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©2013 UpToDate ® Print Email Evaluation of overall response to first-line tyrosine kinase inhibitors in early chronic phase chronic myeloid leukemia [1] Evaluation time, months Response Warnings Optimal Suboptimal Failure Baseline NA NA NA High risk; CCA/Ph+* 3 CHR and at least minor CgR (Ph+ ≤65 percent) No CgR (Ph+ >95 percent) Less than CHR NA 6 At least PCgR (Ph+ ≤35 percent) Less than PCgR (Ph+ >35 percent) No CgR (Ph+ >95 percent) NA 12 CCgR PCgR (Ph+ 1 percent to 35 percent) Less than PCgR (Ph+ >35 percent) Less than MMolR• 18 MMolR• Less than MMolR• Less than CCgR NA Any time during treatment Stable or improving MMolR• Loss of MMolR•; mutationsΔ Loss of CHR; loss of CCgR; mutations◊; CCA/Ph+ Increase in transcript levels§; CCA/Ph- With respect to prior recommendations [2] , a new definition of optimal response was introduced; an earlier definition of suboptimal response is recommended at 3 months in instances of cytogenetic resistance; an earlier definition of failure is recommended at 3 months in instances of hematologic resistance and at 6 months in instances of cytogenetic resistance; clonal progression (ie, CCA/Ph+) during treatment was identified as treatment failure; a deletion of the long arm of chromosome 9 (del9q+) is no longer recognized as a warning. NA: not applicable; CCA: clonal chromosome abnormalities; Ph+: Philadelphia chromosome positive; CHR: complete hematologic response; CgR: cytogenetic response; PCgR: partial cytogenetic response; MMolR: major molecular response; CCgR: complete cytogenetic response; Ph-: Philadelphia chromosome negative. * CCA/Ph+ is a warning factor at diagnosis, although its occurrence during treatment (ie, clonal progression) is a marker of treatment failure. Two consecutive cytogenetic tests are required and must show the same CCA in at least two Ph+ cells. • MMolR indicates a ratio of BCR-ABL1 to ABL1 or other housekeeping genes of ≤0.1 percent on the international scale. Δ BCR-ABL1 kinase domain mutations still sensitive to imatinib. ◊ BCR-ABL1 kinase domain mutations poorly sensitive to imatinib. § The significance of the increase may vary by a factor of 2 to 10, depending on the laboratories.

With respect to prior recommendations [2] , a new definition of optimal response was introduced; an earlier definition of suboptimal response is recommended at 3 months in instances of cytogenetic resistance; an earlier definition of failure is recommended at 3 months in instances of hematologic resistance and at 6 months in instances of cytogenetic resistance; clonal progression (ie, CCA/Ph+) during treatment was identified as treatment failure; a deletion of the long arm of chromosome 9 (del9q+) is no longer recognized as a warning. NA: not applicable; CCA: clonal chromosome abnormalities; Ph+: Philadelphia chromosome positive; CHR: complete hematologic response; CgR: cytogenetic response; PCgR: partial cytogenetic response; MMolR: major molecular response; CCgR: complete cytogenetic response; Ph-: Philadelphia chromosome negative. * CCA/Ph+ is a warning factor at diagnosis, although its occurrence during treatment (ie, clonal progression) is a marker of treatment failure. Two consecutive cytogenetic tests are required and must show the same CCA in at least two Ph+ cells. • MMolR indicates a ratio of BCR-ABL1 to ABL1 or other housekeeping genes of ≤0.1 percent on the international scale. Δ BCR-ABL1 kinase domain mutations still sensitive to imatinib. ◊ BCR-ABL1 kinase domain mutations poorly sensitive to imatinib. § The significance of the increase may vary by a factor of 2 to 10, depending on the laboratories. 1. Reprinted with permission from: Baccarani, M, Cortes, J, Pane, F, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009; 27:6041. Copyright © 2009 American Society of Clinical Oncology. All rights reserved. 2. Baccarani, M, Saglio, G, Goldman, J, et al. Evolving concepts in the management of chronic myeloid leukemia: Recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2006; 108:1809.