Haem 6 - Lymphoma 2 – CLL and lymphoproliferative disorders Flashcards
Hodgkin’s lymphoma epidemiology
• M > F
o Bimodal age incidence – 20-29yo (women, NS subtype, most common), >60yo (smaller peak)
o Women get a sclerosing sub-type more often
Hodgkin’s lymphoma symptoms
o Asymmetrical painless progressive lymphadenopathy
Becomes painful after alcohol consumption
Obstructive symptoms Extrinsic compression of any tube (ureter, bile duct, large blood vessel, bowel, trachea, oesophagus)
o Infiltrate/impair an organ system
Skin rash
Ocular+ CNS
Liver failure
o Recurrent infections
o B symptoms
Drenching night sweats
Weight loss >10% in 6 months unintentional
o Pruritis
o Coincidental e.g. FBC, Imaging
Hodgkin’s lymphoma histology
Cells stain with CD15 + CD30
Reed-Sternberg cell – bi-nucleate/multinucleate (owl eyed) cell on a background of lymphocytes + reactive cells
HL classification Hodgkin’s lymphoma
Classical HL
Nodular sclerosing 80% - Good prognosis
Mixed cellularity 17% - Good prognosis
Lymphocyte rich (rare) – Good prognosis
Lymphocyte depleted (rare) – Poor Prognosis
o Nodular Lymphocyte predominant HL 5% - disorder of the elderly, multiple recurrences
How do you stage HL? Hodgkin’s lymphoma
FDG-PET
CT scan
BM biopsy
+/-Lumbar puncture
Describe the Ann Arbor staging system
Stage 1 – one LN region (LN region can include the spleen)
Stage 2 - >2 LN regions on the same side of the diaphragm
Stage 3 - >2 LN regions on the opposite sides of the diaphragm
Stage 4 – extranodal sites (liver, BM)
A – no constitutional symptoms
B – constitutional symptoms
Constitutional symptoms
Fever
Unexplained Weight loss >10% in 6 months
Night sweats
https://www.lls.org/sites/default/files/National/USA/Image/get_support/HL_Staging_Diagram.JPG
classical HL
Nodular sclerosing subtype sx, epidemiology
Most common (80%) F > M (20-29yo)
Neck nodes + mediastinal mass (may be massive and compress SVC or trachea)
May have B symptoms
Spreads contiguously
Needs tissue diagnosis
Treatment of classical HL
CHEMO All patients get chemotherapy - ABVD Adriamycin Bleomycin Vinblastine Dacarbazine
2-6 cycles
4 weekly intervals
interim PET CT after 2 cycles to assess response to treatment
End of treatment PET CT to assess need for any radiotherapy
Preserves fertility
RADIO
Often given after chemo
Risks of consolidation radiotherapy in the treatment of HL
- Risk of damage to normal tissues (collateral damage)
- Associated with increased risk of breast/lung/skin cancer, leukaemia/myelodysplasia
- Very high risk of breast cancer in women
- Damage to normal tissue
Combined modality (chemo + radio) – greatest risk of 2o malignancy
Which chemotherapy agents are used to treat classical HL?
Side effects?
ABVD
Adriamycin
Bleomycin
Vinblastine
DTIC Dacarbazine
Adriamycin - cardiomyopathy
Bleomycin - pulmonary fibrosis
Relapse of HL mx
Salvage chemo
Autologous HSCT
Autologous vs allogenic SCT where is it used
Autologous - stem cells from peripheral blood, BM, umbilical cord blood
MM, lymphoma
Not in leukaemias
Allogenic
Leukaemias
Deaths in cHL (classical hodgkin’s lymphoma)are due to
highly curable disease, excellent prognosis
80% will be long-term survivors
10% die from relapse of HL (first 10 years)
10% die from treatment complications (after 10 years)
~5 years, patients are more likely to die of a secondary malignancy or cardiovascular complications (complications of curative treatment)
Why is it important to test for Hep B in HL and NHL?
o Many patients are asymptomatic carriers of hepatitis B
o NHL patients may be given treatments that deplete B cells
o This may cure the lymphoma, but the patient might then present with fulminant liver failure because you have reactivated any asymptomatic hepatitis B
The two commonest types of NHL
Diffuse large B cell lymphoma
Follicular lymphoma
Which lymphomas respond better to chemotherapy; indolent or very aggressive?
Very aggressive (curable)
indolent lymphomas are less treatable - incurable but long remissions
exception - enteropathy associated T cell lymphoma
quick clinical course but not responsive to treatment
How are very aggressive lymphomas treated?
