Doctors use staging to help them predict chronic lymphocytic leukemia's (CLL's) progression and develop an appropriate treatment plan. Doctors use one of two staging systems: the Rai staging system or the Binet staging system.
Staging systems consider certain factors such as:
- The elevation of your blood and marrow leukemic lymphocyte counts
- Your lymph nodes' size and distribution
- Your spleen's size
- The extent of your decreased blood platelet counts
- The degree of anemia
Rai Staging System
The Rai staging system classifies CLL into the following five stages based on factors at the time of diagnosis:
|Low Risk 0||
|Intermediate Risk I||
|Intermediate Risk II||
|High Risk III||
|High Risk IV||
Binet Staging System
The Binet staging system is less commonly used. It classifies CLL by three stages: A, B and C:
Other Test Results
When your hematopathologist examines your blood cells to decide staging, he or she may find other factors that can affect your CLL prognosis. The following can be signs of a faster-growing disease (higher-risk CLL):
- Blood lymphocyte doubling time. If your lymphocyte count doubles in one year, you have higher-risk CLL and need closer follow-up care. A lymphocyte number that remains stable shows a relatively lower risk.
- Beta 2-microglobulin (B2M). B2M is protein that's shed from CLL cells. A higher level of B2M may mean a greater extent of the disease.
- CD38. A characteristic marking (antigen) called CD38 (CD stands for "cluster designation") on the cells' surface can indicate higher-risk CLL.
- Unmutated IgHv. The presence of a marker on the CLL cells, called unmutated immunoglobulin heavy chain variable region gene (IgHv), suggests higher-risk disease.
- ZAP 70 (Zeta-associated protein 70). High levels of this cell protein suggest higher-risk disease. It should be noted that further study in clinical trials is needed to standardize the assessment of ZAP-70. The National Comprehensive Cancer Network (NCCN) guidelines state that the evaluation of ZAP-70 expression by flow cytometry can be challenging and is not recommended outside of a clinical trial. There are new tests such as ZAP-70 methylation which may represent a better way to measure this. Additionally, other prognostic markers such as CD49d expression have also been suggested as a better biomarker than ZAP-70.
- NOTCH1 gene mutations. Notch1 is a gene involved in the development of different type of blood cells. In CLL, approximately 10 to 15 percent of patients have mutations of this gene causing it to be more active than it should be. Several studies have suggested that CLL patients who have NOTCH1 gene mutations may progress more quickly, requiring therapy and have a shorter overall survival. These findings are currently being confirmed. Some commercial laboratories do this test, but it is not recommended by the NCCN guidelines.
- SF3B1 gene mutations. The SF3B1 gene is involved in the forming of select proteins in CLL and other blood cancers. It is mutated in several blood cancers including CLL, AML, and MDS. In CLL, approximately 10 to 15 percent of patients have mutations of this gene, resulting in dysfunctional protein processing. Several studies have suggested that CLL patients who have SF3B1 gene mutations may progress more quickly, requiring therapy and have a shorter remission and overall survival. These findings are currently being studied. Some commercial laboratories do this test but it is not included in the NCCN guidelines.
- TP53 gene mutations. The TP53 gene is viewed as the gatekeeper to protecting the DNA of cells from damage. Mutated DNA of cancer cells lead to increased cancer growth and resistance to chemotherapy cancer treatments. Mutation of the TP53 gene is very commonly seen in patients who also have del(17p) findings on their interphase cytogenetics. Some patients just have mutation of the TP53 gene and, in general, these patients have a higher likelihood of progressing more quickly, requiring therapy, not responding well to traditional therapies and having an overall shorter survival. Many commercial laboratories do this test. Select newer therapies work better for patients who have del(17p) or the TP53 gene mutations. Given the rarity of this type of CLL, if the TP53 gene mutation is found, it is important for you to consult a CLL specialist at a major cancer center.