Leukemia's and lymphomas

Question 1

Case 1:
- 48 yr old fire safety officer
- 4 days fatigue and breathlessness 
- 1 day easy bruising 
- O/E pale, bruising and purpura around ankles
What are the differential diagnoses?

Answer 1

differentials of purpura:

• thrombocytopenia (low platelets)
• vasculitis
• drugs e.g. steroids
• senile purpura i.e age related

Question 2

What are the differential diagnoses of thrombocytopenia and how do they occur?

Answer 2

Peripheral consumption of platelets = autoimmune destruction (ITP), splenic pooling, infection, active thrombosis

Reduced production = drug-induced marrow suppression, primary marrow failure (rare), marrow infiltration: primary or secondary

Question 3

Case 1 :
on investigation : low Hb, high WCC, low platelets
- abnormal cells = blast
- bone marrow aspirate = immature cells (blasts, red cell precursor, eosinophil precursor)
What is the diagnosis?

Answer 3

acute leukemia = blasts >20%

Question 4

What is the definition of acute leukemia?

Answer 4

rapid clonal hematopoietic stem cell disorder resulting in accumulation of immature precursors in the bone marrow

Question 5

What other urgent investigations need to be carried out in newly diagnosed acute leukaemia?

Answer 5

1) coagulation screen = risk of life threatening DIC
2) blood group and antibody screen
3) biochemistry = check renal and liver function, calcium, phosphate, magnesium, CRP, uric acid
4) microbiology = blood and urine cultures
5) radiology = consider CXR
6) also consider ECG and echocardiogram

Question 6

How does acute leukemia present?

Answer 6

1) marrow failure
- anaemia, SOB, fatigue, headaches, palpitations, leucopenia, infections, mouth ulcers, bleeding, bruising, thrombocytopenia purpura
2) hyper viscosity due to leucocytosis (due to very high production of blast cells being pumped out)
- headaches, SOB, visual blurring with venous engorgment and retinal hemorrhages, confusion
3) leukemia infiltrations
- swollen gums, skin lesion ‘chloromas’, hepatosplenomegaly

Question 7

What are the different types of acute leukemia?

Answer 7

1) acute myeloid leukemia
- may show no obvious differentiation (poorly differentiated)
- may show features of differentiation (neutrophils, monocytic, erythroid, megakaryocytic)

2) acute lymphoblastic leukemia
- b cell and t cell

3) mixed lineage (rare)

Question 8

How do you identify which type of acute leukemia ?

Answer 8

1) what do the blasts look like? (auer rod= AML)
2) what molecule are expressed on the cell surface and in the cytoplasm? 2 techniques:
- cytochemistry
- immunophenotyping

Question 9

How is immunophenotyping carried out?

Answer 9

using a flow cytometer

• a flow cytometer can determine what molecules a cell is expressing on its surface and in its cytoplasm
• it can therefore distinguish between myeloid and lymphoid blasts
• it uses fluorescent labelled antibodies

Question 10

What are typical myeloid markers?

Answer 10

CD13, 33, 117, MPO

Question 11

What are typical lymphoid markers?

Answer 11

CD10, 19, 79a, TdT

Question 12

What are the causes of acute leukemia?

Answer 12

previous chemo/toxins 
- alkylating agents (long latency)
- topoisomerase II inhibitors (short latency)
- benzene exposure
radiation exposure 
inherited predisposition
down syndrome and acute megakaryoblastic leukemia 
other hematological disorders 
- myelodysplasia 
- myeloproliferative condition

Question 13

What is the prognosis for patients with acute leukemia?

Answer 13

overall cure rate of AML in 18-60 yr olds is 40%
without treatment life expectancy is only weeks to months
identified prognostic factors
- age (outcome poorer as age increases)
- presenting WCC (worse with higher counts)
- response to chemo
- cytogenetics at presentation

Question 14

What cytogenetic combination tends to respond well to treatment, medium risk and poor risk ?

Answer 14

reciprocal translocation in DF’s cells involving chromosomes 8 and 21 = good risk

medium risk = usually normal cytogenetics

poor risk = often very complex cytogenetic changes

Question 15

What is the treatment for acute leukemia?

Answer 15

4 courses of intravenous chemotherapy (2 induction and 2 consolidation)

• one course is typically=> 5-10 days of chemotherapy and then 2-3 weeks of neutropenia often complicated by neutropenic sepsis => marrow recovery
• each course is 4-6 weeks

if poor risk cytogenetics consider bone marrow transplant as course 3 or 4
e.g daunorubicin and ara-c cytarabine

Question 16

What are the treatment side effects?

Answer 16

bone marrow suppression (anaemia, neutropenia, thrombocytopenia)
tumor lysis syndrome 
hair loss 
N+V
profound fatigue 
chemotherapy induced tissue damage: heart, lungs, brain, GI mucosa (mucositis)
increased risk of secondary malignancy 
death

Question 17

What supportive treatment is offered?

Answer 17

blood and platelet transfusions 
antibiotics and antifungals 
antiemetics 
nutrition 
psychological support 
this care has improved over the years

Question 18

What is a hickman line?

