Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high-risk myelodysplastic syndrome, and myeloproliferative disorders

Jorge Cortes, Francis Giles, Susan O'Brien, Deborah Thomas, Maher Albitar, Mary Beth Rios, Moshe Talpaz, Guillermo Garcia-Manero, Stefan Faderl, Laurie Letvak, August Salvado, Hagop Kantarjian

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2760-2766
Number of pages7
JournalCancer
Volume97
Issue number11
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

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Myeloproliferative Disorders
Myelodysplastic Syndromes
Acute Myeloid Leukemia
Polycythemia Vera
Primary Myelofibrosis
Therapeutics
Platelet-Derived Growth Factor Receptors
Imatinib Mesylate
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Phlebotomy
Gene Fusion
Splenomegaly
Platelet Count
Protein-Tyrosine Kinases

Keywords

  • Acute myeloid leukemia
  • Imatinib mesylate
  • Myelodysplastic syndrome
  • Myelofibrosis
  • Platelet-derived growth factor
  • Polythemia vera

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high-risk myelodysplastic syndrome, and myeloproliferative disorders. / Cortes, Jorge; Giles, Francis; O'Brien, Susan; Thomas, Deborah; Albitar, Maher; Rios, Mary Beth; Talpaz, Moshe; Garcia-Manero, Guillermo; Faderl, Stefan; Letvak, Laurie; Salvado, August; Kantarjian, Hagop.

In: Cancer, Vol. 97, No. 11, 01.06.2003, p. 2760-2766.

Research output: Contribution to journalArticle

Cortes, J, Giles, F, O'Brien, S, Thomas, D, Albitar, M, Rios, MB, Talpaz, M, Garcia-Manero, G, Faderl, S, Letvak, L, Salvado, A & Kantarjian, H 2003, 'Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high-risk myelodysplastic syndrome, and myeloproliferative disorders', Cancer, vol. 97, no. 11, pp. 2760-2766. https://doi.org/10.1002/cncr.11416
Cortes, Jorge ; Giles, Francis ; O'Brien, Susan ; Thomas, Deborah ; Albitar, Maher ; Rios, Mary Beth ; Talpaz, Moshe ; Garcia-Manero, Guillermo ; Faderl, Stefan ; Letvak, Laurie ; Salvado, August ; Kantarjian, Hagop. / Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high-risk myelodysplastic syndrome, and myeloproliferative disorders. In: Cancer. 2003 ; Vol. 97, No. 11. pp. 2760-2766.
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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.",
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T1 - Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high-risk myelodysplastic syndrome, and myeloproliferative disorders

AU - Cortes, Jorge

AU - Giles, Francis

AU - O'Brien, Susan

AU - Thomas, Deborah

AU - Albitar, Maher

AU - Rios, Mary Beth

AU - Talpaz, Moshe

AU - Garcia-Manero, Guillermo

AU - Faderl, Stefan

AU - Letvak, Laurie

AU - Salvado, August

AU - Kantarjian, Hagop

PY - 2003/6/1

Y1 - 2003/6/1

N2 - 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.

AB - 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.

KW - Acute myeloid leukemia

KW - Imatinib mesylate

KW - Myelodysplastic syndrome

KW - Myelofibrosis

KW - Platelet-derived growth factor

KW - Polythemia vera

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