CLL and quiz Flashcards
When are Reed Steenberg cells present?
Classical Hodgkin Lymphoma
NLPHL
What is Non-Hodgkins Lymphoma?
Neoplastic proliferation of lymphoid cells.
Originates in lymphoid tissue (lymph nodes, bone marrow, spleen)
What is the incidence of NHL?
Fastest growing human cancer (Burkitt Lymphoma)
Indolent diseases with a 25 year survival
Incidence rising 200/million population/year
Antibiotic responsive disease such as Gastric MALT
What is the presentation of NHL?
Painless lymphadenopathy
Compression symptoms
B symptoms
How do you classify biopsies for NHL?
WHO classification of Lymphoma subtype
How do you diagnose and stage NHL?
CT scan
PET scan (indicated in aggressive lymphomas)
BM biopsy
Lumbar puncture (if risk of CNS involvement )
Histological diagnosis
Blood tests (LDH, albumin, kidney/BM function, HIV/ HepB/ HTLV1)
What tests give prognostic markers for NHL?
LDH
Performance status
HIV serology (if appropriate HTLV1 serology)
Hepatitis B serology (risk of reactivation if B cell depleting therapy given
What therapy would you give someone who has NHL?
Urgent chemotherapy
Monitor only
Antibiotic eradication (H.Pylori gastric MALT lymphoma)
Which cancers are high grade?
V aggressive
Burkitts lymphoma
T/B cell lymphoblastic leukaemia/ lymphoma
Aggressive
Diffuse large B cell
Mantle
What are the low grade blood cancers?
Follicular Small lymphocytic (CLL) Mucosa Associated (MALT)
What is the median survival for very aggressive, aggressive and indolent NHL?
V. Aggressive: 2-5 weeks
Aggressive: 3-12 months
Indolent: 10-15 years
BUT the chances of cure are the highest in the most aggressive tumours.
How do you manage V Aggressive NHL?
These are treated on acute leukaemia type chemotherapy protocols (not discussed further)
What is DLBCL?
Diffuse large B cell (DLBCL) Aggressive B cell NHL 30-40% of all NHL Prognosis and treatment determined by Precise histological diagnosis Anatomical stage IPI (International Prognostic Index)
What is the DLBCL International Prognostic Index?
Age > 60y serum LDH > normal performance status 2-4 stage III or IV more than one extranodal site
What is the 5 year predicted survival by number of risk factors?
0-1: 73%
2: 51%
3: 43%
4-5: 26%
How is DLBCL treated?
Treated by x 6-8 cycles of R-CHOP (Rituximab-CHOP)
combination chemotherapy using a mixture of drugs usually including an anthracycline (e.g. doxorubicin).
R is Immunotherapy using the anti CD20 monoclonal antibody Rituximab
Aim of therapy is curative (overall approx 50%)
Relapse: Autologous Stem Cell transplant salvage 25% of patients
How do you give combination drugs in DLBCL?
Cyclophosphamide 750 mg/m2 i.v. D1
Adriamycin 50 mg/m2 i.v. D1
Vincristine 1.4 mg/m2 i.v. D1
Prednisolone 40 mg/m2 p.o. D1‑D5
What is follicular NHL?
Indolent lymphoma
35% of NHL
Associated with t(14;18) which results in over-expression of bcl2 an anti-apoptosis protein
FLIPI score (modified IPI)
Incurable, median survival 12-15 years
May require 2-3 different chemotherapy schedules over the 12-15 year period
Why is follicular NHL benign?
Incurable
variable/long natural history
What is the treatment of follicular NHL?
Watch and wait
Treatment:
- Immunochemotherapy R CVP
- Maintenance Rituximab
What is a MALT lymphoma?
Is a Marginal zone NHL involving extranodal lymphoid tissue (ie mucosa-associated lymphoid tissue MALT)
Comprise ~ 8% of all NHL
What chronic antigen stimulation may result in MALT lymphoma?
Sjogrens syndrome ; parotid lymphoma (MZL)
H.Pylori ; Gastric MALT lymphoma (MZL)
Hashimoto’s Thyroid; Thyroid (MZL)
Lachrymal gland (?Psittaci infection)
What is the median age of presentation of MALT lymphoma?
55-60y
What are the symptoms of MALT lymphoma?
Most commonly arise in stomach, usually present with dyspepsia or epigastric pain
Usual presentation is Stage I[E] (Extra-nodal site)
‘B’-symptoms uncommon
What is MALT lymphomagenesis?
Chronic gastritis
Caused by H.Pylori infection
Proliferation polyclonal
Antigen specific B cells
Antigen dependent
Transformed B-cell
clone
Antibiotic
Sensitive MALT
Antigen independent
Transformed B cells
-> Antibiotic insensitive MALT
How do you treat gastric MALT?
