Haematology, Oncology & Palliative Care Flashcards
ALL - define, S&S, ix & management
Definition: Malignancy & overproduction of immature lymphoblast cells
Aetiology & Risk factors:
Childhood cancer, peak age 4yrs - can occur in elderly >75
• Environmental RFs: radiation, viruses
• Genetics RFs: Down’s, NF-1 etc
Presentation/Clinical Features: • Tiredness • Recurrent infections • Bleeding/bruising • Weight loss
- Abdo pain
- Lymphadenopathy
- Splenomegaly
Investigations & Diagnosis:
• Bloods: FBC (normocytic anaemia, low plts, variable WCC), high LDH, high uric acid, clotting screen
• Blood film: evident lymphoblast cells
• Bone marrow aspirate/biopsy - hypercellular >30% lymphoblasts
Management:
• Supportive measures - recurrent infection, bleeding
• Induction and consolidation therapy
• HSCT or 2 years of maintenance therapy
○ CNS prophylaxis throughout as can progress to/relapse in brain and spinal cord so intrathecal chemotherapy and possibly radiotherapy to brain and spinal cord
Prognosis:
• 90% 5 yr survival children – excellent, most cured
• 40% 5 yr survival adults
AML - define, S&S, ix & management
Definition: Malignancy & overproduction of immature myeloid WBCs
Aetiology & Risk factors:
Occurs in >65s mainly
• Environmental RFs: radiation, prev chemo
• Genetics RFs: congenital syndromes e.g. Down’s
• MDS
Presentation/Clinical Features:
• Tiredness
• Infections
• Bleeding/bruising
* Pallor * Anaemia * Organomegaly
Investigations & Diagnosis:
• Bloods: FBC (low Hb, low/normal plts, variable WCC), high LDH, high uric acid, clotting screen
• Blood film: Auer Rods
• Bone marrow aspirate/biopsy - hypercellular >30% blast cells
Management:
• Treatment inc 3-4 cycles of combination chemotherapy, HSCT for some patients
Prognosis:
• >50% long term survival in fit patients, 10-20% long term survival in less fit patients
CLL - define, S&S, ix & management
Definition: Overproduction & accumulation of functionally incompetent lymphocytes (monoclonal in origin), mostly B lymphocytes
Aetiology & Risk factors: Sequential genetic mutations & changes in bone marrow • TP53 • BCR-2 proto-oncogene • 11q& 13q14 mutations • NOTCH-1
Presentation/Clinical Features:
• Asymptomatic & incidental finding in 40%
• Lethargy/malaise
• Night sweats
• Bone marrow failure - recurrent infections, anaemia
• Organomegaly
• Lymphadenopathy - often symmetrical
Investigations & Diagnosis:
• Bloods - FBC (v high WCC, low Hb, low plts), high uric acid & LDH
• Blood film - Smudge cells
• Bone marrow biopsy or LN
Management:
• Chemotherapy/targeted therapies.
• 70% will require treatment for their disease
CML - define, S&S, ix & management
Definition: Malignancy & overproduction of myeloid granulocytes in blood & bone marrow
Aetiology & Risk factors:
Associated with Philadelphia chromosome (t 9:22) - Bcr & Abl fusion protein
• Intrinsically activated Tyrosine kinase - promotes cellular replication
Presentation/Clinical Features: Asymptomatic in 20-50% of cases & found incidentally • Splenomegaly • Bone pain • Night swears
* Weight loss * Abdo pain
Investigations & Diagnosis:
• Bloods - FBC (v high WCC, low Hb, high neut/baso/eosino), high uric acid & LDH
• Blood film
• Bone marrow biopsy
Management:
• Supportive/conservative treatment
• Targeted therapy e.g. Imatinib (TKI)
• Stem Cell Transplants
Prognosis:
Some patients can present in ‘blast crisis’ which is a transformation to Acute leukaemia
Common ages for presentations of different leukaemias
ALL CeLL Mates have CoMmon AMbitions
Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)
Over 55 – chronic lymphocytic leukaemia (CeLLmates)
Over 65 – chronic myeloid leukaemia (CoMmon)
Over 75 – acute myeloid leukaemia (AMbitions)
Myelodysplastic Syndromes - define, S&S, ix & management
Definition: A series of haematological conditions characterised by chronic cytopenia - anaemia, neutropenia, thrombocytopenia - & abnormal cellular maturation
Mean age of diagnosis is 65-75yrs, M>F
Twice as common as AML
Aetiology & Risk factors:
May be primary or arise in patients who have received chemo or radiotherapy for previous malignancies
Presentation/Clinical Features:
May be asymptomatic & diagnosed on routine FBC (50%)
Symptoms of bone marrow failure
• Anaemia - tiredness, dizziness, chest pain
• Neutropenia - recurrent infections
• Thrombocytopenia - bruising, bleeding
Investigations & Diagnosis:
• Bloods - FBC (pancytopenia)
• Blood film - characteristic appearance
• Bone marrow biopsy or aspirate
Management:
• Supportive - antibiotics, tranfusions etc
• Chemotherapy
• Bone marrow transplant
Prognosis:
After 2-3yrs 1/3 will transform into AML
Myeloma - define, S&S, ix & management
Definition: Accumulation of malignant plasma cells in bone marrow, increased monoclonal antibodies
Median age at diagnosis is 66
Aetiology & Risk factors:
• Genetic alterations & mutations among common genes e.g. cytokines, IL-6
• RFs may include: agricultural work or occupational chemical exposure
Presentation/Clinical Features:
CRAB
• HyperCa - bone pain, abdominal pain, N&V, confusion, muscle spasms
• Renal - renal failure, abnormal bloods
• Anaemia - tiredness, dizziness
• Back/bone pain - pathological fractures
Investigations & Diagnosis:
• Bloods - FBC, U&Es, bone profile
○ High Ca, high urea, high Cr, high ESR
• Urinalysis
○ Bence Jones Proteins
• Blood film & Protein electrophoresis (shows monoclonal band)
• Bone marrow biopsy or aspirate
• X-ray for any lytic lesions or fractures
Management:
• Induction with combination chemotherapy
• Autologous stem-cell transplant in first remission
• Chronic relapsing course
• Multiple new agents including immunomodulatory drugs and monoclonal antibodies
Lymphoma - define, types, S&S, ix & management
Definition: Neoplasm of lymphoid cells originating in lymph nodes or other lymphoid tissues
• Hodgkin's Lymphoma - 15% of lymphomas is diagnosed histo-pathologically by presence of Reed-Sternberg cells (B-lymphoid lineage) ○ Occurs 15-30yrs & in >65s • Non-Hodgkin's Lymphoma - consist of B-cell lymphomas (85%), T cell (15%), NK cell forms. Referred to as high, intermediate or low grade
Aetiology & Risk factors:
Complex genetic mutational process, accumulation of multiple genetic insults
• Some a/w EBV
Presentation/Clinical Features:
• Painless enlarging mass - most often in neck, can be axilla or groin
○ Painful after alcohol –> Hodgkin’s Lymphoma
• B SYMPTOMS - fevers >38 (can be cyclical), night sweats, weight loss
• Pruritis
• Cough or dyspnoea
• Splenomegaly
Investigations & Diagnosis:
Diagnosis:
· Biopsy of a representative node/involved organ (this may need to be imaging-guided), excision biopsy gold std c.f FNA
· HIV serology for HL/High grade NHL
Staging (Ann Arbor system)
· CT Neck/Chest/Abdomen/Pelvis
· PET-CT for HL/High grade NHL
Management:
• HL: Combination chemotherapy +/- radiotherapy
• High-grade NHL: Combination chemotherapy +/- radiotherapy
• Low-grade NHL: Guided by symptoms/disease extent
• Risk-stratified approaches
• Novel therapies
• Prognosis depends on a number of variables.
