title: Sustained molecular remissions are achievable with tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia and additional cytogenetic clonal evolution.
abstract: Little is known regarding the activity of tyrosine kinase inhibitors (TKis) on chronic myeloid leukemia (CML) clonal evolution (CE). We treated 10 CE CML patients in either hematologic chronic (8 cases) or accelerated (2 cases) phase with imatinib or second generation TKi. Additional chromosomal abnormalities appeared during the course of disease in seven cases, being present at diagnosis in three. A total of 6/10 (60%) patients achieved complete cytogenetic remission (CCyR) with imatinib in 3-14 months. Major or complete molecular remission (CMR) was obtained in four CCyR patients after 21, 25, 22, and 12 months, as well as in a fifth patient who started nilotinib because of suboptimal response after 75 months of imatinib treatment. One patient received nilotinib due to imatinib intolerance after 56 months of therapy while on CMR, and maintained such status. After a median follow-up of 82 months (range, 3-116), six patients are alive, five of which are in continuous CCyR while one patient is in his third CCyR on dasatinib after relapsing on imatinib and nilotinib. Five patients are in complete (four) or major (one) molecular remission, ongoing at 3, 48, 61, 95, and 96 months, on imatinib (three) or nilotinib (two). Although a small number of patients was studied, our results suggest that long-term cytogenetic and molecular remission can be achieved in CML CE patients with TKis treatment.
authors.affiliation: Oncohematology Unit, Department of Clinical and Experimental Medicine, University of Perugia, S. Maria Hospital, Via Tristano di Joannuccio 1, 05100 Terni, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Falchi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rege-Cambrin
authors.forename: Carmen
authors.initials: C
authors.lastname: Fava
authors.forename: Emilio
authors.initials: E
authors.lastname: Donti
authors.forename: Debora
authors.initials: D
authors.lastname: Luzi
authors.forename: Emilia
authors.initials: E
authors.lastname: Giugliano
authors.forename: Marta
authors.initials: M
authors.lastname: Gubbiotti
authors.forename: Monica
authors.initials: M
authors.lastname: Schippa
authors.forename: Anna Marina
authors.initials: AM
authors.lastname: Liberati
mesh_terms: D000328:Adult; D001549:Benzamides; D002999:Clone Cells / Q000187:drug effects* / Q000473:pathology*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate