Haem: Lymphoma 2, CLL and Lymphoproliferative disorder Flashcards
Describe the typical presentation of lymphoma.
Painless progressive lymphadenopathy
- Can cause compression symptoms e.g. dysphagia if compressing oesophagus
Inflitration symptoms - skin rash, visual changes, neurological deficits
Recurrent infection (BM supression)
Constitutional symptoms (B symptoms)
How is lymphoma diagnosed?
Biopsy with histological WHO classification of lymphoma subtype
Which investigations may be used to stage lymphoma?
- Imaging - PET, CT, MRI
- Bone marrow biopsy
- Lumbar puncture (if CNS involvement)
What are some important tests to perform in lymphoma
and why are they important?
- LDH - marker of cell turnover
- HIV serology - HIV can predispose to NHL (HTLV1 serology may also be important)
- Hepatitis B serology - NHL treatment may deplete B cells resulting in fulminant liver failure due to reactivation of hepatitis B in chronic carriers
What are the 2 main types of Hodgkin’s lymphoma
Classical (95%)
Nodular lymphocyte predominant (5%) - causes recurrent disease in elderly
What is the main type of classical HL and which type has a poor prognosis?
Nodular sclerosing is the main type of classical HL (predominantly affects young women aged 20-30)
Lymphocyte depleted HL is the type that has a poor prognosis
What is the chemotherapy regime used in cHL
ABVD
- Adriamycin
- Bleomycin
- Vinblastine
- Dacarbazine (DTIC)
Given at 4 weekly intervals for 2-6 cycles (dependant on stage and response)
How is HL relapse treated
High dose chemotherapy with PB autologous stem cell transplant
Broadly speaking, what are the treatment approaches to non-Hodgkin lymphoma?
- Monitor only (in indolent lymphoma)
- Urgent chemotherapy
- Non-chemotherapy treatment (e.g. antibiotics to eradicate H. pylori in gastric marginal zone lymphoma)
What are the two most common types of non-Hodgkin lymphoma?
Diffuse large B cell lymphoma (DLBCL) - 30%
Follicular lymphoma - 22%
List some types of non-Hodgkin lymphoma that are:
- Very agressive
- Aggresive
- Indolent
-
Very agressive
- Burkitt’s lymphoma
- T or B cell lymphoblastic lymphoma/leukaemia
-
Aggressive
- Diffuse large B cell lymphoma
- Mantle cell lymphoma
-
Indolent
- Follicular lymphoma
- Small lymphocytic lymphoma (CLL)
- MALToma (marginal zone lymphoma)
What is the correlation between how aggressive a lymphoma is and how curable it is?
The more aggressive it is, the more curable
Indolent lymphoma is more likely to recur
Which factors are taken into account by the international prognostic index (IPI) for lymphoma?
- Age
- Ann Arbor stage
- LDH
- Presence of extra-nodal disease
- ECOG performance status
Which chemotherapy treatment is usually used for diffuse large B cell lymphoma?
- R-CHOP
- Rituximab
- Cyclophosphamide
- Doxorubucin
- Vincristine
- Prednisolone
NOTE: usually 6-8 cycles
NOTE: achieves a 50% cure rate
What treatment option may be considered for patients with diffuse large B cell lymphoma who relapse?
Autologous stem cell transplantation
Which genetic abnormality is associated with follicular lymphoma?
t(14;18) - over-expression of Bcl-2 (anti-apoptosis gene)
NOTE: follicular lymphoma is incurable but is indolent - median survival 12-15 years
What is the usual first-line treatment approach to follicular lymphoma?
Watch and wait
Only treat it clinically indicated (e.g. compression symptoms, massive nodes, recurrent infection)
Which chemotherapy regimen may be used in the treatment of follicular lymphoma?
R-CVP (rituximab, cyclophosphamide, vincristine, prednisolone)
Which lymphoid tissue tends to be affected by marginal zone lymphoma?
Extranodal lymphoid tissue (e.g. MALT)
What is the cause of marginal zone lymphoma?
- H. pylori infection - gastric MALToma
- Sjogren’s syndrome - parotid lymphoma
- Hashimoto’s thyroiditis - thyroid lymphoma
Where is marginal zone lymphoma most commonly seen and how does it tend to present?
- Usually in the stomach
- Presenting with dyspepsia or epigastric pain
- Usually Stage 1{E} (E=extranodal)
- B symptoms are uncommon
Outline the process of MALToma pathogenesis.
