Chronic lymphocytic leukemia Flashcards
From which cells does chronic lymphocytic leukemia develop from?
Chronic lymphocytic leukemia is a mature B cell neoplasm characterized by a progressive accumulation of monoclonal B lymphocytes.
What is basic pathogenesis of CLL?
CLL is a hematologic malignancy characterized by progressive accumulation of phenotypically mature malignant B-cell lymphocytes in peripheral blood, bone marrow, and lymph nodes. These lymphocytes are functionally incompetent lymphocytes.
Signs and symptoms are related to the accumulation of functionally incompetent lymphocytes in the bone marrow, lymph nodes, and other organs.
What are some risk factors for CLL?
- Advanced age.
- Environmental factors: organic solvents.
- Genetics: positive family history.
Which cell is most commonly involved in CLL?
B-cells (98%) of cases. T-cells in 2%.
What is epidemiology of CLL? (Age, Sex, Cases…)
- Sex: ♂ > ♀ (∼ 2:1)
- Age: The median age at the time of diagnosis is 70–72 years. (The incidence of CLL increases with age.)
- An average 2 - 3 cases per 100 000 people.
- Most common type of leukemia in adults (about 20-25% of all leukemias)
How can you classify CLL?
Rai staging system (Stage 0 - IV)
or
Binet classification system (Stage A, B, C).
What are the SYMPTOMS of CLL?
Many asymptomatic (a routine CBC shows lymphocytosis). Some have painless swelling of lymph nodes, often in the cervical area, which spontaneously comes and goes.
Five to 10 percent of patients present with the typical “B” symptoms of lymphoma which include one or more of the following:
- Unintentional weight loss ≥10 percent of body weight within the previous six months
- Fevers of (>38°C) for ≥2 weeks without evidence of infection
- Drenching night sweats without evidence of infection
- Extreme fatigue
Sometimes, presenting features are autoimmune hemolytic anemia or autoimmune thrombocytopenia (are comlications).
What are SIGNS of CLL?
- Lymphadenopathy: Common! Firm, rounded, discrete, nontender, freely mobile. (Can be generalized or localized). Often cervical, supraclavicular or axillary.
- Splenomegaly: Palpably enlarged in about 25-50%. Is nontender (as the lymph nodes).
- Hepatomegaly: May be noted. Non-tender.
- Skin: Could present with kin lesions (leukemia cutis) most commonly involve the face and can manifest as macules, papules, plaques, nodules, ulcers, or blisters. Other signs are chronic pruritus or chronic urticaria.
What are the laboratory abnormalities in CLL? (CBC, Smear, Immunophenotype, Biopsy)
- CBC
- Lymphocytosis: In blood and bone marrow. Often >5000/microL (5 x 109/L) B lymphocytes, (small mature lymphocytes).
- Cytopenias: Neutropenia, anemia, and thrombocytopenia may be observed.
- Hypogammaglobulinemia is present in approximately 25 percent of patients (IgM, IgG, IgA). - Peripheral blood smear
- Show lymphocytosis. Leukemic cells are often small, mature-appearing lymphocytes with a darkly stained nucleus. - Immunophenotype
- By flow cytometry, is a key component to the diagnosis of CLL. Show eg. CD5 (abnormal B-cell) - Bone marrow aspirate and biopsy
Not needed for diagnosis. Would show normal to increased cellularity, with lymphocytes accounting for >30 percent of all nucleated cells.
What is the approach in diagnosis of CLL in general? Think about laboratory abnormalities (other question).
The diagnosis of CLL is usually suspected in an adult found to have an absolute lymphocytosis. Evaluation of such patients should include:
- Complete blood count with differential;
- Flow cytometry of the peripheral blood to determine the immunophenotype of circulating lymphocytes; (eg. CD5)
- And examination of the peripheral smear.
→ Evaluation of the bone marrow is not usually necessary, but is included in the evaluation of patients with unexplained cytopenias.
What is the “criteria” for diagnosis of CLL according to National Cancer Institute guidelines?
CLL can be diagnosed using the 2018 iwCLL update of the National Cancer Institute guidelines, when both of the following criteria are met:
- Absolute B lymphocyte count in the peripheral blood ≥5000/microL [5 x 109/L], for at least three months, with a prevalent population of morphologically mature-appearing small lymphocytes.
- Clonality of the circulating B-lymphocytes should be confirmed by flow cytometry of the peripheral blood showing immunoglobulin light chain restriction (kappa or lambda).
- A majority of the population should express the following pattern of markers: extremely low levels of SmIg (surface membrane immunoglobulins) and either kappa or lambda (but not both) light chains; expression of B cell associated antigens (CD19, CD20, and CD23); and expression of the T cell associated antigen CD5.
What is light chain restriction?
Light chain restriction refers to an abnormal light chain (kappa-lambda) ratio, in which either kappa or lambda production is massively increased (occurs in association with monoclonal B-cell proliferation).
How do you treat CLL? Basic approach.
A. Asymptomatic CLL (Rai stage 0, slow disease progression): observe and monitor disease progression. )Is a low-grade malignancy with slow rate of cell division)
- Give vaccinations!
B. Symptomatic CLL or advanced stage (Rai stage > 0, accelerated disease progression).
- – Chemotherapy
- – If CD20 positive: rituximab.
- – Targeted therapy with ibrutinib.
C. Refractory CLL or early recurrence in fit, young patients: allogeneic stem cell transplantation.
→ Medical therapy is palliative and the only curative treatment option is stem cell transplantation!
Example of treatment based on age in CLL?
< 65–70 years
- FCR: fludarabine, cyclophosphamide, rituximab
- Stem cell transplantation.
> 65–70 years
- Chlorambucil + monoclonal antibody (e.g., rituximab)
- Possibly a single agent: chlorambucil or rituximab
- Ibrutinib
Supportive care in CLL includes…?
- Vaccinations. Pneumococcal, flu vaccines.
- Intravenous immunoglobulin (IVIG) in patients with severe hypogammaglobulinemia and repeated infections .
- Antibiotic and antiviral prophylaxis in patients with history of recurrent infection or those undergoing treatment.
- Blood product support.
- Tumor lysis syndrome (TLS) prophylaxis and treatment for selected patients at risk for developing TLS.