Answer 18

its a venous access which is a line going into the right side of the head and up the neck

= reduces infection rates
A Hickman line is a central venous catheter most often used for the administration of chemotherapy or other medications, as well as for the withdrawal of blood for analysis
insertion involves two incisions, one at the jugular vein or another nearby vein or groove, and one on the thoracic wall. At the former incision site, a tunnel is created from there through to the latter incision site, and the catheter is pushed through this tunnel until it “exits” the latter incision

Question 19

What impact does being elderly have on AML?

Answer 19

increasing age results in:
- increased incidence of AML
- reduced tolerance to chemo
- greater proportion of poor risk cytogenetics
- greater proportion of chemo-resistant disease
IV combo chemo is often not indicated in elderly
options are then low dose chemo, supportive care and palliative care
life expectancy is of the order of weeks to months (not years)
work on going to develop better tolerated treatments for the elderly

Question 20

CASE 2:

• 6 year old
• 1 week hx aches in lower limbs
• pale and non-specifically unwell
• HB 6.5, WCC 30 and plt 25
• abnormal cells on blood film

What is the potential diagnosis and the presentation?

Answer 20

Childhood ALL = most common childhood cancer, can affect adults and the prognosis is worsE

• marrow failure = anaemia, infections, purpura / bleeding
• bone pains = ‘off legs’, limping

Question 21

On immunophenotyping what markers are positive of acute lymphoblastic leukemia?

Answer 21

CD10, CD19, CD79a, TdT

Question 22

What cytogenetics are common in ALL?

Answer 22

hyperdiploid = >50 chromosomes

e.g. 56 chromosomes = confers good prognosis possibly due to increased sensitivity to chemotherapeutic agents

Question 23

What are poor prognostic factor in childhood ALL?

Answer 23

High WCC at presentation 
infant or adolescent 
specific cytogenetic abnormalities 
slow response to chemo 
high minimal residual disease levels at end of induction 

overall cure rate = 70-80%

Question 24

What is the treatment for childhood ALL?

Answer 24

ALL treatment is very long and complicated
- induction (steroids and vinca alkaloid)
- consolidation / intensification
- CNS prophylaxis (chemo or radio)
- maintenance
total length in girls is 2 years and boys is 3 years
survival rates = 90-95%

Question 25

CASE 3

• 40 yr old
• 8 week hx of neck lumps
• 6 week drenching night sweats
• O/E cervical lymphadenopathy

What is the differential diagnosis?

Answer 25

Lymphoma
- malignancy of the lymphatic system
lymphatic tissue is a key component of your immune system, WCC and antibodies circulate in the lymph fluid to lymph nodes or glands

Question 26

What are some common presentations of hodgkins lymphoma?

Answer 26

cervical lymphadenopathy
large anterior mediastinal mass
left hilar lymphadenopathy
left pleural effusion

Question 27

What is a histological diagnosis of hodgkins lymphoma?

Answer 27

reed sternberg cells - found on biopsy

Question 28

What are the different stages of lymphoma?

Answer 28

stage one - lumps in one area
stage two - lumps in 2 areas on the same side of diaphragm
stage three - more than 2 areas of lumps on either side of the diaphragm
stage four - disseminated disease affecting other organs

Question 29

What is the treatment for hodgkins lymphoma?

Answer 29

localized disease
- short course of chemo (2-4 cycles) - local radiotherapy, 90% cure 
advanced disease  (stage 3-4)
- 6 cycles chemo and 80% chance of survival 

drugs: doxorubicin, bleomycin, vinblastin, dacarbazine

Question 30

CASE 4

• 64 year old
• enlarged lymph nodes both axillae and sees her GP
• O/E modest cervical and axillary lymphadenopathy and splenomegaly
• referred for lymph node biopsy

What is the differential diagnosis?

Answer 30

non-hodgkins lymphoma - diffuse large b cell lymphoma, follicular lymphoma (most common)

Question 31

What markers are present on the abnormal B cells in non-hodgkin lymphoma?

Answer 31

positive for CD19, 22, 20, bcl-2
negative for CD5, 23
low Ki67 <30% = SLOW GROWING

Question 32

What are the treatment principles of low grade lymphoma?

Answer 32

not curable for vast majority of patients
indications for tx = fevers/sweats, large lymph nodes, organ compression and bone marrow failure
if no indications for tx then watch and wait
tx doesn’t increase survival time
tx usually consists of chemo
medium survival is 10-12 years

Question 33

What is diffuse large B cell NHL?

Answer 33

high grade non-hodgkin lymphoma - most common adult NHL
limited = stage 1 or non-bulky 2
advanced = bulky stage 2, stage 3 and 4
extra nodal common, BM involvement in 10%

Question 34

What is treatment of high grade B cell NHL?

Answer 34

intensive chemo with intent to cure 
R-CHOP is commonest therapy 
- 70-80% chance of survival 
- outpatient chemo, 6 cycles 
- rituximab - anti CD20 mAb

Question 35

How does chronic lymphatic leukemia present?

Answer 35

presents around >/= 60 years
raised WCC
lymphadenopathy
blood film: raised lymphocyte numbers and smear cells

Question 36

What is the treatment for CLL?

Answer 36

Treatment indications as for low grade lymphoma
fludarabine/cyclophosphamide/rituximab
median overall survival 10 years
not curative