Lymphoma 2: Chronic Lymphocytic Leukaemia and Lymphoproliferative disorder quiz Flashcards
HL: Diagnosis and Staging, Tx and Prognosis
Lymphoma morphology process
HL: epidemiology
1% of all cancer
M>F (women sclerosis sub-type more often)
Bimodal age incidence: 20-29 (most common), >60 (smaller peak)
HL: Signs and Sx
Painless enlargement of lymph nodes (-> may cause obstructive symptoms/signs)
- B symptoms: fever, night sweats, weight loss
- rarely: pruritus, alcohol-induced pain
Nodular sclerosino HL sub-type
- F > M (20-29yo)
- Neck nodes and a mediastinal mass; may have B symptoms
- Spreads contiguously
- Needs tissue diagnosis
HL classification
Classical HL:
- Nodular sclerosing 80% Good prognosis (causes the peak incidence in young women)
- Mixed cellularity 17% Good prognosis
- Lymphocyte rich (rare) Good prognosis
- Lymphocyte depleted (rare) Poor Prognosis
Nodular Lymphocyte predominant HL 5% (disorder of the elderly multiple recurrences)
Staging of HL
- FDG-PET / CT scan
- Biopsy if other sites infilitrated
The diaphragm is key for staging see diagram above…
Staging of HL
- FDG-PET / CT scan
- Biopsy if other sites infilitrated
The diaphragm is key for staging see diagram above…
HL tx
- All patients with HL should receive chemotherapy however, radiotherapy is also often given after chemotherapy because HL is highly responsive to radiotherapy to clear up remaining cells
- Combined modality = radiotherapy and chemotherapy used
- Chemo and radiotherapy combined can lead to a HIGH risk of reoccurrence
Outcome of HL therapy
HL Tx dilemma
Treatment dilemma:
- HL is curable (~80%)
- Intensify therapy → more cures (>80%) but more secondary cancers (>10%)
- Reduce therapy → less secondary cancers (<10%) but less cures (<80%)
Non-Hodgkin’s Lymphoma
NHL General
Different types of NHL and their clinical behaviour
Managing NHL
Common and interesting lymphomas
- COMMON = DLBCL, FL
- INTERESTING = H. pylori MALToma, EATL, HIV-associated
DLBC NHL (HIGH-GRADE, AGGRESSIVE)
- Common form of NHL (30-40% of all NHLs)
- Aggressive / high-grade
- Prognosis and treatment determined by:
- Histological diagnosis
- Anatomical stage
- IPI (International Prognostic Index)
DLBCL Tx
Follicular NHL (LOW-GRADE/INDOLENT) features
- Indolent lymphoma
- 35% of NHL
- Associated with a t(14; 18) → over-expression of bcl-2 (an anti-apoptotic protein)
- Used a FLIPI score (a modified version of IPI)
- Incurable (median survival 12-15 years; requires 2-3 chemotherapy schedules over this period)
Follicular NHL (LOW-GRADE/INDOLENT) initial tx options
Extra-nodal Marginal Zone Lymphomas
Enteropathy Associated T-cell Lymphoma (EATL)
CLL definition and epidemiology
- Proliferation of mature B cells
- Epidemiology:
- Most common (UK = 4.2/100,000/year) leukaemia in West
- Tends to affect Caucasians
- Median age at presentation: 72 years (10% aged <55yo)
- Relatives have 7 x increased risk
CLL Lab findings
- Lymphocytosis (5-300 x 109/L)
- Smear cells (weak cells so break when put on a slide)
- Normocytic normochromic anaemia
- Thrombocytopaenia
- Bone marrow lymphocytic replacement of normal marrow elements
NOTE: as this is an indolent leukaemia, it is often only picked up during routine blood tests for other reasons
How do we check maturity of B cells (what about T cells?)
- Maturity of B cells can be determined from its antigen expression, identified through immunophenotyping– B-cells express different antigens as they progress through development – mature B-cells specifically express:
- sIg
- CD-19
CLL Prognosis: VH mutations
- VH = variable heavy chain (the part that undergoes somatic hypermutation by VDJ recombination)
- Pre-germinal centre B cells will have Ig-genes (VH genes) that have NOT undergone somatic hypermutation. In other words, they are UNMUTATED and conform precisely to the germline sequence
- Once antigen selection is complete, the B cell has undergone somatic mutations in the VDJ region and so it can be said that the B cell has had it’s VH region mutated (physiologically), post-germinal centre
- Half of CLL patients have MUTATED VH (i.e. arising from post-germinal centre cells) and half have UNMUTATED VH (i.e. arising from pre-germinal centre cells) prognosis much worse in patients with an UNMUTATED VH
- Mutated = 25 years survival
- Unmutated = 8 years survival
CLL Prognosis: biological prognostic factors which common genetic abnormality is important
- There is a collection of common genetic abnormalities that are screened using FISH:
- Deletion of 13q ~133 months survival
- Trisomy 12 ~114
- Deletion of 11q (ATM) ~79
- Deletion of 17p (TP53) loss of p53 tumour suppressor gene
- The most important is DELETION of 17p (TP53)
- These don’t tend to respond to chemotherapy
CLL clinical issues
- Although high lymphocytes, the cells are mono-clonal and so NOT useful for antibody production and an abundance of non-functioning B cells hypogammaglobulinemia as normal B cells are being suppressed
- This leads to increased risk of infection (e.g. pneumonia, sinusitis)
- Healthy bone marrow will become suppressed leading to bone marrow failure (anaemia, infection, bleeding)
- Malignant lymphocytes can spread to lymphoid organs (e.g. lymph nodes, spleen)
- Although this is an indolent disease, there is a 1% chance every year that CLL can acquire more mutations and undergo a RICHTER TRANSFORMATION (become a high grade lymphoma)
- Presence of a population of malignant B cells deregulation of the surviving normal B cell population
- This can result in autoimmune disease (e.g. autoimmune haemolytic anaemia)
CLL treatment (3)
(1) Supportive (as 50% of CLL-related deaths due to infections)
- Vaccination (flu, pneumococcus) – no live vaccines (i.e. VZV)
- Anti-infective prophylaxis and treatment
- Acyclovir for viral infections
- PCP prophylaxis for those that are immunosuppressed
- IVIG for those with hypogammaglobulinaemia and recurrent bacterial infections
(2) Specific Scenarios:
* High-Grade (Richter) Transformation treat as high grade lymphoma (R-CHOP)
(3) Leukaemia-directed Treatment:
- Tailored to the patient
- Elderly
- Young
- Need irradiated blood products if they are at risk of transfusion-associated graft-versus-host disease
- Incurable by chemo → watch and wait preferred over any active treatment, esp. in elderly patients
- The decision to treat is often dependent on the age and comorbidities of the patient
- The aim of therapy is to establish remission
CLL indications for tx (i.e. when to stop watching and waiting)
- Progressive lymphocytosis (count doubling < 6 months)
- Progressive bone marrow failure (Hb < 100; Platelets < 100; Neutrophils < 1)
- Massive or progressive lymphadenopathy/splenomegaly
- Systemic symptoms (B symptoms)
CLL 1st line chemo-immunotherapy (TP53 intact)
(1) FCR or R-Bendamustine (combination chemotherapy)
- Fludarabine
- Cyclophosphamide
- Rituximab (anti CD20 moab)
(2) Obinutuzumab (anti CD20) + Chlorambucil (single agent chemo)
(3) Supportive care only
High-risk CLL cases
Patients with TP53/17p deleted CLL 1st Line
Refractory disease or early relapse (<24 months)
CLL new agent tx (VERY EXPENSIVE)
