Acute Leukaemia Flashcards
What is leukaemia?
A blood cancer resulting in accumulation of white cells (leucocytes)
What are the classifications of leukaemia?
- Leukaemia is chronic or acute
- Acute can be myeloid (acute myeloid leukaemia) or lymphoid (acute lymphoid leukaemia)
- Chronic leukaemia can be lymphoid or myeloid
What are the symptoms of chronic leukaemia dependent on?
The accumulation of cells
What are the symptoms of an acute leukaemia dependent on?
Symptoms are from marrow failure
What are the pre-leukaemic conditions?
- MDS- myelodysplastic syndrome
* MPDs- Myeloproliferative disorder
What is MDS characterised by?
- Failure of effective haemopoiesis (low blood count)
- Most common in elderly
- ‘dysplastic’ blood and marrow appearances
- Consequences of marrow failure - i.e. bleeding and infection
What is the transformation rate of MDS to AML?
approx rate of transmission is 25%
How can low risk vs low risk MDS be established?
- Proportion of blast cells in the marrow
* Number and severity of cytopenias and cytogenic profile (chromosomal abnormalities)
What is the management of MDS?
- No cure other than a stem cell transplant (<65-70 years)
- supportive care
- Consider drug therapy e.g. azacitidine
What mutation is prevalent in MPDs?
JAK2 mutation
What are MPDs characterised by?
- Too many platelets - essential thrombocythaemia
- Too many red cells - polycythaemia vera
- Too much fibrous tissue - myelofibrosis
Explain myelofibrosis
- Large spleen
- Systemic symptoms
- Blood counts high or low
- Incurable other than with stem cell transplant
- Targeted therapy = JAK2 inhibitors
I think it is a chronic leukaemia
What are acute leukaemias?
- Clonal disorders leading to blastic proliferation in the bone marrow
- Rapid in onset - die in days or weeks if not treated
- Serious compromise of normal marrow elements (so normal counts fall)
- Death within days or weeks if untreated
What are the acute myeloid leukaemias?
- Erythroleukaemia
- Myeloid leukaemia
- Monocytic leukaemia
- Megakaryocytic leukaemia
What are the acute lymphoid leukaemias?
- T lymphoblastic leukaemia
* B lymphoblastic leukaemia
What is the difference in age presentation between acute myeloid and acute lymphoid leukaemias?
- Acute myeloid leukaemias increase in prevalence with age
* Acute lymphoid leukaemias peak in early childhood
What is the aetiology of a leukaemia?
- Largely unknown
- Chemicals
- Chemotherapy
- Radiotherapy
- Genetic - Down’s syndrome or Fanconi Syndrome
- Antecedent blood disorders (MDS, MPD)
- Infection: lack of exposure in infancy and aberrant response in later childhood important in child hood ALL
Explain diagnosis of acute myeloid leukaemia from history
- Rapid onset of symptoms
- Short history of marrow failure
- Anaemia - fatigue
- Leukopenia - fever and infection
- Thrombocytopenia - bleeding/bruise
What are the findings on examination in someone with Acute myeloid Leukaemia?
- Lethargy
- Infection
- Bleeding and bruising
- Bone pain
- Gum swelling
- Lymphadenopathy, skin rash
Describe peripheral blood in acute myeloid leukaemia
- Anaemia
- Neutropenia
- Thrombocytopenia
- Blasts
What do blasts look like?
- High nuclear cytoplasmic ratio
* Not a lot of cytoplasm
Explain the diagnosis of acute myeloid leukaemia from bone marrow
•Blast cells >20%
Explain which diagnosis it is important to look for in the bone marrow in an acute leukaemia
- M3 AML - acute promyelocytic leukaemia
- Key sign is bundle of cells with rods in the cytoplasm
- Can have significant bleeding so need a targeted therapy
- t(15:17)
When is there a poor prognosis of AML?
- Secondary AML
- Relapsed AML
- MDS transformed to AML
- Biphenotypic disease
- Elderly patients
- Refractory to induction
What is the management of AML?
- Intensive chemotherapy ± stem cell treatment (patient less than 60-65)
- Low dose chemotherapy (patients older than 60-65)
- Supportive care only (older patients, major co-morbidities, median survival 3-6 months) i.e. blood transfusion, manage infection with antibodies
- Most young patients are entered into clinical trials
What are the impacts of chemotherapy
- High morbidity- bleeding and infection
- Hair loss
- Sterility
- Muscositis
- Prolonged inpatient stays
- Psychological element
Describe the clinical presentation of acute lymphoid leukaemia
- Limping child
- Purpuric rash (low platelets)
- Unexplained, sometimes severe, bone pains not uncommon
What are the 3 recognised subtypes of ALL?
- L1
- L2
- L3
What are the standard cytogenetics of ALL?
- t(9:22) - Philadelphia chromosome
* t(4:11)
What is the management of ALL?
- Complex, specialist units
- Chemotherapy: prednisolone, cyclophosphamide, vincristine, etoposide based
- CNS directed treatment is essential
- Initial aggressive therapy then oral maintenance for 1-2 years
What is the management of relapsed ALL?
- Blinatumomab - targets CD19 on B cells
* CAR T cells - if not responding to blinatumomab (own T cells used)
What is the supportive management of acute leukaemia?
- Blood transfusion in symptomatic patients
- Fresh frozen plasma for coagulopathy/DIC
- Platelet transfusion
- Antibiotics
- Growth factors
- Granulocytes
What are the complications of acute leukaemia?
- Purpura skin rash
- Retinal haemorrhage
- Viral infection
- Bacterial and fungal infection
Which patients with acute leukaemia are considered for a transplant?
- Relapsed patients
- Refractory patients
- Poor risk disease in first CR (complete remission)
- Age less than 60
- Good performance
