Delayed achievement of cytogenetic and molecular response is associated with increased risk of progression among patients with chronic myeloid leukemia in early chronic phase receiving high-dose or standard-dose imatinib therapy

Alfonso Quintás-Cardama, Hagop Kantarjian, Dan Jones, Jianqin Shan, Gautam Borthakur, Deborah Thomas, Steven Kornblau, Susan O'Brien, Jorge Cortes

Research output: Contribution to journalArticle

Abstract

Patients not in complete cytogenetic response (CCyR) continuously face the competing possibilities of eventually achieving a cytogenetic response versus progressing. We analyzed the probability of achieving a CCyR, major molecular response, and progression in 258 patients with chronic myeloid leukemia in early chronic phase at 3, 6, and 12 months from imatinib start. The initial imatinib dose was 800 mg/day in 208 (81%) and 400 mg/day in 50 (19%) patients. For patients not in CCyR, the probability of achieving CCyR (P = .002) or major molecular response (P = .004) significantly decreased, whereas the risk of progression increased (P = .16) at each time point. Patients with a BCR-ABL1/ABL1 ratio greater than 1% to 10% after 3 months of imatinib had a 92% probability of achieving CCyR with continued therapy, similar to the 98% for those with 1% or less, but their risk of progression (11%) was almost 3-fold that of patients with a BCR-ABL1/ABL1 transcript ratio of 1% or less (4%) and similar to that of patients with transcript levels more than 10% (13%). These results suggest that patients not in CCyR after 12 months on imatinib have a higher risk of progression. This risk is discernible as early as 3 months into imatinib therapy by molecular analysis and may provide the rationale to institute therapies that render higher rates of early response.

Original languageEnglish (US)
Pages (from-to)6315-6321
Number of pages7
JournalBlood
Volume113
Issue number25
DOIs
StatePublished - Nov 19 2009
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytogenetics
Therapeutics
Imatinib Mesylate

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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Delayed achievement of cytogenetic and molecular response is associated with increased risk of progression among patients with chronic myeloid leukemia in early chronic phase receiving high-dose or standard-dose imatinib therapy. / Quintás-Cardama, Alfonso; Kantarjian, Hagop; Jones, Dan; Shan, Jianqin; Borthakur, Gautam; Thomas, Deborah; Kornblau, Steven; O'Brien, Susan; Cortes, Jorge.

In: Blood, Vol. 113, No. 25, 19.11.2009, p. 6315-6321.

Research output: Contribution to journalArticle

Quintás-Cardama, Alfonso ; Kantarjian, Hagop ; Jones, Dan ; Shan, Jianqin ; Borthakur, Gautam ; Thomas, Deborah ; Kornblau, Steven ; O'Brien, Susan ; Cortes, Jorge. / Delayed achievement of cytogenetic and molecular response is associated with increased risk of progression among patients with chronic myeloid leukemia in early chronic phase receiving high-dose or standard-dose imatinib therapy. In: Blood. 2009 ; Vol. 113, No. 25. pp. 6315-6321.
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abstract = "Patients not in complete cytogenetic response (CCyR) continuously face the competing possibilities of eventually achieving a cytogenetic response versus progressing. We analyzed the probability of achieving a CCyR, major molecular response, and progression in 258 patients with chronic myeloid leukemia in early chronic phase at 3, 6, and 12 months from imatinib start. The initial imatinib dose was 800 mg/day in 208 (81{\%}) and 400 mg/day in 50 (19{\%}) patients. For patients not in CCyR, the probability of achieving CCyR (P = .002) or major molecular response (P = .004) significantly decreased, whereas the risk of progression increased (P = .16) at each time point. Patients with a BCR-ABL1/ABL1 ratio greater than 1{\%} to 10{\%} after 3 months of imatinib had a 92{\%} probability of achieving CCyR with continued therapy, similar to the 98{\%} for those with 1{\%} or less, but their risk of progression (11{\%}) was almost 3-fold that of patients with a BCR-ABL1/ABL1 transcript ratio of 1{\%} or less (4{\%}) and similar to that of patients with transcript levels more than 10{\%} (13{\%}). These results suggest that patients not in CCyR after 12 months on imatinib have a higher risk of progression. This risk is discernible as early as 3 months into imatinib therapy by molecular analysis and may provide the rationale to institute therapies that render higher rates of early response.",
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