Lymphoid malignancy Flashcards
What is a lymphoma?
Cancers of lymphoid origen
What can a lymphoma present with?
> enlarged lymph nodes (lymphadenopathy)/ hepatosplenomegaly
Extranodal involvement
B symptoms
Bone marrow involvement
What are the systemic (B) symptoms of a lymphoma?
> Weight loss (>10% in 6 months) > Fever > Night sweats > Pruritis > Fatigue
What are the 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?
○ Neoplastic disorder of lymphoblasts
○ Diagnosed by > 20% lymphoblasts present in bone marrow
What is the epidemiology of ALL?
○ 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 presentation of ALL?
○ Present with 2-3 week history of bone marrow failure or bone/joint pain
- Bone marrow failure +/- raised WCC
- Bone pain, infection, sweats
What are the standard treatments for ALL?
□ Induction chemotherapy to obtain remission
□ Consolidation therapy
□ CNS directed treatment
□ Maintenance treatment for 18 months
When would stem cell transplantation be used to manage ALL?
If the patient is high risk
What are the newer therapies for ALL?
□ Bispecific T-cell engagers (BiTe molecules) – e.g. Blinatumomab
□ CAR (chimeric antigen receptor T-cells)
® Patient/ healthy 3rd party T-cells harvested
® Transfected to express a specific T-cell receptor expressed on leukaemia cells (CD19)
® Expanded in vitro
® Re-infused into patient
What are the risk factors for a poor prognosis in ALL?
- Increasing age
- Increased white cell count
- Immunophenotype (more primitive forms)
- Cytogenetics/molecular genetics
□ t(9;22); t(4;11) - Slow/poor response to treatment
How is chronic lymphocytic leukaemia diagnosed?
- Blood > 5 x 10^9/L lymphocytes
- Bone marrow > 30% lymphocytes
- Characteristic immunophenotyping
□ B-cell markers (CD 19, 20, 23) & CD5 positive
What is the presentation of chronic lymphocytic leukaemia?
- Often asymptomatic at presentation
- Frequent findings:
□ Bone marrow failure (anaemia, thrombocytopenia)
□ Lymphadenopathy
□ Splenomegaly (30%)
□ Fever and sweats (< 25%) - Less common findings:
□ Hepatomegaly
□ Infections
□ weight loss
What are the associated findings of CLL?
- Immune paresis (loss of normal immunoglobulin production)
- Haemolytic anaemia
□ 20% have positive direct antiglobulin test
□ 8% clinical evidence of haemolytic anaemia
What are the indications for treatment of 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 of CLL?
- Often nothing: “watch and wait”
- Cytotoxic chemotherapy e.g. fludarabine, bendamustine
- Monoclonal antibodies e.g. Rituximab, obinutuzamab
- Novel agents
□ Bruton tyrosine kinase inhibitor e.g. ibrutinib
□ PI3K inhibitor e.g. idelalisib
□ BCL-2 inhibitor e.g. venetoclax
What are the poor prognostic factors of CLL?
- Advanced disease (Binet stage B or C)
- Atypical lymphocyte morphology
- Rapid lymphocyte doubling time (<12 months)
- CD 38+ expression
- Loss/mutation p53; del 11q23 (ATM gene)
- Unmutated IgVH gene status
How is a lymphoma assessed?
Lymph node biopsy/ CT scan/ bone marrow aspirate and trephine
How is non-hodkin’s lymphoma classified?
- lineage (B-cell or T-cell) □ Majority are B-cell in origin - grade of disease (high grade or low grade) □ Low grade lymphoma ® Indolent, often asymptomatic ® responds to chemotherapy but incurable ® median survival varies by subtype □ High grade lymphoma ® Aggressive, fast-growing ® Require combination chemotherapy ® Can be cured, but again varies widely - histological features of disease
What is a diffuse large B-cell lymphoma?
□ Commonest subtype of lymphoma (of any kind)
□ High-grade lymphoma
□ Treated with combination chemotherapy: typically anti-CD20 monoclonal antibody + chemo
What is a follicular lymphoma?
□ 2nd commonest subtype of lymphoma
□ Low-grade lymphoma
□ Treated with combination chemotherapy: typically anti-CD20 monoclonal antibody + chemo
What is the epidemioogy of Hodgkin lymphoma?
- 30% of all lymphomas
- bimodal age curve:
□ 1st peak at 15-35y
□ 2nd peak later in life - 1.9 males: 1 female
- association with Epstein Barr virus; familial and geographical clustering
What is the treatment of 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
