Abstract
BACKGROUND
Imatinib mesylate is a selective tyrosine kinase inhibitor of cโabl, bcr/abl, cโkit, and plateletโderived growth factorโreceptor (PDGFโR). cโkit 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. Fortyโeight 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 2โ3 per year to none during the 8 months of therapy and from 3โ6 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, singleโagent imatinib did not achieve a significant clinical response among patients with AML, MDS, atypical CML, or CMML without PDGFโR 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. Cancer 2003;97:2760โ6. ยฉ 2003 American Cancer Society.
DOI 10.1002/cncr.0000