- Lymphocytes will respond chronic antigen stimulation from H. pylori infection and proliferate
- At some point, they will over-proliferate and develop cancer-like features but they will still be dependent on antigenic stimulation by H. pylori
- At this point, treating H. pylori will treat the lymphoma
What are the symptoms of early stage gastric MALToma
Epigastric pain, ulceration, bleed
B-symptoms uncommon
How might gastric MALToma stage I-II disease be treated?
- Tripy therapy to eradicate H. pylori (2 antibiotics + 1 PPI)
- Repeat breath test at 2 months
- Repeat endoscopy every 6 months for 1-2 years then annually
NOTE: failure may require chemotherapy
What are the main features of enteropathy-associated T cell lymphoma?
- Mature T cells
- Involves small intestines
- Aggressive
- Caused by chronic antigenic stimulation by gliadin/gluten
Describe the typical presenting features of enteropathy-associated T cell lymphoma.
- Abdominal pain/ obstruction/ bleeding/ perforation
- Systemic symptoms
Why is it important to prevent EATL by following a strict gluten-free diet?
EATL responds poorly to chemotherapy and is usually fatal
What is the most common leukaemia in the Western world and what is its median age of presentation
Chronic lymphocytic leukaemia - proliferation of mature B-cells
Median age of presentation is 72
What are the typical laboratory findings in a patient with CLL?
- Lymphocytosis
- Smear cells
- Normocytic normochromic anaemia
- Thrombocytopaenia
- Bone marrow lymphocytic replacement of normal marrow elements
NOTE: it is indolent so is often only picked up on routine blood tests
What distinctive antigen phenotype (presence and absence) is suggestive of:
- Mature B cells
- Mature T cells
- Mature B cells:
- CD19 positive
- CD5 negative
- Mature T cells:
- CD19 negative
- CD5 positive
- CD3 positive
- CD4 or CD8 positive
Which antigen phenotype is suggestive of CLL?
CD19+ and CD5+
NOTE: this could potentially also be mantle cell lymphoma
Which staging system is used for CLL?
Rai and Binet
Binet: stages A-C depending on number of lymphoid areas (< or > 3, Hb and platelets)
Which specific tests are used in CLL to help gauge prognosis?
FISH cytogenetic panel
- TP53 mutation status
IgH V gene mutation status
CD38 expression (associated with poor prognosis)
How do TP53 and IgH V gene mutations affect prognosis
TP53 - mutation/deletion associated with worse prognosis
IgH V gene - mutation associated with better prognosis
What is the difference between the VH genes of pre- and post-germinal centre B cells?
Pre-germinal centre: variable region is unmutated and looks identical to germline
Post-germinal centre: undergone somatic hypermutation so variable region is mutated and looks different to germline
Describe the immunoglobulin levels you would expect to see in CLL.
Hypogammaglobulinaemia - because the malignant B cells are suppressing antibody production by other B cells
Leads to increased risk of infection
What is the term used to describe CLL changing into a high grade lymphoma?
Richter transformation - 1% risk per year
What are some supportive measures used in the treatment of CLL?
- Vaccination (covid, flu, pneumococcus)
- Infection prophylaxis and treatment (e.g. PCP prophylaxis)
How would autoimmune cytopaenias caused by CLL be treated?
Steroids
NOTE: 2nd line is rituximab
How would a Richter transformation be treated?
R-CHOP
What is leukaemia-directed therapy?
- Tailored to the patient
- Usually involves watching and waiting because it is incurable by chemotherapy
- Aim to establish remission
NOTE: young people may be cured with allogeneic stem cell transplantation
What are some indications to stop watch and wait and initate treatment of CLL?
- Progressive lymphocytosis (doubling in <6 months or >50% increase in 2 months)
- Progressive bone marrow failure
- Massive or progressive lymphadenopathy/splenomegaly
- Systemic symptoms (B symptoms)
- Autoimmune cytopaenias
What is the first line treatment for TP53 intact CLL?
FCR - Fludarabine, Cyclophosphamide, Rituximab
NOTE: less intensive options may include, rituximab and bendamustine or obinutuzumab (anti-CD20) and chlorambucil (alkylating agent)
What are some newer treatment options for high risk CLL?
B cell receptor kinase inhibitors
- Bruton tyrosine kinase inhibitors - ibrutinib = (p53 mutation)
- PI3K inhibitor - idelalisib
Bcl2 Inhibitors - venetoclax (effective but risk of tumour lysis syndrome)
CAR-T therapy
Describe how CAR-T therapy for CLL works.
- CAR-T are autologous T cells that are modified to contain chimeric antigen receptors
- The internal part of the receptor is responsible for cell signalling
- The external part is designed to target CD19 (on B cells) thereby enabling B cell depletion
