Lymphoproliferative Disorders Flashcards
How is the diagnosis of leukaemia or lymphoma made?
Defined by malignant cell characteristics:
- Diagnosis made by biopsy (of lymph node or bone marrow etc)
How is staging done?
- Clinical examination
- CT scan
What does staging describe?
- Location and extent of disease
- Info about prognosis
- Influences treatment
How is lymphoma classified?
Hodgkin lymphoma is specific disease, non-Hodgkin lymphoma is everything else (more than 70 conditions)
What are the main lymphoproliferative disorders?
- Acute lymphoblastic leukaemia (ALL)
- Chronic lymphoblastic leukaemia (CLL)
- Hodgkin lymphoma
- Non-Hodgkin lymphoma (NHL)
- High grade (diffuse large B-cell lymphoma)
- Low grade (follicular, marginal zone)
What does ALL stand for?
- Acute lymphoblastic leukaemia (ALL)
What does CLL stand for?
- Chronic lymphoblastic leukaemia (CLL)
What does HL stand for?
Hodgkin lymphoma
What does NHL stand for?
- Non-Hodgkin lymphoma (NHL)
What is the most common lymphoproliferative disorder?
Most common is high grade NHL
ALL is a disorder of what cells?
Cancerous disorder of lymphoid progenitor cells
Describe the pathophysiology of ALL?
- Normally immature cells that rapidly proliferate and differentiate into lymphocytes
- In leukaemia, no differentiation and instead rapid and uncontrolled growth and accumulation
- Usually in bone marrow but they can go anywhere
Describe the epidemiology of ALL?
(incidence, age)
- Incidence 1-2/100,000
- 75% cases children <6 years
Describe the presentation of ALL?
- 75-90% cases are B-cell linage
- 2-3 week history of bone marrow failure or bone/joint pain
- Weight loss
- Anaemic symptoms
Describe the investigations for ALL?
- Blood count
- Low haemoglobin
- High WCC
- Low platelet
- Bone marrow aspirate
- Full of B lymphoblasts
- Blood film
- Large cells
- Immunophenotyping
- Used to tell what markers cells carry
- They express CD19 – all B cells have this
- And express CD34, TDT – markers of very early, immature cells
What is seen in the FBC for ALL?
- Low haemoglobin
- High WCC
- Low platelet
What is seen in the bone marrow aspirate for ALL?
- Full of B lymphoblasts
What is immunophenotyping used for?
- Used to tell what markers cells carry
- They express CD19 – all B cells have this
- And express CD34, TDT – markers of very early, immature cells
Describe the treatment of ALL?
- Standard treatment - chemotherapy
- Induction chemotherapy to obtain remission
- Consolidation therapy
- CNS directed treatment
- Maintenance treatment for 18 months
- Stem cell transplantation (if high risk)
- Newer therapies
- Bi-specific T-cell engagers
- Drug – Blinatumumab
- CAR-T cell therapy
- Modify patients own T cells to express receptor for CD19 marker
- Side effects – cytokine release syndrome (fever, hypotension, dyspnoea), neurotoxicity (confusion, seizure, headache, focal neurology, coma)
- Bi-specific T-cell engagers
What does CAR-T cell therapy do?
- Modify patients own T cells to express receptor for CD19 marker
What are possible side effects of CAR-T cell therapy?
- Side effects – cytokine release syndrome (fever, hypotension, dyspnoea), neurotoxicity (confusion, seizure, headache, focal neurology, coma)
Describe the prognosis of ALL?
- Decreases with
- Increasing age
- Increased white cell count
- Cytogenetics/molecular genetics
- T(9;22), T(4;11)
- Slow/poor response to treatment
- Adults
- Complete remission 90%
- Leukaemia free at 5 years 30%
- Children
- 5 year survival 90%
Describe the epidemiology of CLL?
(gender)
- Commonest leukaemia worldwide
- M:F 2:1
What is the commonest leukaemia?
CLL
What are risk factors for CLL?
- Family history
- Occasionally familial
Describe the presentation for CLL?
- Unlike ALL, the abnormal cells are mature and usually resemble normal lymphocytes
- Grow slowly
- Carry many of normal B cell markers
- Is a low grade disorder
Describe the presentation of CLL?
- Most people
- Bone marrow failure
- Anaemia, thrombocytopenia
- Lymphadenopathy
- Splenomegaly
- Fever and sweats
- Immune paresis (loss of normal immunoglobulin production)
- Haemolytic anaemia
- Less common findings
- Hepatomegaly
- Infections
- Weight loss
How is the diagnosis of CLL made?
- Requires lymphocyte count of >5 (normal is <4)
What system is used to stage CLL?
- Binet system
What are indications for treatment of CLL?
- Progressive bone marrow failure
- Massive lymphadenopathy
- Progressive splenomegaly
- Systemic symptoms
- Autoimmune cytopenias
Describe the Binet staging system?
Describe the treatment for CLL?
- Often ‘watch and wait’
- Cytotoxic chemotherapy
- Drugs – fludarabine, bendmustine
- Monoclonal antibodies
- Drugs – Rituximab, obinatuzumab
- Novel agents
- Bruton tyrosine kinase inhibitor
- PI3K inhibitor
- BCL-2 inhibitor
What are examples of cytotoxic chemotherapies?
Drugs – fludarabine, bendmustine
What are examples of monoclonal antibodies?
- Drugs – Rituximab, obinatuzumab
What are poor indicators for prognosis of CLL?
- Advanced disease
- Atypical lymphocyte morphology
- Bad genetics
- Loss or mutated p53 – chemotherapy resistant
Describe the presentation of lymphoma?
- Lymphadenopathy/hepatosplenomegaly
- Extranodal disease
- “B symptoms”
- Bone marrow involvement
How is lymphoma staged?
- Lymph node biopsy/CT scan/bone marrow aspirate and trephine
- Stages
- I – one nodal site
- II – 2 nodal sites, either above or below diaphragm but not both
- III – sites above and below diaphragm
- IV – extra-nodal involvement such as liver
- Also use of A and B
- A – absence of B symptoms
- B – present of B symptoms – fever, night sweats, weight loss
Describe the stages of lymphoma?
How is NHL classified?
- Linage (B-cell or T-cell)
- Majority are B cell (90%)
- High grade/low grade
- Low grade – asymptomatic, responds to chemotherapy by incurable
- High grade – aggressive and fast growing, requires combination chemotherapy, can be cured
Is NHL usually B cells or T cells?
- Majority are B cell (90%)
What is low and high grade NHL?
- Low grade – asymptomatic, responds to chemotherapy by incurable
- High grade – aggressive and fast growing, requires combination chemotherapy, can be cured
What is the most common low and high grade NHL?
- Diffuse large B-cell lymphoma
- Commonest lymphoma
- High grade
- Follicular lymphoma
- 2nd commonest
- Low grade
What is the commonest lymphoma?
- Diffuse large B-cell lymphoma
- Commonest lymphoma
- High grade
Describe the treatment for NHL?
- Combination chemotherapy
- Typically anti-CD20 monoclonal antibody and chemotherapy
Describe the epidemiology of HL?
(age, sex)
- 30% all lymphomas
- Bimodal age curve
- Peak in teenage and young adult, then another peak in late life
- M:F 2:1
What are risk factors for HL?
- Associated with EBV
- Familial
What virus is HL associated with?
EBV
Describe the treatment for HL?
- Combination chemotherapy (ABVD)
- With or without radiotherapy
- Monoclonal antibodies (anti-CD30)
- Immunotherapy (checkpoint inhibitors)
- PET scanning to assess response to treatment
