Chronic leukaemias Flashcards
CML & CLL
What are the clinical features of Chronic myeloid leukaemia? hint: 6
- anorexia, weight loss, lassitude or night sweats (hyper metabolism)
- splenomegaly
- pallor, dyspnoea and tachycardia (anaemia)
- bruising, epistaxis, menorrhagia or haemorrhage (abnormal platelet function)
- gout or renal impairment (hyperuricaemia)
- visual disturbances and priapism (rare)
What are the lab findings of CML? hint: 8
- leucocytosis, main feature (may reach levels greater than 200 x 10^9/L)
- increased circulating basophils
- normochromic, normocytic anaemia
- platelet count may be increased (most times), normal or decreased
- bone marrow is hypercellular with granulocytic predominance
- presence of BCR-ABL1 gene fusion and Ph chromosome
- some pts have mutations in neoplasia associated genes
- serum uric acid is usually raised
What is the first line therapy for patients with chronic phase CML?
- Imatinib (mostly used)
- nilotinib
- dasatinib
what are some additional forms of treatment for CML?
- chemotherapy
- alpha-interferon
- stem cell transplantation
relapse of CML after transplantation is a problem, but donor leukocyte infusions are highly effective in CML. T or F.
True
which drug is effective against CML that carries the T315I mutation within ABL1?
ponatinib
which drug is useful in the event of resistance mediated by a mutation of the ABL kinase?
Asciminib
what occurs in acute transformation?
greater than 20% blasts in the blood or marrow (either lymphoblasts or myeloblasts) may occur rapidly over days or weeks
note: blast crisis- clinically it behaves like acute leukaemia
what occurs in the accelerated phase?
- anaemia, thrombocytopenia, increase in blood basophils to greater than 20% or marrow blast cells 10-19% with blast cells in the blood.
- the spleen may be enlarged and the marrow may be fibrotic
the main cause of death in CML is the transformation to which phase?
the blast phase
CML occurs in either sex, most frequently between the ages of 40 and 60 years. T or F.
True
note: (male:female ratio of 1.4:1)
CLL is characterised by the accumulation of what kinda cells?
mature lymphocytes of either B cell or T cell origin
what is the usual lab finding in chronic lymphocytic leukaemia?
chronic persistent blood lymphocytosis
note: sometimes accompanied by anaemia or thrombocytopenia
If CLL is to be diagnosed, what must be present?
there must be a monoclonal B-cell count of >5 × 10^9/L or tissue involvement outside the bone marrow
What are the B cell types of CLL?
- Chronic lymphocytic leukaemia/ small lymphocytic lymphoma
- B cell prolymphocytic leukaemia
- Hairy cell leukaemia
What are the T cell types of CLL?
- T cell granular lymphocytic leukaemia
- T cell prolymphocytic leukaemia
- adult T cell leukaemia/lymphoma
- Sezary syndrome
what is the peak incidence of CLL?
between 60 and 80 years of age
What is the difference between CLL and SLL
The difference is that in SLL the neoplastic cells accumulate almost exclusively in the lymph nodes, and by definition there are fewer than 5 × 109/L circulating monoclonal B cells.
Pts with CLL are often asymptomatic. T or F.
True
What are the lab findings of CLL?
- lymphocytosis: B cell lymphocyte count ≥ 5 x 10^9/L
- B cells express only 1 light chain; also positive for CD5 & CD23
- 2 surface proteins can be detected: CD38 & ZAP70
- normochromic, normocytic anaemia present in later stages
- thrombocytopenia occurs in many pts
- trephine biopsy shows nodular, diffuse or interstitial involvement by lymphocytes
- reduced concentrations of serum immunoglobulins are found
- autoimmunity against cells of haemopoietic system is common; autoimmune haemolytic anaemia is most frequent
What are the clinical features of CLL?
- mean age of diagnosis is 72 years
- male: female ratio is 2:1
- enlargement of cervical, axillary or inguinal nodes is the most frequent clinical sign
- clinical features of anaemia: pallor & dyspnea
- splenomegaly (& hepatomegaly) often seen in later stages
- immunosuppression: increased risk for herpes zoster infection
How is CLL treated?
what are the new agents used in the treatment of B-CLL?
which drugs suppress signalling through the B cell receptor in CLL?
which drugs suppress the activity of BCL-12 in CLL?
which drugs are effective monoclonal antibodies in CLL?
what are some other forms of treatment for CLL?
CLL may transform into a high-grade lymphoma. T or F.
True
How is B cell prolymphocytic leukaemia (B-PLL) diagnosed?
by the appearance of pro lymphocytes in the blood
B-PLL typically presents with what?
splenomegaly without lymphadenopathy and with a high and rapidly rising lymphocyte count
Treatment for B-PLL is difficult and prognosis is worse than for CLL. T or F?
True
note: anaemia is a poor prognostic factor
how is B-PLL treated?
What is Hairy cell leukaemia (HCL)?
Patients with HCL typically present with what features?
- with infections, anaemia or splenomegaly
- pancytopenia is usual
- lymphocyte count is rarely over 20 x 10^9/L
- monocytopenia is a distinct feature
immunophenotyping for HCL shows what in most cases?
CD11c, CD19, CD25, CD103 and CD123 positivity
what mutation is seen in HCL?
a mutation in exon 15 of the gene for the protein kinase BRAF (V600E) underlies the most frequent classical variant of the disease
note: I think this is responsible for the monocytopenia
what are the treatments done for HCL?
CLL that has acquired somatic mutations in the immunoglobulin genes has a relatively good prognosis compared to unmutated cases. T or F.
True
T-cell prolymphocytic leukaemia?
large granular lymphocytic leukaemia?
adult T cell leukaemia?
