Haem - Malignant Conditions Flashcards
ALL Hx
Child – typically 2-5 yrs old Hepatosplenomegaly Bone pain / limp Fevers CNS symptoms Testicular swelling (rare but specific)§
Adults – similar to AML, lymphadenopathy
ALL - Blood Tests
Usually present with thrombocytopenia and anaemia
High white cell count
Some analysers will indicate presence of blasts but sometimes these will be flagged as lymphocytes.
Circulating blasts are not normal.
ALL - Blood Film
High nucleus – cytoplasm ratio
It is not possible to tell ALL from AML on blood film most of the time!
ALL- Diagnosis
Diagnosis usually relies on Bone Marrow & Flow Cytometry
Typical features:
TdT +
CD19 / CD22 = B cells (more common)
CD 2 / CD 3 / CD 4/8 = T cells
ALL - Genetics (Paeds)
ETV6-RUNX1 fusion gene & hyperdiploidy (extra chromosomes) are most common abnormalities
Both have a favourable prognosis
MLL gene mutations (now renamed KMT2A) have bad prognosis but are rare.
ALL- Genetics (Adults)
BCR-ABL1 t(9;22) associated with 20-30% of ALL in adults
This is the genetic mutation which also causes CML (covered later)
ALL - Rx
Chemotherapy:
Remission induction: Chemo agents often given with steroids
Consolidation: High dose multi drug chemotherapy
CNS treatment
Maintenance: 2 years in girls and adults, 3 years in boys –> remission
Consider allo-Stem Cell Transplant
Also use imatinib/other TKI for BCR-ABL1
Supportive: Blood products, ABx, Allopurinol, fluid, electrolytes – to prevent tumour lysis syndrome
AML - Hx
Incidence increases with age
Might have had pre-existing myelodysplastic syndrome (MDS)
Symptoms of cytopenias
AML - Blood Tests
Anaemia – due to bone marrow suppression
Thrombocytopenia – due to bone marrow suppression
Leukocytosis – high numbers of circulating white cells
Neutropenia – lack of mature white cells due to excess of blasts
High number of circulating blasts (not always flagged by analysers)
Normal INR – normal for AML Abnormal INR (increased) – possible DIC due to acute promyelocytic leukaemia
AML - Blood Film
A single Auer rod is enough to diagnose AML* (or MDS)
But sometimes there are lots… “Faggot cells”
AML - Dx
If no Auer rods present, flow cytometry needed to diagnose
Typical expression pattern: MPO – most specific
APML - Rx
T(15;17) Acute Promyelocytic Leukaemia
Presents with DIC. Good prognosis
All-Trans Retinoic Acid (ATRA) –> Forces cells to differentiate, stops proliferation
AML- Rx
Similar to ALL (i.e. various combos of chemo/consider SC allo-transplant) but no CNS prophylaxis/maintenance therapy needed
Possibility of targeted agents in the future.
Poor prognosis, worse with increasing age - particularly in elderly who won’t tolerate stem cell transplant
Essential Thrombocytopenia (an MPN)
Proliferation of megakaryocytic/thrombocytes
Platelet Count >450 consistently
JAK2 mutation in 55%
No evidence of other cause
Treatment:
Aspirin to reduce stroke risk
Hydroxycarbamide to lower count
Causes of thrombocytosis
Acute infection Chronic inflammation Malignancy (5-10%) Essential thrombocythaemia Polycythaemia rubra vera
Polycythaemia Vera
Proliferation of Erythrocytes
Haematocrit >0.52 / 0.48 (M / F)
Often thrombocytosis as well
High risk of thrombotic events e.g. MI, Stroke, Budd-Chiari
JAK2 mutation in 95%
Treatment:
Aspirin to reduce stroke risk
Venesection (taking blood to lower haematocrit)
Hydroxycarbamide to lower count
Causes of polycythaemia
Primary:
Polycythaemia rubra vera
Secondary:
Altitude
Chronic hypoxia: e.g. severe COPD, cyanotic heart disease
Erythropoietin-secreting renal cancers
Myelofibrosis
Clonal proliferation of stem cells in the bone marrow –> cytokine release and fibrosis of the bone marrow –> reduced production of all cell lineages
Features: JAK2 mutation present in 50% Pancytopenia Splenomegaly (can be massive splenomegaly) “dry tap” on bone marrow aspiration “tear drop poikilocytes” on blood film
Treatment:
Stem cell transplant likely only cure
Ruloxitinib - JAK inhibitor
CML - Hx and Ex
CML classified as a MPN
Typically onset age 35-55 in EMQs
LUQ pain - Splenomegaly
Mostly asymptomatic if diagnosed in chronic phase
May have lethargy, fatigue, fever, night sweats
May present with symptoms of acute leukaemia if in accelerated / blast phase (~10%)
CML - Blood Tests
In chronic phase – unlikely significantly anaemic (but can be)
In chronic phase – unlikely thrombocytopenia. 50% have elevated platelet count
Leukocytosis
Neutrophilia
May be elevated basophil count
Monocyte count should be low (high monocyte count would indicated CMML)
May be precursor cells flagged on blood differential e.g. promyleocytes, myleocytes (left shift)
Leukocytosis
Acute bacterial infection - Usually a high neutrophil : lymphocyte ratio
Acute viral infection - Usually a low neutrophil : lymphocyte ratio
Fungal / parasitic infection - Usually a high eosinophil count
Monocytosis - Unusual but seen in: TB, endocarditis, inflammatory conditions
In severe acute infections, there may be some precursor cells (myelocytes, metamyelocytes)
Elevated basophil AND eosinophil counts are concerning for malignancy
CML - Blood Film
“Left shift” - Precursor cells present
Leukocytosis
Eosinophilia
Basophilia
Hypolobated megakaryocytes in bone marrow
CML - Diagnosis
Nearly all CML is associated with the Philadelphia chromosome
BCR-ABL1 fusion gene results from translocation of
t(9;22) and formation of the
Philadelphia chromosome
In exams they may use one of these three descriptions.
Detected by FISH currently.
