: NCT00495287).
Databáze:	MEDLINE
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