Lymphoid Malignancy Flashcards
What is lymphoma?
- cancers of lymphoid origin
- lymphadenopathy
- extranodal involvement
- bone marrow involvement
- systemic symptoms
- weight loss (> 10% in 6 months)
- fever
- night sweats
- pruritis
- fatigue
How is lymphoma diagnosed?
- defined by the malignanct cell characteristics (50 entities)
- biopsy
- staging- clinical examination + imaging
- location + extent
- prognosis
- treatment
What is Hodgkin and non-Hodgkin lymphoma?
- Hodgkin- specific disease
- non-Hodgkin- everything else (~70 subtypes)
What are some lymphoproliferative disorders?
- acute lymphoblastic leukaemia (ALL)
- chronic lymphocytic leukaemia (CLL)
- Hodgkin lymphoma
- non-Hodgkin lymphoma (NHL)
- high-grade (diffuse large B-cell lymphoma)
- low-grade (follicular, marginal zone)
What is acute lymphoblastic leukaemia (ALL)?
- cancerous disorder of lymphoid progenitor cells
- normal- immature, rapidly proliferating cells that differentiate into lymphocytes
- leukaemia- no differentiation, rapid, uncontrolled growth + accumulation
- usually in bone marrow but can go anywhere
- 1-2/100,000 per year
- 75% cases < 6 yrs
- 75-90% cases B-cell lineage
- 2-3 week history of bone marrow failure or bone/joint pain
What are the presentations of acute lyphoblastic leukaemia (ALL)?
- bone marrow failure
- inc. WCC
- bone pain
- infection
- sweats
What are investigations for acute lymphoblastic leukaemia (ALL)?
- Hb (low)
- WCC (high)
- platelets (low)
- bone marrow
- 90% B-lymphoblasts
What are acute lymphoblastic leukamaemia (ALL) cell characteristics?
- large cells
- express CD19
- CD34, TDT (markers of very early, immature cells)
What is the treatment for acute lymphoblastic leukaemia (ALL)?
- chemotherapy
- consolidation therapy
- CNS directed treatment
- 18 months
- stem cell transplantation (if high risk)
- Bi-specific T-cell engagers (BiTe molecules) (blinatumumab)
- chimeric antigen receptor T-cells (CAR)
What is the process of CAR therapy?
- patient/healthy 3rd party T-cells harvested
- transfected to express a specific T-cell receptor expressed on leukaemia cells (CD19)
- expanded in-vitro
- reinfused into patient
What are the key side effects of T-cell immunotherapy?
- cytokine release syndrome
- fever, hypotension, dyspnoea
- effect of CAR correlates with CRS presence- significant number require ITU support
- neurotoxicity
- confusion, with normal concious level
- seizure, headache, focal neurology, coma
What are risk factors for a poor prognosis in acute lymphoblastic leukaemia (ALL)?
- inc. age
- inc. WCC
- cytogenetic/molecular genetics
- t(9;22), t(4;11)
- slow/poor response to treatment
What is the outcome of acute lymphoblastic leukaemia (ALL)?
Adults:
- ~90% complete remission rate
- 30-35% leukaemia-free survuval at 5 yr
Children:
- 90% overall survival
- 45% 5 yr survival, poor risk patients (slow reponse or Philadelphia +ve)
What is chronic lymphocytic leukaemia (CLL)?
- abnormal cells are mature
- grow slowly, or no growth
- low-grade condition
- carry many normal markers that B lymphocytes have
- lymphocyte count > 5 (normal < 4)
- > 1700 new cases per yr in UK
- M:F, 2:1
What are the presentations of chronic lymphocytic leukaemia (CLL)?
- often asymptomatic
- bone marrow failure
- anaemia, thrombocytopenia
- lymphadenopathy
- splenomegaly
- fever
- sweats
Less common:
- hepatomegaly
- infections
- weight loss
What are features of chronic lymphocytic anaemia (CLL)?
- immune paresis
- haemolytic anaemia
- 20% +ve direct antiglobulin test
- 8% clinical evidence of haemolytic anaemia
What is chronic lymphocytic leukaemia (CLL) Binet staging?
What are indications for treatment in chronic lymphocytic leukaemia (CLL)?
- progressive bone marrow failure
- massive lymphadenopathy
- progressive splenomegaly
- lymphocyte doubling time < 6 months OR 50% inc. over 2 months
- systemic symptoms
- autoimmune cytopenias
What is the treatment for chronic lymphocytic leukaemia (CLL)?
- often nothing
- ‘watch + wait’
- cytotoxic chemotherapy
- e.g. fludarabine, bendamustine
- monoclonal antibodies
- e.g. rituximab, obinatuzumab
- novel agents
- bruton tyrosine kinase inhibitors, e.g. ibrutinin
- PI3K inhibitors, e.g. idelalisib
- BCL-2 inhibitor, e.g. venetoclax
What are risk factors for a poor prognosis in chronic lymphocytic leukaemia (CLL)?
- advanced disease (Binet stage B/C)
- atypical lymphocyte morphology
- rapid lymphocyte doubling time (< 12 months)
- CD38+ expression
- loss/mutation p53; del 11q23 (ATM gene)
- unmutated IgVH gene status
What are the presentations of lymphoma?
- lymphadenopathy.hepatosplenomegaly
- extranodal disease
- “B symptoms”
- bone marrow involvement
What are the investigations and staging for lymphoma?
- lymph node biopsy
- CT scan
- bone marrow aspirate
- trephine
What are the four stages of lymphoma?
- stage I- localised disease, single lymph node region or single organ
- stage II- 2 or more lymph node regions on the same side of the diaphragm
- stage III- 2 or more lymph node regions above + below the diaphragm
- stage IV- widespread disease; multiple organs, with or without lymph node involvement
How is non-Hodgkin lymphoma classified?
- lineage (B-cell or T-cell)
- majority B-cell (90%)
- “grade”
- high grade- agressive fast growing, require combination chemotherapy, can be cured
- low grade- indolent often asymptomatic, responds to chemotherapy bbubt incurable
