Translational Research on Azacitidine Post-Remission Therapy of Acute Myeloid Leukemia in Elderly Patients (QOL-ONE Trans-2).

Autor: Oliva EN; Hematology Unit, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, 89124 Reggio di Calabria, Italy., Cuzzola M; UOSD Tipizzazione Tissutale, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, 89124 Reggio di Calabria, Italy., Porta MD; IRCCS Humanitas Research Hospital, 20089 Milan, Italy., Candoni A; Clinica Ematologica, ASUFC, University of Udine, 33100 Udine, Italy., Salutari P; Dipartimento Oncologico-Ematologico Ospedale Civile Spirito Santo Pescara, 65124 Pescara, Italy., Palumbo GA; Dipartimento di Scienze Mediche Chirurgiche e Tecnologie Avanzate 'G.F. Ingrassia', University of Catania, 95123 Catania, Italy., Reda G; Hematology Department, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico, University of Milan, 20100 Milan, Italy., Iannì G; Dielnet SRL, CRO Reggio Calabria, 89124 Reggio Calabria, Italy., Zampini M; IRCCS Humanitas Research Hospital, 20089 Milan, Italy., D'Amico S; IRCCS Humanitas Research Hospital, 20089 Milan, Italy., Tripepi G; IFC-CNR Institute of Clinical Physiology Reggio Calabria, 89124 Reggio Calabria, Italy., Capelli D; Clinica di Ematologia Azienda Ospedaliera Universitaria, Ospedali Riuniti di Ancona, 60126 Ancona, Italy., Alati C; Hematology Unit, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, 89124 Reggio di Calabria, Italy., Cannatà MC; UOSD Medical Genetics, Great Metropolitan Hospital, 89124 Reggio Calabria, Italy., Niscola P; UO di Ematologia, Ospedale Sant'Eugenio, 00144 Roma, Italy., Serio B; Dipartimento di Oncoematologia, AOU San Giovanni di Dio e Ruggi D'Aragona, 84125 Salerno, Italy., Barillà S; Hematology Unit, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, 89124 Reggio di Calabria, Italy., Musto P; Department of Precision and Translational Medicine with Ionian Area, 'Aldo Moro' University School of Medicine, 70121 Bari, Italy.; Unit of Hematology and Stem Cell Transplantation, AOUC Policlinico, 70124 Bari, Italy., Vigna E; UO di Ematologia, Ospedale L'Annunziata, 87100 Cosenza, Italy., Melillo LMA; UOC Ematologia e Trapianto di Cellule Staminali Emopoietiche, Policlinico Foggia Ospedaliero-Universitario, 71122 Foggia, Italy., Tripepi R; Nephology, Dialysis and Transplantation Unit-GOM 'Bianchi-Melacrino-Morelli', 89124 Reggio Calabria, Italy., Zannier ME; Clinica Ematologica, ASUFC, University of Udine, 33100 Udine, Italy., Nannya Y; Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-0071, Japan., Ogawa S; Institute for the Advanced Study of Human Biology, Kyoto University, Kyoto 606-8303, Japan., Mammì C; UOSD Medical Genetics, Great Metropolitan Hospital, 89124 Reggio Calabria, Italy.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Oct 30; Vol. 25 (21). Date of Electronic Publication: 2024 Oct 30.
DOI: 10.3390/ijms252111646
Abstrakt: The achievement of complete remission (CR) is crucial for acute myeloid leukemia (AML) patients undertaking curative therapy, but relapse often occurs within months, highlighting the need for strategies to prolong disease-free survival (DFS). Our phase III study compared the efficacy and safety of azacitidine (AZA) to best supportive care (BSC) in elderly AML patients who achieved CR following intensive induction and consolidation therapy. This ancillary study (QOL-ONE Trans-2) evaluated biological changes in bone marrow using Next-Generation Sequencing (NGS). We analyzed baseline, randomization, and 6-month post-remission samples from 24 patients (median age of 71 and 12 males). High-throughput NGS targeted 350 myeloid malignancy-related genes, considering variants with a variant allele frequency ≥ 4%. At diagnosis, all patients had 5 to 17 (median = 10) mutations, with DNMT3A (42%), NPM1 (33%), and TET2 (33%) being most frequent. FANCA mutations in four patients were linked to a higher relapse risk (HR = 4.96, p = 0.02) for DFS at both 2 and 5 years. Further HLA-specific NGS analyses are ongoing to confirm these results and their therapeutic implications.
Databáze: MEDLINE
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