Haematological cancers Flashcards
What are the B symptoms
- weight loss >10% in 6 months
- unexplained fever >38
- night sweats (requiring change of clothing)
What is leukaemia
- group of disorders characterised by accumulation of malignant white cells in the bone marrow and peripheral blood
- most common type is CLL
Describe the clinical features of CLL
- mean age 67-75
- most common 1st presentation is incidental finding of lymphcytosis
- Often associated w/ ITP and autoimmmune haemolytic anaemia
- vague hx of insidious onset recurrent infections, enlarge LNs, early satiety of abdo discomfort (enlarged spleen), tiredness and fatigue secondary to anaemia, mucocutaneous bleeding or petichae due to thrombocytopenia
- B symptoms are rare
- enlarged rubber lymph nodes and hepatosplenomegaly may be present on examination
How is CLL investigated and diagnosed?
- blood film needed for diagnosis- showing smudge cells
- FBC, U&E, clotting, LFT, CRP, bone profile, haematinics, retics, LDH also done
- Bone marrow aspirate and biopsy not required for diagnosis but helps to differentiate from ITP and thrombocytopenia from infiltration
- LN aspirate if suspicious nodes as can transform to high grade lymphoma
What are smudge cells?
- aretfacts of lymphocytes thatve been damaged during slide preparation
- seen in CLL
How is CLL managed?
- fludarabine +ritux + cyclophos 1st line
- other immuno and chemo also used
- steroids help with haemolysis
- radiotherapy for LNs and splenomegaly
- stem cell transplants in selected pts
- transfusions for anaemia
- IV immunoglobulins if recurrent infections
Describe the clinical features of chronic myeloid leukaemia
- 40-60yrolds
- most present with high WBC (usually neutrophilia >100)
- Hb usually low so often get anaemic, platelets low or normal
- some present with splenomegaly and associated abdo discomfort
- occasionally present with leukostasis (lung infiltration, priapism, amaurosis fugax)
- gout is common due to purine breakdown
- bleeding disorders sometimes due to thrombocytopenia
How should CML be diagnosed? (what are the key investigations and findings)
- cytogenetics of blood or bone marrow for Philadelphia chromosome (BCR ABL)
- Blood film showing neutrophilia, metamyelocytes, promyelocytes (myelocytes at varying stages of differentiation)
- other routine bloods
How is CML managed?
- allogenic stem cell transplant from HLA matched donor if young and fit
- otherwise tyrosine kinase inhibitors
- lymphoblastic transformation can be treated as ALL
- meyloblastic transformation need allogenic transplant as chemo rarely long lasting
What is acute lymphoblastic leukaemia?
Arrested maturation of B or T cells leading to uncontrolled proliferation of immature blast cells with bone marrow failure and tissue infiltration
- is aggressive and rapidly fatal but curable
What age group of ALL most common in?
- most common childhood cancer
- can occur in adults also however
- important association with xray exposure in pregnancy and downs
Describe the clinical features of ALL and AML?
Bone marrow failure:
- anaemia- sob, fatigue, palpitations, pallor
- neutropenia: increased risk and severity of infections, atypical infections such as PCP
- thrombocytopenia: DIC, petechiae, ecchymosis (bruising), bleeding
- leukostasis- resp distress, altered GCS, priaprism (more in AML than ALL)
- infiltration: testicular, lymph node, spleen, liver, CNS (CN palsies, meningism, CES)
- all acute/ subacute onset
How is ALL investigated/ diagnosed?
- characteristic blast cels seen on blood film and bone marrow
- CXR and CT for LN involvement (mediastinal are common)
- LP for CNS involvement
How is ALL managed?
- supportive: transfusions, IV fluids, allopurinol (prevents tumour lysis syndrome)
- neutropenic regime: prophylactic antivirals, fungals and biotics
- chemo: multi drug, different ones for remission induction and for consolidation/ maintainence
- Allogeneic marrow transplants: best option for standard risk pts, done after 1st remission
How is remission defined in ALL?
