Leukemia's and lymphomas Flashcards
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?
differentials of purpura:
- thrombocytopenia (low platelets)
- vasculitis
- drugs e.g. steroids
- senile purpura i.e age related
What are the differential diagnoses of thrombocytopenia and how do they occur?
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
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?
acute leukemia = blasts >20%
What is the definition of acute leukemia?
rapid clonal hematopoietic stem cell disorder resulting in accumulation of immature precursors in the bone marrow
What other urgent investigations need to be carried out in newly diagnosed acute leukaemia?
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
How does acute leukemia present?
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
What are the different types of acute leukemia?
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)
How do you identify which type of acute leukemia ?
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
How is immunophenotyping carried out?
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
What are typical myeloid markers?
CD13, 33, 117, MPO
What are typical lymphoid markers?
CD10, 19, 79a, TdT
What are the causes of acute leukemia?
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
What is the prognosis for patients with acute leukemia?
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
What cytogenetic combination tends to respond well to treatment, medium risk and poor risk ?
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
What is the treatment for acute leukemia?
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
What are the treatment side effects?
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
What supportive treatment is offered?
blood and platelet transfusions antibiotics and antifungals antiemetics nutrition psychological support this care has improved over the years
What is a hickman line?
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
What impact does being elderly have on AML?
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
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?
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
On immunophenotyping what markers are positive of acute lymphoblastic leukemia?
CD10, CD19, CD79a, TdT
What cytogenetics are common in ALL?
hyperdiploid = >50 chromosomes
e.g. 56 chromosomes = confers good prognosis possibly due to increased sensitivity to chemotherapeutic agents
What are poor prognostic factor in childhood ALL?
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%
What is the treatment for childhood ALL?
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%
