Chronic Lymphocytic Leukemia: Test and Diagnosis

1st-order laboratory parameters-obligatory laboratory tests.

  • Small blood count [Later stage: anemia/poor blood count, thrombocytopenia/platelet deficiency]
  • Differential blood count [persistent leukocytosis/increased white blood cell count with high lymphocyte percentage (>50%):
    • > 5,000/μl B lymphocytes in peripheral blood.
    • Predominance of small, morphologically mature lymphocytes in peripheral blood smear]
  • Coagulation parameters – Quick, PTT (partial thromboplastin time).
  • Inflammatory parameters – CRP (C-reactive protein).
  • Cytology with blood smear [fragments of destroyed lymphocytes, so-called Gumprecht’s nuclear shadows], bone marrow smear [proportion of mature lymphocytes is increased to over 30%], CSF punctate.
  • Flow cytometry (method of laboratory medicine used to analyze cells flowing individually at high speed past an electrical voltage or light beam) [detection of monoclonal B cells].
  • Cytogenetic study and molecular genetics (analyses: morphology, immunohistochemistry, FISH/fluorescence in situ hybridization) [immunophenotyping of lymphocytes in peripheral blood:
    • Expression of typical B-cell markers (CD19, CD20, and CD23) +.
    • T-cell marker CD5
    • Weak expression of the surface immunoglobulins CD20 and CD79B.

    Light chain restriction (κ or λ) can prove monoclonality of cells.

  • 17p deletion or TP53 mutation (mutation of the p53 tumor suppressor gene)?; Indication: in case of progressive CLL or relapse before starting therapy and before any change in therapy.
  • Lymph node extirpation (surgical lymph node removal) – if immunophenotyping does not allow a clear diagnosis or in the case of rapidly growing lymph nodes (exclusion of a transition to an aggressive lymphoma).
  • Identification of very small amounts of malignant cells (“minimal residual disease, MRD) from bone marrow [for therapy management]:
    • Immunophenotyping by flow cytometry.
    • PCR analysis

Prognostic factors

  • TP53 deletion or mutation – this is associated with poor response to chemotherapy
  • NFAT2 – leukemia cells from patients with a slow clinical course have a large amount of the protein NFAT2; in patients with an aggressive course, the protein is significantly reduced
  • CLL-IPI – validated score to predict progression risk related to overall survival in CLL patients; critical factors are TP53 status, IgHV mutation status, ß-microglobulin, clinical status, and age: CLL-IPI calculator.