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Ferrata Storti Foundation
Haematologica 2021 Volume 106(7):1828-1838
Acute Lymphoblastic Leukemia
A multicenter total therapy strategy for de novo adult Philadelphia chromosome positive acute lymphoblastic leukemia patients: final results of the GIMEMA LAL1509 protocol
Sabina Chiaretti,1 Michela Ansuinelli,1 Antonella Vitale,1 Loredana Elia,1 Mabel Matarazzo,1 Alfonso Piciocchi,2 Paola Fazi,2 Francesco Di Raimondo,3 Lidia Santoro,4 Francesco Fabbiano,5 Catello Califano,6 Giovanni Martinelli,7 Francesca Ronco,8 Felicetto Ferrara,9 Nicola Cascavilla,10 Catia Bigazzi,11 Alessandra Tedeschi,12 Simona Sica,13,14 Nicola Di Renzo,15 Angela Melpignano,16 Germana Beltrami,17 Marco Vignetti2 and Robin Foà1
1Section of Hematology, Department of Translational and Precision Medicine, Sapienza University, Rome; 2GIMEMA Data Center, Fondazione GIMEMA, Rome; 3Section of Hematology, Department of General Surgery and Medical-Surgical Specialties, University of Catania, Catania; 4Struttura Complessa di Ematologia e Trapianto Emopoietico-A.O. S.G.Moscati, Avellino; 5Division of Hematology and Bone Marrow Transplantation, Ospedali Riuniti Villa Sofia-Cervello, Palermo; 6Onco-Ematologia Ospedale Pagani, Salerno; 7Seragnoli Institute of Hematology, Bologna University School of Medicine, Bologna; 8Operative Unit of Hematology, Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli", Reggio Calabria; 9Division of Hematology and Stem Cell Transplantation Program, AORN Cardarelli Hospital, Naples; 10Casa Sollievo della Sofferenza IRCCS, San Giovanni Rotondo; 11Department of Hematology and Stem Cell Transplantation Unit, C.G. Mazzoni Hospital, Ascoli Piceno; 12ASST Grande Ospedale Metropolitano Niguarda, Milan; 13Fondazione Policlinico Universitario A. Gemelli, Rome; 14Università Cattolica del Sacro Cuore, Rome; 15Department of Hematology and Stem Cell Transplant, Presidio Ospedaliero Vito Fazzi, Lecce; 16A. Perrino Hospital, Brindisi and 17Policlinico San Martino, Genoa, Italy
ABSTRACT
The GIMEMA LAL1509 protocol, designed for adult (≥18-60 years) de novo Philadelphia chromosome positive (Ph+) acute lym- phoblastic leukemia (ALL) patients, was based on dasatinib plus steroids induction - with central nervous system prophylaxis - followed by dasatinib alone in patients in complete molecular response or by chemotherapy and/or allogeneic transplant in patients not reaching com- plete molecular response. Sixty patients (median age 41.9 years) were enrolled: 33 were p190+, 18 p210+ and nine p190/p210+. At the end of induction (day +85), 58 patients (97%) achieved complete hematologic remission. No deaths in induction were recorded. Eleven patients (18.3%) obtained complete molecular response. Among the incomplete molecular responders (n=47), 22 underwent an allogeneic transplant. Seventeen hematologic relapses occurred (median 7 months; range, 3- 40.1): 13 during consolidation and four post-transplant. ABL1 mutations (five T315I, three V299L, one E281K and one G254E) were found in ten of 13 relapsed cases. With a median follow-up of 57.4 months (range, 4.2-75.6), overall survival and disease-free survival were 56.3% and 47.2%. A better disease-free survival was observed in patients who obtained a molecular response at day +85 compared to cases who did not. The presence of additional copy number aberrations - IKZF1 plus CDKN2A/B and/or PAX5 deletions - was the most important unfavor- able prognostic factor on overall and disease-free survival (P=0.005 and P=0.0008). This study shows that in adult Ph+ ALL long-term survivals can be achieved with a total-therapy strategy based on a chemotherapy- free induction and, in complete molecular responders, also without fur- ther systemic chemotherapy. Finally, the screening of additional copy number aberrations should be included in the diagnostic work-up (clini- catrial gov. Identifier: EudraCT 2010-019119-39).
Correspondence:
SABINA CHIARETTI
chiaretti@bce.uniroma1.it
ROBIN FOÀ
rfoa@bce.uniroma1.it
Received: May 29, 2020. Accepted: December 24, 2020. Pre-published: February 4, 2021.
https://doi.org/10.3324/haematol.2020.260935
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