Types of Stem Cell Transplants
Autologous – from patient’s own stem cells
· Allows delivery of very high doses of chemotherapy
· Can be curative (e.g. relapsed Hodgkin lymphoma) or to extend remission (e.g. myeloma)
· Mortality 2-5%
· Most common indication = myeloma
Allogeneic
· From a donor (sibling or unrelated donor)
· Done always with curative intent (all types of haematological malignancy, but most commonly in acute leukaemia)
· Mortality 10-40% depending on clinical situation
Polycythaemia - define & causes
An increase in Hb concentration above upper limit of normal i.e. persistently raised HCT (haemocrit) - women >0.48 (48%), men >0.52
• Relative polycythaemia - normal red cell mass but decreased plasma volume Absolute/True polycythaemia - increased RCC
Causes of polycythaemia – majority are secondary causes, either due to:
○ Reduced plasma volume OR
§ i.e. dehydration or diuretics
○ Increased red cell mass (EPO dependent)
§ Hypoxia increasing EPO – altitude, smoking, sleep apnoea
§ Ectopic source of EPO – renal/cerebral malignancy
Primary Polycythaemia – occurs when no secondary cause found – tends to be because of a genetic mutation
○ EPO supressed as bone marrow producing inappropriately high amounts of RBC
○ 95% of patients JAK 2 positive
○ Can be associated with raised platelet/WBC
○ Risk of arterial and venous clots
○ Acute treatment (esp if recent clot) venesection– aiming for HCT < 0.45
○ Small risk of transformation into acute leukaemia or myelofibrosis
Causes of platelet abnormaltiies
Thrombocythemia - majority are transient & reactive (secondary)
○ Acute bleeding, malignancy, recent operation or IDA
Consider infection, bleeding iron deficiency inflammation and cancer as common secondary causes
Thrombocytopenia
• Normally asymptomatic if platelets >50 - so most cases picked up incidentally
• Causes include:
○ ‘Mistake’; platelet clumping, delayed transfer of sample
○ Reduced production - drugs, B12/folate deficiency, viral infection etc
○ Increased destruction - ITP, hypersplenism
○ Drugs - alcohol, thiazides, quinines, heparin, valproate, phenytoin, carbamazepine, gold
○ Acute or chronic infections
Pregnancy associated - gestational, HELLP syndrome
Malignant HyperCa - aetiology, S&S, inx & management
Definition: Serum calcium >2.6 mmol/L secondary to a malignant process
Aetiology & Pathophysiology Most common associated malignancies include: • Breast • Multiple myeloma • Lymphoma • Lung cancer
Three main mechanisms: • Osteolytic metastasis • PTH-related protein (PTHrP) secretion ○ Released from tumour • Increased 1,25-dihydroxylvitamin D production
Presentation/Clinical Features:
‘‘Stones, bones, thrones, abdominal groans & psychiatric moans’’ - although many are asymptomatic
Investigations & Diagnosis:
Malignant causes of hyperCa tend to cause a rapid increase in serum Ca levels whereas benign causes tend to have a more prolonged & asymptomatic course
* Bedside - general examination (full exam inc breast) * Bloods - serum Ca, PTH (supressed) * Imaging may be required to identify underlying cancer
Management:
‘‘Rehydrate, rehydrate & bisphosphonates’’
• IV fluids - 4L+ in 24hrs
○ Monitoring for signs of overload & electrolytes
• Bisphosphonates (after 24hrs of rehydration)
○ Inhibit osteoclastic bone action
SVCO - define, aetiology, S&S, inx & management
Definition: Obstruction to the flow of blood through SVC, in 60-80% of cases this is secondary to cancer
Aetiology & Risk factors:
Infections (Syphilis) used to cause the majority of SVCO, however malignancy is now the leading cause
SVCO may result from direct tumour growth or lymphadenopathy.
Presentation/Clinical Features: Symptoms • Dyspnoea • Facial swelling • Head fullness • Sx worse on lying down or bending forwards • Cough • Dysphagia
Signs • Facial swelling • Distended neck & chest wall veins • Upper limb oedema • Facial plethora • Cyanosis • Cognitive dysfunction
Pemberton’s Sign; elevate arms above head for 1-2mins, +ve if causes congestion, cyanosis or respiratory distress
Investigations & Diagnosis:
• Radiological dx
• Histological - especially if no current dx of malignancy
Management: • Stenting • Radiotherapy - tends to be first line therapy • Chemotherapy • Anti-coagulation
Define neutropenic sepsis
Fever > 38° or features of sepsis in a patient with a neutrophil count of < 0.5 x 109/L (or expected to fall to below 0.5).
