Leukaemia

Question 1

Clinical Features of ALL

Answer 1

BM function failure: anaemia, thrombocytopenia, neutropenia
Organ infiltration: hepatomegaly, splenomegaly, lymphadenopathy +++, bone pain, gum hypertrophy, CNS involvement +++, testicular enlargement, thymic enlargement (mediastinum)

Question 2

Epidemiology of ALL and AML

Answer 2

ALL: Childhood
AML: Adulthood (risk increase with age), and under 2’s (infant peak)

Question 3

Clinical features of AML

Quick Subtype facts:
M3 -
M4&5 -

Answer 3

BM function failure: anaemia, thrombocytopenia (bleeding), neutropenia (infection)
Organ infiltration: hepatomegaly, splenomegaly, bone pain, gum hypertrophy, some CNS, lymphadenopathy less common
M3: Acute promyelocytic leukaemia (prone to DIC)
M4&5: Monoblasts/monocytes - skin/gum infiltration + hypokalaemia

Question 4

What investigations aid in the diagnosis and differentiation of a haem malignancy?

Answer 4

Basic: FBC (WCC), blood smear, Bone marrow biopsy

For Differentiation:
Morphology +/- cytochemistry (stains) (Ph Chromosom +ve or -ve)
Immunophenotyping (lineage,, differentiation)
Cytogenetics (chromosomal translocations)
Molecular Genetics (PCR, point mutations etc.)

Question 5

How can ALL and AML be differentiated?

Answer 5

BM smear: Myeloblasts with Auer rods in AML

Myeloperoxidase aand Sudan Black B stains: +ve in AML

Question 6

What is used to provide a definitive diagnosis of an Acute Leukaemia? and what would be a positive result?

Answer 6

Bone marrow biopsy: Immature blasts >20% BM cells

Question 7

List some aetiologies of Acute Leukaemias

Answer 7

Idiopathic, Ionising radiation, Cytotoxic drugs, Benzene, Pre Leukaemic Disorders (MDS/MPD), Down Syndrome
Neonates: 30% develop transient abnormal myelopoeisis; resembles AML but resolves spontaneously and completely after a few weeks

Question 8

How do you treat ALL?

Split into Remission Induction, Consolidation, Maintenance, and Supportive

Answer 8

Remission Induction: Chemo agents with steroids
Consolidation: high dose multi drug chemotherapy, CNS treatment
Maintenance: 2 years in girls and adults, 3 years in boys. Consider allo-stem cell transplant

Supportive: Blood products, ABx, Allopurinol, fluid, electrolytes - to prevent tumour lysis syndrome

Question 9

How do you treat AML?

Split into Remission Induction, Consolidation, Maintenance, and Supportive

Answer 9

Remission Induction: chemo agents with steroids
Consolidation: high dose multi drug chemotherapy, no CNS prophylaxis
Maintenance: none needed
ATRA fro M3
Supportive: blood products, ABx, Allopurinol, fluid, electrolytes - to prevent tumour lysis syndrome

Question 10

Epidemiology and median survival of CML

Answer 10

Middle-aged (40 to 60), median survival 3-5 years

Question 11

Investigation for CML

Answer 11

FBC: raised WCC, Neutrophils 50-500, basophilia
BM & blood smear: hypercellular bone marrow with spectrum of immature and mature granulocytic cells in theblood
PCR: BCR-ABL fusion gene (Philidelphia chromosome) +ve in 80% of cases

Question 12

Clinical Features of CML

Answer 12

Massive splenomegaly, weight loss, night sweats, features of anaemia & thrombocytopenia (bruising/bleeding), gout, lethargy, thrombotic event (monocular blindness, CVA)

Question 13

What are the 3 phases of CML? How are they differentiated (blood/BM smear)?

Answer 13

Chronic Phase: under 5% blasts in BM/blood
Accelerated Phase: >10% blasts in BM/blood
Blast Phase: >20% blasts in BM/blood

Question 14

How do the 3 phases of CML present clinically?

Answer 14

Chronic Phase: WBC slowly increases over years (indolent)
Accelerated Phase: increasing manifestations such as splenomegaly lasting up to 1 year
Blast Phase: Resembles acute leukaemia; timeframe = months (+/- WL, lethargy, night sweats)

Question 15

How are the 3 phases of CML treated?

Answer 15

Chronic Phase: Oral hydroxyurea/interferon suppress WCC. Imatinib (BCR-ABL TKI) or Dasatinib/Nilotinib for resistance; extremely effective. BMT potentially curative
Accelerated Phase: Less responsive to therapy (but same as above?)
Blast Phase: treatment similar to AML, possibly with allogenic SCT for young patients

Question 16

Where is the chromosomal translocation in the Philidelphia chromosome and what fusion gene does this make?

Answer 16

Chromosomal translocation (9;22)
Fusion gene BCR-ABL

Question 17

Epidemiology of CLL

Answer 17

M>F, elderly (median 65-70)
Commonest Leukaemia in Western World
Caucasian associated

Question 18

Clinical features of CLL

Answer 18

80% asymptomatic (diagnosed on routine bloods)
Symmetrical painless lymphadenopathy, BM failure (anaemia, thrombocytopenia, neutropenia), FLAWS
Less prominent splenomegaly and hepatomegaly

Question 19

What is Richter’s Transformation?

Answer 19

Transformation of CLL to a high grade lymphoma, occurs in 8-10% of patients (may have become more common with increasing use of Fludarabine and intense 1st line therapies)

Question 20

How do you treat Richters Transformation?

Answer 20

CHOP-R/Rituximab

Question 21

What investigations and what would you find on a patient with CLL?

Answer 21

FBC/Blood film: high WCC (high % of WBC composed of small mature lymphocytes, normocytic normochromic anaemia, thrombocytopenia, SMEAR CELLS
Electrophoresis: Low serum Ig
BM biopsy: lymphocytic replacement

Question 22

List 4 bad and 3 good prognostic factors of CLL

Answer 22

Bad: raised LDH, CD38 +ve, 11q23 (ATM) deletion, 17p (TP53) deletion (this deletion is associated with bad response to main chemo so put on newer drugs)
Good: Hypermutated Ig gene, low ZAP-70 expression, 13q14 deletion

Question 23

Define the 3 stages of CLL (as defined by Binet Staging) and state their prognosis.

Answer 23

Stage A: high WBC, less than 3 groups of enlarged lymph nodes, usually no treatment required. 12 year survival
Stage B: over 3 groups of enlarged lymph nodes. 5 year survival
Stage C: anaemia or thrombocytopenia, Hb under 100, Plt under 1000. 2 year survival

Question 24

Management/ Treatment of CLL

Answer 24

Immunize again Pneumococcus and flu, PCP, IVIG, Acyclovir (prophylaxis for infections)
1st line = Chlorambucil (commences as pt becomes more symptomatic)
Alt: Fludarabine (purine analog), Alemtuzumab (anti-CD52), and steroids
SCT considered in young, fit patients

Question 25

UK incidence of CLL is 4.2/100,000/year. How much does this increase if you have a relative with CLL?

Answer 25

7 times