Haematological cancers Flashcards
Multiple myeloma.
a) Malignancy of…?
b) Pathogenesis and risk factors
c) Presentation
d) Myeloma screen
e) Criteria for diagnosis of symptomatic myeloma (3)
f) Management of malignancy
g) Adjuvant Rx
h) What is smouldering myeloma?
a) Plasma cells, which produce a monoclonal antibody (immunoglobulin/paraprotein), detected in serum/urine
b) - Progresses from MGUS to myeloma (may be very insidious; risk of progression is 1% per year)
- Risks: age (median = 70), Afro-Caribbean, male
c) - Asymptomatic (incidental raised globulins)
- Back pain and other CRAB features
- AKI, spinal cord compression
- Hyperviscosity syndrome (dizziness, headaches, confusion, stroke)
d) - FBC (normocytic anaemia) and ESR (raised)
- Blood film (Rouleaux formation)
- UEs/creatinine (renal failure)
- LFTs (raised globulins)
- Calcium
- Urinary protein electrophoresis (Bence-Jones)
- Serum protein electrophoresis and IgG levels
- XR any symptomatic areas (eg. lumbar spine)
e) All three of: (absence of all 3 = MGUS)
1. Bone marrow biopsy (> 10% monoclonal plasma cells)
2. Monoclonal antibody in serum or urine
3. Evidence of myeloma-related organ damage (CRAB)
Also perform:
- Immunophenotyping
- Whole body MRI for staging
f) - If fit: autologous SCT to induce induction (note: they will inevitably relapse)
- If unfit: chemotherapy
g) - Corticosteroids
- Analgesia: standard + neuropathic
- Bone protection
h) >10% plasma cells + paraprotein WITHOUT symptoms
ALL.
a) Malignancy of…? (2 basic types)
b) Main risk factors
c) Presentation
d) Investigations
e) Diagnostic finding
f) Management - induction, maintenance
g) Adjuvants therapies
a) Lymphoid blast cells (B cell and T cell), which differentiate into lymphocytes
b) Genetic (translocations; twins have higher risk), Trisomy 21, Fanconi anaemia, ataxia telangiectasia, radiation exposure
c) - Non-specific with acute deterioration
- Pancytopenic features: pallor, fatigue, weakness, bleeding, bruising, fever, infection
- Infiltration: bone pain, splenomegaly (LUQ pain), headache, meningism, irritability, lymphadenopathy
d) - FBC: usually pancytopenic
- If abnormal FBC, do blood film - blast cells (note: may be confined to the bone marrow)
- Gold standard: bone marrow aspirate (blast cells)
- Immunophenotyping and cytogenetic studies (eg. translocations like t12:21 = TEL-AML)
- CXR (?mediastinal mass)
e) > 20% lymphoid blast cells in peripheral blood and/or bone marrow is diagnostic for ALL
f) - Induction: chemotherapy + corticosteroids (usually via CVC) - remission rates ~ 80%
- Maintenance: daily 6-mercaptopurine + weekly methotrexate for ~ 2-3 years
- Alternative curative Rx: HSCT
f) - Allopurinol during induction (tumour lysis = hyperuricaemia),
- Antibiotics + antifungals (for opportunistic infection)
- CNS prophylaxis/Rx: radiation, intrathecal methotrexate and steroids
AML.
a) Malignancy of…?
b) Risk factors
c) Demographics
d) Presentation
e) Investigations and findings
f) Diagnostic findings
g) Management
a) Myeloid blast cells (myeloblasts), which differentiate into granulocytes: neutrophils, basophils and eosinophils
b) MYELOdysplastic syndrome, aplastic anaemia, polycythaemia rubra vera, Fanconi anaemia, Down syndrome, radiation exposure
c) Incidence increases with age (but also contributes around 15% childhood leukaemia)
d) Acute features of pancytopenia (as with ALL)
e) - FBC: pancytopenia usually (though total WCC may be raised)
- Blood film: blast cells, Auer rods
- Immunophenotyping and cytogenetic studies
f) > 20% myeloid blast cells in peripheral blood / bone marrow
g) As per ALL (different regimens but same principles)
- Induction remission as for ALL ~ 80% (lower as patients get older)
CML.
a) Malignancy of…?
b) Risk factors - main 1 (90% cases), and others
c) 3 phases
d) Presentation
e) Investigations and findings
f) Management
g) How is remission assessed?