Omep 20mg/Clarith 500mg/amox 1gm bd
Repeat breath test at 2 months
Repeat endoscopy every 6 months for 1st 2years then annually
How good is gastric MALT treatment?
Durable remission in 75% of patients
response may be delayed until 1yr
If fails eradication therapy then may require chemotherapy
Who gets CLL?
- Proliferation of mature B-lymphocytes
- Commonest leukaemia in the western world
Caucasian
UK incidence 4.2/100,000/year
Age at presentation median 72 (10% aged <55yrs)
Relatives x7 increased incidence
What are the lab findings of CLL?
- Lymphocytosis between 5 and 300 x 109/l
- Smear cells in peripheral blood
- Normocytic normochromic anaemia
- Thrombocytopenia
- Bone marrow Lymphocytic replacement of normal marrow elements
What is the diagnostic algorithm for CLL?
Immature lymphoblasts ( TdT positive) Think Acute Lymphoblastic Leukaemia (ALL)
Small mature lymphocytes +smear cells (need immunophenotype)
+ Mature B cells CD5 +ve
= Mantle cell lymphoma
Small mature lymphocytes +smear cells (need immunophenotype)
+ Mature B cells CD5 +ve
+ Immunophenotype CLL score 4-5/5
= CLL
What are the prognostic factors of CLL?
Clinical (quantify the burden of malignant cells)
Rai staging
Binet staging
Laboratory/malignant cell based
CD38 expression bad prognosis
Cytogenetics (FISH panel)
Immunglobulin gene mutation status
IgH mutated
IgH unmutated
How do you determine clinical stage?
A= <3 Lymphoid areas, 60% patients, 12y survival
B= >3 Lymphoid areas, 30% of patients, 5y survivial
C= Hb <100 g/l, Platelets <100x109/l, 10% patients, 2y survival
How does IgH gene mutation status affect survival?
Mutated: 25 yrs
Unmutated: 8 years
What is the median survival in months of patients who have: A) Normal Karyotype B) Deletion of 13q C) Trisomy 12 D) Deletion of 11q (ATM) E) Deletion of 17p (TP53)
A) 111 B) 133 C) 114 D) 79 E) 32
Why do CLL patients have increased risk of infection and bone marrow failure?
Malignant (non functional) mature B cells+ hypogammaglobulinaemia
Proliferate within Bone marrow (efface)
What complications may occur in CLL?
Lymphadenopathy+/splenomegaly, lymphocytosis
Transform to high grade lymphoma
Auto-immune complications e.g. haemolytic anaemia
What are is the treatment of CLL?
Suportive treatment
Vaccination
Anti-infective prophylaxis and treatment
Specific scenarios
Auto-immune cytopaenias
High grade (Richter) transformation
Leukaemia directed treatment
Tailored to patient
How do you do prophylactic treatment of infections in CLL?
Aciclovir
PCP prophylaxis for those receiving fludarabine or alemtuzumab (Campath)
IVIG is recommended for those with hypogammaglobulinemia and recurrent bacterial infections
Immunisation against pneumococcus, and seasonal flu
How to you treat autoimmune phenomena?
Steroids
Rituximab
If CLL transforms to high grade lymphoma what is it called?
Richter’s syndrome
What is the indication for more than watch and wait?
Watch and wait unless Progressive lymphocytosis lymphocyte doubling time <6 months Progressive marrow failure Hb < 100, platelets <100, neutrophils <1 Massive or progressive lymphadenopathy/splenomegaly Systemic symptoms (B symptoms) Autoimmune cytopenias (treat with steroids)
What is first line therapy for TP53 intact disease
Young patient:
FCR
Fludarabine Cyclophosphamide Rituximab (anti CD20 moab)
Rituximab-Bendamustine
Obinutuzumab (anti CD20) +Chlorambucil
Older patients:
Supportive care only
How do you manage high risk cases of CLL?
How to manage high risk cases
Patients with TP53/17p deleted CLL 1st Line
Refractory disease or early relapse (<24 months)
Patients failed 2 lines of chemotherapy
New agents
Ibrutinib (Bruton Tyrosine Kinase Inhibitor)
Venetoclax (anti Bcl2 oral agent)
What are some treatment options in CLL?
BCR Kinase Inhibitors
Ibrutinib (BTK)
idelalisib (PI3K)
BCL2 inhibitors
Venetoclax
Experimental Cell Based Therapies
Chimaeric Antigen Receptor T cells (CAR-T)
What is the presentation of lymphoma?
