The Significance of Myelosuppression during Therapy with Imatinib Mesylate in Patients with Chronic Myelogenous Leukemia in Chronic Phase

Thomas B. Sneed, Hagop M. Kantarjian, Moshe Talpaz, Susan O'Brien, Mary Beth Rios, B. Nebiyou Bekele, Xian Zhou, Debra Resta, William Wierda, Stefan Faderl, Francis Giles, Jorge E. Cortes

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Imatinib mesylate induces high rates of hematologic and cytogenetic response in patients with chronic myelogenous leukemia (CML). During therapy with imatinib, up to 45% of patients with CML reportedly experience myelosuppression ≥ Grade 3, requiring interruption of therapy and/or dose reductions. The significance of myelosuppression for response to imatinib is unknown. METHODS. The authors analyzed 143 patients with late chronic-phase CML who were treated with imatinib after failing interferon. Univariate and multivariate analyses were performed to determine patient characteristics that were correlated with myelosuppression response and the association between myelosuppression and cytogenetic response. RESULTS. Neutropenia ≥ Grade 3 (according to National Cancer Institute Common Toxicity Criteria) occurred in 64 patients (45%), and thrombocytopenia ≥ Grade 3 occurred in 31 patients (22%). Any myelosuppression ≥ Grade 3 was associated with a lower rate of major (P = 0.04) or complete (P = 0.01) cytogenetic responses. This was more pronounced with myelosuppression that lasted > 2 weeks. The major cytogenetic response rate was 58% with Grade ≥ 3 myelosuppression compared with a rate of 75% without Grade ≥3 myelosuppression (P = 0.03); the complete cytogenetic response rates were 36% and 63%, respectively (P = 0.001). In a multivariate analysis, pretreatment platelet count, imatinib dose reductions, and duration of myelosuppression were associated significantly with response. CONCLUSIONS. Myelosuppression is an independent adverse factor for achieving cytogenetic response with imatinib in patients with CML. Intervention with hematopoietic growth factors in patients with CML who are treated with imatinib should be investigated.

Original languageEnglish (US)
Pages (from-to)116-121
Number of pages6
JournalCancer
Volume100
Issue number1
DOIs
StatePublished - Jan 1 2004
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Cytogenetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Therapeutics
Multivariate Analysis
National Cancer Institute (U.S.)
Imatinib Mesylate
Neutropenia
Platelet Count
Interferons
Intercellular Signaling Peptides and Proteins

Keywords

  • Chronic myelogenous leukemia
  • Cytogenetic response
  • Imatinib
  • Myelosuppression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The Significance of Myelosuppression during Therapy with Imatinib Mesylate in Patients with Chronic Myelogenous Leukemia in Chronic Phase. / Sneed, Thomas B.; Kantarjian, Hagop M.; Talpaz, Moshe; O'Brien, Susan; Rios, Mary Beth; Bekele, B. Nebiyou; Zhou, Xian; Resta, Debra; Wierda, William; Faderl, Stefan; Giles, Francis; Cortes, Jorge E.

In: Cancer, Vol. 100, No. 1, 01.01.2004, p. 116-121.

Research output: Contribution to journalArticle

Sneed, TB, Kantarjian, HM, Talpaz, M, O'Brien, S, Rios, MB, Bekele, BN, Zhou, X, Resta, D, Wierda, W, Faderl, S, Giles, F & Cortes, JE 2004, 'The Significance of Myelosuppression during Therapy with Imatinib Mesylate in Patients with Chronic Myelogenous Leukemia in Chronic Phase', Cancer, vol. 100, no. 1, pp. 116-121. https://doi.org/10.1002/cncr.11863
Sneed, Thomas B. ; Kantarjian, Hagop M. ; Talpaz, Moshe ; O'Brien, Susan ; Rios, Mary Beth ; Bekele, B. Nebiyou ; Zhou, Xian ; Resta, Debra ; Wierda, William ; Faderl, Stefan ; Giles, Francis ; Cortes, Jorge E. / The Significance of Myelosuppression during Therapy with Imatinib Mesylate in Patients with Chronic Myelogenous Leukemia in Chronic Phase. In: Cancer. 2004 ; Vol. 100, No. 1. pp. 116-121.
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abstract = "BACKGROUND. Imatinib mesylate induces high rates of hematologic and cytogenetic response in patients with chronic myelogenous leukemia (CML). During therapy with imatinib, up to 45{\%} of patients with CML reportedly experience myelosuppression ≥ Grade 3, requiring interruption of therapy and/or dose reductions. The significance of myelosuppression for response to imatinib is unknown. METHODS. The authors analyzed 143 patients with late chronic-phase CML who were treated with imatinib after failing interferon. Univariate and multivariate analyses were performed to determine patient characteristics that were correlated with myelosuppression response and the association between myelosuppression and cytogenetic response. RESULTS. Neutropenia ≥ Grade 3 (according to National Cancer Institute Common Toxicity Criteria) occurred in 64 patients (45{\%}), and thrombocytopenia ≥ Grade 3 occurred in 31 patients (22{\%}). Any myelosuppression ≥ Grade 3 was associated with a lower rate of major (P = 0.04) or complete (P = 0.01) cytogenetic responses. This was more pronounced with myelosuppression that lasted > 2 weeks. The major cytogenetic response rate was 58{\%} with Grade ≥ 3 myelosuppression compared with a rate of 75{\%} without Grade ≥3 myelosuppression (P = 0.03); the complete cytogenetic response rates were 36{\%} and 63{\%}, respectively (P = 0.001). In a multivariate analysis, pretreatment platelet count, imatinib dose reductions, and duration of myelosuppression were associated significantly with response. CONCLUSIONS. Myelosuppression is an independent adverse factor for achieving cytogenetic response with imatinib in patients with CML. Intervention with hematopoietic growth factors in patients with CML who are treated with imatinib should be investigated.",
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AU - Talpaz, Moshe

