Chronic lymphocytic leukemia
Tests
1st tests to order
CBC count with differential
Test
Required for diagnosis and staging.
Patients with CLL usually present with absolute lymphocytosis as an incidental finding on a routine CBC.
A diagnosis of CLL requires an absolute monoclonal B-lymphocyte count ≥5000 cells/microliter (≥5 × 10⁹/L) in the peripheral blood that persists for at least 3 months (see flow cytometry).[2][33]
Patients may present with cytopenias (anemia, thrombocytopenia), which could be disease-related (i.e., due to leukemic cells infiltrating the bone marrow) or related to an autoimmune complication (e.g., autoimmune hemolytic anemia, immune thrombocytopenic purpura).[2][34][35]
The presence of cytopenias can guide staging and treatment. See Diagnostic criteria and Management sections.
Result
elevated WBC count with absolute lymphocytosis (monoclonal B lymphocyte count ≥5000 cells/microliter [≥5 × 10⁹/L]); anemia (Hb <11.0 g/dL) and/or thrombocytopenia (platelets <100,000/microliter [<100 × 10⁹/L]) may be present
flow cytometry
Test
Required for diagnosis.
Flow cytometry confirms clonality and the immunophenotype of circulating B lymphocytes.[2][33]
Flow cytometry may also identify markers for prognostication (e.g., zeta-associated protein [ZAP-70], CD38, and CD49d).[2][28][29][30] Although expression of ZAP-70, CD38, or CD49d predict a worse prognosis, there is no evidence to suggest that early treatment improves survival in patients with these markers.
Result
typical immunophenotype of CLL: CD5+, CD23+, CD43+/-, CD10-, CD19+, CD200+, CD20 dim, surface immunoglobulin (sIg) dim+ (with restricted expression of either kappa or lambda immunoglobulin light chains), and cyclin D1-; prognostic markers (e.g., ZAP-70, CD38, CD49d) may be present
peripheral blood smear
Test
Required to identify (morphologically) the presence of CLL cells in the blood.[2][36][37]
Smudge cells (damaged lymphocytes) are a common finding on a blood smear of patients with CLL.[38] Patients with higher numbers of smudge cells typically experience less aggressive disease.[38][39] Smudge cells are not diagnostic of CLL.
Result
presence of leukemic cells that appear as small mature lymphocytes with a narrow border of cytoplasm, a dense nucleus lacking discernable nucleoli, and having partially aggregated chromatin; smudge cells may be present; spherocytes and polychromasia may be present if there is active hemolysis
Tests to consider
serum beta-2 microglobulin
Test
An important prognostic factor included in the CLL International Prognostic Index (CLL-IPI; see Diagnostic criteria section).[33][40]
Elevated serum beta-2 microglobulin is associated with a poor prognosis.[41][42]
Result
may be elevated
fluorescent in situ hybridization (FISH)
Test
Peripheral blood should be subject to FISH (cytogenetic analysis) to help determine prognosis and to aid treatment decisions.[2][33][36]
Cytogenetic abnormalities of prognostic significance in chronic lymphocytic leukemia include: del(13q), del(11q), trisomy 12, and del(17p).[25] Del(17p) is associated with resistance to chemoimmunotherapy, rapid disease progression, and a poor prognosis.[25][43]
Result
may show cytogenetic abnormalities (e.g., del(13q), del(11q), trisomy 12, del(17p))
molecular genetic tests
Test
Used to determine TP53 and immunoglobulin heavy chain (IgHV) mutation status, which can inform prognosis and treatment.[2][33]
TP53 gene mutations are associated with a poor prognosis.[23] Patients with mutated IgHV have a good prognosis and respond well to chemotherapy.[47][48][49]
Other genetic mutations of potential clinical relevance include NOTCH1, SF3B1, ATM, and BIRC3; however, their role in guiding management of CLL requires further investigation.[22][36][44]
Result
may show genetic mutations (e.g., IgHV, TP53)
direct antiglobulin test (DAT)
Test
Ordered if patient is anemic.
Result
positive test suggests autoimmune hemolytic anemia
serum quantitative immunoglobulin
Test
Ordered if patient has recurrent infections.
Result
may show hypogammaglobulinemia
CT scan/fluorodeoxyglucose (FDG)-PET/CT
Test
Imaging studies are not typically required for diagnosis, staging, or follow-up.[2][33][36][37][45][46]
CT scans do not improve the outcome for patients with early-stage CLL and do not aid with staging or prognosis; they also expose patients to radiation and may detect incidental, clinically irrelevant findings that lead to further tests.[45]
Staging is based on physical exam and blood counts (see Diagnostic criteria section).[2][37]
CT scan may be used to assess symptoms of bulky disease, or to assess the risk for tumor lysis syndrome (TLS) prior to initiating treatment (e.g., venetoclax).[33][36]
Fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT scan may be used to direct nodal biopsy if histologic (Richter) transformation is suspected.[33][46]
Result
may show hepatosplenomegaly; retroperitoneal or mediastinal adenopathy
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