Side effects of Radiotherapy
o Side effects can vary & depend on site of treatment & affect tissues in radiation field
o Examples:
Breast – swelling, skin redness –Abdomen – nausea, vomiting, diarrhoea
Chest – cough, shortness of breath, oesophageal irritation
Head and neck – taste alterations, dry mouth, mucositis, skin redness
Brain – hair loss, scalp redness
Pelvis – diarrhoea, cramping, urinary frequency, vaginal irritation
Prostate – impotence, urinary symptoms, diarrhoea
Fatigue is often seen when large areas are irradiated
o Unlike the systemic side effects from chemotherapy, radiation therapy usually only impacts the area that received radiation
Basics of Radiotherapy - MOA
o Radiation works by damaging DNA of cells & destroys ability to reproduce
Via direct action; directly break & damage DNA
Via indirect action; photons hit water, make free radicals & then they damage DNA
• This is the main MOA
o RT is fractionated – divided into smaller daily fractions & then given over several weeks
Takes advantage of differential repair abilities of normal & malignant tissues
4Rs: repair, redistribution, reoxygenation & repopulation
o RT dose expressed in Gray (Gy) – 1 joule absorbed/kg
Define euthanasia & physician assisted suicide
Euthanasia is defined as: a good death
• Active euthanasia the intentional bringing about of the death of a patient at the request of the person
• Passive euthanasia selective non treatment of a patient
® More appropriate to call this withdrawing/stopping or withholding treatment
Physician assisted suicide (PAS)
‘‘Suicide by a patient facilitated by means (prescription) or by information (what dose would be lethal) provided by a physician aware of the patient’s intent’’
Tumour lysis syndrome - define, clinical effects & management
Definition: Massive breakdown of tumour cells leading to increased serum urate, potassium, phosphate & secondary hypoCa (due to high phosphate).
• Clinical toxic effects including: renal insufficiency, cardiac arrhythmias, seizures, and death due to multiorgan failure • Cancers with a high potential for cell lysis include high-grade lymphomas, acute leukemias, and other rapidly proliferating tumours • Prevention w/ allopurinol or other urate oxidase inhibitors • Management; ○ Hydration with diuretics to maintain high urine output ○ Monitoring ○ Dialysis
What malignancy are the following tumour markers ‘mainly’ used in:
1) AFP & hCG
2) CA125
3) HER2 & OR & BRCA
4) CA15.3
5) CEA
6) CA19.9
1) Testicular/Germ-cell cancer
2) Ovarian
3) Breast Ca
4) Breast Ca
5) Colorectal Ca
6) Pancreatic
Metastatic Spinal Cord Compression - define, S&S, ix & management
Definition: Malignant cord compression is defined by radiological evidence of indentation of the thecal sac secondary to cancer.
Rare complication of cancer & treated as an emergency
Presentation/Clinical Features: • Lower thoracic/lumbar back pain ○ Radicular ○ Radiates bilaterally ○ Worse on straining e.g. coughing • Arm or leg weakness - ''off legs'' • Paraesthesia • Bowel or bladder disturbances
O/E • Spinal bony tenderness • Limb weakness • Altered gait • Altered sensation • Urinary retention +/- constipation • Altered anal tone
Investigations & Diagnosis:
Urgent whole spine MRI - imaging technique of choice, need to nurse & lie flat
• Within 24hrs
Management:
• High dose dexamethasone 8mg PD with PPI cover
• Analgesia
• Consider catheterisation & laxatives
• Definitive treatment - surgery or radiotherapy
Brain metastasis - define, common primaries, S&S, ix & management
Definition: Metastasis from primary malignancy to the brain
Aetiology & Risk factors:
Most common primary malignancies include: breast, lung, renal & melanoma
• Think pairs
Presentation/Clinical Features: • Headaches - dull, aching, constant • Features of raised ICP ○ Headache & nausea ○ Worse on bending & straining & in morning ○ Relief on vomiting • Cognitive changes ○ Personality or confusion • Neurological symptoms ○ Foccal wekaness, gait ataxia, seizures
Investigations & Diagnosis:
CT or MR Head
Management:
• Steroids - dexamethasone 8mg PO BD for 48hrs + PPI, followed by gradual reduction of steroid (maintenance dose)
• If seizures consider anti-epileptic
• Whole brain radiotherapy
Prognosis - poor
49 year old man with known advanced kidney cancer. Has received several lines of treatment. On “a new cancer drug”, started about 7 weeks ago. Presents to A+E with diarrhoea and dizziness.
○ Diarrhoea is watery, non-bloody, no vomiting and patient is afebrile, T36.7, P114, BP 98/56
○ Appetite a bit reduced, no one else unwell
• O/E abdomen soft non tender, no masses/LNs
Diagnosis? Ix & Management?
