Pocket Drug Guide

Patients being treated for chronic myelogenous leukemia can be monitored by hematologic, cytogenetic, and molecular tests such as fluorescence in situ hybridization and RT-PCR. Based on these assays, therapy outcome may be defined in terms of hematologic remission (normalization of blood cell counts and spleen size), varying degrees of cytogenetic response (decline in percentage of Ph-positive cells), or a molecular remission (PCR-negative). Several studies have shown that PCR-negativity indicates complete eradication of the leukemic clone, and PCR-positivity is associated with relapse in T-depleted transplanted patients and those undergoing transplantation in the advanced phase. PCR-positive patients undergoing transplantation in the chronic phase or those receiving nonmanipulated bone marrow have a slightly higher risk of relapse than do PCR-negative patients. In these cases, competitive PCR has shown that a low number of BCR-ABL transcript molecules are associated with prolonged complete remission, and patients with an increasing number of transcript molecules are subject to earlier relapse.

TABLE . Poor Prognostic Factors for Chronic-Phase Chronic Myelogenous Leukemia presents clinical characteristics related to the host or the disease. It lists features related to therapy response that have been identified as having prognostic significance. These factors have been incorporated into scoring systems that enable clinicians to classify patients into groups with different prognoses. One commonly used tool is the Sokal score, which uses a patient’s age, spleen size, platelet count, and percentage of peripheral blasts in a complicated formula to determine the patient’s risk category. This classification divides patients into three groups with four-year survival rates of 62% (low risk), 43% (medium risk), and 33% (high risk). Because studies have found this model to be inaccurate for patients undergoing treatment with interferon-alpha (IFN-ct, the most common therapy used in the treatment of chronic myelogenous leukemia), an alternative scoring system, sometimes called the Hasford score, has been developed for these patients. In addition to the variables used in the Sokal score, the Hasford score uses the level of eosinophils to calculate a patient’s risk category.

TABLE . Poor Prognostic Factors for Chronic-Phase Chronic Myelogenous Leukemia

Investigators have proposed new prognostic models based on imatinib-treated patients, but these models have yet to be validated in large trials. In one study of patients who received imatinib after interferon-a failure, four variables were associated with a lower probability of achieving a major cytogenetic response: hematologic resistance to interferon-a, time from diagnosis to treatment > 12 months, bone marrow basophils >5%, and a percentage of Ph-chromosome metaphases >90%. This study identified three risk groups based on the number of adverse features. The first group (zero to one adverse features) has a 93% probability of achieving a major cytogenetic response, the second (two adverse features) a 53% probability, and the third (three to four adverse features) a 34% probability. Another model based on two adverse features has been proposed: (1) development of neutropenia < 1 x 109/L between days 45 and 90 of imatinib therapy, and (2) failure to achieve at least a major cytogenetic response at three months. In this model, three groups were defined with progression-free survival probabilities at two years of 100% (no adverse features), 66% (one adverse feature), and 15% (two adverse features). However, when this model was tested, the two-year progression-free survival rates for the three groups were 98%, 80%, and 96%, respectively.

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