malignant haematology and acute leukaemia Flashcards
persistent, unexplained high lymphocyte count for years
low-grade lymphoproliferative disorder
what usually characterises malignant haemopoiesis
increased numbers of abnormal and dysfunctional cells
loss of normal activity
what are haematological malinancies due to (one or more of these)
increased proliferation (in absence of a stimulus)
lack of differentiation/maturation
lack of apoptosis
proliferation of abnormal progenitors with block in differentiation/maturation
acute myeloid leukaemia
proliferation of abnormal progenitors but NO differentiation/ maturation block
chronic myeloid leukaemia
classifications of haematological malignancies
based on lineage
based on developmental stage (precursor) within lineage
based on anatomical site involved
types of haematological malignancies based on lineage
myeloid
lympoid
haematological malignancy based on blood involvement
leukaemia
haematological malignancy based on lymph node involvement with lympoid malignancy
lymphoma
which haematological cancers are histologically and clinically more aggressive
acute leukaemia
high grade lymphomas
features of histological aggression
large cells with high nuclear-cytoplasmic ration, prominent nucleoli, rapid proliferation
features of clinical aggression of haematological cancers
rapid progression of symptoms
acute leukaemia
rapidly progressive clonal malignancy of the marrow/blood with maturation defects
defined as an excess of blasts in either the peripheral blood or bone marrow
types of acute leukaemia
acute myeloid leukaemia
acute lymphoblastic leukaemia
what is acute lymphoblastic leukaemia
malignant disease of primitive lympoid cells
most common childhood cancer
presentation of acute lymphoblastic leukaemia
due to marrow failure: anaemia, infections, bleeding
leukaemic effects: high count with obstruction of circulation, involvement of areas outside the marrow and blood (CNS, testes)
bone pain
what is acute myeloid leukaemia
more common in the elderly
may be de novo or secondary
presentation of AML
similar to ALL: marrow failure (anaemia, infections, bleeding)
subgroups have specific presentations: coagulation defect- DIC in acute promyelocytic
gum infiltration
investigations for acute leukaemia
- Blood count and film
- Coagulation screen
- Bone marrow aspirate
- Morphology
- Immunophenotype
- Cyto/molecular genetics - diagnostic utility, prognostic significance
- Trephine - enables better assessment of cellularity and is helpful when aspirate is sub-optimal
what would you see on a blood film in acute leukaemia
reduction in normal
presence of abnormal
- blasts: high nuclear: cytoplasmic ration
what would you expect to see in bone marrow in acute leukaemia
morphology: large cells, with high nucleus: cytoplasmic ration and prominent nucleoli
immunophenotyping: distuingish between myeloid and lymphoblastic
cyto/molecular genetics: diagnostic utility
trephine: enables better assessment of cellularity and helpful when aspirate sub-optimal
treatment of ALL
can last up to 2-3 years
- different phases of treatment of varying intensity
- targeted treatments in certain subsets
- CNS directed treatment
treatment of AML
between 2-4 cycles of chemotherapy
prolonged hospitalisation
targeted treatments in subsets
hickman line used
complications of marrow suppression
anaemia
neutropenia
thrombocytopenia
what is neutropenia
increased severity and duration of infections
gram negative bacteria can cause fulminant life-threatening sepsis in neutropenic patients
patients also susceptible to fungal infections
what is thrombocytopenia presenting as
bleeding
- purpura
- petechiae
complications of treatment for acute leukaemia
nausea and vomiting
hair loss
liver, renal dysfunction
tumour lysis syndrome (during first course of treatment)
infection
what infections can be complications of chemo
bacterial: empirical treatment with broad spectrum ABx as soon as neutropenic fever
fungal: if prolonged neutropenia and persisting fever unresponsive to anti-bacterial agents
penumocystis jirovecci penumomnia
what is chronic myeloid leukaemia
proliferation of myeloid cells- granulocytes and their precursors
aetiology of chronic myeloid leukaemia
the philadelphia chromosome
- translocation of genes between chromosome 9 and 22
- results in a new gene- BCR-ABL1
3 typical phases of CML
the chronic phase, the accelerated phase and the blast phase
what is the chronic phase of CML
can last around 5 years
often asymptomatic and patients are diagnosed incidentally with raised white cell count
what is the accelerated phase of CML
occurs where the abnormal blast cells take up a high proportion of the cells in the bone marrow and blood
- patients become symptomatic: anaemia, thrombocytopenia, immunocompromised
what is the blast phase of CML
involves an even higher proportion of blast cells to the accelerated phase
severe symptoms and pancytopenia
often fatal
presentation of CML
splenomegaly
hypermetabolic symptoms: night sweats, weight loss, gout, hyperuricemia, fever
investigations for CML
bloods:
- FBC: normal/decreased HB, increased WBC, decreased platelets
- blood film: neutrophilia
- leukocyte alkaline phosphatase (LAP)- usually reduced
bone marrow biopsy: would show increased cellularity with increase granulocytes
management of CML
fatal without stem cell/bone marrow transplant in the chronic phase
durable treatment response with tyrosine kinase inhibitors: imatinib
what is chronic lymphocytic leukaemia
occurs where there is chronic proliferation of a single type of well differentiated lymphocyte: usually B-lymphocytes
who gets CLL
usually adults over 55
presentation of CLL
often asymptomatic
can present with infections, anaemia, bleeding and weight loss
can cause warm autoimmune haemolytic anaemia
investigations for CLL
bloods:
- blood count: Hb normal/low, increased WCC, platelets normal/low
- blood film: increased lymphocytes (smear or smudge cells)
bone marrow:
- may be heavily infiltrated with lymphocytes
- immunophenotyping- mainly CD19/20 and CD5 B cells
- cytogenetic: deletion of 13 q
coombs test in CLL
may be positive if there is haemolysis
management of CLL
depends on the stage of the disease
- chemotherapeutic interventions in early stage disease is not usually necessary
- absolute indications for treatment include weight loss, night sweats, progressive marrow failure
management of neutropenia and sepsis
piperacillin/tazobactam
