Malignant Haematology and Acute Leukaemia Flashcards
What are the kinetics of normal haemopoiesis?
Self-renewal Proliferation Differentiation or lineage commitment Maturation Apoptosis
What enzyme is expressed on neutrophils?
Myeloeroxidase
How can we identify normal, more mature cells?
Morphology
Cell surface antigens (e.g. glycophorin A=red cells)
Enzyme expression
How can we identify normal progenitors/stem cells?
Cell surface antigens
Cell culture assays
Animal models (not routine)
What is malignant haemopoiesis characterised by?
Increased numbers of often dysfunctional cells and may have loss of the normal haemopoietic reserve
One or more of: increased proliferation, lack of differentiation/maturation/apoptosis
What causes haematological malignancies?
Genetics, epigenetic, environmental interaction
Somatic mutations in regulatory genes (driver/passenger mutations)
Multiple ‘hits’ or single event
Recurrent cytogenetic abnormalities (not causal in most, but contributory)
What do driver mutations do on the cells carrying them?
Confer growth advantage and have been +vely selected during the evolution of the cancer
What do passenger mutations do on the cells carrying them?
Do not confer growth advantage, but happened to be present in an ancestor of the cancer cell when it acquired one of its drivers
What can somatic mutations observed in 10% of persons older than 65 without a blood disorder predict?
Subsequent risk of haem malignancy
What is a clone?
Population of cells derived from a single parent cell
Parent cell has a genetic marker (driver or chromosomal change shared by daughter cells
However clonal diversity is possible
Is normal haemopoiesis poly or monoclonal?
Poly, malignancy haemopoiesis is usually mono
How are haematological malignancies classified?
Speed of presentation- acute or chronic, usually depends on type and stage of defect
Site- medullary (marrow)/extramedullary, blood (leukaemia)/LN (lymphoma)
Lineage- myeloid/lymphoid
What are the types of leukaemias?
Acute Myeloid Leukaemia
Acute Lymphoblastic Leukaemia
Chronic Myeloid Leukaemia
Chronic Lymphocytic Leukaemia
What are the types of lymphomas?
High grade and low grade
What can CLL involve?
Both blood/bone marrow and lymph nodes
What is myeloma?
Plasma cell malignancy in marrow
Describe acute leukaemia
Rapidly progressive clonal malignancy of the marrow/blood with maturation defect(s)
Decrease/loss of normal haemopoietic reserve
What is acute leukaemia defined as?
Excess of ‘blasts’ (≥20%)in either the peripheral blood or bone marrow
What is ALL?
Malignancy disease of lymphocytes
Most common childhood cancer (30/40 cases per million)
What is the presentation of ALL?
Due to marrow failure (naemia, infections, bleeding)
Leukaemic effects: high WCC and involvement of extra-medullary areas e.g. CNS, lymph nodes sometimes causing venous obstruction
Bone pain
Describe AML
More common in the elderly (>60 years)
May be ‘de novo’ or secondary
Presentation can be similar to ALL (marrow failure)
Subgroups of AML may have characteristic presentation- DIC, gum infiltration
What are the Ix for acute leukaemia?
Blood count and film
Coag screen
Bone marrow aspirate (morphology, immunophenotype by flow cytometry, cytogenetics- diagnostic utility/prognostic significance, trephine (piece of bone)- enables better assessment of cellularity and helpful when aspirate is sub-optimal)
What will be seen on the blood film in acute leukaemia?
Reduction in normal cells
Presence of abnormal cells
Blasts with high nuclear:cytoplasmic ratio
What is required for a definitive diagnosis between AML and ALL?
Immunophenotyping- as they will express different lineage associated proteins
What is the treatment for ALL?
Multi agent chemo- Hickman line
Can last up to 2-3 years
Different phases of treatment of varying intensity (induction, consolidation, intensification, maintenance)
Targeted treatments in certain subsets
What is the treatment for AML?
Multi agent chemo-Hickman line
Normally intensive
Between 2-4 cycles of chemotherapy (5-10 days of chemotherapy followed by 2-4 weeks of recovery)
Prolonged hospitalisation
What are the problems with marrow suppression?
Anaemia
Neutropenia- infections (G-ve bacteria can cause fulminant life threatening sepsis)
Thrombocytopenia- bleeding (purpura, petechiae when PTL <20)
What are the complications of chemo?
Nausea and vomiting
Hair loss
Liver, renal dysfunction
Tumour lysis syndrome (during first course of treatment)
Infection
-Bacterial: empirical treatment with broad spectrum antibiotics (particularly covering Gram negative organisms) as soon as neutropenic fever
-Fungal (if prolonged neutropenia and persisting fever unresponsive to anti-bacterial agents)
-Protozoal e.g PJP (more relevant in ALL therapy)
Late- loss of fertility, cardiomyopathy with anthracyclines
Will many AML/ALL patients go into remission?
Yes- <5% marrow blasts with recovery of normal haemopoiesis
Many will also relapse
What is the cure rate for ALL?
Childhood >85-90% (depending on bio-markers)
Adult ~30-40%
What is the cure rate for AML?
Adult <60yo 40-50% (depending on bio markers)
>60yo ~10% or less
What can be potentially curative in a minority of patients, and can be used in some after initial therapy or at relapse?
Allogenic stem cell transplantation
