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More recently, researchers have focused on developing additional prognostic markers that may prove to be more accurate in helping to determine the prognosis for patients with chronic lymphocytic leukemia (CLL). These prognostic markers include:

• Lymphocyte Doubling Time
• Chromosomal Abnormalities
• Zeta-Associated Protein 70 (ZAP-70)
• CD38 Antigen
• IgVH Gene Status

Lymphocyte Doubling Time

As mentioned previously, the major blood abnormality in patients with CLL is an absolute increase in the numbers of lymphocytes in the bloodstream - a condition known as lymphocytosis. The lymphocyte doubling time (LDT) is a measure of the time (number of months) that it takes for the absolute lymphocyte counts (ALC) to double. In general, studies have shown that patients with CLL with a LDT of less than 12 months survive for a shorter period of time than patients with a LDT of greater than 12 months. Although the LDT is not an absolute prognostic marker for CLL, it does provide useful information to doctors about the rate of progression of the disease and helps to identify patients with early-stage CLL who may need treatment sooner.

Chromosomal Abnormalities

Using a technique called fluorescence in situ hybridization (FISH), doctors are now able to identify specific chromosomal abnormalities in patients with CLL as well as other hematological malignancies. For example, studies have shown that CLL patients with no chromosomal abnormalities or those patients with an isolated 13q14 chromosomal deletion have a much better prognosis than CLL patients with either 17p13 or 11q23 chromosomal deletions. Analysis of chromosomal abnormalities by FISH is now recommended for all newly diagnosed CLL patients.

Zeta-Associated Protein 70

Recent studies have shown that the expression of a protein called zeta-associated protein 70 (ZAP-70) by leukemic cells may be a useful means of identifying CLL patients who have a more aggressive form of the disease. In a 2004 study published in the New England Journal of Medicine (Volume 351; pages 893-901), researchers reported that patients with CLL whose cells did not produce the ZAP-70 protein survived for a significantly longer period of time than CLL patients whose cells produced the ZAP-70 protein. The results of this study suggest that ZAP-70 expression may be an important prognostic marker for identifying a subgroup of CLL patients with a more aggressive form of the disease who may benefit from earlier treatment of their disease.

The abstract of this article can be found at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15329427

CD38 Antigen

CD38 is an antigen that is often expressed on the surface of leukemic B-cells in patients with chronic lymphocytic leukemia. Studies have found that patients with CLL where 30% of more of the leukemic cells are positive for CD38 antigen are at higher risk for early progression of the disease and, in general, have a lower survival rate than CLL patients with CD38 antigen levels below 30%. Patients with CLL who are positive for the CD38 antigen are also much less likely to respond to treatment with fludarabine.

IgVH Gene Status