Pretreatment Evaluation

Continuous development of investigational treatments, identification of prognostic variables, and the recent success of targeted therapy with imatinib mesy-late in selected CMML patients with specific chromosomal alterations associated with activation of receptor tyrosine kinases (RTKs, see below), all support the need for an extended initial evaluation. In addition to clinical assessment and the standard laboratory tests used to establish a diagnosis, the pretreatment workup should include bone marrow aspiration, biopsy, and cytogenetic analysis. Information on ^-microglobulin and plasma lactate dehydrogenase (LDH) concentrations are useful because high plasma levels are associated with a worse prognosis.4 In patients up to 65-70 years old, HLA tissue typing of patients and their siblings should be considered, given the possibility of a reduced-intensity conditioning regimen and allogeneic stem cell transplantation (SCT). Both karyotyping and molecular screening for the BCR/ABL translocation are therapeutically relevant, as they have prognostic implications and are necessary to exclude BCR/ABL-positive disease with monocytosis and to identify rare cases with specific translocations involving genes coding for RTK.5-8 (This is discussed in detail elsewhere.) Cells from patients with translocations involving platelet-derived growth factor receptor (PDGFR)p may be further evaluated by molecular assays to verify such molecular abnormalities, and result in abnormally functioning RTK sensitive to TK inhibitors, such as imatinib mesy-late.5-8 In myeloproliferative disorders (MPD), including CMML, translocations involving PDGFRp [such as t(5;12)] frequently appear to be associated with marrow dysplasia and blood eosinophilia.8 In the absence of an abnormal karyotype, the possibility of a cryptic translocation involving the 5q33 region may mandate further molecular screening using, for example, polymerase chain reaction (PCR) and specific primers.

Ideally, the final therapeutic decision is made on the basis of both the patient's clinical status and the prog-nostically significant features of the disease.4 With the exception of SCT in certain patients, however, the available treatment modalities rarely, if ever, result in the eradication of CMML. The relative rarity of the disease, lack of agreement on a "standard of care," and lack of uniform criteria for patient response hamper initiation of well-designed randomized clinical trials needed to answer such questions. This said, numerous treatment modalities, which are all by definition investigational, provide various levels of disease control and improvements in quality of life.

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