title: Age and dPCR can predict relapse in CML patients who discontinued imatinib: the ISAV study.
abstract: Imatinib is effective for the treatment of chronic myeloid leukemia (CML). However even undetectable BCR-ABL1 by Q-RT-PCR does not equate to eradication of the disease. Digital-PCR (dPCR), able to detect 1 BCR-ABL1 positive cell out of 10(7) , has been recently developed. The ISAV study is a multicentre trial aimed at validating dPCR to predict relapses after imatinib discontinuation in CML patients with undetectable Q-RT-PCR. CML patients under imatinib therapy since more than 2 years and with undetectable PCR for at least 18 months were eligible. Patients were monitored by standard Q-RT-PCR for 36 months. Patients losing molecular remission (two consecutive positive Q-RT-PCR with at least 1 BCR-ABL1/ABL1 value above 0.1%) resumed imatinib. The study enrolled 112 patients, with a median follow-up of 21.6 months. Fifty-two of the 108 evaluable patients (48.1%), relapsed; 73.1% relapsed in the first 9 months but 14 late relapses were observed between 10 and 22 months. Among the 56 not-relapsed patients, 40 (37.0% of total) regained Q-RT-PCR positivity but never lost MMR. dPCR results showed a significant negative predictive value ratio of 1.115 [95% CI: 1.013-1.227]. An inverse relationship between patients age and risk of relapse was evident: 95% of patients <45 years relapsed versus 42% in the class ≥45 to <65 years and 33% of patients ≥65 years [P(χ(2) ) < 0.0001]. Relapse rates ranged between 100% (<45 years, dPCR+) and 36% (>45 years, dPCR-). Imatinib can be safely discontinued in the setting of continued PCR negativity; age and dPCR results can predict relapse.
authors.affiliation: Department of Health Sciences, University Of Milano-Bicocca, Monza, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Mori
authors.affiliation: Department of Health Sciences, University Of Milano-Bicocca, Monza, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Vagge
authors.affiliation: Department of Haematology And Oncology, Charité - Humboldt-Universität, Campus Virchow, Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: le Coutre
authors.affiliation: Department of Haematology, S. Eugenio Hospital, Tor Vergata University, Roma, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Abruzzese
authors.affiliation: Department of Haematology, Bianchi Melacrino Morelli Hospital, Reggio Calabria, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Martino
authors.affiliation: Department of Haematology, Niguarda Ca' Granda Hospital, Milano, Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Pungolino
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy and Department of Haematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Elena
authors.affiliation: Haematology Clinic, IRCSS AOU S. Martino-IST, University Of Genova, Genova, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Pierri
authors.affiliation: Division of Haematology, Jewish General Hospital, McGill University, Montreal, QC, Canada.
authors.forename: Sarit
authors.initials: S
authors.lastname: Assouline
authors.affiliation: Haematology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: D'Emilio
authors.affiliation: Haematology, AOU Careggi, University Of Firenze, Firenze, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Gozzini
authors.affiliation: Haematology, Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Giraldo
authors.affiliation: Haematology, University Of Catania, Catania, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Stagno
authors.affiliation: Oncohaematology Division, IRCCS Ca' Granda Maggiore Policlinico Hospital Foundation, University Of Milano, Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Iurlo
authors.affiliation: Department of Health Sciences, University Of Milano-Bicocca, Monza, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Luciani
authors.affiliation: Department of Health Sciences, University Of Milano-Bicocca, Monza, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: De Riso
authors.affiliation: Department of Health Sciences, University Of Milano-Bicocca, Monza, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Redaelli
authors.affiliation: Haematology Department, Cancer Research Institute, The Catholic University Of Korea, Seoul, South Korea.
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Health Sciences, University Of Milano-Bicocca, Monza, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pirola
authors.affiliation: Department of Health Sciences, University Of Milano-Bicocca, Monza, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Mezzatesta
authors.affiliation: Clioss S.R.L., Nerviano (MI), Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Petroccione
authors.affiliation: Clioss S.R.L., Nerviano (MI), Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Lodolo D'Oria
authors.affiliation: Clioss S.R.L., Nerviano (MI), Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Crivori
authors.affiliation: Department of Health Sciences, University Of Milano-Bicocca, Monza, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Piazza
authors.affiliation: Department of Health Sciences, University Of Milano-Bicocca, Monza, Italy.|Clinical Research Unit, Haematology, San Gerardo Hospital, Monza, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Gambacorti-Passerini
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C581634:BCR-ABL1 fusion protein, human; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl