Acute Lymphoblastic Leukaemia Flashcards
What is it a malignancy of?
Lymphoid cells affecting B or T lymphocyte cell lineages, arresting maturation and promoting uncontrolled proliferation of immature blast cells, with marrow failure and tissue infiltration
When does it mainly occur?
Mainly a disease of childhood - peak incidence = 2 to 5
Male more than female
What causes it?
No identifiable cause in most cases
Ionising radiation e.g x ray during pregnancy
Past chemotherapy
Genetic conditions: Down’s syndrome, Fanconi anaemia, neurofibromatosis type 1
Smoking
Weakened immune system e.g HIV
The monoclonal proliferation looses the ability to differentiate, while retaining ability to…
Replicate
What do the blasts do?
Replace BM cells - crowd out normal haematopoiesis
Enter peripheral blood
Metastasise throughout body - esp liver, spleen, LNs, testes, skin, mediastinum
Are the onset of signs and symptoms slow or abrupt?
Abrupt
What signs and symptoms are associated with ALL?
Marrow failure:
Anaemia- fatigue, pallor, SOB
Low WCC - Frequent infections
Thrombocytopenia- bleeding gums, epistaxis, petichiae, purpura, blood in urine/stool
Infiltration:
Hepatosplenomegaly
Lymphadenopathy (painless) - superficial or mediastinum
Orchidomegaly
Fever, weight loss, night sweats
Bone pain
Airway obstruction - mediastinal or thymic infiltration
If CNS involved - meningism, CN involvement, seizures, nausea
What common infections can occur?
Especially chest, mouth, perianal, skin
Sepsis
Zoster, CMV, measles, candidiasis, pneumocystis pneumonia
What does FBC typically show?
Raised WCC usually
Anaemia
Thrombocytopenia
What does peripheral blood film show?
Large blast cells
What does bone marrow and aspiration show?
More than 20% blasts
Why is flow cytometry done?
Confirm lineage - myeloid or lymphoid
Why should a CXR be done?
Look for mediastinal widening
Why should a LP be performed?
Check for CNS involvement
What genetic test can be done?
FISH - examine chromosome number and translocations
PCR sequencing of DNA mutations
In chemotherapy regime, the choice of agent depends on…
Cytogenetics
Describe the chemotherapy regime
Induction e.g vincristine, prednisolone
Consolidation - high-medium-dose therapy in blocks over several weeks
CNS prophylaxis e.g intrathecal methotrexate +/- irradiation
Maintenance- prolonged chemotherapy for 2 years
What supportive management is often required?
Blood/ platelet transfusion IV fluids Allopurinol / rasbucase to prevent TLS Antiemetics e.g ondansetron Monitor for infections - check oropharynx, skin, catheter sites regularly
Describe the blast appearance
No granules
Increased nucleus to cytoplasmic ratio
Nucleolus less prominent than in myeloid blasts
Describe T cell ALL
Typically occurs in young adults
Mass in mediastinum - pleural effusion, respiratory distress, SVCO
CD3+ and CD7+
What types of ALL are there?
Pre B cell ALL
B cell ALL
T cell ALL
Describe pre B cell ALL
Common in children, especially Down syndrome
CD10+, CD19+, CD20+
T(9;22) = bad prognosis
T(12;21) = good
What are some unfavourable prognosticators?
Age > 60
WBCs > 100,000
Mature B or early T types
Philadelphia chromosome t(9:22)
Will pre B cell with t(12:21) have a good response to chemotherapy?
Yes in 80% there is a cure
Why might there be macrocytic anaemia?
Low folate levels due to rapid cell turnover
ALL is the most common type of leukaemia that affects children. True or false?
True
What is the role of remission induction?
Reduce blast cells into undetectable levels
Restore normal marrow function
Why is consolidation necessary?
Relapse occurs in almost 100% of cases
What should happen before chemotherapy?
Stabilise patient
If they have thrombocytopenia give platelets
If fever and granulocytopenia - blood culture and antibiotics
If leukostasis - leukopharesis
Prevent TLS - hydrate and give allopurinol
In terms of management, what can be done as last resort?
BM transplant
If patient has Philadelphia chromosome, what treatment can they have?
A tyrosine kinase inhibitor - imatinib
What complications can occur due to treatment?
Chemotherapy - TLS leading to AKI
Direct testicular radiation - permanently low testosterone, consider sperm banking
Intrathecal radiation and RT - neurocognitive dysfunction