- no evidence of leukaemia in blood
- normal blood count
- <5% blast cells in normal regenerating marrow
What is AML
proliferative blast cells derived from marrow myeloid elements, progresses rapidly
- commonest leukemia in adults
How does AML present slightly differently to ALL
- leukostasis is more likely to be AML
- gum hypertrophy is classic sign
- can get skin involvement
- CNS involvement at diagnosis is rare
- AUER RODS SEEN in AML CELLS NOT IN ALL CELLS
How is AML investigated/ diagnosed and how is it differentiated from ALL?
- few blast cells in peripheral blood so diagnosis may require bone marrow biopsy, immunophenotyping and molecular methods
- AML differentiated from ALL on biopsy by auer rods seen in AML myeloblast cells
- cytogenetic analysis guides treatment
How is AML managed?
- supportive treatment same as for ALL
- chemo: very intense, long periods of neutropenia and thrombocytopenia
- bone marrow transplant and allogeneic transplants (stem cells collected from peripheral blood) and used after cylophosphamide + total body irradiation (kills all immune cells so transplanted can replace them in the marrow)
What is leukostasis and how does it present
- extremely high blast cell count and symptoms of decreased tissue perfusion due to white cells plugging the microvasculature
- usually presents with resp distress, fever, neuro signs (visual changes, headache, dizziness, tinnitus, confusion), MI, AKI, acute limb ischaemia, priaprism, bowel infarction
- will cause stroke if left
how is leukostasis managed?
stem cell transplants and cytoreduction with chemo (hydrocycarbamide) to bring down leukocyte count, can cause significant tumour lysis but necessary to prevent stroke
What is a myelodysplastic syndrome?
disorders causing immature blood cells in bone marrow not to mature- thought to be due to mutations in multipotent bone marrow stem cells. 30% transform to acute leukaemia (usually AML). lots of types, depending on specific changes seen in blood cells or bone marrow
how do myelodysplastic syndromes present?
- bone marrow failure (anaemia (low retics), thrombocytopenia, neutropenia)
- usually in 70s
- most is primary but can develop after chemo or radiotherapy
- increased bone marrow cellularity due to ineffective haematopoesis, ring sideroblasts may be seen on bone marrow
How are meylodysplastic syndromes managed?
- multiple blood and platelet transfusions
- allogeneic stem cell transplants are curative but pt is rarely fit enough
- low risk, not for transplant= lenolidamide
- high risk, not for transplant= chemo
What is lymphoma
Malignant disorders of lymphocytes, which usually accumulate in lymph nodes causing lymphadenopathy but may also be found in peripheral blood or infiltrate organs. Hisologically divided in hodgekins and non hodgekins then further subdivided
Describe the clinical features of lymphoma
- 2 peaks- young adult and elderly
- RFs inc fhx, EBV, SLE, post transplant
- Usually presents with an enlarged rubbery lymph node- usually cervical, axillary and inguinal less common. The node size can be variable and can become matted.
- 25% have B symptoms such as fever, night sweats, weight loss, lethargy
- Some get pruritis
- Can present with alcohol induced lymph node pain
- Mediastinal lymph node involvement can cause bronchial or SVC obstruction or pleural effusions
- Can have hepato or/ and splenomegaly
How is lymphoma investigated/ diagnosed?
- Lymph node excision biopsy or image guided needle biopsy, lapatomy or mediastinoscopy may be needed
- FBC, U&E, ESR, LFT, LDH, urate, bone profile and blood film needed
- CXR for mediastinal involvement
- CT/ PET CAP needed for staging
Describe the staging system for lymphoma
- Ann Arbor
I= single LN or extranodal site
II= 2 or more sites on same side of diaphragm
II1= regional LN involved
II2= distant LN involved
III= LNs detected on both sides of diaphragm
IV= disseminated disease and other extranodal sites (liver, marrow, abdo wal)
A= no systemic symptoms except pruritis
B= presence of B syptoms
E= localised extranodal involvement
How is hodgekins lymphoma managed?
- radiotherapy + short course chemo or stages Ia and IIa
- longer courses chemo for IIa through to IVb
- ABVD chemo regime cures 80%, more intense regimes if more aggressive/ worse prognosis
- high dose chemo and stem cell transplants in relapsed pts
Give 4 complications of hodgekins lymphoma and its treatment
- radiotherapy increases risk of other malignancies
- ischaemic heart disease
- hypothyroidism
- lung fibrosis
- chemo can cause myelosurpression, nausea, alopecia, infection
- non hodgekins lymphoma
- infertility
What is non hodgekins lymphoma and what are the commonest types
- diverse group of lymphoma without reed sternberg cells
- most derived from b cell lines
- diffuse large b cell lymphoma is most common
- not all go to nodes
Give 4 risk factors of non hodgekins lymphoma
- immunodeficiencies
- HTLV-1
- H. pylori
- toxins
- congenital
How may non hodgekins lymphoma present
- most present with superficial lymphadenopathy
Extranodal disease: - MALT tissue in stomach-= presents like gastric ca, caused by H pylori and will regress if treat as that
- non MALt gastric lymphoma- usually LBCL high grade
- small bowel- diarrhoea, vomiting, abdo pain
- skin- erythroderma
- waldeyers ring lymphomas can cause sore throat/ sleep apnoea
- systemic features less common and indicate systemic disease
- pancytopenia from marrow involvement (anaemia, bleeding, infections)
What is the difference in clinical course between high and low grade lymphomas, give examples of each
High grade- aggressive but curable (inc burkitts lymphoma, diffuse large b cell, ALL)
Low rade- indolent but less curable and often disseminated - follicular lymphomas, MALT lymphoma, lymphocytic lymphoma
How is non hodgekins lymphoma managed?
- Depends on subtype
- If low grade and symptomless- no treatment may indicated and you can wait till it starts growing fast/ causing problems, a course of radiotherapy may be curative if localised. Chemo can also be used. Remission can be maintained with rituximab. If disseminated, cure rates are low but people like for a long time with it.
- High grade lymphomas are usually treated with R- CHOP regime (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine (oncovin) and prednisolone.
- GCSF can help with neutropenias
What is myeloma
Abnormal proliferation of a single clone of plasma cells or lymphplasmacytic cells leading to secretion of immunoglobulins. Leads to dysfunction of many organs esp the kidney.
Describe the clinical features of myeloma
- peak age 70
- AKI due to light chains deposition in tubules which have toxic inflammatory effects on PCT- hypercalcaemia can result
- anaemia, neutropenia, thrombocytopenia due to bone marrow infiltration
- osteolytic bone lesions (back ache, pathological fractures, cord compression, vertebral collapse) due to increase osteoclast activity due to signals from myeloma cells
- hypercalcaemia- abdo pain, vomiting, constipation dehydration, polyurea, polydipsia, depression, anorexia, weakness, confusion, stones, AKI
- recurrent infections
- rarer presentations are liver or cardiac amyloidosis
Describe the diagnostic criteria for myeloma (4)
- > 10% plasma cells in bone marrow
- Serum or urine monoclonal protein band on electrophoresis
- Myeloma related organ dysfunction (anaemia, renal insufficiency, hypercalcaemia)
- Osteolytic bone lesions detected on skeletal survey
How should suspected myeloma be investigated
- Have high index or suspicion- Must do serum free light chains in all >50 with new back pain
- FBC, blood film, U&E, bone profile, LDH, urate, LFT
- Bone marrow biopsy needed
- Serum/ urine electrophoresis
- Xrays/ ct/ mri
How is myeloma managed?
- incurable
- Younger pts: induction chemo- IMIDs, dexamethasone, cyclophosphamide, proteaseome inhibitors. Then consider high dose chemo and a stem cell transplant.