Like leukaemia
Enteropathy associated T cell lymphoma mx
Responds poorly to chemo, generally fatal
aim is to prevent - strict adherence to gluten free diet
Most likely subtype of cHL in
young women
eldelry
young women - nodular sclerosing
elderly - lymphocyte rich
both have a good prognosis
NHL Monitoring only appropriate for asymptomatic small volume disease in this lymphoma sub type
Follicular lymphoma
Gastric MALT mx -
indolent lymphoma but needs abx to prevent complications
Which cells are proliferating in CLL?
Mature B cells
lots of monoclonal lymphocytes
CLL clinical features
Asymptomatic Painless lymphadenopathy BM failure B symptoms Hepatosplenomegaly Associated with autoimmunity (Evan's syndrome) - AIHA, ITP
CLL laboratory features
Bloods
Blood film
flow cytometry
FBC Massive lymphocytosis (>200x10^9/L) Normocytic anaemia thrombocytopenia neutropenia low serum immunoglobulin
Blood film
Smear cells (smear CLLs)
Normocytic normochromic anaemia
B cells - CD19 +, CD5+
flow cytometry to confirm monoclonal population
What risk is there with CLL/SLL?
Can transform to the aggressive diffuse large B cell lymphoma via Richter transformation
How can CLL be staged clinically?
Rai or Binet staging
CLL IPI score • Age >60y • Serum LDH > normal • Performance status 2-4 • Stage III or IV • >1 extra-nodal site
Cell based prognostic factors in CLL
• IgH mutation status unmutated = bad • CLL FISH cytogenetic panel • tp53 mutation status • chr 17p deletion (tp53) [loss of tp53 tumour suppressor gene]
Worst case scenario in CLL
- Binet stage C
- IgH unmutated
- 17p del
- p53 mutated
CLL prognosis
Initially 5-10 years good health until progression to a 2-3 year terminal phase
Rapid progression to death within 2-3 years
In a disorder of elderly
1/3 never progress
1/3 Progress, respond to CLL Rx (death from unrelated disorder)
1/3 Progress, require multiple lines of Rx, refractory disease, death from CLL
Binet staging
Binet stage
• A
<3 groups of enlarged lymph nodes
High WBC
Usually no treatment required
• B
>3 groups of enlarged lymph nodes
• C
Anaemia (<100g/l) or thrombocytopenia (<100x10^9/l)
Rai staging
0 - lymphocytosis only
I - lymphadenopathy
II - hepatosplenomegaly +/- lymphadenopathy
III - Hb <110 g/l
IV - plt <100x10^9/l
Indication for Ig replacement therapy in CLL
Recurrent infections + IgG <5 g/l
Vaccination in CLL
annual influenza
pneumococcal
covid19
avoid live vaccines
Indications to treat CLL
Watch and wait unless
Progressive lymphocytosis
• >50% increase over 2 months
• Count doubling < 6 months
Progressive bone marrow failure (Hb < 100; Platelets < 100; Neutrophils < 1)
Massive or progressive lymphadenopathy/splenomegaly
Systemic symptoms (B symptoms)
Autoimmune cytopenias
• Treat with immunosuppression not chemotherapy
How to treat CLL in young people vs eldelry
Elderly
Watch and wait
Chemo to establish remission
Young patients
Allogenic SCT
CLL targeted therapy
BCR kinase inhibitors
Ibrutinib (BTK)
- irreversibly binds to BTK
- for refractory CLL P53 mutation
- initially high lymphocyte count which then falls
- associated with
Bruton’s x-linked hypogammaglobulinemia (=Abnormal BTK (B cell tyrosine kinase) gene – mutation in B cell tyrosine kinase
• Pre-B cells cannot develop into mature B cell Absence of mature B cells no antibody production)
Idelasibe (PI3K)
BCL-2 inhibitors
Venetoclax
- for refractory CLL P53 mutation
(bcl-2 is an anti-apoptotic protein therefore ventoclax permits apoptosis of CLL cells)
CLL therapy if it transforms to high grade B cell NHL through Richter transformation (diffuse large B cell NHL)
treat as high grade lymphoma
R-CHOP (6-8 cycles)
Rituximab (anti-CD10 monoclonal antibody) Cyclophosphamide Adriamycin Vincristine Prednisolone
Which is the biggest risk when initiating Venetoclax
Risk of tumour lysis syndrome at start of therapy (potentially fatal) – rapid cell death over a 24h period, release of intracellular electrolytes, mediators
