CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) Flashcards
CLL is a characterized by a progressive accumulation of malignant ____________ in the blood, bone marrow and lymphoid tissues.
It tends to affect ____________.
naïve mature B lymphocytes
older adults (most patients above 60 and almost exclusively older than 50).
What are the clinical features of CLL?
Can be asymptomatic at time of diagnosis. Normally insidious in onset and patients can live for a very long time.
Malignant mature B cells are non-functional:
- Increased risk of infection, particularly of the respiratory tract (bacteria pneumonia, sinusitis) by encapsulated organisms such as Streptococcus pneumoniae and Haemophilus influenzae secondary to hypogammaglobulinaemia.
- Requires Haemophilus and pneumococcal vaccines
- Recommended IVIG in those who have hypogammaglobulinaemia and recurrent bacterial infections.
Proliferation of B cells in bone marrow: Bone marrow failure leading to signs and symptoms of anaemia and thrombocytopenia
Circulation to lymph nodes and spleen: There is General Lymphadenopathy + Splenomegaly
Rarely Hypermetabolic State
- Drenching Night Sweats
- Weight Loss
- Fever
What are the complicatons of CLL?
Infection due to hypogammaglobulinaemia: Common complication and most common cause of death in CLL.
Autoimmune phenomena:
- Antibodies produced by the neoplastic B cells attack the patient’s own cells (e.g. red blood cells).
- This leads to autoimmune haemolytic anaemia (AIHA) and autoimmune thrombocytopenic purpura (ITP).
High grade transformation (Richter’s syndrome):
- The transformation of CLL into an aggressive lymphoma (most commonly diffuse large B cell lymphoma).
- Richter’s syndrome occurs in approximately 2% to 10% of CLL patients during the course of their disease with a transformation rate of 0.5% to 1% per year.
- Patient typically present with enlarging lymph node or enlarging spleen.
What are the investigations of CLL?
Peripheral blood film: Increased number of small mature lymphocytes, smear cells (lymphocytes disrupt more easily than normal lymphocytes; pathognomonic of CLL)
FBC: Lymphocytosis > 5x109
Immunophenotyping:
- B cells acquire different cell surface antigens at different stages of maturity.
- Cells co-express CD5 and CD20. CD5 is a marker that is normally present on a T cell but in CLL is aberrantly expressed.
- CLL score considers CD5, CD23, FMC7, CD22, SmIg (results 0-5).
Cytogenetics and molecular genetics
- Aberations in CLL are deletions and trisomies (no translocation). E.g. 17p deletions (p53) are refractory to chemotherapy and have a dismal prognosis.
- CD38 and ZAP70 expression associated with poor prognosis.
What is the prognosis of CLL?
50% of patients die from an unrelated cause. CLL is incurable by chemotherapy and there is no benefit from early treatment.
What is the managagement for CLL?
Supportive:
- Vaccinations against HiB & Pneumococcus
- Steroids for AIHA/ITP
- IVIg for recurrent infections
Standard 1st line therapy – chemotherapy
- Combination chemotherapy: FCR – fludarbine, cyclophosphamide, and rituximab (anti-CD20 Ab)
- For older patients or unfit for FCR: oral chlorambucil
Treatment for increased risk of infection
- Haemophilus and pneumococcal vaccines and recommended
IVIG in those who have hypogammaglobulinaemia and recurrent bacterial infections
What are the indications of treatment of CLL?
Progressive marrow failure
Massive/progressive lymphadenopathy
Progressive lymphocytosis (>50% increase over 2 mths/lymphocyte doubling time < 6 mths)
Systemic symptoms (weight loss > 10% in previous 6 mths, fever >38degC for 2 or more wks, extreme fatigue, night sweats)
Autoimmune cytopenias (v low Hb/platelet count not reflection of BM infiltration but rather the coincidental autoimmune process – can occur in v early CLL.
Standard 1st line therapy: chemotherapy
9- Combination chemotherapy: FCR – fludarbine, cyclophosphamide, and
rituximab (anti-CD20 Ab)
For older patients or unfit for FCR: oral chlorambucil
