Monitoring

Following therapy, disease response is assessed using three parameters: hematologic, cytogenetic, and molecular status. Hematologic remission is achieved when the blood counts and spleen size have normalized. Cytogenetic response is quantified and graded based on the percentage of residual Ph-positive cells, with a major complete response defined as 0% Ph-positive cells, a major-partial response as 1% to 34% Ph-positive cells, a minor response as 35% to 94% Ph-positive cells, and no response as >95%

Ph-positive cells.12 Traditionally, the cytogenetic response serves as the "gold standard" for assessment and is an important predictor of patient survival.

Once conventional hematologic remission and cytoge-netic complete response have been achieved, monitoring relies on more-sensitive molecular techniques. When the BCR-ABL1 fusion transcript is no longer detectable, molecular remission has been attained. However, a widely accepted definition of molecular remission does not yet exist, and its designation varies with test method and sensitivity. Nonetheless, a single negative or positive qualitative reverse transcription-polymerase chain reaction (RT-PCR) result is, in itself, of little clinical predictive value, since such assays may lack precision, depending on the sensitivity of the specific test. In contrast, serial quantitative tests that assess the kinetics of tumor clearance (response) or reappearance (relapse) have greater predictive value. Rising levels of BCR-ABL1 messenger RNA (mRNA) have been shown to precede disease recurrence and may signal a need for therapeutic intervention, while low, diminishing, or stable fusion transcript levels identify patients in whom treatment has been effective.

A rational understanding of laboratory monitoring is predicated on an appreciation of therapeutic goals and options. Indeed, eradication of the neoplastic clone cannot always be achieved, in which case therapeutic intent focuses on tumor control with an attempt to forestall disease progression. Standard treatments available to patients in the chronic phase of CML include allogeneic stem cell transplantation (ASCT), imatinib mesylate, inter-feron-a, and hydroxyurea (Table 35-2), with imatinib mesylate having become the new gold standard for initial therapy.13,20

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