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
