Prognosis

The median survival of patients with CLL is about 10 years. Some patients have a survival not different from that of the general population, but there are others who have a rapidly fatal course. Clinical stages have been the most useful prognostic parameters in CLL1112 (Table 25.2; Figure 25.1). They, however, have some limitations. For example, an important condition of all prognostic parameters is that they identify a substantial proportion of patients with different outcome. Since the majority of patients with CLL are diagnosed on the occasion of routine medical examinations, when still asymptomatic, most patients (70-80%) are in early clinical stage at diagnosis, thus limiting the prognostic value of clinical stages.1314 Moreover, progressive and indolent forms of the disease are not identified. In addition, the mechanisms accounting for cytopenias are not taken into consideration, yet there is some indication that patients with cytopenias of immune origin may have a better outcome than those in whom the cytopenia is caused by a massive infiltration of the bone marrow by neoplastic cells.1516

Because of the limitations discussed above, other prognostic factors able to increase the prognostic power of clinical stages have been proposed. In addition to clinical stages, other widely used prognostic factors include the degree of bone marrow infiltration, blood lymphocyte levels, lymphocyte doubling time, and lymphocyte morphology. A number of serum markers, including lactate dehydrogenase (LDH), thymidine kinase, B2-microglobulin, CD23, CD25, and CD20 serum levels have also been found to be good indicators of survival(reviewed in Refs. 17,18).

Differences in the natural history of CLL and its prognosis reflect the biological heterogeneity of the disease, which is rapidly unfolding. Thus, in up to 90% of the patients it is possible to detect cytogenetic abnormalities by fluorescent in situ hybridization studies. Although nonspecific, there are interesting correlates between some cytogenetic aberrations and clinical features and prognosis. For example, patients with del(13q) as a single anomaly have an excellent prognosis whereas those with del(11q) or del(17p) do not respond to chemotherapy and tend to have a rapidly evolving disease. Moreover, trisomy 12 is associated with atypical morphology and immunophenotype of the leukemic cells, and del(6q) is more frequently observed in patients whose lymphocytes display plasmacytoid features and intermediate prognosis.19-21 Also, overexpression of MDR-1 and MDR-3 genes and P-glycoprotein detection on neoplastic cells has been correlated in some studies with resistance to therapy and poor prognosis.2223

Staging systems for chronic lymphocytic leukemia

Staging system

Stage

Clinical features

Median survival (yrs)

Staging system

Stage

Clinical features

Median survival (yrs)

Low-risk

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