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Ferrata Storti Foundation
Haematologica 2021 Volume 106(10):2578-2587
Clinical significance of chromatin-spliceosome acute myeloid leukemia: a report from
the Northern Italy Leukemia Group (NILG) randomized trial 02/06
Chiara Caprioli,1* Federico Lussana,1* Silvia Salmoiraghi,1,2 Roberta Cavagna,1 Ksenija Buklijas,1 Lara Elidi,1 Pamela Zanghì,1 Anna Michelato,1 Federica Delaini,1 Elena Oldani,1 Tamara Intermesoli,1 Anna Grassi,1 Giacomo Gianfaldoni,3 Francesco Mannelli,3 Dario Ferrero,4 Ernesta Audisio,4 Elisabetta Terruzzi,5 Lorella De Paoli,6 Chiara Cattaneo,7 Erika Borlenghi,7 Irene Cavattoni,8 Monica Tajana,9 Anna Maria Scattolin,10 Daniele Mattei,11 Paolo Corradini,12,13 Leonardo Campiotti,14 Fabio Ciceri,15 Massimo Bernardi,15 Elisabetta Todisco,16 Agostino Cortelezzi,17 Brunangelo Falini,18 Chiara Pavoni,1 Renato Bassan,10 Orietta Spinelli1 and Alessandro Rambaldi1,13
1Azienda Socio-Sanitaria Territoriale (ASST) Ospedale Papa Giovanni XXIII, Bergamo; 2FROM Research Foundation, Ospedale Papa Giovanni XXIII, Bergamo; 3Azienda Ospedaliera Universitaria Careggi (AOU), Firenze; 4AOU Città della Salute e della Scienza, Torino; 5Azienda Ospedaliera San Gerardo, Monza; 6Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria; 7Spedali Civili, Brescia; 8Ospedale San Maurizio, Bolzano; 9ASST Ospedale di Cremona, Cremona; 10Ospedale dell'Angelo e SS. Giovanni e Paolo, Venezia Mestre; 11Azienda Ospedaliera S. Croce e Carle, Cuneo; 12Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milano; 13Department of Oncology and Hematology, Università degli Studi di Milano, Milano; 14Università dell’Insubria, Varese; 15IRCCS Ospedale San Raffaele, Milano; 16IRCCS Istituto Clinico Humanitas di Rozzano, Rozzano; 17Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano and 18Università di Perugia, Perugia, Italy
*CC and FL contributed equally as co-first authors.
ABSTRACT
Secondary acute myeloid leukemia (sAML) after myelodysplastic or myeloproliferative disorders is a high-risk category currently iden- tified by the clinical history or specific morphological and cytoge- netic abnormalities. However, in the absence of these features, uncer- tainties to identify the secondary nature of some cases, otherwise defined as de novo AML, remain. In order to test whether a chromatin- spliceosome (CS) mutational signature might better define the de novo AML group, we analyzed a prospective cohort of 413 newly diagnosed AML patients who were enrolled in a randomized clinical trial (NILG AML 02/06) and who provided samples for accurate cytogenetic and molecular characterization. Among clinically defined de novo AML, 17.6% carried CS mutations (CS-AML) and showed clinical characteris- tics 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 sur- vival, 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 multi- variable 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 implica- tions. (NILG AML 02/06; clinicaltrials gov. Identifier: NCT00495287).
Acute Myeloid Leukemia
Correspondence:
ALESSANDRO RAMBALDI
arambaldi@asst-pg23.it
Received: March 22, 2020. Accepted: August 25, 2020. Pre-published: August 27, 2020.
https://doi.org/10.3324/haematol.2020.252825 ©2021 Ferrata Storti Foundation
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