Leukaemia Flashcards
1
Q
Leukaemia
A
- The generalised term for WBC cancers
- Most common childhood cancer but affects 3 times as many adults
2
Q
The leukaemias you need to remember
A
1) Acute Myeloid Leukaemia (AML)
2) Acute Lymphoblastic Leukaemia (ALL)
3) Chronic Myeloid Leukaemia (CML)
4) Chronic Lymphoid Leukaemia (CLL)
3
Q
Lymphoma
A
- Cancer of lymphoid tissues
- Results in swollen lymphoid tissue
- 40% are Hodgkin lymphoma = Just lymphocytes
4
Q
Incidence vs Prevalence
A
- Incidence = Rate of new cases in a given time period, or the number/% of the population at risk of developing the condition
- Prevalence = Number of people with the condition
5
Q
Causes of leukaemia
A
- Usually idiopathic
- Previous chemotherapy with alkylating agents, increases risk
- Radiation exposure
- Benzene/Formaldehyde exposure
- Genetic conditions ie Down’s Syndrome
- Myelodysplasia (Pre-leukaemia)
6
Q
Myeloproliferative neoplasms
A
- The excess production of myeloid cells, with 4 main types:
+ CML = Excessive granulocytes
+ Excessive thrombocytosis
+ Polycythaemia vera = Excess RBC
+ Primary myelofibrosis = Replacement of bone marrow with collagenous connective tissue
7
Q
Acute leukaemia characteristics
A
Little/no maturation in defected cells, >20% blast cells in blood/bone marrow at clinical presentations
8
Q
Chronic leukaemia characteristics
A
Many maturing/mature WBCs
9
Q
AML
A
- Uncontrolled proliferation of myeloid stem cell resulting in large numbers in immature WBCs, particularly granulocytes + monocytes
- Affects all ages, increasing in risk with age
- In blood we can see elevated blast cells (>2-%) + promyelocytes
10
Q
AML signs + symptoms
A
- Acute, often critically ill
- Malaise, fever + sweats
- Anaemia symptoms
- Neutropenia = More infections, bacterial in particular
- Thrombocytopenia = Bleeding more if injured
- Overproduction of myeloid blast cells results in overcrowding in bone marrow
11
Q
ALL
A
- Uncontrolled proliferation of lymphoid stem cell resulting in large numbers of abnormal lymphoblasts in the bone marrow
- Cause of 80% of childhood leukaemias
- 85% B cell incidence, remaining 15% are T cell incidences
- In blood we see more lymphoblasts (>20%) = prolymphocytes
12
Q
ALL signs + symptoms
A
- Abruptly starts
- Bone + joint pain
- Symptoms of bone marrow failure
- Generalised lymphadenopathy - Enlarged lymph nodes due to lymphocytes to lymph nodes to filter lymph
- Hepatosplenomegaly
- Testicular + CNS manifestations as “sanctuary site”
13
Q
CML
A
- Uncontrolled proliferation of myeloid stem cell resulting in large numbers of circulating leukocytes, particularly neutrophils
- Peak onset at 65-85 years
- More common in males than females
- Caused by ABL gene translocation from chr9 to fuse with breakpoint cluster region gene on chr22
- In blood we see more differentiated cells of neutrophils + myelocytes
- Consistently associated with presence of a Philadelphia chromosome
- Can be either MPO positive or MPO negative
14
Q
CML signs + symptoms
A
- Fatigue
- Weight loss
- Sweaty
- Splenomegaly + sensation of fullness
- Hepatomegaly
- Gout, bruising
- Leukostasis - Clumping of leukocytes is often seen
15
Q
CLL
A
- Uncontrolled proliferation of B lymphocytes
- Disease of the elderly <50+ years, peak 90+
- More common in males than females
- Almost all cases are B cells
- Considerable overlap with lymphomas
16
Q
CLL signs + symptoms
A
- Often asymptomatic, many patients survive long periods with minimal symptoms, with elderly patients more likely to die from other causes
- Symmetrical + painless enlargement of lymph nodes is most common clinical sign
- May have symptoms of anaemia
- Immunosuppression resulting in bacterial infections in early stages + viral/fungal infections later
- Weight loss
17
Q
Hodgkin’s Lymphoma
A
- Malignant B cells that accumulate in lymph nodes, they however only a minority of the tumour, but majority comprising inflammatory cells
- More common in men than females
- Peaks at 2 ages = 15-35 years, + <50 years old
18
Q
Hodgkin’s lymphoma sign + symptoms
A
- Asymmetrical + painless lymphadenopathy, usually in cervical region, disease spreads via lymphatic chain
- Splenomegaly
- Fever, night sweats, weight loss, itching + fatigue in the minority
- Leukopeptidase + bradykinin appear to be the pruritogenic mediators released as an autoimmune response is mounted against malignant lymphoid cells
19
Q
Non-Hodgkin’s Lymphoma
A
- Large group of lymphoid tumours with more variable presentation + history than Hodgkin’s lymphoma
- 11th most common in UK
- Highest incidence of all haematological cancers
- Increased risk with age, typically >45 years, peak 85-89 year
20
Q
Non- Hodgkin’s Lymphoma signs + symptoms
A
- Asymmetrical painless lymphadenopathy
- Less fever + night sweats + weight loss than Hodgkin’s
