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
Open Access
- 18 June 2009
- journal article
- Published by American Society of Hematology in Blood
- Vol. 113 (25), 6315-6321
- https://doi.org/10.1182/blood-2008-07-166694
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.Keywords
This publication has 24 references indexed in Scilit:
- Desirable performance characteristics for BCR-ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trialsBlood, 2008
- T-cell homeostasis: the dark(ened) side of common variable immunodeficiencyBlood, 2008
- Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid LeukemiaNew England Journal of Medicine, 2006
- Comparison Between Patients With Philadelphia-Positive Chronic Phase Chronic Myeloid Leukemia Who Obtained a Complete Cytogenetic Response Within 1 Year of Imatinib Therapy and Those Who Achieved Such a Response After 12 Months of TreatmentJournal of Clinical Oncology, 2006
- Molecular Responses in Patients with Chronic Myelogenous Leukemia in Chronic Phase Treated with Imatinib MesylateClinical Cancer Research, 2005
- Real-time quantitative PCR analysis can be used as a primary screen to identify patients with CML treated with imatinib who have BCR-ABL kinase domain mutationsBlood, 2004
- High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome–positive chronic phase chronic myeloid leukemiaBlood, 2004
- Result of high-dose imatinib mesylate in patients with Philadelphia chromosome—positive chronic myeloid leukemia after failure of interferon-αBlood, 2003
- Imatinib Compared with Interferon and Low-Dose Cytarabine for Newly Diagnosed Chronic-Phase Chronic Myeloid LeukemiaNew England Journal of Medicine, 2003
- Detection and quantification of residual disease in chronic myelogenous leukemiaLeukemia, 2000