Lymphoproliferative disorders Flashcards
What are lymphomas?
What do lymphomas tend to present with (hallmark feature)?
Cancers of lymphoid origin
Typically present with enlarged lymph nodes (lymphadenopathy)
but occasionally present with:
- extranodal involvement
- bone marrow involvement
What are the general symptoms seen with lymphoma?
Lymphadenopathy (rubbery)
Systemic symptoms:
- weight loss
- fever
- fatigue
- drenching night sweats
- pruritis
How is a diagnosis of lymphoma (or leukaemia) made?
How is it staged?
Biopsy - eg lymph node, bone marrow, extranodal mass
Diagnosis made based on malignant cell characteristics - not on clinical presentation or any of that stuff
Staging of disease based on clinical examination and imaging (CT etc)
What groups of lymphoproliferative disorders involve:
a) lymphoid progenitor cells
b) B & T lymphocytes
c) Plasma cells
a) Acute Lymphoblastic leukaemias (ALL)
b) Chronic lymphocytic leukaemias (CLL) & Lymphomas
c) Multiple myeloma* (not in this lecture)
*not sure if its a lymphoproliferative disorder
Where do the following groups of disorders tend to occur:
a) ALL
b) CLL
c) Lymphoma
d) MM
a) Acute lymphoblastic leukaemia = Bone marrow
b) Chronic lymphocytic leukaemia = Marrow/nodes
c) Lymphoma = lymph nodes
d) Multiple myeloma = bone marrow
What are the types of lymphoma?
Hodgkin Lymphoma
Non-hodgkin lymphoma:
- high grade non-hodgkin
- low grade non-hodgkin
Hodgkin = specific disease
Non-hodgkin is everything else and has lots of discrete types
What are the most common lymphoproliferative disorders?
(most to least common)
1) Non-Hodgkin lymphoma:
- High grade - most common high grade is diffuse large B cell lymphoma
- Low grade - most common low grade is follicular and marginal zone
2) Chronic lymphocytic leukaemia (CLL)
3) Hodgkin lymphoma
4) Acute lymphoblastic leukaemia (ALL)
What happens in ALL?
Acute lymphoblastic leukaemia
Rapid, uncontrolled proliferation (but no differentiation) of lymphoid progenitor cells
This causes an accumulation of these ‘blast’ cells, usually in the bone marrow
Concerning the epidemiology n stuff of ALL…
a) How common is it?
b) What age group is most commonly affected?
c) What lineage of cells is most commonly affected?
a) Rarest lymphoproliferative disorder
b) Usually in children < 6 - most common blood cancer of children
c) B-cell ALL is most common
What is the typical presentation of ALL?
2-3 week history of bone marrow failure (anaemia symptoms etc) & bone/joint pain
May have systemic symptoms (as with all leukaemias) of fatigue, weight loss etc
What blood count would you expect to see in ALL?
What would the bone marrow show?
Low haemoglobin
Very high white cell count
Very low platelets
Bone marrow would be dominated by lymphoblasts (‘blasts’) - usually B-lymphoblasts
A patient presents with typical symptoms of Acute Leukaemia and has a blood count in keeping with this…
Her blood film shows lots of blasts, however it is difficult to differentiate between lymphoblasts and myeloid blast cells
What testing is needed to diagnose ALL?
What results would give this diagnosis?
Immunophenotyping
(shows specific molecules expressed that are unique to the blasts)
CD19 - expressed in B cell lineage
CD34 & TDT - markers of very immature cells which should not be in the blood
How is ALL treated?
Multi-agent chemotherapy
3 phases…
1) Induction - which aims to achieve remission
2) Consolidation - patient may receive allogeneic stem cell transplant if high risk
3) Maintenance - for 18 months
CNS directed therapy
What are risk factors for a poor outcome in ALL?
Increasing age
Increased white cell count in blood
Slow/poor response to treatment
Cytogenetics:
Philadelphia chromosome (t9;22)
What is the prognosis for ALL in:
adults
children
Adults = good but many go into remission and need bone marrow transplant
Children = very good - 90% 5 year survival
How is CLL different from ALL, in terms of:
a) maturity
b) proliferative speed
a) maturity
* in CLL, the cells are much more mature
b) proliferative speed
* proliferate slowly (often dont at all) which means CLL has a much more gradual onset than ALL - hence ‘chronic’
What lymphocyte count is needed for a diagnosis of CLL?
Lymphocyte count > 5
Normal is < 4
Describe the epidemiology n stuff of CLL
Commenest leukaemia worldwide - but remember NHL is more common than this
Tends to affect adults
More common in men (2:1)
Occasionally familial
Rare in far east
How does CLL present?
Often asymptomatic
If symptomatic:
- bone marrow failure (anaemia, thrombocytopenia)
- lymphadenopathy
- splenomegaly
- fever & sweats
Others - hepatomegaly, infections, weight loss
What 2 conditions are associated with CLL, and may be part of the presentation?
Immune paresis
- loss of normal immunoglobulin production which leads to infections
Autoimmune cytopenias - specifically haemolytic anaemia
How is CLL staged?
Binet staging system
- A - <3 lymph node areas involved
- B - 3 or more lymph node areas
- C - Stage B + anaemia or thrombocytopenia
What are the indications for treatment for CLL?
Progressive bone marrow failure
Massive lymphadenopathy
Progressive splenomegaly
Rapid lymphocyte proliferation:
- doubling time < 6 months
- > 50% increase in 2 months
Systemic symptoms
Autoimmune cytopenias
Give an overview of the treatment for CLL
“Watch and wait”
- if indications for treatment:*
1) Cytotoxic chemotherapy
2) Monoclonal antibodies
3) Novel agents - eg Bruton TKIs ‘i**brutinib’
What are poor prognostic factors for CLL?
Advanced disease (Binet B or C)
Atypical lymphocyte morphology
Rapid lymphocyte proliferation (doubling time <12 months)
Genetics:
- p53 mutations
- CD38+ expression