Painless progressive lymphadenopathy
Palpable node
Extrinsic compression of any “tube”
Eg Ureter, Bile duct, large blood vessel, bowel, trachea, oesophagus
Infiltrate/impair an organ system
E.g. skin rash, ocular&CNS, liver failure
Recurrent infections
Constitutional symptoms
Coincidental e.g. FBC, Imaging
Which of these are NOT true?
Marginal Zone Lymphoma of the parotid is linked to Sjogrens Syndrome
MALT lymphoma of the stomach is linked to H Pylori
Ciclosporin therapy is linked to increased EBV which can cause lymphoma
Chronic EBV is linked to adult leukaemia and lymphoma
NOT TRUE: Chronic EBV is linked to adult leukaemia and lymphoma
EBV is not linked to leukaemia
In certain NHL subtypes, chromosome translocations involving a proto-oncogene are seen. Which statement is NOT true?
Follicular NHL: IgH -BCL2
Mantle Cell Lymphoma: IgH-Cyclin D1
Follicular NHL: BCR-ABL1
Burkitt Lymphoma: IgH- cMYC
NOT TRUE: Follicular NHL: BCR-ABL1
All the other answers include the immunoglobulin gene which is important in B cell lymphomas
Lymph node biopsy: Reed Sternberg Cells are present with a background of chronic inflammatory cells and eosinophils: what is the report outcome?
Hodgkins lymphoma
What is the epidemiology of Hodgkin Lymphoma?
1% of all cancer, 3:100,000 population
HL is more common in males than females.
Bimodal age incidence
Most common age 20-29, young women NS subtype
Second smaller peak affecting elderly >60 years old
What are the symptoms of Hodgkins lymphoma?
Painless enlargement of lymph node/nodes.
May cause obstructive symptoms/signs
Constitutional symptoms; (the B symptoms 1)fever, 2) night sweats 3) weight loss . Pruritis and rarely alcohol induced pain
What is nodular sclerosing Hodgkins lymphoma?
Young women(>men) 20-29 years
Neck nodes and mediastinal mass(may be massive and compress SVC or trachea)
May have B symptoms
Needs a Tissue diagnosis
What do bad coeliacs get?
Enteropahy Associated T cell lymphoma (EATL)
What is EATL?
mature T cells (not precursor)
Involving small intestine Jejunum and Ileum
Has an aggressive (not indolent clinical course)
NHL: Monitoring only is appropriate for asymptomatic small volume disease in this lymphoma sub type:
Burkitt
Gastric MALT
Follicular lymphoma
Diffuse large B cell lymphoma
Follicular lymphoma
Is an indolent lymphoma and Gastric MALT can be cured with antibiotics/ eradication therapy (HPylori)
cHL PET CT shows disease involving mediastinum spleen and liver. What Ann Arbor Stage?
Stage 4 (liver is not lymphatic)
NHL: Monitoring only is appropriate for asymptomatic small volume disease in this lymphoma sub type:
Burkitt
Gastric MALT
Follicular lymphoma
Diffuse large B cell lymphoma
Follicular lymphoma
Is an indolent lymphoma and Gastric MALT can be cured with antibiotics/ eradication therapy (HPylori)
22 year old female with cHL, mediastinal mass- what is the most likely subtype?
Nodular sclerosis
What is the natural history of CLL?
Highly variable natural history
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
How does venetoclax work?
Orally active Bcl 2 inhibitor, permits apoptosis of CLL cells
In high risk CLL p53 mutated 85% response and maintained at greater than 1 year
Main risk is Tumour lysis syndrome when initiating therapy (potentially fatal)
What is CLL therapy?
Combination Immuno-chemotherapy (being superseded by targeted Rx)
Targeted Therapy
BTK inhibitor
BCL2 inhibitor
Cellular therapy only for relapsed high risk cases
Allogeneic SCT
CAR-T therapy
What’s the worse toxicity for the direct treatments?
financial lmao, like tens of thousands of pounds
What is CLL therapy?
Combination Immuno-chemotherapy (being superseded by targeted Rx)
Targeted Therapy
BTK inhibitor
BCL2 inhibitor
Cellular therapy only for relapsed high risk cases
Allogeneic SCT
CAR-T therapy
What’s the worse toxicity for the direct treatments?
financial lmao, like tens of thousands
CLL: who has the worst prognosis?
IgHV mutated, TP53 wt
IgHV mutated, TP53 mutated
IgHV unmutated, TP53 wt
IgHV unmutated, TP53 mutated
IgHV unmutated, TP53 mutated
How does venetoclax work?
Blocks BCL2 protein
Targets CD20 antigen on B cells
inhibits TP53 protein
Irreverisbly binds to BTK (Bruton Tyrosine Kinase)
PD1 ligand inhibitor
Blocks BCL2 protein
