Chronic Lymphocytic Leukemia: Complications

The following are the most important diseases or complications that may be contributed to by chronic lymphocytic leukemia (CLL):

Blood, blood-forming organs – Immune system (D50-D90).

  • Anemias (anemia)
    • Autoimmune hemolytic anemias (AIHA; form of hemolytic anemia in which the body’s immune system produces antibodies that induce hemolysis of erythrocytes) – usually triggered by IgG polyclonal heat antibodies
    • Pure-red-cell anemias
  • Autoimmune cytopenias (about 20%).
  • Autoimmune thrombocytopenias (AITP).
  • Bleeding
  • Hypersplenism – complication of splenomegaly (enlargement of the spleen). Due to this, its functional capacity of the spleen increases beyond the necessary level and leads to increased elimination of erythrocytes (red blood cells), leukocytes (white blood cells) and platelets (blood platelets) from the peripheral blood, resulting in pancytopenia (synonym: tricytopenia; reduction of all three series of cells in the blood).
  • Hyperviscosity syndrome (HVS) – clinical symptom complex, which has its cause in the increase in the concentration of paraproteins of blood plasma. Due to the increased viscosity, there is a reduction in the fluidity of the blood.
  • Cytopenias / reduction in the number of cells in the blood (anemia (anemia), thrombocytopenia (reduced number of platelets / platelets), neutropenia (reduction of neutrophil granulocytes in the blood)) or their clinical consequences (infections, bleeding, fatigue).

Infectious and parasitic diseases (A00-B99).

  • Infections of all kinds

Neoplasms – tumor diseases (C00-D48)

  • Recurrence – recurrence of the disease.
  • Infiltration of CLL can affect any organ
  • Transformation of CLL into:
    • Hodgkin’s lymphoma (0.7%).
    • Transition of low-malignant CLL to a higher stage or in transformation to high-malignant lymphoma (Richter syndrome; in 5-10% of cases); Richter syndrome is defined by the presence of high-malignant NHL (non-Hodgkin’s lymphoma) and CLL at the same time (poor prognosis); clinical picture: rapid increase in B-symptomatology* and LDH levels.

Further

  • Infections; these are the main causes of death in CLL.

* B symptomatology

  • Unexplained, persistent or recurrent fever (> 38 °C).
  • Severe night sweats (wet hair, soaked sleepwear).
  • Unwanted weight loss (> 10% percent of body weight within 6 months).

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 (see below): CLL-IPI calculator.

CLL-IPI (CLL-International Prognostic Index).

Variable Risk factor Points
TP53 (17p) Deletions and/or mutation 4
IGHV Unmutated 2
Beta-2 microglobulin (mg/L) < 3,5 1
Age > 65 years
Stage* Binet B/C, Rai I-IV 1
Total score 0 to 10

* Stage classification according to Binet or Rai.

Score Risk group 5-year survival rates (%) Frequency of subgroups (%)
0-1 “low” 93,2 28
2-3 “intermediate 79,3 39
4-6 “high” 63,3 28
7-10 “very high” 23,3 6

More hints

  • Type of progression after CLL therapy: occurrence of lymphadenopathy after first-line therapy (significantly lower survival); significantly less time to next therapy.
  • Factors that provide evidence in patients with relapsed or refractory CLL that a higher probability of survival can be expected are beta-2-microglobulin, lactate dehydrogenase (LDH), hemoglobin, and length of time since initiation of last therapy (acronym: “BALL”; recall B2M, anemia, LDH, last therapy):Interpretation: low risk. Score: 0 or 1; intermediate risk: score: 2 or 3; high risk: score of 4.
    • Patients in the ibrutinib group with a high-risk score: probability of being alive at 24 months was 56%; with a low-risk score, 90%.
    • Patients in the venetoclax group with a high-risk score: probability of being alive at 24 months was 95%; with a low risk, 82%.

    The risk score can be calculated using a program available on the Calculate by QxMD website.