Impact Of Recently Identified Biologic And Cytogenetic Prognostic Markers On Treatment Decisions

Considerable degrees of excitement and hopes for improving the treatment of CLL have recently been generated following the discovery of four prognostic features.


Leukemic lymphocytes of nearly 50% of the CLL patients have somatic mutations in IgVH genes, and the remaining 50% have unmutated VH genes.4 5 There is a strong correlation between longer survival and overall better clinical course among patients with mutated VH genes compared to their unmutated counterparts. Thus, it is reasonable to consider the unmu-tated VH gene patients for early therapeutic intervention. This, we believe, will happen in the foreseeable future, but at this moment, the testing for the mutation is neither generally available (it is labor intensive and costly), nor has its methodology been standardized. Also, there is a lack of consensus among experts as to how to define "mutated." Does it require 2% mutations, or 2.5%, or 3%? This is not a trivial issue, because the counterparts of each of these ratios will thus be called unmutated, and whether those patients labeled "unmutated" will have to have more than 98% homology, more than 97.5%, or more than 97% homology is a matter which is yet to be resolved. Once this is resolved, it is possible that a symptom-free, early stage CLL patient who might otherwise be followed on wait-and-watch basis would become a candidate for immediate chemotherapeutic intervention if that patient has unmutated VH genes. However, at this time we include this parameter only in research-based investigational therapeutic trials.

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