title: Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high-risk myelodysplastic syndrome, and myeloproliferative disorders.
abstract: BACKGROUND
  Imatinib mesylate is a selective tyrosine kinase inhibitor of c-abl, bcr/abl, c-kit, and platelet-derived growth factor-receptor (PDGF-R). c-kit is expressed in most patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) and PDGF has been implicated in the pathogenesis of myeloproliferative disorders (MPD).
  
  
  METHODS
  The authors investigated the efficacy of imatinib in patients with these disorders. Forty-eight patients with AML (n = 10), MDS (n = 8), myelofibrosis (n = 18), atypical chronic myeloid leukemia (CML; n = 7), chronic myelomonocytic leukemia (CMML; n = 3), or polycythemia vera (n = 2) were treated with imatinib 400 mg daily.
  
  
  RESULTS
  None of the patients with AML or MDS responded. Among patients with myelofibrosis, 10 of 14 patients with splenomegaly (71%) had a 30% or greater reduction in spleen size, 1 patient had trilineage hematologic improvement, 2 had erythroid hematologic improvement, and 1 had improvement in platelet count. One patient with atypical CML had erythroid hematologic improvement. Both patients with polycythemia vera needed fewer phlebotomies (from 2-3 per year to none during the 8 months of therapy and from 3-6 per year to 1 during 9 months of therapy). None of the three patients with CMML responded. Treatment was well tolerated. The side effects were similar to those observed in patients with CML.
  
  
  CONCLUSIONS
  Within these small subgroups of disease types, single-agent imatinib did not achieve a significant clinical response among patients with AML, MDS, atypical CML, or CMML without PDGF-R fusion genes. Preliminary data on polycythemia vera are promising and deserve further investigation. Responses among myelofibrosis patients were minor. Therefore, a combination treatment regimen including imatinib may be more effective.
authors.affiliation: Department of Leukemia, The University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA. jcortes@mdanderson.org
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Rios
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Laurie
authors.initials: L
authors.lastname: Letvak
authors.forename: August
authors.initials: A
authors.lastname: Salvado
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D001549:Benzamides; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D015477:Leukemia, Myelomonocytic, Chronic / Q000188:drug therapy; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D009196:Myeloproliferative Disorders / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use* / Q000633:toxicity; D011087:Polycythemia Vera / Q000188:drug therapy; D055728:Primary Myelofibrosis / Q000188:drug therapy; D011743:Pyrimidines / Q000627:therapeutic use* / Q000633:toxicity; D012008:Recurrence
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate