Download acute leukaemias

The Leukaemias
- FAR TOO MANY CELLS; FAR TOO MANY VOWELS -
toby m robins
Leukaemia may be
Acute
or
Chronic
and it may be
Lymphoblastic
or
Myeloid
Put that all together and you get
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Chronic lymphoblastic leukaemia
Chronic myeloid leukaemia
For each, we will briefly cover
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Definition
Epidemiology
Aetiology
Pathogenesis
Clinical features
Investigations
Management
Prognosis
but first
What exactly IS leukaemia?
Leukaemia is
Production
of abnormal WBCs
at an excessive rate
+/- reduced destruction
i.e. it is
malignancy of the
leukocytes
and it is clonal - ie all the
malignant cells have a recent
common ancestor
it is classified according to
1. the dominant cell type
and
2. the duration from onset to death
Chronic leukaemia
Untreated, exceeds one year (with
gradual onset of symptoms)
Acute leukaemia
Untreated, death ensues within a few
months
The acute ones
ALL (acute lymphoblastic leukaemia)
AML (acute myeloid leukaemia)
firstly
Acute Myeloid Leukaemia
Definition of AML
Neoplastic proliferation of myeloid
blast cells
Myeloid blast cells explained
Mature blood cells are
derived originally from
pluripotent stem cells
Meyloid blast cells explained
Pluripotent stem cells then
divide and differentiate
M either into myeloid stem L
cells or lymphoid stem cells
Myeloid blast cells explained
Lymphoid stem cells make
lymphocytes
Myeloid stem cells make all
the other blood cells
SEW
There’s more than ONE kind of AML
• Morphologically, there are seven and a half:
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M1 = undifferentiated blast cells
M2 = myeloblastic
M3 = promyelocytic
M4 = myelomonocytic
M4eo = myelomonocytic with dysplastic eosinophils
M5 = monocytic
M6 = erythroleukaemia
M7 = megakaryoblastic leukaemia
Epidemiology
70-year-old,
male, Eastern
European Jews
Aetiology
Aetiology
• All implicated have been
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Heredity
Radiation
Mutagenic drugs
Chemical & other occupational exposures
secondary to previous chronic leukaemia or
myelodysplasia
Clinical features
• Symptoms and signs are a result of 3 things:
– 1. Marrow failure
– 2. Leukaemic infiltration of tissues
– 3. Consitutional upset
Symptoms relating to marrow failure
• Infection
• Bleeding or easy bruising
• symptoms of anaemia - shortness of breath, etc
Symptoms relating to leukaemic infiltration
• Symptoms of a mass lesion (rarer, since
leukaemias by definition tend not to form masses)
– bone
– breast, uterus, ovary
– cranial or spinal dura
– GI tract
– lung or mediastinum
– prostate
Symptoms relating to constitutional upset
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Malaise
Fatigue
Weakness
Fever or sweats
Anorexia or weight loss
Non-specific cough
Signs relating to marrow failure
• Evidence of infection
• Signs of anaemia
• Purpura or signs of bruising/bleeding
– including retinal haemorrhages
Signs relating to leukaemic infiltration
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Hepatosplenomegaly
Lymphadenopathy
Sternal tenderness
Thymic mass
Gingival hypertrophy
Signs relating to constitutional upset
• Fever
Investigations
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FBC
Blood film
U&Es
LFTs
coagulation (especially for the DIC of M3)
Bone marrow examination
cell markers and molecular studies (eg of
marrow cells)
FBC
• Anaemia
• Neutropenia
• Thrombocytopenia
Blood film
• Blast cells that contain
– granules
– Auer rods
U&Es, LFTs
• The following are occasionally increased
– calcium
– urea
– LFTs
Bone marrow examination
• Blast cells constituting > 20% of the bone
marrow cells is diagnostic
Cell markers, molecular studies
• Flow cytometry (immunophenotyping) may
aid in morphological (ie appearance-based)
diagnosis and may add further prognostic
information
• Karyotyping, FISH, and PCR may confirm
diagnosis (eg acute promyelocytic leukamia;
=M3), + may add information not otherwise
obtainable
Management includes
• Intensive chemotherapy
• Bone marrow transplant
• Supportive care
Chemotherapy
• Divided into 3 phases
– 1. Remission induction
– 2. Remission consolidation
– 3. Remission maintenance
1. Chemotherapy for remission induction
• Complete remission (CR)
– full recovery of haematopoiesis, with
– blasts accounting for < 5% of bone marrow cells
• Involves mainly
– anthracyclines
– cytosine arabinoside
Why have they chosen these drugs?
• Anthracyclines
– because AML is like cycling a “myel” and a half
with anthrax
• Cytosine arabinoside
– think “sight-o-seen arabocide”
– because some (ignorant,misinformed,prejudiced)
people because think an Arab that comes within
a “myel” radius should be shot on sight
– sorry, Tarik, no offence :)
2. Chemotherapy for remission consolidation
• Involves similar chemotherapy to that of
remission induction
3. Chemotherapy for remission maintenance
• Treatment is continued for 2 years in ALL, but
for a much shorter time in AML
Bone marrow transplant (BMT)
• Suitable marrow may be
– allogeneic (from histocompatible siblings or
unrelated donors)
– syngeneic (from an identical twin)
– autologous
BMT continued
• Used increasingly as a form of consolidation
• Use depends on the pt’s age
– the elderly develop more complications
BMT continued
• Marrow is infused intravenously to “rescue”
the pt from otherwise supralethal
chemoradiotherapy
• Enables destruction of (almost) all leukaemic
cells and the entire immune system with eg
cyclophosphamide plus total body irradiation
Why use cyclophosphamide?
• ‘cause you midas well make phossels out of
all those nasty leukaemia cells in one foul
swoop (cycle)
A FOUL SWOOP
BMT continued
• To reduce graft vs host effect
– cyclosporin +/– methotrexate
• Complications
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graft vs host disease
infections (commonly CMV)
veno-occlusive disease
relapse of leukaemia
Supportive treatment
• Blood transfusion for anaemia
• Platelet transfusion for thrombocytopenic
bleeding
• Prompt antibiotic treatment, and prevention,
of infections
• Hygeine
Prognosis
• 70% achieve complete remission lasting (on
average) 12 months
• Long-term survival (~ 50%)
Secondly
Acute Lymphoblastic Leukaemia
Definition
Neoplastic proliferation of
lymphoblasts
Types of ALL
• Common
– phenotypically pre-B lymphocytes
– 75% of cases
• T-cell
• B-cell
• Null-cell
Aetiology
as for AML
Epidemiology (Common ALL)
• 4-year-olds
Epidemiology (T-cell ALL)
• Adolescent
males
Clinical features
as for AML
Investigations
• As for AML
• Blood film shows
– small blasts with
– a high nuclear-cytoplasmic ratio