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Kat's Pathology > CLL and Lymphoproliferative Disorders > Flashcards

CLL and Lymphoproliferative Disorders Flashcards

1
Q

Reed Sternberg Cells

A

Classical Hodgkin Lymphoma

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2
Q

NHL

A

Neoplastic proliferation of lymphoid cells.
Originates in lymphoid tissue (lymph nodes, bone marrow, spleen)
Incidence rising 200/million population/year

Fastest growing human cancer (Burkitt Lymphoma)
Indolent diseases with a 25 year survival

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3
Q

Presentation of NHL

A

Painless lymphadenopathy
Compression symptoms
B symptoms

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4
Q

Why is a biopsy taken in NHL

A

WHO classification of lymphoma subtype

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5
Q

Management NHL

A

Stage the disease: CT scan, PET scan (indicated in aggressive lymphomas), BM biopsy, LP (if risk of CNS involvement)
Prognostic markers and important tests: LDH, performance status, HIV serology (if appropriate HTLV1 serology), Hepatitis B serology (risk of reactivation if B cell depleting therapy given)
Plan therapy: urgent chemotherapy, monitor only, antibiotic eradication (H.pylori gastric MALT lymphoma)

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6
Q

NHL subtypes

A 
Follicular lymphoma 
Small lymphocyte lymphoma 
Marginal zone lymphoma 
Diffuse large B cell lymphoma 
Burkitt's lymphoma
B cell lymphoblastic lymphoma 
Mantle cell lymphoma 
Lymphoblastic lymphoma 
NK cell/T cell lymphoma
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7
Q

Very aggressive NHL

A

Burkitt lymphoma

T or B cell lymphoblastic leukaemia/lymphoma

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8
Q

Aggressive NHL

A

Diffuse large B cell

Mantle cell

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9
Q

Indolent NHL

A

Follicular
Small lymphocytic/CLL
Mucosa associated (MALT)

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10
Q

Incurable NHL

A

Indolent forms

Prognosis 10-15 years

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11
Q

Curable NHL

A

Very aggressive forms

Prognosis 2-5 weeks (without treatment)

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12
Q

How are very aggressive NHL treated

A

The same as for acute leukaemia

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13
Q

Features of DLBCL

A

Aggressive B cell NHL
30-40% of all NHL

Prognosis and treatment determined by:
Precise histological diagnosis
Anatomical stage
IPI (International Prognostic Index)

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14
Q

What is the IPI for DLBCL

A 
Age > 60y
serum LDH > normal
performance status 2-4
stage III or IV
more than one extranodal site
5 year predicted survival is by number of risk factors: 
0-1 = 73%
2 = 51%
3 = 43%
4-5 = 26%
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15
Q

Treatment of DLBCL

A

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).

Combination drug regimens e.g. CHOP
Cyclophosphamide 750mg/m2 IV
Adriamycin 50mg/m2 IV
Vincristine 1.4mg/m2 IV
Prednisolone 40mg/m2 PO

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

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16
Q

Features of follicular NHL

A

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

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17
Q

Treatment of follicular NHL

A

Indolent slow progressing B cell NHL
Incurable
variable/long natural history

At presentation Watch and wait only treat “if clinically indicated”
Nodes compressing;eg bowel, ureter, vena cava
Massive painful nodes, recurrent infections

Treatment:
combination Immuno-chemotherapy R-CVP
Maintenance rituximab delays Time to next progression
Conventional treatment is not curative

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18
Q

Features of MALT lymphomas

A

Is a Marginal zone NHL involving extranodal lymphoid tissue (ie mucosa-associated lymphoid tissue MALT)
Comprise ~ 8% of all NHL
Chronic antigen stimulation
Sjogrens syndrome ; parotid lymphoma (MZL)
H.Pylori ; Gastric MALT lymphoma (MZL)
Hashimoto’s Thyroid; Thyroid (MZL)
Lachrymal gland (?Psittaci infection)
Median age at presentation 55-60y
Most commonly arise in stomach, usually present with dyspepsia or epigastric pain
Usual presentation is Stage I[E]
‘B’-symptoms uncommon

19
Q

Pathogenesis of MALT lymphomas

A

Proliferation polyclonal antigen specific B cells (due to chronic gastritis caused by h.pylori infection)
Antigen dependent transformed B cell clone (at this point is an antibiotic sensitive MALT)
Antigen independent transformed B cells (antibiotic insensitive MALT)

