CBL: Malignancies Flashcards
Li Fraumeni Syndrome - what is this? - what mutation does it involve?
Li-Fraumeni syndrome is a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults
Mutation: TP53
Li Fraumeni Syndrome - when to consider (ages, FHx)
Consider if: - sarcoma <45 years old and 1st degree relative with any cancer <45 years old or sarcoma at any time
Li Fraumeni Syndrome 1. What cancers does it predispose to? 2. What management is there for a person with that syndrome?
- Rhabdomyosarcoma ( cancer of soft tissue, connective tissue or bone)
- ALL ( acute lymphoblastic leukemia )
- breast Ca, brain tumours, adenocorticoid tumours, colorectal cancer
. Genetic counselling and regular screening for cancers
Leukaemia presentation (symptoms)
- General malaise - Intermittent fevers Symptoms secondary to cytopenias: -Bleeding(mucosal), bruising, petechial rash - Anaemia, SOB, fainting, fatigue - Infection ; bacterial, fungal, viral -Pain (Bone, Joints, Abdomen, Chest, Head) - Lymphadenopathy & hepatosplenomegaly - Skin nodules
Leukaemia: What happens in the bone marrow and what does it do to the cells produced there?
Disruption in the regulation and proliferation of lymphoid precursor cells in the bone marrow leads to excessive production of immature blast cells and drop in the other three cell lines
What cancer is the most common among children?
Acute Lymphoblastic Leukaemia (ALL)
4 most common cancers in children are…
- Leukaemia (Acute Lymphoblastic Leukaemia)
- Brain and spinal tumours
(e. g. medulloblastoma, neuroblastoma, glioma) - Nephroblastoma (Wilm’s tumour)
- Lymphoma
Which are two sites difficult to treat in leukaemia?
Why?
Testicles -> due to blood-testicular barrier
CNS -> due to blood-brain barrier
- What’s tumour lysis syndrome? What happens?
- Tumour lysis syndrome - metabolic abnormalities resulting from a large number of tumour cells being killed off (lysed) -> cancer cells will release their content into blood stream
Happens in cancers that respond well to chemotherapy (e.g. leukaemia and lymphomas)
large amounts of: phosphorus, potassium and calcium leading to potential kidney damage
Complications of tumour lysis syndrome
nausea and vomiting, but more seriously acute uric acid nephropathy, acute kidney failure, seizures, cardiac arrhythmias, and death
Prevention of tumour lysis syndrome
- supportive
- drugs (two)
- prophylactic oral or IV allopurinol (a xanthine oxidase inhibitor à uric acid (following cell lysis) formation prevented
- IV hydration to maintain high urine output (> 2.5 L/day)
- Rasburicase is an alternative to allopurinol (reserved for people who are high-risk in developing TLS) àIt is a synthetic urate oxidase enzyme àacts by degrading uric acid
Leukaemia management:
Immediate/supportive, if:
- if WBCs are very high
- mass in mediastinum
- infection
Leukaemia management:
Immediate/supportive:
- Stabilise unwell child
- Hyperhydration -> if WBCs is very high -> in order to prevent hyperviscosity
- If a mass present in mediastinum and airways are at risk to be compromised -> steroids
- If infection/ sepsis -> antibiotics
FBC results in ALL
- Low haemoglobin
- Thrombocytopenia
- Evidence of leukemic blast cells
What is ALL
one marrow produces specialised cells called stem cells, which have the ability to develop into three important types of blood cells:
red blood cells – which carry oxygen around the body
white blood cells – which help fight infection
platelets – which help stop bleeding
Normally, bone marrow doesn’t release stem cells into the blood until they are fully developed blood cells.
But in acute lymphoblastic leukaemia, large numbers of white blood cells are released before they are ready. These are known as blast cells.
As the number of blast cells increases, the number of red blood cells and platelet cells decreases
Drugs used in chemotherapy for Leukaemia
Leukaemia management:
Drugs used in chemotherapy:
- 3 or 4 drug depending on risk group
(Dexamethasone, Vincristine, Asparaginase +/- Doxorubicin)
IX for suspected Leukaemia
- FBC - anaemia, leukocytosis, neutropenia, thrombocytopenia
- Peripheral blood smear - leukemic lymphoblasts
Bone marrow biopsy - Hypercellularlity and infiltrations by lymphoblasts
- U and E and LFTs - may be abnormal
- Coagulation profile - distorted
- Serum electrolytes - high calcium, K, uric and lactic acid
Leukaemia management:
- Simply outline what’s the main mode of Rx and supportive care
- is radiotherapy used?
- chemotherapy -> given IV, orally, and intra-thecally (into the CSF
- blood products(red cells, platelets)
- prophylactic anti-fungal therapy throughout treatment
*There is no role for radiotherapy in the management of ALL
2 types of T cell malignancies
- Acute lymphoblastic leukaemia
- Non hodgkin’s lymphoma
Signs and symptoms of bone marrow infiltration
- Anaemia - Pallor & Lethargy
- Neutropenia -Infection
- Thrombocytopenia - Bruising, petichae, nose bleeds
- Bone pain
Do we use cranial radiation (prophylactic) in the management of Leukaemia?
IT Methotrexate replaced prophylactic cranial RT
What medications are used in the ‘maintenance’ therapy for leukaemia?
MTX & Mercaptopurine +/- Steroids & Vincristine
How long is ‘maintenance’ therapy for Leukaemia?
girls -> 2 year
boys -> 3 years
Red flags for symtpoms (suspicion of leukaemia)
- Non-tender, firm or hard LN
- LN > 2cm
- Progressively enlarging
- Features of ill-health, fever or weight loss
- Pallor
- Unexplained bruising
- Hepatosplenomegaly
- Axillary nodes involved
–(in absence of local infection or dermatitis)
•Supraclavicular nodes involved
Risk factors for the development of Lymphoma
- being immunocompromised (transplant recipients)
- Epstein-Barr virus (EBV)
- past treatment for other cancers
Lymphoma
- what to look for in Hx
- what are ‘B symptoms’?
- non-specific symptoms
- a visible or palpable mass
- “B symptoms” such as:
- Weight loss
- Night sweats
- Fevers
- Non-specific symptoms of malignancy: such as lethargy and anorexia
Why there may be an airway compromise in Lymphoma?
- Mediastinal lymphadenopathy
- superior vena cava obstrution
Presentation: cough, wheeze, difficulty in breathing
Staging of Lymphoma
Lymphoma is staged according to how many groups of lymph nodes or organs are involved:
- Stage 1: Disease is present in a single group of lymph nodes or a single organ
- Stage 2: Disease is present in 2 or more groups of lymph nodes or organs on the same side of the diaphragm
- Stage 3: Disease is present in lymph nodes or organs on both sides of the diaphragm
- Stage 4: There is diffuse involvement of lymph nodes and organs such as the liver and bones
Treatment options for gliomas
Surgery (if possible), radiotherapy and chemotherapy (may be also used)
What’s prognosis and treatment options for Diffuse Intrinsic Pontine Glioma?
•Diffuse Intrinsic Pontine Glioma (DIPG)
–Cannot resect
–Radiotherapy may slow progression
–Fatal in >95% (9 months)
Treatment options and prognosis for medulloblastoma
•Multi-modal therapy
–Surgical resection
–Radiotherapy (age dependent)
–Chemotherapy
•Affected by Blood Brain Barrier
•Prognosis
–Varies significantly depending on age, mets, histology/ genetic subgroup
