Haematological Malignancies Flashcards
Classification is based on…
Clinical features, morphology, immunophenotyping and genetic alterations
Cancer of the myeloid stem cell causes…
Acute leukaemia
Cancer of the lymphoid stem cell causes…
Acute leukaemia
Cancer of the plasma cell causes…
Myeloma
Cancers of the B, T, and NK cells cause…
B, T and NK cell lymphomas
Cancers of the RBCs, platelets or granulocytes cause…
Myeloproliferative / myelodysplastic neoplasms
Granulocytes include…
Eosinophils, basophils and neutrophils
Is myeloid neoplasm morphology normal or abnormal?
Either
Myeloid neoplasms are all…
Clonal disorders of haematopoeisis
Morphology of myeloproliferative neoplasms:
Increased mature-appearing cells
Are myeloproliferative neoplasms acute or chronic?
Chronic
Myeloproliferative neoplasms have a variable risk of transformation to…
Acute myeloid leukaemia
Morphology of myelodysplastic syndromes:
Neutrophils usually have 3 lobes
Reduced number of cells and reduced lobes in neutrophils
Are myelodysplastic syndromes acute or chronic?
Chronic
Risk of myelodysplastic syndromes transforming to AML?
30%
Morphology of AML:
Decreased mature peripheral blood cells
Immature cells in the BM and periphery
Decreased RBCs and platelets
Increased white cell count
PV (myeloproliferative, too many RBCs) =
Polycythaemia vera
ET (myeloproliferative, too many platelets)
Essential thrombocytopenia
PM (myeloproliferative, fibrosis in BM)
Primary myelofibrosis
CML (myeloproliferative, 9-22 translocation on the Philadelphia chromosome)
Chronic myeloid leukaemia
Loss of normal BM function in acute leukaemia causes…
Anaemia, fatigue, fever, infection, bruising, bleeding
Infiltration of organs in acute leukaemia causes…
Hepatomegaly, splenomegaly, lymphadenopathy (mediastinal mass in lymphoblastic)
Which type of acute leukaemia develops mediastinal mass?
Lymphoblastic
CNS symptoms in acute leukaemia?
Headache, nausea, nerve palsy
Which acute leukaemia does Auer Rods indicate?
Myeloid
Leukaemia treatment is guided by testing for?
Minimal residual disease
Which medical emergency can be suggested by WCC>100 and lymphoma mass>10cm?
Tumour lysis syndrome
TLS cellular breakdown causes what?
Hyperuricaemia
Three symptoms of TLS are?
Arrhythmia, renal failure, neuromuscular irritability
TLS can be treated with which drugs?
Allopurinol or rasburicase
The translocation of chromosomes 15 and 17 bringing together RARA and PML genes causes which condition?
Acute promyelocytic leukaemia
High PT, high APTT, high D-dimers
Low fibrinogen, low platelets, low TT:
Acute promyelocytic leukaemia
Cure for acute promyelocytic leukaemia?
ATRA and arsenic
What are lymphoid neoplasms?
Clonal tumours of B, T or NK cells
Where does the B cell neoplasia responsible for B lymphoblastic leukaemia / lymphoma occur?
Bone Marrow
Where does the B cell neoplasia responsible for Mantle cell lymphoma occur?
Interfollicular area
Where does the B cell neoplasia responsible for follicular lymphoma occur?
Follicular area
Where does the B cell neoplasia responsible for Burkitt lymphoma occur?
Follicular area
Where does the B cell neoplasia responsible for Hodgkin’s lymphoma occur?
Follicular area
Where does the B cell neoplasia responsible for MALT lymphoma occur?
Perifollicular area
Where does the B cell neoplasia responsible for plasmacytoma occur?
Perifollicular area
Where does the T cell neoplasia responsible for T lymphoblastic lymphoma / leukaemia occur?
Thymus and BM
Where does the T cell neoplasia responsible for peripheral (mature) T cell + NK cell lymphomas / leukaemia occur?
Spleen, mucosa, peripheral blood, skin, organ specific, follicle
Which haematological malignancy can be detected through clonal abnormal Ab secretion?
Plasma cell myeloma
15-20% of plasma cell myelomas are…
Light chain
Prognosis of plasma cell myelomas is based on what?
Genetics, albumin and beta-2 microglobulin
Hypercalcaemia, renal failure, lytic lesions, anaemia, recurrent infections and amyloid plaques are symptoms of which haematological malignancy?
Plasma cell myeloma
How do you diagnose plasma cell myeloma?
Paraprotein and serum free light chains
What do 50% of plasma cell myeloma patients present with?
Renal insufficiency
What are the three effects on the kidney of cast nephropathy?
Reduced GFR, interstitial nephritis and tubular nephropathy
What is the effect of cast nephropathy on the glomerulus?
No effect
What are the two main conditions that cause renal insufficiency in PC myeloma?
Cast nephropathy or secondary AL amyloidosis
What is the histological triad of cast nephropathy?
Proximal tubular injury, waxy casts in distal tubules and interstitial fibrosis
Is secondary AL amyloidosis a nephrotic or nephritic syndrome?
Nephrotic
How does secondary AL amyloidosis affect the glomerulus?
Glomerular deposition of light chains (nephrotic syndrome)
How do you diagnose secondary AL amyloidosis?