20
Q

Treatment of gastric MALT (MZL) stage 1-2 disease

A

Omep 20mg/Clarith 500mg/amox 1gm bd
Repeat breath test at 2 months
Repeat endoscopy every 6 months for 1st 2years then annually

Durable remission in 75% of patients
response may be delayed until 1yr
If fails eradication therapy then may require chemotherapy

21
Q

Features of CLL

A 
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
22
Q

Laboratory findings in CLL

A 
Lymphocytosis between 5 and 300 x 109/l 
Smear cells
Normocytic normochromic anaemia
Thrombocytopenia
Bone marrow	Lymphocytic replacement of normal marrow elements
23
Q

Important targets in CLL treatment

A

sIg
CD19
CD5

24
Q

Diagnostic algorithm in CLL

A

Lymphocytes + morphology –> immature lymphoblastic (TdT positive) think acute lymphoblastic leukaemia (ALL)

Lymphocytes + morphology –> small mature lymphocytes + smear cells (need immunopheotype) –> mature B cells CD5 +ve (COULD BE A MANTLE CELL LYMPHOMA) –> immunophenotype CLL score 4-5/5 –> CLL

25
Q

What is the CLL score

A 
CD5
CD23
FMC7
CD79b
SmIg
26
Q

Prognostic factors in CLL

A

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

27
Q

How is clinical stage determined in CLL

A

Stage A: <3 lymphoid areas
B: >3 lymphoid areas
C: >3 lymphoid areas, Hb<100, platelets <100

28
Q

What are the steps of normal B cell development

A

Stem cells produce primary repertoire, undergo VDJ joining to produce low affinity antigen specific B cells, which then undergo class switching to produce high affinity antigen-specific B cells

Class switching can lead to IgH mutations. Unmutated VH accounts for 56% of CLL, whilst mutated VH accounts for 44% of CLL.

29
Q

What IgH is associated with better long-term prognosis in CLL

A

Mutated median survival 25 years

Unmutated median survival is 8 years

30
Q

What chromosomal abnormality is associated with a worse prognosis in CLL

A

Deletion of 17p - median survival is 32 months

31
Q

Malignant (non functional) mature B cells+ hypogammaglobulinaemia

Clinical issue?

A

Increased risk of infection

32
Q

Proliferate within Bone marrow (efface)

Clinical issue?

A

Bone marrow failure

33
Q

Circulating to nodes, spleen and blood

Clinical issue?

A

Lymphadenopathy +/- splenomegaly, lymphocytosis

34
Q

Acquired further mutations

Clinical issue?

A

Transform to high grade lymphoma

35
Q

Disease of immune cells

Clinical issue?

A

Auto-immune complications e.g. haemolytic anaemia

36
Q

Treatment principles in CLL

A

Suportive treatment:
Vaccination
Anti-infective prophylaxis and treatment

Specific scenarios:
Auto-immune cytopaenias
High grade (Richter) transformation

Leukaemia directed treatment: Tailored to patient

37
Q

Principles of supportive treatment in CLL

A

Prophylaxis and treatment of infections:
Account for 50% of all CLL related deaths
Most are bacterial, but fungal and viral are becoming increasingly prevalent
Prophylaxis: 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

38
Q

Management of auto-immune phenomena in CLL

A

Auto-immune phenomena:
1st Line Steroids
2nd Line Rituximab

Irradiated Blood products if risk of TA GVHD

39
Q

Richter’s syndrome

A

CLL transformation to high grade lymphoma

40
Q

Principles of leukaemia directed treatment in CLL

A

Incurable by chemotherapy: Watch and wait versus active treatment

Conventional not to treat Stage A: What are the indications for treatment?

If required tailor treatment (age/co-morbidities)

Aim of therapy obtain response/remission: disease will relapse, 2nd line therapy

Young patients may be cured by allogeneic stem cell transplants

41
Q

Indications for CLL treatment

A 
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)
42
Q

Chemo-immunotherapy for CLL

A 
1st line 
Given if TP53 intact 
FCR: fludarabine cyclophosphamide, rituximab (anti CD20)
Rituximab-Bendamustine 
Obinutuzumab (anti CD20) + chlorambucil 
Supportive care only
43
Q

How are high risk CLL cases managed

A

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 9anti Bcl2 oral agent)

44
Q

Emerging treatment options for CLL

A

BCR kinase inhibitors: ibrutinib, idelalisib
BCL2 inhibitors: venetoclax
Experimental cell based therapies: chimaeric antigen receptor T cells (CAR-T)

Kat's Pathology (105 decks)

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