title: Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib.
abstract: Imatinib slows development of chronic myeloid leukemia (CML). However, available information on morbidity and mortality is largely based on sponsored trials, whereas independent long-term field studies are lacking.
  
  
  
  Consecutive CML patients who started imatinib treatment before 2005 and who were in complete cytogenetic remission (CCyR) after 2 years (± 3 months) were eligible for enrollment in the independent multicenter Imatinib Long-Term (Side) Effects (ILTE) study. Incidence of the first serious and nonserious adverse events and loss of CCyR were estimated according to the Kaplan-Meier method and compared with the standard log-rank test. Attainment of negative Philadelphia chromosome hematopoiesis was assessed with cytogenetics and quantitative polymerase chain reaction. Cumulative incidence of death related or unrelated to CML progression was estimated, accounting for competing risks, according to the Kalbleisch-Prentice method. Standardized incidence ratios were calculated based on population rates specific for sex and age classes. Confidence intervals were calculated by the exact method based on the χ(2) distribution. All statistical tests were two-sided.
  
  
  
  A total of 832 patients who were treated for a median of 5.8 years were enrolled. There were 139 recorded serious adverse events, of which 19.4% were imatinib-related. A total of 830 nonserious adverse events were observed in 53% of patients; 560 (68%) were imatinib-related. The most frequent were muscle cramps, asthenia, edema, skin fragility, diarrhea, tendon, or ligament lesions. Nineteen patients (2.3%) discontinued imatinib because of drug-related toxic effects. Forty-five patients lost CCyR, at a rate of 1.4 per 100 person-years. Durable (>1 year) negative Philadelphia chromosome hematopoiesis was attained by 179 patients. Twenty deaths were observed, with a 4.8% mortality incidence rate (standardized incidence ratio = 0.7; 95% confidence interval = 0.40 to 1.10, P = .08), with only six (30%) associated with CML progression.
  
  
  
  In this study, CML-related deaths were uncommon in CML patients who were in CCyR 2 years after starting imatinib, and survival was not statistically significantly different from that of the general population.
authors.affiliation: Hematology and Clinical Research Unit, San Gerardo Hospital, Italy. carlo.gambacorti@unimib.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Gambacorti-Passerini
authors.forename: Laura
authors.initials: L
authors.lastname: Antolini
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Mahon
authors.forename: Francois
authors.initials: F
authors.lastname: Guilhot
authors.forename: Michael
authors.initials: M
authors.lastname: Deininger
authors.forename: Carmen
authors.initials: C
authors.lastname: Fava
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Chiara Maria
authors.initials: CM
authors.lastname: Della Casa
authors.forename: Enrica
authors.initials: E
authors.lastname: Morra
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Abruzzese
authors.forename: Anna
authors.initials: A
authors.lastname: D'Emilio
authors.forename: Fabio
authors.initials: F
authors.lastname: Stagno
authors.forename: Philipp
authors.initials: P
authors.lastname: le Coutre
authors.forename: Rafael
authors.initials: R
authors.lastname: Hurtado-Monroy
authors.forename: Valeria
authors.initials: V
authors.lastname: Santini
authors.forename: Bruno
authors.initials: B
authors.lastname: Martino
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pane
authors.forename: Andrea
authors.initials: A
authors.lastname: Piccin
authors.forename: Pilar
authors.initials: P
authors.lastname: Giraldo
authors.forename: Sarit
authors.initials: S
authors.lastname: Assouline
authors.forename: Muheez A
authors.initials: MA
authors.lastname: Durosinmi
authors.forename: Onno
authors.initials: O
authors.lastname: Leeksma
authors.forename: Enrico Maria
authors.initials: EM
authors.lastname: Pogliani
authors.forename: Miriam
authors.initials: M
authors.lastname: Puttini
authors.forename: Eunjung
authors.initials: E
authors.lastname: Jang
authors.forename: Josy
authors.initials: J
authors.lastname: Reiffers
authors.forename: Rocco
authors.lastname: Piazza
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate