Flashcards in haematological malignancies Deck (81):
what conditions consist of myeloproliferative disorders?
polycythaemia vera, CML, essential thrombocythaemia, myelofibrosis,
what causes myeloproliferative disorders?
In these disorders, there is uncontrolled clonal proliferation of one or more of the cell lines in the bone marrow, namely erythroid, myeloid and megakaryocyte lines.
what is the Ann Arbor staging system for hodgkin lymphoma?
1. Disease is confined to one lymph node group
2. Disease is in 2 adjacent lymph node groups
3. Present in lymphoid tissues on both sides of the diaphragm
4. Present in a non lymph node/extranodal organ (e.g. brain, bone marrow
what are the "B" symptoms?
night sweats and 10% weight loss and fever
what is the treatment of Hodgkin Lymphoma?
All given IV
= ABVD treatment
+/- GM CSF subcutaneous injection
What is the treatment for Non Hodgkin lymphoma?
Hydroxydornorubison (adriomycin) IV
Oncovan (mitotic spindle inhibitor) IV
what is the difference between a leukaemia and a lymphoma?
leukaemias affect the bone marrow as well. Lymphoma only affects a lymphoid tissue outside the bone marrow
what are the signs of bone marrow failure?
anaemia, bleeding and infection
what is the mutation associated with CML?
BCR-ABL mutation. This BCR ABL fusion gene codes for a 210 kDa protein with tyrosine kinase activity, which plays a causative role in the disease as an oncogene influencing cellular proliferation, differentiation and survival.
what is the most common leukaemia? What mutation is it associated with?
CLL. BCL2 dysregulation leading to impaired Caspase path towards apoptosis. This causes cell survival
which is more common- B or T cell lymphoma?
B cell lymphomas
why do we give G-CSF for CHOP-R treatment?
CHOP-R treatment is myelosuppressive
what is light chain restriction a marker of?
a marker of malignancy
What does MGUS stand for? what is it a risk factor for?
Monoclonal gammopathy of undermined significance. Higher chance of progressing to myeloma
how do we investigate multiple myeloma?
Bone marrow aspirate- film + flow cytometry, CRAB, urine test, FBE, U and E, B-2 microglobulin, serum albumin, LDH, serum and urine protein electrophoresis and measurement of free light chains. Do imaging for lytic bone lesions (a skeletal survey of spine, skull, long bones + spinal MRI).
2. Renal insufficiency
4. Lytic bone lesions
what do you think of a normal protein level with a low albumin?
Traditional chemotherapy for multiple myeloma?
Alkylating agents (cyclophosphamide)
Supportive therapy for myeloma?
1. Plasmapheresis, dialysis, radiotherapy/surgery
2. Bisphosphonate- (prevent orthopaedic complications)
3. Infection control (bc they may be immune suppressed)
4. Pain management (crush fractures/plasmacytomas)
5. Psychological/supportive management
what protein do we look for in the urine for Multiple myeloma?
Bence Jones protein
does everyone with paraprotein have multiple myeloma?
no. Unless they demonstrate CRAB features
what is a lymphoma?
malignancy derived from lymphoid tissue
Clinical aggressiveness of Burkitt Lymphoma?
High grade. Need to come into hospital and need treatment ASAP
what is the clinical aggressiveness of follicular lymphoma?
what directs prognosis in Non hodgkin lymphoma?
the grade (histological aggressiveness)
what symptoms might make you think of a lymphoma as a ddx?
palpable pathological lymphadenopathy (firm, rubbery, non-tender ) – rate of growth depends on biological aggressiveness of subtype
• dyspnoea and cough with subsequent demonstration of a mediastinal mass
• abdominal swelling and/or progressive discomfort( although non-specific )
• PUO and night sweats
what determines the prognosis of a hodgkin lymphoma?
the stage or subtype determines the prognosis
in lymphoproliferative disorders like NHL what marker is always raised?
what kind of lymphoma causes a mediastinal mass? what might you see on blood film?
T cell lymphoma
-on blood film may see eosinophillia
what is something you want to ask yourself when you have a patient with leukaemia?
Acute or chronic?
Myeloid or lymphoid?
Secondary acute leukaemia is caused by what?
previous cytotoxic therapy is the most important reason
- exposure to ionising radiation/chemicals
Kids with down syndrome is more susceptible to which type of leukaemia
clinical presentation of acute leukaemia
1. anaemia- lethargy, chest pain, pallor
2. neutropenia- fevers/rigors/infections
3. thrombocytopenia- bruising and bleeding
4. B symptoms- fevers, sweats, weight loss
5. Less commonly- lymphadenopathy, hepatosplenomegaly, hyperleucocytosis
key ix for acute leukaemia
1. FBE and FILM
2. Bone marrow biopsy- is this disease lymphoid or myeloid?
3. immunophenotyping- flow cytometry for cell surface markers
5. molecular studies
how can we tell if the leukaemia is lymphoid or myeloid in origin?
bone marrow biopsy and flow cytometry
if you see blasts in the peripheral blood-
CALL A HAEMATOLOGIST
what defines acute leukaemia?
if you see infiltration of malignant cells= blasts greater than 20% nucleated cells on BONE marrow biopsy
auer rods indicate?
implication of CD34 from flow cytometry
marker of immature cells- indicates leukaemia
What do we use immunophenotyping/flow cytometry for when we ix for suspected leukaemia?
helps to determine the type of acute leukaemia by the pattern of surface antigen expression
what indicates good response to standard chemo for AML?
cytogenetics and molecular findings, and whether there is residual disease after therapy
ALL prognosis child vs adult?
child ALL generally has better prognosis than adult ALL. mainly due to implementation of good intensive paediatric protocols
Key medical treatment for ALL
main features of APML at presentation
Signs of DIC, low fibrinogen, thrombocytopenia
key histological cell of APML from bone marrow biopsy
Faggot cells- cytoplasm full of auer cells (promyelocyte)
cytogenetics fo APML?
15:17 translocation-RARa and PML genes
APML acute management?
1. Correct coagulopathy, with platelets, cyroprecipitate, and fibrinogen as needed
2. Transfer to hospital who has ATRA (all trans retinoid acid) to induce promyelocytic differentiation
3. Add arsenic
Philadelphian 9:22 chromosomal translocation associated with which leukaemias?
ALL and CML
3 stages of chronic myeloid leukaemia?
2. accelerated (if remains untreated)
3. blast (untreated)--> acute leukaemia
what would you see under the microscope for a blood film of CML?
full spectrum of myeloid development
management of CML?
Tyrosine kinase inhibitor
Selectively kill CML cells, and has eliminated the need for allograft.
how does imatinib work?
blocks ATP binding site for BCR ABL protein reducing signalling for cell proliferation
commonest adult leukaemia?
What symptoms constitute advanced CLL
hypogammaglobulinemia and recurrent infections
CLL morphology- blood and bone marrow?
small mature, lymphocytosis with smear cells
What are the cell markers we are looking for on flow cytometry for CLL?
what is the significance of 17 p deletion in CLL?
loss of TSG p53 indicates poor prognosis
how might we ix cytogenetics of CLL?
FISH (fluorescent in situ hybridisation)
when do we start treating CLL?
when the patient is symptomatic.
prognosis of CLL?
can either be indolent disease or an aggressive disease if p53 lost due to 17p deletion
what is the only curable option of CLL
how do we manage symptomatic CLL patients?
1. chemotherapy inc. rituximab
2. monoclonal antibodies
which leukaemia are associated with splenomegaly
any leukaemias with a monocytic or monoblastic origin
describe a reed steinberg cell. what is it associated with?
binuclear cells with prominent eosinophillic nucleolus
Diagnostic of hodgkin lymphoma
what is the most common type of monoclonal M protein in multiple myeloma?
overproduction of one or more immunoglobulins
what is the clinical criteria for multiple myeloma
Diagnosis= increased malignant plasma cells in the bone marrow + detection of serum/urinary M protein + skeletal lytic lesions (only 2 needed)
where do we normally see malignant plasma cells for multiple myeloma?
in the bone marrow
what are bence jones proteins and where do we see them?
free light chains in the urine.
in light chain only multiple myeloma
what is a paraprotein?
monoclonal protein--> immunoglobulin.
why do we get lytic lesions in multiple myeloma?
malignant plasma cells produce cytokines --> stimulate OC and results in net bone resorption --> lytic lesions
why do we get renal failure from multiple myeloma?
paraprotein deposition, hypercalcaemia, NSAIDs, amyloid
COMPLICATIONS OF MULTIPLE MYELOMA
Spinal cord compression --> treated with dexamethasone
symptoms of multiple myeloma
Symptoms of anaemia
Symptoms of hypercalcaemia (renal stones)
Symptoms of renal failure
treatment of symptomatic CLL?
FCR chemotherapy regime
what is the chemotherapy drugs for AML in fit patients (i.e. the patients that are not going to be palliated)
what is a plasmacytoma
clonal proliferation of plasma cell
cell marker for myeloma
what can MGUS progress to?
myeloma, lymphoproliferative disorder, amyloidosis
difference between plasmacytoma and myeloma?
what is primary amyloidosis associated with?
associated with a plasma cell or lymphoplasmatcytic lesion including MGUS