Haematology - Leukaemia Flashcards
What is leukaemia and some features?
A neoplastic process affecting blood precursor cells
- Acute, rapidly progressing + fatal
- Immature blasts >20% of bone marrow cells (rapid proliferation replaces normal bone marrow)
What are some clinical features of an acute leukaemia?
BM function failure (ANT)
- A: Anaemia
- N: Neutropenia (infection)
- T: Thrombocytopenia (bleeding)
Organ infiltration:
- Hepatosplenomegaly
- Lymphadenopathy (mild)
- Bone pain
- CNS
- Skin
- Gum hypertrophy
+ Fevers
What are some causes of acute leukaemia?
- UNKNOWN
- Ionising radiation
- Benzene
- Pre-leukaemic disorders (myelodysplastic syndromes/myeloproliferative disorders)
- Down’s: Increased risk of AML/ALL
How is acute leukaemia diagnosed?
- Morphology +/- cytochemistry (stains)
- Immunophenotyping using flow cytometry (lineage, differentiation)
- Cytogenetics (chromosomal translocations)
- Molecular genetics (PCR, point mutations)
What is leukostasis, its signs and management?
Haematological emergency
- Increased WBC causes viscous blood and end-organ damage
Features:
- Retinopathy
- Pulmonary infiltrates
- Bleeding
- Thrombosis
Mx:
- Leukophoresis
OR
- Chemotherapy/steroids
What is the epidemiology of ALL?
Childhood
What are some clinical features of ALL?
- Hepatosplenomegaly
- Lymphadenopathy
- CNS involvement
- Testicular enlargement (rare)
- Thymic enlargement (mediastinum)
- Bone pain + lump
- Fevers
How is ALL investigated?
- High WCC (blasts)
- Thrombocytopenia
- Anaemia
Flow cytometry:
- CD34 = precursor/stem cells
- CD3, 4, 8 = T-lymphocytes
- CD19, 20, 22 = B-lymphocytes
What is the treatment for ALL?
Chemotherapy
- Remission induction = Chemo + steroids
- Consolidation = High dose multi-drug chemo + CNS Tx (intrathecal chemo)
- Maintenance = 2yrs in girls/adults + 3yrs in boys
?Allo-stem cell transplant IF high risk of relapse
Targeted Tx:
- Nelarabine
- CAR-T cells
- Inotuzumab
- Blinatumumab (B-ALL), imatinib (IF: t9;22)
Supportive:
- Blood products
- Abx
- Allopurinol
- Fluid
- Electrolytes (prevent tumour lysis syndrome)
What is the epidemiology of AML?
Adulthood
- Risk increases with age
OR under 2s (infant peak)
What are some clinical features of AML?
- Lymphadenopathy
- Sx of cytopenias
- M3 = prone to DIC + bleeding
- M4/5 = Monoblasts/monocytes (skin/gum infiltration + hypokalaemia)
How is AML investigated?
- High WCC (blasts)
- Auer rod + granules
Flow cytometry:
- CD34 = precursor/stem cells
- CD33, 13, 117, MPO = myeloid cells
What is the treatment for AML?
Chemotherapy
- Remission induction = Daunorubicin + Cytarabine
- Consoloidation = Cytarabine
Older pts = azacytidine +/- venetoclax
?Allo-SCT IF high risk of relapse
Targeted Tx:
- ATRA (for acute promyelocytic leukaemia)
- Midostaurin - FLT3 mutations
- Gemtuzumab - CD33 immunotherapy
- Enasidenib - IDH mutations
Supportive Tx:
- Blood products
- Abx
- Allopurinol
- Fluid
- Electrolytes (prevents tumour lysis syndrome)
What is the prognosis of AML?
Worse with age
What mutation causes Acute Promyelocytic leukaemia, how does it present, how is it treated and what’s the prognosis?
- T(15;17)
- Presents with DIC
- Tx: ATRA (All-trans retinoic acid) - forces cells to differentiate (stops proliferation)
- Px: Good after induction
What is a common mutation causing ALL in adults?
t(9;22) - BCR-ABL1 (Philadelphia chromosome)
What blood results are a concern for malignancy?
