Pruebas diagnósticas

Primeras pruebas diagnósticas para solicitar

CBC count with differential

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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.

Resultado

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

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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. 

Resultado

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

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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.

Resultado

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

Pruebas diagnósticas que deben considerarse

serum beta-2 microglobulin

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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]

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may be elevated

fluorescent in situ hybridization (FISH)

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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]

Resultado

may show cytogenetic abnormalities (e.g., del(13q), del(11q), trisomy 12, del(17p))

molecular genetic tests

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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]​ 

Resultado

may show genetic mutations (e.g., IgHV, TP53)

direct antiglobulin test (DAT)

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Ordered if patient is anemic.

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positive test suggests autoimmune hemolytic anemia

serum quantitative immunoglobulin

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Ordered if patient has recurrent infections.

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may show hypogammaglobulinemia

CT scan/fluorodeoxyglucose (FDG)-PET/CT

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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]

Resultado

may show hepatosplenomegaly; retroperitoneal or mediastinal adenopathy

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