CML and CLL

Question 1

difference between CLL and small cell lymphoma

Answer 1

essentially the same disease process with
slightly different presentations – CLL is primarily seen in the BM, SLL in the LNs.

Question 2

clinical features of CLL

Answer 2

• Symmetrical painless lymphadenopathy +/- splenomegaly
• • BM failure - anaemia & thrombocytopenia symptoms,
• hypogammaglobinaemia >>> recurrent infections (50% deaths)
• FLAWS
• Associated with autoimmunity (Evan’s Syndrome) – AIHA, ITP
• Can progress to a form of high grade lymphoma (DLBC, see later) – Richter’s transformation

Question 3

prognostic factors of CLL

Answer 3

LDH raised, unmutated IgH, CD38 +ve, 11q23 deletion = bad

p53 mutation = bad = does not respond to chemo

Hypermutated Ig gene, Low ZAP-70 expression, 13q14 deletion = good

Question 4

investigations for CLL

Answer 4

laboratory featureS:

• High WBC with lymphocytosis >5 (high % of WBC composed of lymphocytes, small mature)
• Low serum immunoglobulin >> infections
  
  • the reason you get low serum immunoglobulin is because the B cells that are produced are not producing enough immunoglobulins
• Lymphocytosis >>>> 5-300x10⁹/L
• Smear cells
• Normocytic, normochromic anaemia
• Low platelets
• BM replacement

immunophenotyping:

• Flow cytometry to confirm a monoclonal population Usually CD5+ CD23+ >> (normal B cells dont express CD5)
• CD19 >>> MATURE B cells
• CD38

Question 5

binet staging for CLL

Answer 5

Stage A •

• High WBC
• <3 groups of enlarged lymph nodes
• Usually no treatment required >>> 12 year survival

Stage B •

• >3 groups of enlarged lymph nodes >>> 5 year survival

Stage C >>> Anaemia or thrombocytopenia

Question 6

treatment for CLL

Answer 6

Many patients benefit from watchful waiting if they are asymptomatic with slowly progressive disease

Supportive treatment with transfusions, infection prophylaxis:

• Vaccination >>> flu, pneumococcus
• Anti-infective prophylaxis + treatment >>> acyclovir, PCP prophylaxis, IVIg)

1st line: if p53 deletion = alemtuzumab / ibrutinib / idalalisib + transplant;

otherwise if TP53 Intact CLL = clinical trial or chlorambucil/fludarabine/rituximab etc

Ritcher transformation - R CHOP

Question 7

what is CLL

Answer 7

Chronic lymphocytic Leukaemia of mature B cells

Question 8

what is CML

Answer 8

A myeloproliferative disease (

Question 9

investigations for CML

Answer 9

bloods- (large number of differentiated neutrophils)

• Ph+ve (Philadelphia chromosome) in 80% = chromosomal translocation (9;22) >>> FISH is used for diagnosis
• PCR for BCR-ABL (Philadelphia Ch) fusion gene
• High White Blood Cell count with high neutrophils and high basophils (note: very few conditions cause an elevated basophil count!)
• Hypercellular BM with spectrum of immature (e.g. myelocytes) and mature granulocytic cells in the blood

Question 10

prognosis for CML

Answer 10

95% remission rate with imatinib

Question 11

clinical examination finding of CML

Answer 11

O/E: splenomegaly - often massive

Question 12

chronic phase of CML

Answer 12

Chronic phase

• <5% blasts in BM/blood
• WBC increases over years
• Rx = Imatinib (BCR-ABL tyrosine kinase inhibitor) or dasatinib/nilotinib for resistance
• Treatment usually started immediately after diagnosis confirmation regardless of symptoms

Question 13

Accelerated Phase of CML

Answer 13

Accelerated Phase

• >10% blasts in BM/blood
• Increasing manifestations, such as splenomegaly, lasting up to a year
• Less responsive to therapy

Question 14

Blast Phase of CML

Answer 14

Blast Phase •

• >20% blasts in BM/blood
• Resembles acute leukaemia; timeframe = months (+/- WL, lethargy, night sweats)
• Treatment similar to AML, possibly with allogeneic SCT for young pts