Diagnosis: Immunotherapy induced Colitis
Investigations & Diagnosis:
• Bloods: FBC, U+Es, LFTs, inflammatory markers (TFTs, cortisol)
• Stool culture
• Radiology: AXR, erect CXR
Management:
• Fluid resuscitation
• Contact acute oncology (9-5)/ on-call registrar at CCC:
○ Grade 1 (mild, up to 3extra stools, no blood or pain); treat w/ fluids & loperamide
○ Grade 2 (moderate, 4-6 extra stools or mild/moderate pain or blood/mucus); admit under gastro, investigations, oral pred, omit next immunotherapy dose, monitor closely
○ Grade 3 (>7stools extra a day, severe pain, fever, dehydration, blood/mucus); admit, flexible sigmoidscopy, high dose IV corticosteroid therapy, daily bloods, discontinue immunotherapy
Opioid Conversions:
IV morphine –> Oral
S/C morphine –> Oral
Oxycodone –> Morphine
Codeine –> Morphine
IV morphine = 3x stronger than oral morphine
S/C morphine = 2x stronger than oral morphine
Oxycodone = 2x stronger than morphine (if using same route)
Codeine –> morphine x0.1
How to titrate medications?
• Background analgesia should be equivalent to total analgesia given in the day
○ Old background + all PRNs
• Breakthrough (immediate release) = 1/10 to 1/6 of new background
○ Prescribed 4hrly PRN
• NOTES
○ Morphine/oxycodone come in 5mgs so round up to nearest 5 if possible
What extra information is needed when prescribing CDs?
• Name of drug, strength & formulation (e.g. tablets, liquid, capsules)
• Dose & frequency; e.g. 5mg up-to 2hourly as required for pain
Total quantity supplied in numbers & words; e.g. supply 20 (twenty) tablets
Anticipatory Medication & Symptoms
Pain - morphine & other opiates (Alfentanil - renal dysfunction)
Agitation - midazolam 2.5-5mg or Levomepromazine 6.25 mg - 12.5 mg PRN
Secretions - glycopyrronium 200 micrograms PRN or hyoscine hydrobromide 400 micrograms PRN
N&V - Cyclizine/Metoclopramide/Levomepromazine/Ondansetron
GSF Stages
GOLD STANDARDS FRAMEWORK STAGES & STEPS AT EACH STAGE
• Green Patients: Death expected in the next months
○ Put referrals in place e.g. extra benefits, carers, funding
○ Start to discuss plans & worries
○ DNACPR, ACP, Advance directives & POA
• Amber Patients: Death expected within weeks
○ Revisit the above ensure in place
○ Consider supplying anticipatory medications
○ Medication review to stop any medications that aren't of benefit
• Red Patients: Death expected in the next couple of days to week
○ Ensure above in place
○ Anticipatory medications in place & provision for syringe driver
○ Stop all non-essential medications, med review, convert to s/c
○ Revisit holistic assessment inc ACP & DNACPR
○ Is the patient where they want to be? .e.g. home, hospice
o May be time (if family wishes) to talk about what will happen/what to expect
What is ACP?
Advanced Care Planning; offers people the opportunity to plan their future care and support, including medical treatment, while they have the capacity to do so.
Not everyone will want to make an advance care plan, but it may be especially relevant for:
• People at risk of losing mental capacity - for example, through progressive illness.
People whose mental capacity varies at different times - for example, through mental illness.
ITP - define, S&S & management
Definition: Immune mediated or idiopathic reduction in platelet count
Antibodies are against the glycoprotein IIb/IIIa or Ib-V-IX complex. Children usually have acute thrombocytopenia that may follow infection or vaccination. In contrast, adults tend to have a more chronic condition
Presentation/Clinical Features: • Incidental finding on routine bloods • Petechiae or purpura • Bleeding - epistaxis • Catastophic bleeding e.g. intracranial ○ Not common presentation
Management:
• First line management is oral prednisolone
○ Suppresses the immune mediated destruction of the platelets
• Pooled human immunoglobulin (IVIG) may also be used
○ Raised plt count quicker than steroids
○ May be used in active bleeding or if urgent invasive procedure is required
• Splenectomy - less commonly used