- Elderly: oral combination regimes, corticosteroids, thalidomide. The induction regime is to keep the serum paraprotein levels at a plateau, it is usually maintained for 12-18 months or until the levels start to rise, when chemo or other treatments are started (proteasome inhibitors) or stem cell transplants are considered
- Radiotherapy, bisphosphonates (zolendronate) and pain relief for bone pain from lytic lesions (avoid NSAIDs)
- Orthopaedic surgery may be helpful for vertebral collapse
- Transfusions, sometimes EPO for anaemia
- Rehydration and adequate fluid intake of 3L/ day to prevent further light chain induced renal impairment, dialysis may be needed in AKI
- Regular IV immunoglobulin infusions may be needed if infections are recurrent
Give 4 common complications of myeloma and how theyre managed
- Hypercalcaemia: treat with rehydration of 4-6L/day IV 0.9% saline +/- IV bisphosphonates
- Spinal cord compression- dexamethasone and local chemo
- Hyperviscosity: causes reduced cognition, disturbed vision, bleeding. Treat with plasmapheresis to remove light chains.
- AKI: rehydration, dialysis may be needed
What is a myeloproliferative disorder
Where the bone marrow overproduces cells, which are often defected. It is Philadelphia chromosome negative and so different to CML. There are many different types eg meylofibrosis, polycythaemia vera, essential thrombocytopenia, and it is important to think of secondary causes.
What is myelofibrosis?
Hyperplasia of megakarykocytes/ disorder of other haematopoetic stem cells leading to platelet derived growth factor release leading to intense fibrosis of bone marrow and initiation of haematopoesis in liver and spleen
What mutation is commonly associated with myeloproliferative disorders
JAK2 mutation
Describe the clinical features of myelofibrosis
- Hypermetabolic symptoms (night sweats, fever, weight loss)
- splenomegaly causing abdo pain, anorexia etc
- bone marrow failure causing pancytopenia (infections, bleeding anemia)
How is myelofibrosis investigated and diagnosed (what findings are characteristic)
- Blood film: leucoerythroblastic cells (nucleated red cells) and tear drop red cells are characteristic.
- FBC usually shows pancytopenia
- Bone marrow trephine is needed for diagnosis (shows fibrosis)
How is myelofibrosis managed?
- Definitive treatment is with bone marrow transplant
- Supportive care, splenectomy, JAK2 inhibitors, cytoreductive drugs all have a role in management
What is polycythaemia vera?
- Malignant proliferation of a clone derived from a pluripotent stem cells, leading to excess proliferation of RBC, WBC and platelet lineages independent of EPO production
- Commonest in >60y/os
How may polycythaemia present?
- May be incidental finding on FBC
- May present with symptoms from hyperviscosity (headaches, dizziness, tinnitus, visual disturbance), itching after a hot bath is classic, erythromelalgia (burning sensation in toes and fingers), gout (high RBC turnover), splenomegaly, arterial (MI) or venous thrombosis (DVT, stroke), plethoric complexion
What will an FBC show in polycythaemia vera?
high fbc, hb, hct, pcv, wbc and platelets
- also if you do EPO, this will be low
How do you differentiate polycythaemia vera from CML?
cytogenetics- CML is philadelphia chromosome positive
What does the bone marrow biopsy show in polycythaemia vera?
- hypercellularity with erythroid hyperplasia
What are main complications of polycythaemia vera?
- 10-20% develop myelofibrosis
- some develop leukaemia
- thrombosis
- haemorrhage
How is polycythaemia vera managed?
- Keep HCT < 0.45 to reduce thrombosis risk- by venesection for younger/ low risk pts
- Higher risk pts (age >60, previous venous thrombosis) get hydroxycarbamide and aspirin
- Monitor FBC every 3 months
What is essential thrombocythaemia
Clonal proliferation of megakaryocytes leading to persistently high platelets- often >1000x10^9/L, with abnormal function leading to bleeding, arterial or venous thrombosis and microvascular occlusion
How may essential thrombocythaemia present?
headache, atypical chest pain, light headedness, erythromelalgia, DVT, stroke, MI, haemorrhage, splenomegaly
How is essential thrombocythaemia managed?
