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Acute Lymphoblastic Leukemia
Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome.
First report of the minimal residual disease-oriented GIMEMA LAL1913
Ferrata Storti Foundation
Haematologica 2021 Volume 106(6):1559-1568
Sabina Chiaretti,1* Monica Messina,1,2* Irene Della Starza,1,2
Alfonso Piciocchi,2 Luciana Cafforio,1 Marzia Cavalli,1 Akram Taherinasab,1 Michela Ansuinelli,1 Loredana Elia,1 Guglielmo Albertini Petroni,1
Roberta La Starza,3 Martina Canichella,1 Alessia Lauretti,1 Maria Cristina Puzzolo,1 Valentina Pierini,3 Alessandra Santoro,4 Orietta Spinelli,5 Valerio Apicella,1 Saveria Capria,1 Francesco Di Raimondo,6 Paolo De Fabritiis,7 Cristina Papayannidis,8 Anna Candoni,9 Roberto Cairoli,10 Marco Cerrano,11 Nicola Fracchiolla,12 Daniele Mattei,13 Chiara Cattaneo,14 Antonella Vitale,1 Enrico Crea,2 Paola Fazi,2 Cristina Mecucci,3 Alessandro Rambaldi,5
Anna Guarini,15 Renato Bassan16 and Robin Foà1
1Hematology Unit, Department of Translational and Precision Medicine, Sapienza University, Rome; 2GIMEMA Data Center, Fondazione GIMEMA Franco Mandelli Onlus, Rome; 3Hematology and Bone Marrow Transplantation Unit, Department of Medicine, University of Perugia, Perugia; 4Hematology and Bone Marrow Transplant Unit, Ospedali Riuniti Villa Sofia-Cervello, Palermo; 5Hematology and Bone Marrow Transplant Unit, Ospedale Papa Giovanni XXIII, Bergamo; 6Haematology Unit, Department of General Surgery and Medical-Surgical Specialties, University of Catania, Catania; 7Hematology Unit, S. Eugenio Hospital, Rome; 8Seragnoli Institute of Hematology, Bologna University School of Medicine, Bologna; 9Clinica di Ematologia e Unità di terapie Cellulari 'Carlo Melzi'-Azienda Sanitaria-Universitaria Integrata, Udine; 10Hematology Unit, Niguarda Hospital, Milan; 11Hematology Unit, Department of Oncology, Presidio Molinette, AOU Città della Salute e della Scienza di Torino, Torino; 12UOC Oncoematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Università degli Studi di Milano, Milan; 13Department of Hematology, Ospedale S. Croce, Cuneo; 14Department of Hematology, ASST Spedali Civili, Brescia; 15Department of Molecular Medicine, Sapienza University, Rome and 16Hematology Unit, Ospedale dell'Angelo and Ospedale Ss Giovanni e Paolo, Mestre, Venezia, Italy
*SC and MM contributed equally as co-first authors.
ABSTRACT
Early recognition of Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) cases could impact on the management and outcome of this subset of B-lineage ALL. In order to assess the prognostic value of the Ph-like status in a pediatric-inspired, minimal residual disease (MRD)- driven trial, we screened 88 B-lineage ALL cases negative for major fusion genes (BCR-ABL1, ETV6-RUNX1, TCF3-PBX1 and KTM2Ar) enrolled in the GIMEMA LAL1913 front-line protocol for adult BCR/ABL1-negative ALL. The screening - performed using the “BCR/ABL1-like predictor” - identified 28 Ph-like cases (31.8%), characterized by CRLF2 overexpression (35.7%), JAK/STAT pathway mutations (33.3%), IKZF1 (63.6%), BTG1 (50%) and EBF1 (27.3%) deletions, and rearrangements targeting tyrosine kinases or CRLF2 (40%). The correlation with outcome highlighted that: i) the com- plete remission rate was significantly lower in Ph-like compared to non-Ph- like cases (74.1% vs. 91.5%, P=0.044); ii) at time point 2, decisional for trans- plant allocation, 52.9% of Ph-like cases versus 20% of non-Ph-like were MRD-positive (P=0.025); iii) the Ph-like profile was the only parameter asso- ciated with a higher risk of being MRD-positive at time point 2 (P=0.014); iv) at 24 months, Ph-like patients had a significantly inferior event-free and disease-free survival compared to non-Ph-like patients (33.5% vs. 66.2%, P=0.005 and 45.5% vs. 72.3%, P=0.062, respectively). This study documents
Correspondence:
SABINA CHIARETTI
chiaretti@bce.uniroma1.it
Received: January 24, 2020. Accepted: May 20, 2020. Pre-published: May 28, 2020.
https://doi.org/10.3324/haematol.2020.247973
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