Lymphoproliferative Disorders Flashcards
What does leukaemia mean?
‘White blood’
Generally used to describe a cancer that you can see in the blood
What does lymphoma mean?
Cancers of lymphoid origin
Can present with enlarged lymph nodes or with extra-nodal involvement or bone marrow involvement
Can cause B symptoms - weight loss, fever, night sweats, pruritic and fatigue
How is lymphoma/ leukaemia diagnosed?
Defined by the malignant cell characteristics
Biopsy - tells the type
Clinical examination and imaging (CT) - tells where it is (staging)
When can lymphomas occur in haematopoiesis?
When lymphoid progenitor - all
Then in the stage of B-lymphocytes and T-lymphocytes
How is lymphoma sub-classed?
Hodgkin and non-Hodgkin lymphoma (high grade and low grade)
What are some key lymphoproliferative disorders?
Acute lymphoblastic leukaemia (ALL)
Chronic lymphoblastic leukaemia (CLL)
Hodgkin lymphoma
Non-Hodgkin lymphoma (NHL)
What is acute lymphoblastic leukaemia?
Cancerous disorder of lymphoid progenitor cells
Normally immature and rapidly proliferating cells that differentiate into lymphocytes
Leukaemia - no differentiation but rapid, uncontrolled growth + accumulation
Usually in bone marrow but can go anywhere
What is the prevalence of ALL?
75% of cases are in children under 6 years
70-90% are B-cell lineage
Present with 2-3 week of bone marrow failure or bone/ joint pain
What is the bloods seen in ALL?
Low haemoglobin, high WCC and low platelets
Bone marrow has 90% B-lymphoblasts in B-cell ALL
What is seen in the immunophenotyping used for in bone marrow - normal cells?
Can see large cells
Express CD19 - all B cells have this
CD34 and TDT markers for early immature cells
What is the treatment for ALL?
Induction to chemo to obtain remission, consolidation therapy, CNS directed treatment and maintenance treatment for 18 months
Stem cell transplant if high risk
What are some new treatments for ALL?
CAR - chimeric antigen receptor T cell
Bi-specific T cell engagers
What are the key side effects of T cell immunotherapy?
Cytokine release syndrome - fever, hypotension, dyspnoea
Neurotoxicity - confusion with normal conscious levels, seizure, headache, focal neurology and coma
What are the poor risk factors for ALL?
Increasing age, increased WCC, cytogenetics/ molecular genetics and slow/ poor response to treatments
What is the outcome of ALL?
Adults - 90% remission but 30-35% leukaemia free
Children - 90% survival
What is the typical presentation of ALL?
Bone marrow failure and maybe raised WCC
Bone pain, infection and sweats (B symptoms)
What is CLL?
Abnormal cells are mature unlike ALL - usually resemble normal, well behaved lymphocytes
Grow slowly, low grade condition and carry many normal markers that B lymphocytes have
What does CLL require on lymphocyte count?
> 5
Normal is <4
What is the prevalance of CLL?
Commonest leukaemia worldwide
2 males: 1 female
Occasionally familial
Rare in far east
What is the CLL presentation?
Often asymptomatic
Frequent - bone marrow failure, lymphadenopathy, splenomegaly, fever and sweats
Less common - hepatomegaly, infection and weight loss
What are some CLL associated findings?
Immune paresis (loss of normal immunoglobulin production) and haemolytic anaemia
How is CLL staged?
A - <3 lymph node areas
B - 3 or more
C - stage B plus anaemia or thrombocytopenia
Binet staging
What are the indications for treatment for CLL?
Progressive bone marrow failure, massive lymphadenopathy, progressive splenomegaly, lymphocyte doubling time is more than 6 months or 50% increase over 2 months, systemic symptoms and autoimmune cytopenia
What is the treatment for CLL?
Often nothing - watch and wait
Cytotoxic chemotherapy
Monoclonal antibodies
Novel agents - Bruton tyrosine kinase inhibitor, P13K inhibitor and BCL-2 inhibitor
What are the poor prognostic markers for CLL?
Advanced disease, atypical lymphocyte morphology, raised lymphocyte doubling time, CD 38+ expression, loss/ mutation p53 and unmutated IgVH gene status
What is the presentation of lymphoma?
Lymphadenopathy, hepatosplenomegaly, extra-nodal disease, B symptoms and bone marrow involvement
How are lymphomas assessed?
Lymph node biopsy, CT scan, bone marrow aspirate and trephine
How is lymphomas staged?
Stage I - IV
I - only on nodal site
II - separate nodal sites above diaphragm
III - multiple nodal sites including under the diaphragm
IV - extra-nodal involvement
A is absence of B symptoms and B is B symptoms
How is Non-Hodgkin lymphoma classified?
Lineage - B-cell or T-cell (majority are B-cell)
Grade - high and low grade
What are low grade NHL?
Indolent, often asymptomatic
Responds to chemo but incurable
What are high grade NHL?
Aggressive, fast-growing, require combination chemo and can be cured
What are the specific disease entities of NHL?
Diffuse large B-cell lymphoma - commonest subtype and high grade
Follicular lymphoma - 2nd commonest and low grade
How is diffuse large B-cell lymphoma and follicular lymphoma treated?
Combination chemotherapy - typically anti-CD20 monoclonal antibody and chemo
What is the prevalence of Hodgkin lymphoma?
Bimodal age curve - 1st peak at 15-35 years and 2nd peak in later life
More males than females
Associated with EBV, familial and geographical clustering
What is the treatment for Hodgkin lymphoma?
Combination chemo (ABVD)
Maybe plus radiotherapy
Monoclonal antibodies
Immunotherapy
PET scanning central to assessment of response to treatment
