Malignant Haematology Flashcards
why do you determine non lymphoid blood cells
(erythrocytes, platelets, granulocytes, macrophages)
MORPHOLOGY
cell surface antigens (glycophorin A = red cells) enzyme expression (myeloperoxidase= neutrophils)
how do you identify normal progenitor/ stem cells
IMMUNOPHENOTYPING (cell surface antigens e.g. CD34)
cell culture assays
what characterises malignant haemopoiesis
increased number of abnormal and dysfunctional cells
loss of normal activity
what types of cancers have a loss of normal haemopoiesis
acute leukaemias
what cancers have loss of normal immune function
certain lymphomas
what cell mechanisms cause malignant haemopoiesis
increased proliferation
lack of differentiation, maturation and apoptosis
what is the causative mechanisms of acute leukaemia
proliferation of ABNORMAL progenitor with block in differentiation/ maturation
what causes acute myeloid leukaemia
neoplastic proliferation of blast cells derived from marrow myeloid elements
what causes chronic myeloproliferative disorders
proliferation of abnormal progenitors but NO differentiation/ maturation block
what is the aetiology of malignant haemotology
genetic
epigenetic
environment
somatic mutations in regulatory genes (driver mutations/ passenger mutations)
what are clones
populations of cells derived from a single parent cell
the parent cell has a genetic marker (driver mutation/ chromosomal change) that is shared by the daughter cells
clones can diversify but contain a similar genetic background
how do driver mutations and malignancy affect clones
driver mutations can select clones (be shared by entire lineage) : can confer growth advantage on the cells and are then selected during the evolution of the cancer
normal haemopoiesis is polyclonal
malignant haemopoesis is MONOCLONAL
what is a passenger mutation
do not confer a growth advantage but where present in an ancestor of the cancer cell when is acquired one of its drivers
how are haematological malignancies classified
based on lineage
based on developmental stage (precursor within lineage)
based on anatomical site involved
what are the lineage classifications of malignancy
myeloid and lympoid
what are the developmental stage classifications of malignancy
stem cells= chronic myeloid leukaemias/ myeloproliferative disorders
oligolineage progenitors: acute myeloid leukaemia/ acute lymphoblastic leukaemia
mature cells= lymphomas/ chronic lymphocytic leukaemia
plasma cells= myeloma
what are the classifications of malignancy on anatomical site
blood= leukaemia
lymph node involvement with lymphoid malignancy= lymphoma
what anatomical sites can chronic lymphocytic leukaemia involve
blood and lymph nodes
what sites does myeloma involve
is a plasma cell malignancy in marrow
which types of haem malignancy are most aggressive
acute leukaemias and high grade lymphomas (both histologically and clinical more aggressive than chronic leukaemias and low grade lymphomas)
what makes a cancer histologically aggressive
large cells with high nuclear cytoplasmic ration
prominent nucleoli
rapid proliferation
what makes a cancer clinically aggressive
rapid progression of symptoms
how do acute leukaemias present
failure of normal bone marrow function
define acute leukaemia
rapidly progressing clonal malignancy of the marrow/ blood with maturation defects (cancer of immature blast cells)
=an excess of blasts (>20%) in either the peripheral blood or bone marrow causing a decrease/ loss of normal haemopoietic reserve
what are the types of acute leukaemia
acute myeloid
acute lymphoblastic
what is the most common childhood cancer
acute lymphoblastic leukaemia
what is acute lymphoblast leukaemia
malignancy of primitive lymphoid cells (lymphoblasts)
what is the presentation of acute lymphoblastic leukaemia
usually in children
marrow failure= anaemia, infections, bleeding
leukaemic effects: high count with obstruction of circulation (DVT/PE), extramedullary involvement (CNS, testis)
bone pain
what is the presentation of acute myeloid leukaemia
elderly (>60)
can be de novo or secondary
present similar to ALL (anaemia, bleeding, infections, extramedullary involvement, bone pain) + subgroups can cause: DIC, gum infiltration
what Ix for acute leukaemia
blood count and film
coagulation screen
bone marrow aspirate: morphology and IMMUNOPHEONTYPING (required for definitive diagnosis)
cyto/moleular genetics (used in diagnosis and prognosis)
trephine (piece of bone)- enables better assessment of cellularity and helpful if aspirate sub optimal
what is seen on a blood film in leukaemia IMPORTANT
reduction in normal cells
presence of abnormal cells: blasts with high nuclear: cytoplasmic ratio
ANUER rod in acute myeloid leukaemia
how is immunophenotyping done
by flow cytometry (looks for lineage specific proteins on the cell surface)
what is required for a definitive diagnosis of acute leukaemia
immunophenotyping
what is the curative Tx for acute leukaemia
multi agent chemo ALL- can last 2-3 years -can use different/ targeted Tx for different phases/ subsets AML- normally intensive -2-4 cycles -prolonged hospitalisation
what is a hickman line
central venous catheter used for the administration of chemo therapy
what problems can arise from marrow suppression
anaemia
neutropenia: infections
thrombocytopenia: bleeding
what organisms pose a high risk to neutropenic patients
gram -ve bacteria (cause fulminant life threatening sepsis)
what are the complications of chemotherapy
Nausea and vomiting hair loss liver and renal dysfunction tumour lysis syndrome infections: bacterial, fungal, protozoal (e.g. PJP)
late effects: loss of fertility, cardiomyopathy with anthracylines
how do you manage infections in chemo patients
bacterial: treat empirically with broad spectrum (esp covering gram -ves) AS SOON AS NEUTROPENIC FEVER
fungal (Tx as this if prolonged neutropenia and persisting fever unresponsive to antibacterial agents)
protozoal (more relevant in ALL)
what are the usualy outcomes of AL treatment
many go into remission (<5% marrow blasts + normal haemopoiesis)
however many relaplse
some die of treatment related toxicity
cure rates: childhood ALL >85-90% adult ALL ~30-40% adult AML <60 ~40-50% adult AML >60 ~10%/less
what options other than chemo exists for AL
targeted Txs (molecular targeting with kinase inhibitors) allogenic stem cell transplantation