AU - O'Brien, Susan

AU - Rios, Mary Beth

AU - Bekele, B. Nebiyou

AU - Zhou, Xian

AU - Resta, Debra

AU - Wierda, William

AU - Faderl, Stefan

AU - Giles, Francis

AU - Cortes, Jorge E.

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N2 - BACKGROUND. Imatinib mesylate induces high rates of hematologic and cytogenetic response in patients with chronic myelogenous leukemia (CML). During therapy with imatinib, up to 45% of patients with CML reportedly experience myelosuppression ≥ Grade 3, requiring interruption of therapy and/or dose reductions. The significance of myelosuppression for response to imatinib is unknown. METHODS. The authors analyzed 143 patients with late chronic-phase CML who were treated with imatinib after failing interferon. Univariate and multivariate analyses were performed to determine patient characteristics that were correlated with myelosuppression response and the association between myelosuppression and cytogenetic response. RESULTS. Neutropenia ≥ Grade 3 (according to National Cancer Institute Common Toxicity Criteria) occurred in 64 patients (45%), and thrombocytopenia ≥ Grade 3 occurred in 31 patients (22%). Any myelosuppression ≥ Grade 3 was associated with a lower rate of major (P = 0.04) or complete (P = 0.01) cytogenetic responses. This was more pronounced with myelosuppression that lasted > 2 weeks. The major cytogenetic response rate was 58% with Grade ≥ 3 myelosuppression compared with a rate of 75% without Grade ≥3 myelosuppression (P = 0.03); the complete cytogenetic response rates were 36% and 63%, respectively (P = 0.001). In a multivariate analysis, pretreatment platelet count, imatinib dose reductions, and duration of myelosuppression were associated significantly with response. CONCLUSIONS. Myelosuppression is an independent adverse factor for achieving cytogenetic response with imatinib in patients with CML. Intervention with hematopoietic growth factors in patients with CML who are treated with imatinib should be investigated.

AB - BACKGROUND. Imatinib mesylate induces high rates of hematologic and cytogenetic response in patients with chronic myelogenous leukemia (CML). During therapy with imatinib, up to 45% of patients with CML reportedly experience myelosuppression ≥ Grade 3, requiring interruption of therapy and/or dose reductions. The significance of myelosuppression for response to imatinib is unknown. METHODS. The authors analyzed 143 patients with late chronic-phase CML who were treated with imatinib after failing interferon. Univariate and multivariate analyses were performed to determine patient characteristics that were correlated with myelosuppression response and the association between myelosuppression and cytogenetic response. RESULTS. Neutropenia ≥ Grade 3 (according to National Cancer Institute Common Toxicity Criteria) occurred in 64 patients (45%), and thrombocytopenia ≥ Grade 3 occurred in 31 patients (22%). Any myelosuppression ≥ Grade 3 was associated with a lower rate of major (P = 0.04) or complete (P = 0.01) cytogenetic responses. This was more pronounced with myelosuppression that lasted > 2 weeks. The major cytogenetic response rate was 58% with Grade ≥ 3 myelosuppression compared with a rate of 75% without Grade ≥3 myelosuppression (P = 0.03); the complete cytogenetic response rates were 36% and 63%, respectively (P = 0.001). In a multivariate analysis, pretreatment platelet count, imatinib dose reductions, and duration of myelosuppression were associated significantly with response. CONCLUSIONS. Myelosuppression is an independent adverse factor for achieving cytogenetic response with imatinib in patients with CML. Intervention with hematopoietic growth factors in patients with CML who are treated with imatinib should be investigated.

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