Response definitions and European Leukemianet Management recommendations

Imatinib is the standard front-line therapy of chronic myeloid leukaemia (CML). The evaluation of the response is based on blood counts and differential (haematologic response, HR), on the examination of marrow cell metaphases (cytogenetic response, CgR) and on a quantitative assessment of BCR-ABL transcripts level (molecular response, MolR). An optimal response to imatinib is defined by complete HR and at least minimal CgR (Ph+ < 95%) at 3 months, at least partial CgR (Ph+ < 35%) at 6 months, complete CgR at 12 months and major MolR (BCR-ABL: ABL ≤ 0.1%) at 18 months. Failure is defined by incomplete HR at 3 months, no CgR (Ph+ > 95%) at 6 months, less than partial CgR (Ph+ > 35%) at 12 months, less than complete CgR at 18 months and loss of a complete HR or a complete CgR. In any other situation, the response is defined suboptimal. Treatment recommendations are to continue on imatinib in case of optimal response and to move to second-generation tyrosine kinase inhibitors (TKIs) and/or to allogeneic haematopoietic stem cell transplantation in case of failure. In case of suboptimal response, treatment may be continued with imatinib, at the same dose or a higher dose, but some patients may become eligible for second-generation TKIs. A provisional definition of the response to second-generation TKIs second line is provided.