a) One or all haematopoetic cell lines (erythroid, platelet and myeloid; not lymphoid)
b) Philadelphia chromosome (BCR from Ch22 and ABL from Ch9)
c) - Chronic phase (< 15% blast cells): asymptomatic, lasts ~ 5 years (90% patients diagnosed here)
- Accelerated phase (15 - 29% blast cells): anaemia, thrombocytopenia, splenomegaly, some treatment resistance
- Blastic phase (>30% blast cells): acute leukaemia presentation (fever, night sweats, weight loss, bone pain, infections, bleeding, etc.), refractory to therapy, rapidly fatal
d) Dependent on phase:
- Most asymptomatic (chronic phase) - incidental finding
- Constitutional symptoms
- MASSIVE SPLENOMEGALY (LUQ pain)
e) - FBC: leukocytosis, anaemia
- Blood film: all stages of maturation seen
- Bone marrow aspirate: quantify % blast cells for staging
- Cytogenetic studies - PHILADELPHIA CHROMOSOME (diagnostic finding in CML presentation)
- LDH - elevated
f) - Tyrosine-kinase inhibitors (TKIs), e.g. imatinib: inhibition of tyrosine kinase encoded by BCR-ABL gene, inducing apoptosis in cells positive for BCR-ABL
- If TKIs fail, HSCT is an option
g) - Haematological remission: FBC normalise, no organomegaly
- Cytogenetic remission: no BCR-ABL chromosomes present
CLL.
a) Malignancy of…?
b) Risk factors
c) Presentation
d) Investigations and findings
e) Management
f) What is Richter syndrome?
a) B lymphocytes
b) Age (median age = 72), family history
c) - Asymptomatic (most are diagnosed incidentally)
- Insidious onset and progression
- Recurrent infections, lymphadenopathy, splenomegaly (LUQ pain), anaemia and thrombocytopenia
d) FBC: lymphocytosis (+ anaemia/ thrombocytopenia in more advanced disease)
- Blood film: lymphocytosis, SMUDGE CELLS (basket cells)
- Bone marrow aspirate (not always required): may show bone marrow infiltration
- Lymph node biopsy (if enlarged LN present) - may exclude lymphoma/ Richter syndrome
- Immunophenotyping
- ?imaging - spleen, liver, chest
e) - Asymptomatic: watch and wait, with 3-12 monthly blood counts and clinical examination
- Symptomatic: chemotherapy (eg. alklyating agents) plus adjuvants (eg. steroids, antibiotics, allopurinol) - note: chemotherapy is non-curative, but extends survival
- The only curative therapy is HSCT
f) Transformation of CLL into an aggressive lymphoma (eg. DLBCL): presents with fever, night sweats, weight loss, pain; occurs in ~ 5% CLL patients
Myelodysplastic syndromes (MDS).
a) What are they?
b) Causes
c) Presentation
d) Investigations and findings
e) Types (progression)
f) Management
g) Prognosis
a) Group of disorders characterised by:
- Dysplastic changes in one or more cell lineages
- Ineffective haematopoiesis (anaemia or pancytopenia)
- Risk of development into AML
b) - Primary MDS: idiopathic, increased risk with age + smoking
- Secondary MDS: previous chemotherapy (eg. alkylating agents) and radiotherapy
c) Signs of anaemia +/- neutropenia / thrombocytopenia
(note: organomegaly and lymphadenopathy = rare)
d) - FBC: anaemia +/- neutropenia / thrombocytopenia
- Blood film: dysplasia, Pappenheimer bodies
- Bone marrow aspirate: hyper/hypocellular
e) - Refractory anaemia (single lineage)
- Refractory pancytopenia (multiple lineage)
- MDS with excess blasts - type 1 (5 - 9% blasts)
- MDS with excess blasts - type 2 (10 - 19% blasts)
- AML (> 20% blasts)
f) - Asymptomatic/low risk: watch and wait, haematology monitoring, supportive care (eg. transfusions, iron chelation therapy, EPO +/- G-CSF)
- Prompt treatment of neutropenic sepsis (ABx + G-CSF)
- Chemotherapy
g) Median survival: 2 years
- Commonest cause of death: bone marrow failure (infection and haemorrhage); usually occurs before progression to AML
Non-Hodgkin’s lymphoma.
a) Types
b) Risk factors and age peaks
c) Presentation
d) Investigations and findings
e) Management
f) What is the response to treatment?