- Exclude other causes of thrombocytosis
- Aspirin 75mg OD
- Hydroxycarbamide for cytoreduction if high risk pt
- Often transforms to myelofibrosis/ PRV/ leukaemia
Give 4 secondary causes of thrombocytosis
- bleeding
- iron deficiency
- inflammation
- infection
- post surgery
- splenectomy
What is the difference between relative and absolute polycythaemia?
Relative- normal RBC mass, decreased plasma volume
Absolute- increase RBC mass (primary= polycythaemia vera)
Give 3 secondary causes of relative and absolute polycythaemia
Relative= dehydration (commonest acute), obesity, HTN, high alcohol, tobacco intake Absolute= hypoxia (altitudes, chronic lung disease, cyanotic heart disease, heavy smoking) or inappropriate EPO (RCC, hepatocellular carcinoma, doping)
What is aplastic anaemia
reduction in all major cell lineages due to a stem cell disorder, it is very rare
what can cause aplastic anaemia?
- most are autoimmune (esp if during pregnancy)
- drugs
- viruses (cytomegalovirus, parovirus, hepatitis, EBV)
- radiation
- inherited (in case of fanconia anaemia)
Describe the clinical features of aplastic anaemia
- anaemia
- bleeding, bruising, petechiae
- infections
- commonest in teens and 20s
- another spike in elderly
how should aplastic anaemia be investigated and what are key findings to confirm diagnosis
- bone marrow aspirate and trephine: normal marrow has 30-70% blood stem cells, in aplastic anaemia these cells are mostly gone and replaced by fat. This test also excluded infiltrative causes.
- FBC, U&E, LFT, TFT, haematinics, viral studies, autoantibodies
- kidney CT, xray hand and arm- may be abnormal in fanconi anaemia
Give 5 differentials for pancytopenia
Decreased production:
- aplastic anaemia
- infiltration (leukaemias, myelodysplasia, meyloma, lymphoma, solid tumours)
- myelofibrosis
- megaloblastic anaemia (B12/ folate deficiency)
Increased peripheral destruction:
- Hypersplenism (primary or secondary to cirrhosis, lymphoma, malaria, TB etc)
How is aplastic anaemia managed?
- mainly supportive if symptomatic: blood product transfusions, neutropenic regime
- allogeneic stem cell transplants if younger and more aggressive disease- this is often curative
- immunosurpression with ciclosporin and antihymocyte globulin (ATG- targets T cells which attack bone marrow) may be effective but not curative in most
- no clear role for G- CSF
What are the 3 indications of pack red cells transfusions
- Hb<70g/l
- Hb <80 if acute coronary syndrome
- major haemorrhage
- pts with chronic anaemia who receive regular transfusions have individual thresholds
How should packed red cells be prescribed? (how much, what are targets, how long is it given over)
- only prescribe one bag at a time if no active bleeding
- then reassess after each bag
- give enough to get to 70-90 g/l or 80-100g/l in ACS
- give over 1-4 hrs
Give 3 alternatives to pack red cell infusions if theyre refused
- EPO
- IV or oral iron
- cell salvage and tranexaemic acid
What are the 2/3 indications for FFP
- major haemorrhage
- clinically significant bleeding without major haemorrhage if abnormal coagulation test results (prolonged PT or APTT)
- DO NOT give simply to correct abnormal coagulation results unless for reversal of vit K antagonist or undergoing invasive procedure to critical site or high risk of bleeding
- give one dose then restest coag studies and give further if needed
What are the 3 indications of cryoprecipitate
- major haemorrhage
- without major haemorrhage if: clinically significant bleeding AND fibrinogen level <1.5g/l
- consider prophylactic if fibrinogen <1 and have invasive procedure with high risk of bleed / to critical site
What dose of cryoprecipitate should be given to adults and children
- give adult 2 pools (each pool is 5 units)
- give child 5-10ml/kg up to max of 2 pools
- reassess and do fibrinogen after each dose and give more if needed
What are the 5 indications for platelet transfusions
- clinically significant bleeding and platelet count <30
- use higher threshold up to 100 for severe bleeding or bleeding into critical sites
- Prophylaxis if <10 and DONT have chronic bone marrow failure, autoimmune thrombocytopenia, heparin induced thrombocytopenia or TTP
- consider prophylactic use to get platelet count >50 if theyre having invasive procedure
- consider higher threshold of 50-75 if high risk of bleeding during procedure and >100 if surgery to critical site such as to CNS or eyes
State 10 risks of transfusions
- transfusion related circulatory overload
- acute haemolytic reaction (ABO incompatibility)
- transfusion related lung injury
- infection
- graft vs host disease
- Iron overload
- clotting abnormality
- electrolyte abnormality
- hypothermia
- transfusion related acute lung injury
- mild allergic reactions
- non haemolytic febrile reactions
- anaphylaxis
- bacterial contamination
Give 3 risk factors for TACO
- many units of transfusions
- kidney failure
- heart failure
How is TACO managed and what can help avoid it?