- Sore throat
- Symptoms of anaemia, thrombocytopenia or neutropenia with infections
- Acute abdominal symptoms due to spleen/liver enlargement + involvement of GI tract
- 5-10% of patients have diseased oropharyngeal lymphoid structures, causing sore throat or obstructed breathing
- Recurring chromosomes abnormalities often seen in Non-hodgkin’s
21
Q
AML blood tests
A
- Includes FBC, with an increase in blast cells in blood film
- We can’t really predict WBC count as it could be high, low or normal
- NN anaemia often seen, with erythrocytes unaffected
- The blasts will usually be MPO positive, allowing us to differentiate + indicate that it is myeloid related
22
Q
AML prognosis
A
- Chemotherapy leads to complete remission, but older patients tolerate chemo less well, with cure being rarely achievable
- Chemo targets dividing cells + will affect the most frequently dividing first
23
Q
ALL blood tests
A
- Similar to AML, but instead we see overcrowding of lymphocytes
- NN anaemia, neutropenia + thrombocytopenia
- The WBCs are MPO negative
- > 20% are lymphoblasts as a result of overcrowding in bone marrow
24
Q
ALL prognosis
A
- Majority of children are curable with standard chemo + CNS prophylaxis
- Cure in adults is less frequent, stem cell transplant may be considered
- Few drugs can reach CSF, so specific drug treatment is required to prevent or treat CNS disease
25
CML blood tests
- Overproduction of myeloid cells resulting in over-crowding in bone marrow causing, primarily leukocytosis + neutrocytosis
- Increase in complete spectrum of myeloid cells seen in peripheral blood, levels of neutrophils + myelocytes exceed those of blast cells + promyelocytes
- Increase in basophils
- NN anaemia
- Can have thrombocytosis, thrombocytopenia or normal count of platelets
- Neutrophil alkaline phosphatase score is invariably low, it is increased in the myeloproliferative diseases + infections
- Increased LDH + urate
- FISH used for Philadelphia chromosome
26
CML prognosis
- 50% 5 yr survival
- Indolent chronic phase, followed by period of acceleration, then generally fatal acute leukaemic phase
- Stem cell transplant is the only known cure but is associated with significant mortality
- Tyrosine kinase inhibitor Imatinib is the preferred initial therapy
27
CLL blood tests
- Overproduction of lymphocytes results in overcrowding in bone marrow causing lymphocytosis + 70-99% WBCs appear as small round lymphocytes
- Smear cells where fragile lymphocytes burst during processing
- Immunotyping of lymphocytes shows them to almost always be B cells, often surface CD19 positive
- NN anaemia at later stages
- Thrombocytopenia
28
CLL prognosis
- Initially indolent, chemo is often not needed in early CLL
- 70% 5 yr survival
- Patients often die of other causes
- Becomes more aggressive in advanced stages
29
Hodgkin's lymphoma blood tests
- NN anaemia is most common, bone marrow involvement is unusual in early disease
- Eosinophilia + neutrophilia
- Normal/increased platelet count in early disease
- In advanced disease - Lymphopenia, thrombocytopenia
- Requires lymph node biopsy for diagnosis
30
Hodgkin's lymphoma prognosis
- Good prognosis = 80% 10 yr survival rate
- Largely determined by disease state
- Chemotherapy leads to high cure rates even in advanced disease
- Significant risk of secondary malignancy as a late side effect of treatment
31
Non-Hodgkin's lymphoma blood tests
- NN anaemia but maybe autoimmune haemolytic anaemia
- In advanced disease with marrow involvement get neutropenia, thrombocytopenia
- Cytogenetics used
32
Non-Hodgkin's lymphoma prognosis
- 63% have 10 yr survivial rate
- Indolent Non-Hodgkin's lymphoma responds well to chemo but cure is elusive
- Aggressive Non-Hodgkin's lymphoma may be cured with chemo combined with rituximab
- Stem cell transplants are increasingly used
33
Multiple myeloma
- Cancer of clonal plasma cells in the bone marrow
- Ab-secreting B cells that secrete a single homogenous Ig called paraprotein
- Rare before 40 years, peak 85-89 years
- More common in men than women
- More common in African Americans than Caucasians
34
Multiple myeloma signs + symptoms
- Bone pain, fracturs most common presenting symptom
- Symptoms of anaemia + thrombocytopenia, leukopenia
- Renal failure
- Hypercalcaemia from bone destruction, resulting in kidney damage = renal failure
- Amyloidosis
35
Multiple myeloma blood tests
- Bone marrow overcrowded with plasma cells, which can then cause:
+ Increased plasma cells in bone marrow
+ Presence of paraprotein in serum +/or in urine
+ NN anaemia or normochromic + macrocytic anaemia
+ Pancytopenia
+ Elevated Ca2+ levels
36
Multiple myeloma prognosis
- Cure is elusive, chemotherapy followed by stem cell transplant
- 33% chance of 10 year survival
- Good palliative care is crucial
