Chronic myeloid leukemia treatment guidelines: Brazilian Association of Hematology, Hemotherapy and Cell Therapy. Brazilian Medical Association Guidelines Project – 2012 Does molecular evaluation by quantitative real time polymerase chain reaction have an impact on prognosis? The BCR-ABL/ABL ratio is almost always below 2% in chronic phase CML patients who attain cytogenetic response on imatinib treatment. Patients with the BCR-ABL/ABL ratio below 0.0001% are regarded as having complete molecular response. For patients who lose the cytogenetic response within 24 months (2.5%) the mean value of the ratio is 0.12%. Some relapsed patients evolve with disease progression (15.4%) with BCR- ABL/ABL ratios that vary from 0.3% to 0.0075%, which, within the usefulness of quantitative real time PCR (qPCR) in molecular evaluation defines the extremes of positive or negative residual disease, but with a great variability in the mean(53)(B). In CML patients investigated using qPCR, the estimated 5-year major molecular response rate is 67.1% and the cytogenetic response is 81.7%. In respect to event-free survival, including transformation to accelerated and blast crisis phases, death from any cause, loss of adherence to treatment or loss of cytogenetic response, patients who attain molecular response have a higher response compared to those who do not. Patients with major molecular response have better survival than patients with complete cytogenetic response, who do not achieve major molecular response(54)(B). The estimated molecular response obtained by PCR analysis in CML patients treated with imatinib, also allows a comparison with hematologic and cytogenetic responses over time. Thus, in an 18-month follow-up, the molecular, cytogenetic and hematologic responses were 79%, 83% and 93%, respectively(55)(B). Cytogenetic progression (loss of response, clonal evolution, 20% increase of the Philadelphia clone) occurs in 13% of CML patients under imatinib treatment in 2 years of follow-up. At the time of progression, none of these patients had major molecular response (reduction ≥ 3log in BCR-ABL). Thus, there is a suggestion that cytogenetic analysis should be restricted to cases that do not attain or lose molecular response as measured by qPCR(56)(B). To evaluate changes in the levels of BCR-ABL transcripts as prognostic markers by qPCR, monitoring during 4 years demonstrates major molecular response (≥ 3-log reduction) and predicts higher disease-free survival rates. A minimal increase of 0.5-log predicts shorter relapse-free survival. Loss of molecular response (< 2.5-log reduction) also defines reduction in disease- free survival. A complete molecular response (PCR undetectable) corresponds to an increased disease-free survival(57)(B). Recommendation: the prognosis (survival, relapse, progression) of CML patients under imatinib treatment can be predicted using qPCR. Can cytogenetics be replaced by quantitative real-time polymerase chain reaction to monitor CML patients taking tyrosine kinase inhibitors who attain complete cytogenetic response? Rev Bras Hematol Hemoter. 2012;34(5):367-82 There is a correlation between the levels of transcripts in the bone marrow and peripheral blood at 3 months of treatment and obtaining molecular response at 6 months(58)(B). The comparison between qPCR, cytogenetics and fluorescence in situ hybridization (FISH) to monitor response to treatment using TKIs in CML patients demonstrates the following correlations and/or concordances: qPCR in bone marrow and peripheral blood; cytogenetics in the bone marrow, FISH in peripheral blood and qPCR in peripheral blood(59)(B). Despite the correlation between qPCR and cytogenetic analysis, other prognostic factors may be associated with molecular or cytogenetic responses, affecting the outcomes during TKI treatment of chronic phase CML patients. This shows the need of multivariate analyses that estimate the impact of the interaction of prognostic factors present in the medical practice. However in multivariate analysis, just the 3-month cytogenetic response is predictive of the response at 6 months and disease- free survival at 2 years(58)(B). Relapse occurs at 24 months in 2.5% of patients who have obtained cytogenetic response and these patients may experience disease progression to the accelerated and blast crisis phases. The correlation between PCR analysis and cytogenetic response may contain a raneg of values that hamper interpretation and thus not favor the substitution of methods(53)(B). Three-monthly monitoring using qPCR may provide the prognostic data needed for decision making in CML patients thereby reducing the need of bone marrow aspirations. The reasons that PCR monitoring is sufficient include: the level of log reduction in the BCR-ABL/ABL ratio correlates with cytogenetic response; in the 12 -month follow-up, no patient has disease progression without there being an indication in the risk by qPCR (half-log increase or 5-fold increase in the previous value of the BCR-ABL/ABL ratio); and no patient has cytogenetic progression when they have molecular response(56)(B). Recommendation: qPCR in peripheral blood can be used as the examination of choice to monitor chronic-phase CML patients under imatinib treatment. Cytogenetics is a fundamental option for monitoring that may be used in association with PCR, or may be reserved for cases where either there is no molecular response or the molecular response was lost. What is the treatment of choice for chronic-phase CML patients resistant to imatinib 400 mg? A comparison of treatment with dasatinib 140 mg and an increase in the dose of imatinib (800 mg) in chronic phase CML patients resistant to imatinib 400 mg (lack of complete hematological response at 3 months or lack of cytogenetic response at 6 months, or lack of major cytogenetic response at 12 months of treatment) demonstrates the following results: complete hematologic response increases in 11% of patients (NNT: 9), complete cytogenetic response increases by 23% (NNT: 4) and major molecular response increases by 12% (NNT: 8). Moreover, 371