- CXR for diagnosis, treat with oxygen and diuretics
- 20mg furosemide can be given as prophylaxis
- dont give too many units too quickly
How do acute haemolytic reactions present? What will be findings of blood tests?
- urticaria
- hypotension
- fever
- reduced hb
- low hapotoglobin
- high LDH
- high bilirubin
- positive direct antiglobulin test
What is transfusion related acute lung injury
A form of ARDS where they get pulmonary odema
Has high mortality- give high flow o2, urgent CXR and intensive care input
What infections could be incurred by transfusions
- Hep B
- Hep C
- HIV
- Syphillis
- Malaria
- vCJD
- in reality risk is negligible as blood is screen and selection criteria is strict
What is graft vs host disease and how does it present
- HLA mis matched between donor and recipient
- commonest in transfusions of non irradiated blood into immunocompromised pt
- clinical features inc fever, skin involvement, diarrhoea and vomiting
- often a delayed presentation
Why do transfusions lead to clotting abnormalities and how should this risk be managed
- Packed red cells don’t contain platelets or clotting factors so can dilute the pts and cause coagulopathy
- FFP and platelets should be given concurrently with the 4th unit of RBCs
What electrolyte abnormalities are most commonly associated with transfusions
- Hypocalcaemia: chelation of calcium by calcium binding agent in the preservative
- Hyperkalaemia: due to inevitable partial haemolysis of red cells and release of intracellular potassium
Why can transfusions lead to hypothermia
RBCs are stored at cool temps so may need warming during/ before transfusion if possible
How should non haemolytic febrile reactions and mild allergic reactions to transfusions be managed?
- stop transfusion, check right blood, right pt
- assess pt and give paracetamol and antihistamine
- continue unless rise of >2 degrees or temp >39 or symptoms/ signs present (other than pruritus/ rash)
When should a person receiving a transfusion have obs done?
Before, 15 mins in and after giving the transfusion
How is acute haemolytic reaction/ ABO incompatibility managed?
- stop tranfusion, dont flush line
- high flow O2 through non rebreath mask, secure airway
- neb salbutamol if wheeze (this suggests anaphylaxis though)
- fluid and lie flat if hypotensive
- contact ITU urgently for inotropic/ resp support
- take cultures if ?bacterial contamination
- contact transfusion lab immediately to prevent further wrong blood incident
Give 5 indications for irradiated blood products
- Intrauterine transfusions of packed RBCs and platelets to foetus
- Congenital immune deficiency (SCID, di George etc)
- Hodgkins lymphoma
- Bone marrow transplants
- Exchange transfusions of neonates >1200g
- Transfusion from first degree relative
- Some chemotherapy agents
What is the point of giving some pts irradiated blood products?
Prevents GvHD as radiation damages any T cells which may have slipped through filtering process