Increased basophils + eosinophils
What is CML and its epidemiology?
Myeloproliferative disease with a slower proliferation of malignant cells
Epi:
- Middle ages (40-60yrs)
- Males
How does CML present?
Asymptomatic if in chronic phase
Accelerated/blast phase Sx:
- General unwell feeling
- Weight loss
- Infections
- Bruising
- MASSIC SPLENOMEGALY
- Lymphadenopathy
What are the three phases of CML?
- Chronic phase
- Accelerated phase
- Blast phase
What are some investigations for CML and how is it usually diagnosed?
Dx:
- Routine bloods (Increased differentiated neutrophils)
Ix:
- Bloods (High WCC, neutrophils + basophils)
- Hypercellular BM with spectrum of immature (myelocytes) + mature granulocytic cells in blood
- Left shift (precursors present)
- BM: Hypolobulaetd megakaryocytes
- PCR (BCR-ABL1)
- Chromosome studies (t(9;22) - Philadelphia chromosome)
What is seen in the chronic phase of CML and how is it treated?
- <5% blasts in BM/blood
- WBC increases over years
Tx:
- Imatinibi (BCR-ABL tyrosine kinase inihibitor)
OR dasatinib/nilotinib for resistance
- Tx started immediately
What is seen in the accelerated phase of CML and how is it treated?
- > 10% blasts in BM/blood
- Increasing manifestations (e.g. splenomegaly), lasting <1yr
Less responsive to therapy (?imatinib)
What is seen in the blast phase of CML and how is it treated?
- > 20% blasts in BM/blood
- Resembles acute leukaemia (timeframe = months)
Tx:
- Similar to AML (daunorubicin/cytarabine + supportive)
- ?Allo-SCT for young pts
What is CLL and how does it differ from SLL (Small lymphocytic lymphoma)?
Lymphoproliferative disease (like lymphoma)
- CLL primarily seen in BM
- SLL primarily seen in LNs
What is the epidemiology of CLL?
- Males more common than females
- Elderly (Mean: 65-70yrs) - incidence increases with age
What are some clinical features of CLL?
Asymptomatic (often diagnosed on routine bloods)
OR
- Symmetrical, painless lymphadenopathy
- BM failure (Anaemia + thrombocytopenia Sx)
- Weight loss, low-grade fevers, night sweats
- Hepatosplenomegaly
- Associated with autoimmunity (Evan’s syndrome) - AIHA/ITP
What is Richter’s syndrome?
The transformation of CLL to aggressive disease (e.g. ALL/high-grade lymphoma)
What investigations are done for CLL and what are the results?
- High WCC (lymphocytosis >5%)
- Low serum immunoglobulin
- Blood film = SMEAR CELLS (+lymphocytosis) or SMUDGE CELLS
- Flow cytometry = monoclonal population (CD5+ CD23+)
- Abnormal BM (lymphocytic replacement)
What mutation statuses indicate a better and worse prognosis for CLL?
TP53 = worse
IGHV = better
What are some good and bad prognostic factors for CLL?
Good:
- Hypermutated Ig gene
- Low ZAP-70 expression
- 13q14 deletion
Bad:
- LDH raised
- CD38 +ve
- 11q23 deletion
What staging criteria is used for CLL and what are the different factors in it?
Binet staging (A, B, C)
A:
- High WBC
- <3 groups enlarged LNs
- No cytopenia
B:
- >3 groups enlarged lymph nodes
- No cytopenia
C:
- Anaemia or thrombocytopenia
- Cytopenias
What stages of CLL require treatment?
B + C
A = watch + wait
What is the treatment for CLL?
- Watchful waiting if asymptomatic
OR - Anti-20 (rituximab) + chemotherapy
- Oral BTK inhibitors (ibrutinib)
- BCL2 inhibitor (venetoclax)
Supportive Tx:
- Transfusions
- Infection prophylaxis
What treatment is required fro TP53 + IGHV mutations in CLL?
TP53 = BTK inhibitors (e.g. ibrutinib)
IGHV = rituximab + chemotherapy
