Chronic Lymphocytic Leukaemia without cards on lymphoma Flashcards

1
Q

What is chronic lymphocytic leukaemia?

A

Proliferation of mature B-lymphocytes.

Commonest leukaemia in the western world. Caucasian.

Age at presentation median 72 (10% <55y)

Relatives x7 increased incidence

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2
Q

What are 5 common laboratory features of CLL?

A

Lymphocytosis: 5-300 x 10^9/l

Smear cells

Normocytic normochromic anaemia

Thrombocytopenia

BM: Lymphocytic replacement of normal marrow elements

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3
Q

What is the timecourse of CLL?

A

Highly variable natural hx:

  • Initially 5-10y good health until progression to a 2-3y terminal phase.
  • Rapid progression to death within 2-3y.

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
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4
Q

What are prognostic features of CLL and how is it staged?

A

Cell based prognostic factors:
* TP53 mutation status (Chr 17p del +/- TP53 point mutation)
* IgHV mutation status
* CLL FISH cytogenetic panel

Clinical staging systems:
* Binet or Rai (clinical staging)
* CLL IPI score

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5
Q

Give 3 bad prognostic indicators in CLL

A

LDH raised
CD38 +ve
11q23 deletion

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6
Q

Give 3 good prognostic indicators in CLL

A

Mutated IgHV
Low ZAP-70 expression
13q14 deletion

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7
Q

What is the median survival of CLL?

A
  • Mutated: 25y
  • Unmutated: 8y
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8
Q

What are clinical complications with CLL?

A

Population of malignant (non functional) mature B cells+ hypogammaglobulinaemia: Increased risk of infection

Proliferate within BM (efface): BM failure

Circulate to nodes, spleen + blood: Lymphadenopathy+/ splenomegaly, lymphocytosis

Acquire further mutations: Transform to high grade lymphoma; Richter Transformation (1% per year)

Disease of immune cells: AI complications e.g. Immune haemolytic anaemia

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9
Q

How can sino-pulmonary infections in CLL be treated?

A

Early Rx with abx

Pneumocystis prophylaxis (may also require zoster ppx)

Recurrent infection + IgG < 5g/l : IVIG replacement therapy

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10
Q

Which 3 vaccinations should be offered to patients with CLL?

A

Pneumococcal

Covid19

Seasonal flu

Avoid live vaccines

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11
Q

Watch and wait is the preferred approach to CLL.

When should treatment be given?

A

Progressive lymphocytosis:

  • >50% Increase over 2m
  • Lymphocyte doubling time <6m

Progressive BM failure:

  • Hb < 100, platelets <100, neutrophils <1

Massive or progressive lymphadenopathy/splenomegaly

Systemic Sx

AI cytopenias (treat with immunosuppression not chemo)

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12
Q

What therapy can be offered for CLL patients?

A

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
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13
Q

Which BTK inhibitor can be used to treat CLL?

A

Ibrutinib (BTK)

Idelalisib (PI3K)

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14
Q

Which BCL2 inhibitors can be used to treat CLL?

A

Venetoclax

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15
Q

Which experimental cell based therapies can be used to treat CLL?

A

Chimeric Antigen Receptor T cells (CAR-T)

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16
Q

How does venetoclax work in CLL?

A

Orally active Bcl 2 inhibitor, permits apoptosis of CLL cells.

In high risk CLL p53 mutated 85% response + maintained at >1y.

Main risk is tumour lysis syndrome when initiating therapy (potentially fatal).

17
Q

How is 80% of CLL diagnosed?

A

On routine bloods
May be asymptomatic

18
Q

Give 6 signs and symptoms of CLL

A

Symmetrical painless lymphadenopathy
BM failure: anaemia, thrombocytopenia + leukopenia
Weight loss
Fever (low grade)
Night sweats
Hepatomegaly + splenomegaly (less prominent)

19
Q

What autoimmune syndrome is CLL associated with?

A

Evans syndrome:
AIHA + ITP

20
Q

What can CLL progress to? What is this called?

A

Diffuse Large B cell lymphoma
Richter’s transformation

21
Q

What is CLL very similar to? How does it differ?

A

Same disease process as small lymphocytic lymphoma
CLL primarily seen in BM
SLL primarily in LNs

22
Q

What immunophenotype is seen in CLL?

A

B cells that are CD5 +ve and CD19+ve

(normal mature B cells should be CD5 -ve, CD19 +ve)