Oncology 1 Flashcards
Epidemiology of childhood malignancy
1 in 500 by 15yrs
32% leukaemia 24% brain and spinal tumours 10% lymphomas 7% neuroblastomas 7% soft tissue sarcomas 6% Wilms tumour
At which age are children affected by leukaemia?
at all ages
At which age are children affected by neuroblastoma?
Almost always in the first 6 years of life
At which age are children affected by Wilms tumour?
Almost always in the first 6 years of life
At which age are children affected by Hodgkin lymphoma?
Adolescence and early life
Commonest leukaemia in children?
Acute lymphoblastic leukaemia (ALL) - 80%
Most of the remainder is acute myeloid/non-lymphocytic leukaemia
Presenting symptoms of acute lymphoblastic leukaemia
Peak at 2-5yrs.
Usually insidious onset over several weeks.
General - malaise, anorexia
Bone marrow infiltration : Bone pain Anaemia (pallor, lethargy) Neutropenia (infection) Thrombocytopenia (bruising, petechiae, nose bleeds)
Reticulo-endothelial infiltration: hepatosplenomegaly, Lymphadenopathy.
Other infiltration (usually when relapse):
CNS (headaches, vomiting, nerve palsies)
Testes: testicular enlargement
Diagnosis of acute lymphoblastic leukaemia
FBC - usually low Hb, thrombocytopenia and circulating leukaemic blast cells
Bone marrow examination is ESSENTIAL for diagnosis.
Also for immunology and cytology (=prognosis)
CXR for mediastinal mass (in T cell disease)
Common subtype is in 75%, T cell subtype only in 15%.
Treatment varies according to subtype
What is the general outline of treatment of standard-risk acute lymphoblastic leukaemia
Induction 5 weeks.
Week 5-8: consolidation.
Week 8-16: interim maintenance.
Week 16-23: delayed intensification.
Maintenance treatment continues from week 23 for further 2 (girls) or 3 (boys) years
Agents used for Induction
Vincristine
Steroid (dexamethasone)
L-asparaginase
Intrathecal methotrexate
Agents used in consolidation and CNS protection
IT methotrexate
Vincristine
Steroid
Thiopurine
Agents used in interim and maintenance
Monthly vincristine and pulse (5days) steroid (dexamethasone)
Daily 6-mercaptopurine.
Weekly oral methotrexate.
Prophylactic co-trimoxazole to prevent pneumocystis carinii pneumonia
IT methotrexate
Agents used in delayed intensification
Vincristine Dexamethasone Doxorubicin L-Asparaginase IT methotrexate Cyclophosphamide
Symptomatic management of acute lymphoblastic leukaemia
Blood transfusions for platelets and whole red cells (reduces bruising and bleeding and breathlessness)
What is tumour lysis syndrome. Presentation and management
May develop at initial induction:
metabolic derangements caused by systemic and rapid release of intracellular contents as chemo destroys leukaemic blast cells
Hyperuricaemia
Hyperphosphataemia
Hypocalcaemia
Hyperkalaemia
Monitor electrolyte and uric acid levels
IV fluid therapy
Allopurinol may be useful
How does remission induction work
Before starting, may require correction of anaemia (and risk of bleeding+infection) with blood transfusion.
Additional hydration and allopurinol are given to protect the kidney against the effects of rapid cell lysis.
Remission implies eradication of the leukaemic blasts and restoration of normal marrow function.
4 weeks of combination chemotherapy is given and current induction treatment schedules achieve remission rates of 95%
What is intensification of chemotherapy?
A block of intensive chemotherapy given to consolidate remission.
Improves cure rate, but there is higher toxicity
Why is intrathecal methotrexate used?
Cytotoxic drugs penetrate poorly into CNS (where leukaemic cells may survive).
It is used to prevent CNS relapse
What is the role of continuing therapy?
Chemotherapy of modest intensity continued over a relatively long period of time (up to 3 years from diagnosis)
With co-trimoxazole prophylaxis to prevent Pneumocystis cariniipneumonia
What treatment method is available for relapse?
High-dose chemotherapy with total body irradiation and bone marrow transplantation
What are high-risk factors for the prognosis of acute lymphoblastic leukaemia
Age <1yr or >10yrs
WCC >50x10^9/L
Cytogenetic/molecular genetic abnormalities in tumour cells: MLL rearrangement, hypodiploidy (<44 chromosomes)
Speed of response to initial chemo: persistence of leukaemic blasts in the bone marrow is bad
High minimal residual disease Assessment score
These factors are used to group ALL by risk
Which treatment adjustment is beneficial for the T-cell subtype of ALL
Addition of cyclophosphamide and intensive treatment with asparaginase
