European LeukemiaNet criteria for failure or suboptimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor

Abstract

The majority of patients with chronic myeloid leukemia in chronic phase gain substantial benefit from imatinib but some fail to respond or lose their initial response. In 2006, the European LeukemiaNet published recommendations designed to help identify patients responding poorly to imatinib. Patients were evaluated at 3, 6, 12, and 18 months and some were classified as "failure" or "suboptimal responders." We analyzed outcomes for 224 patients with chronic myeloid leukemia in chronic phase treated in a single institution to validate these recommendations. Patients were followed for a median of 46.1 months. At each time point, patients classified as "failure" showed significantly worse survival, progression-free survival, and cytogenetic response than other patients; for example, based on the assessment at 12 months, the 5-year survival was 87.1% versus 95.1% (P ‫؍‬ .02), progression-free survival 76.% versus 90% (P ‫؍‬ .002), and complete cytogenetic response rate 26.7% versus 94.1% (P < .001). Similarly, the criteria for "suboptimal response" at 6 and 12 months identified patients destined to fare badly, although criteria at 18 months were less useful. The predictive value of some other individual criteria varied. In general, the LeukemiaNet criteria have useful predictive value, but a case could now be made for combining the categories "failure" and "suboptimal response." (Blood. 2008;112:4437-4444)

Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML)

“…4,11 Treatment failure at these time points has been shown to be closely related to PFS and overall survival (OS). 12 CCyR has been established as the gold standard for outcome prediction within the International Randomized Study of Interferon and STI571 (IRIS). 13 More recently, molecular response determined by BCR-ABL transcript levels according to the international scale (BCR-ABL IS ) at defined time points has been used as a predictive marker.…”

Seeking the causes and solutions to imatinib-resistance in chronic myeloid leukemia

“…Marin and colleagues also retrospectively evaluated clinical outcomes on the basis of the 2006 ELN criteria using a cohort of 224 patients treated at a single institution. 16 Patients with a treatment failure per Indicates that the data are from the CCyR rate at 24 months rather than 18 months.…”

Current Role of Genetics in Hematologic Malignancies

“…Similarly, molecular response is assessed at 3,6,12 and 18 months and thereafter periodically for follow-up. It is evident from the literature that the patients who have suboptimal cytogenetic or molecular response at a given point of time fare poorly in the long run [32][33][34]. Interpretation of these tests and alteration in treatment for management of suboptimal response is out of purview of this article.…”