When a person has just been diagnosed with early stage CLL, it is important to exercise caution in making long-term predictions. The course of CLL is highly variable. Some patients remain without symptoms for years while in others the disease progresses much more rapidly. Only after a physician has had an opportunity to monitor a newly diagnosed, early stage patient for a period of approximately one year can a more reliable long-term prognosis be given.
A number of prognostic indicators are available to CLL patients and their physicians. Very few early stage patients will be tested for all of the indicators listed below, but they are some of the main indicators that are available. One should never rely on a single indicator, but should use as many of the indicators as possible in determining the prognosis. Most physicians experienced in treating individuals with CLL have developed their own set of indicators/tests that they use at different points in time after the initial diagnosis.
Newly diagnosed patients who are in early-stage disease will find these indicators particularly helpful in determining how their CLL might progress. Patients with more advanced disease will also find these indicators useful. These patients are often already aware of the indicators and their impact on prognosis.
| Indicator | Prognostic Implications |
|---|---|
| Lymphocyte doubling time | Peripheral lymphocyte doubling times of less than one year are indicative of aggressive CLL, whereas, doubling times of greater than one year suggest a more indolent situation. |
| Absolute lymphocyte count | Once an abnormal cell population is noted on a differential, the traditional method of reporting (the percentage) is no longer valid. Only the absolute counts correctly reflect the white cell population in the peripheral blood. The lymphocyte doubling can be seen here and together with the absolute granulocyte count, the general state of the individual's immune system can be seen. The absolute lymphocyte count is usually listed as either #LY or ABS LY on a differential report. |
| Hemoglobin level | Hemoglobin levels of greater than 13 grams per deciliter of blood (13g/dL) are desired. Levels of less than 13g/dL may indicate aggressive or advanced disease. Some laboratories report hemoglobin levels in liters and not deciliters. In that situation the desired level is greater than 130 grams. |
| Bone marrow histology | Diffuse bone marrow involvement correlates with progressive or advanced disease, while nodular or interstitial (non-diffuse) patterns in the bone marrow indicate a better prognosis. |
| Beta-2-microglobulin | Beta-2-microglobulin (ß2m) is a piece of the cell membrane. When cells are particularly active or are damaged easily, this piece is broken off and remains in the plasma where it can be quantified. The slower the cell's activity or the less damage within the cell, the lower the amount of ß2m in the plasma. Patients with ß2m values below 2.0 mg/L seem to have a more favorable outlook than those with values above 2.0. |
| CD38 expression | Patients with less than 20 percent CD38+ CLL cells are likely to have a more favorable clinical course requiring minimal or no therapy, whereas, patients with greater than 20 percent CD38+ B-CLL cells are more likely to have an unfavorable clinical course requiring earlier and ongoing treatment. CD38 seems to be closely linked with IgVH gene mutation; however, this correlation is a matter of debate. |
| Serum lactate dehydrogenase (LD or LDH) | Most cells in the body require this enzyme in their production of energy. As cells are damaged or die inappropriately, they will spill the contents of their cytoplasm into the peripheral blood where it can be quantified. There are five major types of LD and each can be identified through a procedure known as isoenzyme electrophoresis. Increases in LD can be seen when there is increased cell death due to chemotherapy or when a person is relapsing from remission. |
| Soluble CD23 | CD23 is supposed to be found on all B-cells and a few other cells. B-cells are supposed to constitute less than 25% of the total number of lymphocytes in the peripheral blood. If CD23 levels begin to increase in the peripheral blood, it can be assumed that the number of B-cells in the blood stream is greater than expected (or wanted) in the blood stream. |
Chromosome and gene abnormalities - normal chromosome profiles (karyotypes) are predictive of a more stable situation. However, chromosome abnormalities are found in a large percentage of CLL patients. Using molecular testing techniques, it is estimated that abnormalities can now be identified in approximately 80 percent of CLL cases. Prior to the availability of current molecular testing techniques, conventional testing detected abnormalities in 40 to 50 percent of cases. These abnormalities are helpful in predicting the course of CLL. Some of the most important disease-associated abnormalities and their implications for disease progression are shown below:
| 17p deletion | Aggressive disease progression. |
| 11q deletion | Associated with a poor prognosis and often accompanied by bulky lymph node involvement. This deletion also identifies patients who are at high risk for disease persistence after high-dose therapy and autologous transplantation. |
| trisomy 12 | Predictive of a shorter treatment free interval. |
| 13q deletion | 13q deletion is a positive indicator that predicts indolent disease progression. |
| p53 gene mutations | These mutations predict for non-response to treatment with alkylating agents and purine analogs. |
| p53 gene deletions | Patients with p53 deletions are thought to have a shorter survival time and to be more resistant to treatment than those without this deletion. |
| IgVH gene mutation status | Unmutated IgVH genes suggest an inferior prognosis; whereas, mutated IgVH genes indicate a much better prognosis. |
Some patients will have combinations of these abnormalities. When looking at chromosomal abnormalities, it is also useful to consider the IgVH gene mutational status. Patients with chromosomal abnormalities and mutated IgVH genes have a better outlook than those with chromosomal abnormalities and unmutated IgVH genes. Checking for IgVH gene status is currently available only for research purposes. It is anticipated that it will soon be available in the clinical laboratory.