As a part of routine evaluation of CLL, we do a complete blood count where we look at the number and the type of blood cells in a patient. In CLL, we often see an increased number of lymphocytes, which are a type of white blood cell that are commonly elevated in this disease.

Another type of blood test performed for diagnosis of CLL is called flow cytometry. The patient's blood sample is analyzed in a device called a flow cytometer, and that helps detect the surface proteins that are present on these lymphocytes, which helps in determining the specific types of lymphocytes detected in patients with CLL.

Another blood test that is sometimes performed are molecular and cytogenetic tests such as fluorescent in situ hybridization or FISH, as well as next generation sequencing or NGS. CBC, or complete blood count, is a type of blood test that provides information on the number and the type of blood cells in a patient. This is a routine test that is performed in the initial assessment of patients with CLL. In CLL patients, there may be an increased number of lymphocytes, a type of white blood cell that's commonly increased in CLL.

Imaging may or may not be a part of the initial diagnostic evaluation of CLL. In certain situations, based on a patient's symptoms and their medical risk factors and medical assessment on the physical exam, imaging may be recommended. We commonly use a CT scan in the initial diagnosis and assessment of patients with CLL, and sometimes a PET scan, which is positron emission tomography, is recommended in the initial evaluation.

Genetic tests are a very important component of assessment of patients with CLL. This helps in determining the genetic profile of the patient with CLL. There are a number of complex diagnostic tests used, but some of the common ones are fluorescent in situ hybridization or the FISH test. This is a molecular genetic test used to look for specific gene alterations in CLL. It uses fluorescent probes to look for DNA sequences associated with genetic changes. For example, in CLL, some of the genetic mutations noted are TP53 mutations and ATM gene mutations, which can be detected by FISH. FISH testing is relatively commonly performed in the initial diagnosis and evaluation of patients with CLL.

Another test used is next generation sequencing or NGS. Next generation sequencing is a complex test that provides simultaneous assessment of multiple gene alterations in CLL. It provides a comprehensive assessment of various genetic alterations possible in CLL, such as TP53 alterations, NOTCH1, ATM gene, and SF3B1 mutations, which helps in determining prognosis in patients with CLL and also guides treatment decision-making. Genetic testing in CLL can provide more information about the genetic profile of the CLL cells. There are genes associated with slightly better prognosis in patients with CLL, as well as genes associated with adverse prognosis and inferior responses to treatment. There are genes that predict chances of relapse or time to progression as well. This information helps in prognosticating patients early and in determining treatment decisions. The information gathered from genetic testing helps in identifying specific genetic alterations unique to a patient's CLL, stratifying them into specific disease risk groups that predict progression of disease and guide treatment decisions.

Risk stratification and tests performed after the diagnosis include a panel of FISH tests, including looking for p53 deletion, which is the worst of the group. There is also a minority called 11q deletion, which is second in terms of prognostic impact on the FISH panel. The 13q deletion is not that bad, and chromosome 12q deletion carries a favorable prognosis. Additionally, mutations in the immunoglobulin heavy chain gene are examined, with unmutated phenotype carrying a higher risk than a mutated phenotype.