a) B cell (majority) and T cell;
- Very high grade - e.g. Burkitt’s
- High grade - e.g. diffuse large B-cell (DLBCL) - 50%
- Low grade - e.g. follicular lymphoma - 25%
b) Generally aged > 50 years; EBV (Burkitt’s/ HL), HIV and immunosuppression, coeliac (small intestinal lymphoma) and h.pylori (gastric MALT lymphoma)
c) - Low grade: painless, peripheral lymphadenopathy
- High grade: rapidly progressive lymph node enlargement, B symptoms more common
- Signs: LN enlargement, hepatosplenomegaly
d) - FBC: may be pancytopenic (may also have lymphocytosis)
- UEs, creatinine (obstructive nephropathy), LFTs
- Serology: HIV, Hep B and Hep C testing
- Lymph node biopsy
- Bone marrow biopsy and CT for staging
e) - Options: Watchful waiting, chemotherapy and RT
- Usual chemotherapy regimen: R-CHOP (rituximab + CHOP)
- if CNS lymphoma - dexamethasone adjuvant treatment
f) High-grade NHL: usually respond well to chemo
- Low-grade NHL: generally incurable but patients often live for around 10 years with follicular lymphoma
Hodgkin’s lymphoma.
a) Define
b) Risk factors (and age peaks)
c) Presentation
d) Investigations and findings
e) Give 3 biochemical poor prognostic indicators
f) Staging
g) Management
h) Prognosis
a) Malignant tumour of B lymphocytes characterised by multinucleated Reed-Sternberg cells
b) Age peaks at 20-35 and 70+; EBV, HIV, smoking
c) - Single enlarged lymph node in the neck; otherwise asymptomatic; alcohol-induced nodal pain (10%)
- B symptoms (25%): fever, night sweats, weight loss
- C symptoms: Cough/Chest symptoms
- Signs o/e: possibly lymphadenopathy, hepatomegaly, splenomegaly, and superior vena cava syndrome
d) - FBC: may be normal (if abnormal, could indicate alternative diagnosis or poor prognosis)
- ESR, LFTs, LDH
- Monospot test (glandular fever)
- Serology: HIV, Hep B and Hep C testing
- Lymph node biopsy
- Bone marrow biopsy, CXR and CT for staging
e) - Raised ESR and LDH; low albumin
f) Ann Arbor:
- Stage 1 - one nodal site or lymphoid structure (spleen, thymus)
- Stage 2 - > 1 nodal site on same side of diaphragm
- Stage 3 - > 1 nodal site on either side of diaphragm
- Stage 4 - extranodal involvement
g) - Chemotherapy (ABVD) + RT
- Adjuvants: G-CSF (reduces duration of neutropenia)
h) - 80-90% remission (cure)
- Complications of Rx: secondary AML or solid tumour, CVD, infertility (freeze eggs/sperm pre-treatment), hypothyroidism
Childhood leukaemia.
a) Highest incidence overall (~80%): peak age 2-4
b) Highest in infants < 1 year
c) Risk factors
d) Differentials
e) Primary care investigations
f) Secondary care investigations
a) ALL
b) AML
c) Genetics (translocations), Down syndrome, Fanconi anaemia, myelodysplastic syndromes, radiation exposure (eg. maternal abdominal XR during pregnancy), ataxia telangiectasia
d) - Infection: sepsis, glandular fever, septic arthritis/OM, influenza
- Autoimmune: JIA, other
- Haematological: aplastic anaemia, SCD, Fanconi anaemia, myelodysplasia
- Other malignancy: primary bone tumour, lymphoma
e) FBC and blood film
f) - LDH - elevated due to cell turnover and tissue destruction (often a poor prognostic factor)
- Bone marrow biopsy
- Imaging (eg. CT for staging)
- Lumbar puncture (if CNS infiltration suspected)
- Cytogenetic analysis (eg. FISH)
Short-term effects of chemo/radiotherapy
- Pancytopenia: aemorrhage, anaemia and infection (neutropenic sepsis)
- Hair loss, rashes, nausea, vomiting, constipation, diarrhoea, mucositis.
- Electrolyte disturbances, nephrotoxicity, hepatotoxicity.
- Tumour lysis syndrome (uric acid, phosphate and potassium are raised; calcium is low)
- Graft-versus-host disease with HSCT
Graft-versus-host disease (GvHD).
a) What is it?
b) Presentation - when and how?
c) Management
d) Why can an element of GvHD be a good thing?
a) T cells in the graft reacts against the host.
b) Within 100 days of transplant (usually 2-3 weeks after) - Skin: Rash on palms, soles, ears and face
- GI: Diarrhoea, nausea, loss of appetite
- Liver: jaundice, pruritis, deranged LFTs
c) - Steroids (eg. pred); if just skin rash - topical steroid
- Biologics/DMARDs
- Fluid replacement in diarrhoea
- Antiemetics
- Liver disease - transfusions, anti-pruritics
d) The graft T cells attack any remaining cancer cells
