Cytogenetic Remission

Cytogenetic remission is defined as a reduction in the number of identifiable Philadelphia (Ph+) chromosomes by standard metaphase karyotypic analysis. The degree of reduction determines the completeness of remission, and this degree of reduction has prognostic significance with regard to survival. The importance of achieving a major or complete cytogenetic remission (CCR) is highlighted by the results of several randomized clinical trials comparing interferon-a to chemotherapy such as hydroxyurea. In these studies, the only patients achieving a significant cytogenetic remission were those treated with interferon.145 For patients achieving CCR on interferon, the 10-year overall survival rate was 72%.6

With interferon alone, however, only a minority of patients actually achieved a CCR. In a randomized trial of interferon alone versus the combination of interferon plus low-dose cytarabine in chronic-phase CML patients, the combination treatment arm induced more major cytogenetic remissions than did the interferon alone arm (35% vs 21%; P = 0.001).7 This difference translated into a 5-year overall survival advantage for the combination arm of 70% versus 62% (P = 0.02). Thus, cytogenetic remission, and in particular CCR, is an important endpoint not only to determine efficacy, but also to maximize the chances for long-term disease-free survival.

Cytogenetic analysis is the gold standard method for predicting clinical outcomes in CML and is typically performed on bone marrow samples. However, there are many practical disadvantages to monitoring CML therapy by bone marrow cytogenetics, including the requirement for proliferating cells and the poor sensitivity (typically 5%) for detecting low-level minimal residual disease. Fluorescent in situ hybridization (FISH) allows for detection of the bcr/abl translocation in either metaphase or interphase cells. Because interphase cells are suitable, FISH can be performed on blood leukocytes. Moreover, large numbers of cells can be examined, which increases the sensitivity over that of metaphase cytogenetics. A negative FISH result correlates very well with CCR.89

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