title: Long-term results of high-dose imatinib in children and adolescents with chronic myeloid leukaemia in chronic phase: the Italian experience.
abstract: Imatinib mesylate (IM) is used for the management of childhood chronic myeloid leukaemia (CML). The most effective dosage of IM and its long-term efficacy in children are not well defined. The purpose of this multicentre study is to report on the long-term results of high-dose IM (340 mg/m2 /d) in CML patients in chronic phase (CP-CML) aged <18 years at diagnosis. A total of 47 CP-CML patients with a median age at diagnosis of 11 years 9 months were enrolled in nine Italian centres. Complete cytogenetic response was achieved in 91.5% of the evaluable patients at a median time of 6 months. BCR-ABL1 International Scale ≤ 0.1% (major molecular response; MMR) and ≤0.01% (molecular response; MR) at 12 months were 66.6% and 33%, respectively. During follow-up, MMR and MR were achieved in 78.6% and 61% of children, respectively. IM was safely discontinued in 3 long-term treated children with a durable MR. Twelve patients (eight cytogenetic/molecular responders) underwent stem cell transplantation. The progression-free survival probabilities at 96 months for responding patients who continued IM and for those transplanted were 60% and 50%, respectively. After a median follow-up of 52 months (range 3-146), all patients are alive. High-dose IM is a long-term effective therapy in children and adolescents with CP-CML.
authors.affiliation: Haematology, Department of Cellular Biotechnologies and Haematology, 'Sapienza' University, Rome, Italy.
authors.forename: Fiorina
authors.initials: F
authors.lastname: Giona
authors.affiliation: Haemato-Oncology Unit, Department of Women's and Children's Health, University of Padua, Padua, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Putti
authors.affiliation: Clinical Experimental Haematology Unit, Gaslini Research Institute of Genoa, Genoa, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Micalizzi
authors.affiliation: Paediatric Haematology Unit, Pausilipon Hospital, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Menna
authors.affiliation: Haematology, Department of Cellular Biotechnologies and Haematology, 'Sapienza' University, Rome, Italy.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Moleti
authors.affiliation: Department of Paediatrics, Paediatric Unit 'F. Vecchio', University of Bari, Bari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Santoro
authors.affiliation: Division of Haematology, 'Bianchi-Melacrino-Morelli' Hospital, Reggio Calabria, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Iaria
authors.affiliation: Department of Paediatrics, Haemato-Oncology Unit, 'Casa Sollievo della Sofferenza' Hospital, San Giovanni Rotondo, Italy.
authors.forename: Saverio
authors.initials: S
authors.lastname: Ladogana
authors.affiliation: Paediatric Haemato-Oncology Unit, Sant'Anna Hospital, Ferrara, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Burnelli
authors.affiliation: Haemato-Oncology Unit, Azienda Ospedaliera 'Pugliese-Ciaccio', Catanzaro, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Consarino
authors.affiliation: Haemato-Oncology Unit, Department of Women's and Children's Health, University of Padua, Padua, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Varotto
authors.affiliation: Paediatric Haematology Unit, Pausilipon Hospital, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Tucci
authors.affiliation: Haemato-Oncology Unit, Department of Women's and Children's Health, University of Padua, Padua, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Messina
authors.affiliation: Haematology, Department of Cellular Biotechnologies and Haematology, 'Sapienza' University, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Nanni
authors.affiliation: Haematology, Department of Cellular Biotechnologies and Haematology, 'Sapienza' University, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Diverio
authors.affiliation: Department of Paediatrics, University of Milano-Bicocca, Monza, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.affiliation: Haemato-Oncology Unit, Department of Paediatrics, University of Bologna, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.affiliation: Department of Paediatrics, University of Pavia, Pavia, Italy.|Paediatric Haematology-Oncology, IRCCS Ospedale Paediatrico Bambino Gesù, Rome, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Biostatistics Unit, GIMEMA Foundation, Rome, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Piciocchi
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin at Orbassano, Turin, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Gottardi
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin at Orbassano, Turin, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.affiliation: Haematology, Department of Cellular Biotechnologies and Haematology, 'Sapienza' University, Rome, Italy.
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D007558:Italy; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000235:genetics / Q000401:mortality* / Q000628:therapy*; D008297:Male; D010879:Piperazines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D033581:Stem Cell Transplantation; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; C581634:BCR-ABL1 fusion protein, human; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL1; childhood; chronic myeloid leukaemia; imatinib; tyrosine kinase inhibitors