Biopsy or BM aspirate and trephine
Acute leukaemia with blast cells > 100 can cause which complication?
Hyperviscosity syndrome
Acute leukaemia, Waldenstroms macroglobulinaemia and polycythaemia vera can all cause which complication?
Hyperviscosity syndrome
Is myeloma acute or chronic?
Chronic
Is myeloma curable?
No
When do we treat myeloma?
When symptomatic
What is the mainstay of myeloma treatment?
Supportive
What is given for bone protection?
Bisphosphonates
How do we treat a first myeloma relapse in the young patient?
Stem cell transplant
Definition of lymphoma:
Replacement of normal lymphoid structures with malignant cells
What cell-type of NHL is most common?
B cell
What is the commonest high grade B-NHL?
Diffuse large B-cell lymphoma
What is the commonest low grade B-NHL?
Follicular lymphoma
Morphology of Hodgkin’s lymphoma (HL)?
Reed-Sternberg cells (owl eyes)
In which lymph nodes does HL normally arise?
Upper body
In which lymph nodes does NHL normally arise?
Anywhere
Lymphoma can be…
Extra-nodal
What is a lymphoma tumour made up of?
Cancer surrounded by reactive cells
Lymphoma shared symptoms:
Hepatomegaly, splenomegaly, extra-nodal sites, fever, lymphadenopathy, malaise
Differentials for HL:
Alcohol-induced pain, Pal-Ebstein fever, mediastinal mass
Differentials for NHL:
Itches
What are the features of Pal-Ebstein fever?
40 degrees fever every two weeks
(Lymphoma) 1 site
Stage I
(Lymphoma) 2 or more sites, one side of diaphragm
Stage II
(Lymphoma) 2 or more sites, both sides of the diaphragm
Stage III
(Lymphoma) Spleen involvement
Stage III
(Lymphoma) Extra-lymphatic site
Stage III
(Lymphoma) Diffuse involvement of extra lymphatic sites +/- nodal disease
Stage IV
t(14;18)
Follicular lymphoma
t(11;14)
Mantle cell lymphoma
t(8;14)
Burkitt lymphoma
Deletion 17p-
Chemoresistance
Myd88 mutation
Waldenstrom macroglobulinaemia
BRAF mutation
Hairy cell leukaemia
p53 mutation
Chemoresistance
High grade B cell lymphoma treatment?
Chemo and Rituximab
Early low grade (symptomatic) lymphoma cure?
Radiotherapy
Hodgkin’s stage I/II treatment regimen:
2-4 cycles of chemo and radio
Hodgkin’s stage III/IV treatment regimen:
6 cycles of chemo
Novel therapies for lymphoma?
Brentuximab, Nivolumab
Temperature > 38 degrees and neutrophils < 0.5 x 10^9 =
Neutropenic Sepsis
Tazocin (meropenem if fungal) +/- aminoglycoside (if shocked) +/- Teicoplanin/Vancomycin is an example of broad spec Abx with g-ve coverage. But in which condition would you commence this regimen?
Neutropenic Sepsis
What is the R-CHOP regimen used to treat?
Diffuse large B-cell lymphoma
What does the acronym ‘R-CHOP’, which represents a chemo regimen for NHL, stand for?
Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone
40-70% BM involvement in which NHL?
Follicular lymphoma
Treatment for symptomatic follicular lymphoma?
6-8 cycles of chemo and rituximab
How does chronic lymphocytic leukaemia present?
Asymptomatic lymphocytosis
Where is chronic lymphocytic leukaemia found?
Peripheral blood, BM and lymph nodes
What are the symptoms of chronic lymphocytic leukaemia?
Fatigue, weight loss, anorexia, infection, bulky lymphadenopathy, BM failure and splenomegaly
What are the bloodworm findings in chronic lymphocytic leukaemia?
AI haemolytic anaemia, thrombocytopenia, hypogammaglobulinaemia and T cell defects
(Chronic lymphocytic leukaemia) 2 lymph node areas or under:
Stage A
(Chronic lymphocytic leukaemia) 3 lymph node areas or over:
Stage B
(Chronic lymphocytic leukaemia) Haemoglobin 10g/dL or over; platelets 100 x 10^9/L or under:
Stage C
(Chronic lymphocytic leukaemia) Isolated lymphocytosis:
Stage 0
(Chronic lymphocytic leukaemia) Lymphadenopathy:
Stage I
(Chronic lymphocytic leukaemia) Splenomegaly:
Stage II
(Chronic lymphocytic leukaemia) Lymphadenopathy + Splenomegaly:
Stage III
(Chronic lymphocytic leukaemia) Haemoglobin 10g/dL or over; platelets 100 x 10^9/L or under:
Stage IV
Ibrutinib is a targeted treatment for…
Chronic lymphocytic leukaemia
Idelalisib is a targeted treatment for…
Chronic lymphocytic leukaemia
Venetoclax is a targeted treatment for…
Chronic lymphocytic leukaemia
Obinutuzumab is an Ab treatment for…
Chronic lymphocytic leukaemia
Ofatumumab is an Ab treatment for…
Chronic lymphocytic leukaemia
Chemoimmunotherapy for chronic lymphocytic leukaemia:
FCR, FR, BR, CR, ORR
What is the principle treatment for myeloma?
Analagous stem cell transplant
When do we treat lymphoma with a stem cell transplant?
Relapse