title: Early intervention during imatinib therapy in patients with newly diagnosed chronic-phase chronic myeloid leukemia: a study of the Spanish PETHEMA group.
abstract: BACKGROUND
  Despite the favorable results of imatinib front line in chronic-phase chronic myeloid leukemia there is room for improvement.
  
  
  METHODS
  Early intervention during imatinib therapy was undertaken in 210 adults with chronic-phase chronic myeloid leukemia less than three months from diagnosis (Sokal high risk: 16%). Patients received imatinib 400 mg/day. At three months, dose was increased if complete hematologic response was not achieved. At six months, patients in complete cytogenetic response were kept on 400 mg and the remainder randomized to higher imatinib dose or 400 mg plus interferon-alfa. At 18 months, randomized patients were switched to a 2(nd) generation tyrosine kinase inhibitor if not in complete cytogenetic response and imatinib dose increased in non-randomized patients not in major molecular response.
  
  
  RESULTS
  Seventy-two percent of patients started imatinib within one month from diagnosis. Median follow-up is 50.5 (range: 1.2-78) months. At three months 4 patients did not have complete hematologic response; at six months 73.8% were in complete cytogenetic response; among the remainder, 9 could not be randomized (toxicity or consent withdrawal), 17 were assigned to high imatinib dose, and 15 to 400 mg + interferon-alpha. The low number of randomized patients precluded comparison between the two arms. Cumulative response at three years was: complete hematologic response 98.6%, complete cytogenetic response 90% and major molecular response 82%. On an intention-to-treat basis, complete cytogenetic response was 78.8% at 18 months. At five years, survival was 97.5%, survival free from accelerated/blastic phase 94.3%, failure free survival 82.5%, and event free survival (including permanent imatinib discontinuation) 71.5%.
  
  
  CONCLUSIONS
  These results indicate the benefit of early intervention during imatinib therapy (ClinicalTrials.gov Identifier: NCT00390897).
authors.affiliation: Hematology Department, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. fcervan@clinic.ub.es
authors.forename: Francisco
authors.initials: F
authors.lastname: Cervantes
authors.forename: Pilar
authors.initials: P
authors.lastname: López-Garrido
authors.forename: María-Isabel
authors.initials: MI
authors.lastname: Montero
authors.forename: Fermín
authors.initials: F
authors.lastname: Jonte
authors.forename: Jesús
authors.initials: J
authors.lastname: Martínez
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Hernández-Boluda
authors.forename: María
authors.initials: M
authors.lastname: Calbacho
authors.forename: Anna
authors.initials: A
authors.lastname: Sureda
authors.forename: Gloria
authors.initials: G
authors.lastname: Pérez-Rus
authors.forename: José B
authors.initials: JB
authors.lastname: Nieto
authors.forename: Cristina
authors.initials: C
authors.lastname: Pérez-López
authors.forename: José
authors.initials: J
authors.lastname: Román-Gómez
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.forename: Arturo
authors.initials: A
authors.lastname: Pereira
authors.forename: Dolors
authors.initials: D
authors.lastname: Colomer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001549:Benzamides; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D013030:Spain; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate