Chronic Myeloid Leukemia: How Can Minimal Cytogenetic Response After 3 Months of Treatment Be Classified According to the New European LeukemiaNet Recommendations?

Abstract

TO THE EDITOR: Baccarani et al, on behalf of European LeukemiaNet, recently published the new recommendations for the management and monitoring of patients with chronic myeloid leukemia (CML). These recommendations, which are based mainly on the greater experience obtained during the past few years with tyrosine kinase inhibitors, update and improve the previous recommendations, published in 2006. One of the main proposals consists of the definition of optimal and suboptimal response and therapeutic failure after 3 months of imatinib treatment. The latest recommendations define the optimal response at 3 months as a complete hematologic response (CHR) with at least a minor cytogenetic response (CgR), which means that the number of Ph metaphases is equal to or lower than 65%. A suboptimal response is defined as a CHR associated with failure in the CgR (meaning that more than 95% of metaphases will be Ph ) and therapeutic failure is considered when CHR response is not achieved. Depending on the group in which the patient is included, subsequent clinical and therapeutic management will differ. However, these new recommendations result in a group of patients remaining unclassified. Patients with CHR and minimal CgR (between 66% and 95% Ph metaphases) at 3 months of imatinib treatment cannot be included in any of the three definitions mentioned (ie, optimal, suboptimal, or failure). Consequently, no recommendations currently exist for this group of patients with CML. The frequency of minimal CgR at 3 months becomes difficult to estimate, given that the IRIS (International Randomized IFN versus STI571) study did not publish results, though data suggest that the number of patients belonging to this group could be relevant. de Lavallade et al performed cytogenetic analyses on 203 patients at 3 months and found that 110 (54%) had between 36% and 95% Ph metaphases. Although this study did not distinguish between patients with minor or minimal CgR, the likelihood of the whole group obtaining a complete CgR at 5 years reached 96.4%. In contrast, Baccarani et al, in the previous European LeukemiaNet recommendations, showed that the group with minimal CgR at 3 months in combination with the group of null CgR could still obtain a complete CgR of 50% at 2 years. Unfortunately, neither of these studies analyzed separately the minimal CgR group, and the response or survival estimations therefore remain speculative. Given that the approach to the group in question could be very open, with several acceptable alternatives, we consider that the authors should clarify this point in order to manage more accurately and uniformly our patients with CML.