title: Anagrelide and imatinib mesylate combination therapy in patients with chronic myeloproliferative disorders.
abstract: OBJECTIVE
  The tyrosine kinase inhibitor imatinib mesylate inhibits the function of the Bcr-Abl oncoprotein associated with Philadelphia-positive chronic myelogenous leukemia (CML). Anagrelide suppresses megakaryocyte proliferation and differentiation. The objectives of this study were to investigate the feasibility and safety of imatinib mesylate and anagrelide combination therapy in patients with Ph-positive CML or chronic myeloproliferative disorders (MPD) with persistent thrombocythemia.
  
  
  METHODS
  This study was a retrospective review of all available records of patients with chronic MPD presenting to the M.D. Anderson Cancer Center between October 1998 and May 2002, treated with imatinib mesylate combined with anagrelide.
  
  
  RESULTS
  Of 22 patients identified, 18 had Ph-positive CML (chronic phase, 16 patients; accelerated phase, 2 patients), 1 had agnogenic myeloid metaplasia (AMM), 2 had essential thrombocythemia (ET) and 1 had MPD transformed into refractory anemia with excess blasts (RAEB). The median age was 57 years (range 26-82 years). The median dose of imatinib mesylate administered was 400 mg (range 300-800 mg) and the median dose of anagrelide was 1.5 mg (range 0.5-4.0 mg). Imatinib mesylate and anagrelide combination therapy was feasible and tolerable. Of the 18 patients with Ph-positive CML, 15 in chronic phase and 1 in accelerated phase achieved a complete hematologic response (CHR), and 9 of the 18 achieved cytogenetic response (complete in 8 patients). No responses were noted in patients with AMM, ET or MPD transformed into RAEB.
  
  
  CONCLUSIONS
  The combination of imatinib mesylate and anagrelide was safe and was associated with an 89% CHR rate in patients with CML in chronic phase and persistent thrombocythemia.
authors.affiliation: Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, 1400 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Apostolia M
authors.initials: AM
authors.lastname: Tsimberidou
authors.forename: Dawn E
authors.initials: DE
authors.lastname: Colburn
authors.forename: Mary Alma
authors.initials: MA
authors.lastname: Welch
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Susan M
authors.initials: SM
authors.lastname: O'Brien
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D016347:Medical Records Systems, Computerized; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000401:mortality; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D005343:Fibrinolytic Agents; D010879:Piperazines; D011743:Pyrimidines; D011799:Quinazolines; D000068877:Imatinib Mesylate; C021139:anagrelide