Haem - Leukaemia Flashcards
(31 cards)
What are the features of acute leukaemia
Rapid onset
Early death if untreated (weeks or months)
Immature cells (blast cells)
Bone marrow failure → anaemia (pallor, fatigue, SoB), neutropoenia (infections), thrombocytopaenia (bleeding)
What are the types of leukaemia
Myeloid:
Acute myeloid leukaemia (AML)
Acute Promyelocytic Leukaemia (APML)
Myelodysplasia
Myeloproliferative
Chronic myeloid leukaemia (CML)
Lymphoid:
Precursor: Acute lymphoblastic leukaemia (ALL)
Mature:
- Chronic lymphocytic leukaemia (CLL)
- Multiple myeloma
- Lymphomas: Hodgkin’s, non-hodgkin’s
what are the two overarching types of Leukaemogenesis
Type 1: problem with proliferation (tyrosine kinase B) → proliferation of mature cells e.g. BCR-Abl in CML
Type 2: problem with differentiation → blast accumulation e.g. AML-ETO, APML-RARA
Transcription factor dysregulation - NOT sufficient on its own to cause leukaemia (you need T1 AND T2 mutations)
What is the epidemiology of CML
M>F
40-60yo peak (however, affects any age)
RF: radiation
What is the aetiology of CML
BCR-ABL Ph Chr translocation t(9;22) → philadelphia chromosome (oncogenic novel fusion oncoprotein) → greater TK activity (ABL = TK)
→ proliferation of mature granulocytes → ↑ neutrophils, eosinophils, basophils
What are the signs and symptoms of CML
Anaemia: lethargy, pallor, SOB
Infections
Bleeding, bruising
Splenomegaly (splenic infiltration)
What is found on investigations for CML
FBC:
- Hb/Plt NORMAl/RAISED
- Massive leucocytosis (neutrophils 50-500), myelocytes, basophils
- Platelet count: raised
Blasts: No excess (<5%)
Blood film: mature myeloid cells
Conventional karyotyping: BCR-ABL
FISH
RQ-PCR - molecular response (reduction in BCR-ABL transcripts) - most sensitive
What are the phases of CML
- Chronic phase (5-6 years): <5% blasts
- Leukocytosis phase: 500-5000 myeloid cells (neutrophils, myelocytes), bone marrow hypercellular
- Accelerated phase (6-12 months): 10-19% blasts
- Blast crisis: >20% blasts, survival 3-6 months
What is the management for CML
Imatinib (tyrosine kinase-R inhibitor)
Monitor response (FBC, cytogenetics, RQ-PCR for complete cytogenic response (CCyR)
Second line: switch to other gen TK inhibitor
Third line: SCT
Other TK inhibitors: dasatinib, nilotinib, bosutinib
What is the epidemiology of AML
Seen in adults (40%) and children < 2
Incidence increases with age, prognosis worsens with increasing age
What is the aetiology of AML
- Duplication (trisomy): trisomy 8 and trisomy 21
- Inversion or translocation: t(8;21), inv (16), t(16;16) → fusion genes (RUNX1/RUNX1T1, CBG-beta/MYH11) → transcription factor function disturbance
- Chr loss/deletion (most common): del (5q) or del (7q)
What are the risk factors for AML
Familial or constitutional predisposition (e.g. Down syndrome)
Irradiation
Anti-cancer drugs
Cigarette smoking
Unknown
What are the signs and symptoms of AML
Anaemia: SOB, lethargy, pallor
Thrombocytopenia: bleeding, bruising
Neutropenia: infections
Bone pain
Local infiltration: hepatosplenomegaly, Lymphadenopathy (less than other malignancies)
± hyperviscosity (very high WCC) → retinal haemorrhage/retinal exudate
What would investigations for AML show
Cytology: Auer rods, fin-speckled granules
Cytochemistry: stains with myeloperoxidase, Sudan Black stain
FBC: raised WCC
Blood film/BM aspirate: circulating blasts
Immunophenotyping: flow cytometry, immunocytochemistry, immunohistochemistry (determine AML from ALL)
Molecular studies and FISH (some patients) → enable sub-classification of the acute myeloid leukaemia and adds prognostic value and aids treatment decisions (certain cytogenetic findings aid prognosis)
What is the management for AML
- Supportive: red cells, platelets, FFP/cryoprecipitate, Abx, long line insertion, allopurinol
- Chemotherapy
- Danorubicin + cyfabine - Targeted molecular therapy
- APML = All-trans-retinoic acid (ATRA) and A2O3
- Biologics = anti-CD33 antibody linked to cytotoxic antibody (e.g. gemtuzumab) - SCT
What is Acute Promyelocytic Leukaemia (APML)
t(15;17) → PML-RARA fusion gene → monocytic leukaemia
Acute myeloid leukaemia that causes sudden haemorrhage (DIC + hyperfibrinolysis)
± gum infiltration
± skin, CNS infiltration → CN palsy
Characterised by an excess of abnormal promyelocytes (Auer rods)
What is the epidemiology of ALL
Children, 2-5yo
Most common childhood malignancy
What is the aetiology of ALL
Lymphoblastic infiltration → B OR T cell lineages
Bone marrow → B-lineage
Thymus → T-lineage (more common)
May get philadelphia chromosome +ve (Transformation from CML)
What are the signs and symptoms of ALL
Children:
Bone marrow failure (anaemia, thrombocytopenia, neutropoenia)
Local infiltration
- Lymphadenopathy (± thymic enlargement)
- Splenomegaly
- Hepatomegaly
- Testes, CNS (these are ‘sanctuary sites’as chemotherapy cannot reach them easily)
- Bone (causing pain)
Adults: similar presentation to AML + lymphadenopathy ± thymic mass
What may investigations show for ALL
FBC: Anaemia, Raised WCC (BUT Neutropenia), thrombocytopenia
>20% blasts
Film: high nucleus: cytoplasm ratio
Bone marrow biopsy
Immunophenotyping: differentiate between AML and LL AND between T and B lineage
Cytogenetic/molecular genetic analysis: Ph Chr +ve → imatinib
What is the management for ALL
- Supportive: blood products, Abx prophylaxis, hyperK+ Mx, hyperUricaemia Mx, central venous catheter)
- Chemotherapy: systemic (2-3 years) + CNS specific
- Molecular treatment
- Ph +ve → imatinib
- Rituximab (anti-CD20) - Transplant
What is the prognosis of ALL
Children: 5-year disease-free survival of 80% (85% of children are cured)
Adults: 5-year disease-free survival of 30-40%
Prognosis worsens with increasing age
Prognosis is very dependent on cytogenetic/genetic subgroups: hyperdiploidy = good prognosis
What is the epidemiology of CLL
Most common (UK = 4.2/100,000/year) leukaemia in West
Tends to affect Caucasians
Median age at presentation: 72 years (10% aged <55yo)
Relatives have 7 x increased risk, but usually sporadic
What is CLL
Most common = proliferation of mature B cells
Risk of Richter transformation → Diffuse large B cell lymphoma
