Lymphoid Malignancies Flashcards
What is lymphoma?
Cancer of lymphoid origin which can present with
- Lympadeonpathy OR
- Extranodal involvement OR
- Bone marrow involvement
- Systemic B symptoms including weight loss (>10 % in 6 months), fever, night sweats, pruritus, fatigue
How is are differnt types of lymphoma defined?
By the malignant cell characteristics
What investigation tells us what type of lymphoma it is?
Biopsy
What investigations tells us where the lymphoma is?
Clinical examination and imaging
What is a high grade non-Hodgkin lymphoma?
A diffuse large B cell lymphoma
Give examples of lymphoproliferative disorders in order from most common.
- Most common
- Non-Hodgkin lymphoma (NHL)
- High-grade (diffuse large B-cell lymphoma)
- Low-grade (follicular, marginal zone)
- Chronic lymphocytic leukaemia (CLL)
- Hodgkin lymphoma
- Acute lymphoblastic leukaemia (ALL) (common in children)
What is acute lymphoblastic leukaemia?
Cancerous disorder of lymphoid progenitor cells
How is acute lymphoblastic leukaemia diagnosed?
By >20% lymphoblasts present in bone marrow
What is the epidemiology of acute lymphoblastic leukaemia?
- Incidence 1-2/100,000 population/year
- -75% cases occur in children < 6 years
- 75-90% cases are of B-cell lineage
What is the standard treatment for acute lymphoblastic leukaemia?
- Induction chemotherapy to obtain remission
- Consolidation therapy
- CNS directed treatment
- Maintenance treatment for 18 months
What other treatment is there for acute lymphoblastic leukaemia?
- Stem cell transplantation (if high risk)
- Bispecifc T-cell engagers (BiTe molecules): e.g. Blinatumumab
- CAR (chimeric antigen receptor T-cells)
How is CAR treatment carried out?
- Patient/ healthy 3rd party T-cells harvested
- T-cells are genetically modified so that they target CD19 expressed on leukaemia cells
- Expanded in vitro
- Re-infused into patient
How does T-cell immunotherapy associated neurotoxicity present?
- Confusion with normal conscious level
- Seizure, headache, focal neurology, coma
How does T-cell immunotherapy associated cytokine release syndrome present?
- Fever, hypotension, dyspnoea
- CAR T-cell effect correlated to presence of CRS (significant number require ITU support)
What are poor prognostic factors associated with acute lymphoblastic leukaemia?
- Increasing age
- Increased white cell count
- Immunophenotype (more primitive forms)
- Cytogenetics/molecular genetics: t(9;22); t(4;11)
- Slow/poor response to treatment
What are the outcomes of acute lymphoblastic leukaemia?
Adults with ALL
- Complete remission rate 78–91%
- Leukaemia-free survival at 5y 30–35%
Children with ALL
- 5y overall survival ~90%
- Poor risk patients (slow response to induction or Philadelphia positive) 5y OS 45%
What is the typical presentation of acute lymphoblastic leukaemia?
- Bone marrow failure +/- raised white cell count
- Bone pain, infection, sweats
How is chronic lymphocytic leukaemia diagnosed?
- Blood > 5 x 109/L lymphocytes (normal is <4)
- Bone marrow > 30% lymphocytes
- Characteristic immunophenotyping (B-cell markers (CD 19, 20, 23) & CD5 positive)
What is the incidence of CLL?
- > 1700 new cases CLL per year in the UK
- Commonest leukaemia worldwide
- M:F 2:1
- Occasionally familial
- Rare in far East
How does CLL present?
Often asymptomatic
Frequent findings
- Bone marrow failure (anaemia, thrombocytopenia)
- Lymphadenopathy
- Splenomegaly (30%)
- Fever and sweats (< 25%)
Less common findings
- Hepatomegaly
- Infections
- Weight loss
What conditions/states are associated with CLL?
- Immune paresis (loss of normal immunoglobulin production)
- Haemolytic anaemia (20% have positive direct antiglobulin test, 8% clinical evidence of haemolytic anaemia)
What system is used to stage CLL?
Binet
What are the stages of CLL according to the Binet system?
- Stage A -<3 lymph nodes
- Same survival as age matched controls
- Stage B -3 or more lymph node areas
- -~8 year survival
- Stage C -Stage B + anaemia or thrombocytopenia
- ~6 years survival
What are the indications for treatment in CLL?
- Progressive bone marrow failure
- Massive lymphadenopathy
- Progressive splenomegaly
- Lymphocyte doubling time <6 months or >50% increase over 2 months
- Systemic symptoms
- Autoimmune cytopenias
What is the treatment for CLL?
- Often nothing: “watch and wait”
- Cytotoxic chemotherapy e.g. fludarabine, bendamustine
- Monoclonal antibodies e.g. Rituximab, obinutuzamab
- Novel agents: (Bruton tyrosine kinase inhibitor eg ibrutinib) (PI3K inhibitor eg idelalisib) (BCL-2 inhibitor eg venetoclax)
What are poor prognostic factors in CLL?
- Advanced disease (Binet stage B or C)
- Atypical lymphocyte morphology
- Rapid lymphocyte doubling time (<12 mth)
- CD 38+ expression
- Loss/mutation p53; del 11q23 (ATM gene)
- Unmutated IgVH gene status
How is chronic lymphocytic leukaemia different from acute lymphoblastic leukaemia?
- Unlike ALL, the abnormal cells are mature - they usually resemble normal, well-behaved lymphocytes
- Grow slowly (or not at all)
- Classic example of a low-grade condition
- Carry many of the normal markers that B lymphocytes have
How does lymphoma present?
- Lymphadenopathy/ hepatosplenomegaly
- Extranodal disease
- “B symptoms”
- Bone marrow involvement
How is lymphoma assessed and staged?
- Lymph node biopsy
- CT scan
- Bone marrow aspirate and trephine
What are the stages of lymphoma?
- Can be classified by presence of B symptoms
- Stage 1 = 1 node involved
- Stage 2 = 2 nodes
- Stage 3 = multiple nodes
- Stage 4 = node and hepatosplenomegaly
How is non-Hodgkin lymphoma classified?
- Lineage (B-cell or T-cell) (Majority are B-cell in origin)
- Grade of disease (high grade or low grade)
- Histological features of disease
What are the features of low grade NH lymphoma?
- Indolent, often asymptomatic
- Responds to chemotherapy but incurable
- Median survival varies by subtype
What are the features of high grade NH lymphoma?
- Aggressive, fast-growing
- Require combination chemotherapy
- Can be cured, but again varies widely
Give examples of specific NH lymphoma disease entitie.
- Diffuse large B-cell lymphoma
- Commonest subtype of lymphoma (of any kind)
- High-grade lymphoma
- Follicular lymphoma
- 2nd commonest subtype of lymphoma
- Low-grade lymphoma
How is NH lymphoma treated?
Combination chemotherapy, typically anti-CD20 monoclonal antibody and chemo
What is the epidemiology of Hodgkin lymphoma?
- 30% of all lymphomas
- Bimodal age curve with 1st peak at 15-35y and 2nd peak later in life
- M:F 1.9:1
- association with Epstein Barr virus; familial and geographical clustering
What is the treatment for Hodgkin lymphoma?
- Combination chemotherapy (ABVD)
- +/- radiotherapy
- Monoclonal antibodies (anti-CD30)
- Immunotherapy (checkpoint inhibitors)
- Use of PET scan to assess response to treatment and to limit use of radiotherapy
