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C Anemia (hemoglobin 32

< 10gm%) and/or thrombocytopenia (platelet <100,000/mm3)

C Anemia (hemoglobin 32

< 10gm%) and/or thrombocytopenia (platelet <100,000/mm3)

Rate of increase in absolute lymphocyte count

In an untreated patient, if the absolute lymphocyte count (ALC) is increasing at a rapid rate, doubling in a short period, usually considered to be less than 6 months, (although some observers consider doubling in less than 12 months as rapid rate), the disease is progressing rapidly, and therapy should be started. It is our opinion that this feature of rapid lymphocyte doubling time should not be enough if it exists as a sole feature, i.e., in absence of "B" symptoms or worsening of clinical stage, etc. Also, the height of the ALC should also be taken into account; for example, ALC doubling from a relatively low number, e.g., 6000 to 12,000/mm3 in 6-12 months in an asymptomatic patient carries less weight than a high baseline, e.g., 100,000/mm3 ALC projected to be doubling in the same period of 6-12 months. Similarly, hyperlymphocytosis, for example, an ALC of 250,000/mm3 or higher, might cause hyperviscos-ity of circulating blood, and thus pose an increased risk of thromboembolic events in the microcirculation in an organ, with potentially catastrophic results. Thus, hyperlymphocytosis by itself in some circumstances should become a trigger to initiate therapy.

Is histopathologic pattern of lymphoid infiltration in the biopsy specimens of bone marrow by itself a factor in decision making? In our opinion, although a diffuse infiltration pattern is generally associated with a worse prognosis than nodular or interstitial (nondiffuse) patterns, this feature is not powerful enough to deserve to be factored in making this decision.

Other clinical characteristics that have been reported to be helpful in determining whether CLL is active or progressing are elevated serum levels of p2-microglobulin, thymidine kinase, and soluble CD23.1 Although each one of these tests has some validity as a prognostic marker in CLL, none of them has been tested and proven to be powerful in prospectively conducted studies; nor have they been consistently used by all clinicians. Therefore, we have not integrated any of these in our decision-making algorithm in this disease.

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