Malignant Haematology

Question 1

why do you determine non lymphoid blood cells

Answer 1

(erythrocytes, platelets, granulocytes, macrophages)
MORPHOLOGY

cell surface antigens (glycophorin A = red cells) 
enzyme expression (myeloperoxidase= neutrophils)

Question 2

how do you identify normal progenitor/ stem cells

Answer 2

IMMUNOPHENOTYPING (cell surface antigens e.g. CD34)

cell culture assays

Question 3

what characterises malignant haemopoiesis

Answer 3

increased number of abnormal and dysfunctional cells

loss of normal activity

Question 4

what types of cancers have a loss of normal haemopoiesis

Answer 4

acute leukaemias

Question 5

what cancers have loss of normal immune function

Answer 5

certain lymphomas

Question 6

what cell mechanisms cause malignant haemopoiesis

Answer 6

increased proliferation

lack of differentiation, maturation and apoptosis

Question 7

what is the causative mechanisms of acute leukaemia

Answer 7

proliferation of ABNORMAL progenitor with block in differentiation/ maturation

Question 8

what causes acute myeloid leukaemia

Answer 8

neoplastic proliferation of blast cells derived from marrow myeloid elements

Question 9

what causes chronic myeloproliferative disorders

Answer 9

proliferation of abnormal progenitors but NO differentiation/ maturation block

Question 10

what is the aetiology of malignant haemotology

Answer 10

genetic
epigenetic
environment

somatic mutations in regulatory genes (driver mutations/ passenger mutations)

Question 11

what are clones

Answer 11

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

Question 12

how do driver mutations and malignancy affect clones

Answer 12

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

Question 13

what is a passenger mutation

Answer 13

do not confer a growth advantage but where present in an ancestor of the cancer cell when is acquired one of its drivers

Question 14

how are haematological malignancies classified

Answer 14

based on lineage
based on developmental stage (precursor within lineage)
based on anatomical site involved

Question 15

what are the lineage classifications of malignancy

Answer 15

myeloid and lympoid

Question 16

what are the developmental stage classifications of malignancy

Answer 16

stem cells= chronic myeloid leukaemias/ myeloproliferative disorders
oligolineage progenitors: acute myeloid leukaemia/ acute lymphoblastic leukaemia
mature cells= lymphomas/ chronic lymphocytic leukaemia
plasma cells= myeloma

Question 17

what are the classifications of malignancy on anatomical site

Answer 17

blood= leukaemia

lymph node involvement with lymphoid malignancy= lymphoma

Question 18

what anatomical sites can chronic lymphocytic leukaemia involve

Answer 18

blood and lymph nodes

Question 19

what sites does myeloma involve

Answer 19

is a plasma cell malignancy in marrow

Question 20

which types of haem malignancy are most aggressive

Answer 20

acute leukaemias and high grade lymphomas (both histologically and clinical more aggressive than chronic leukaemias and low grade lymphomas)

Question 21

what makes a cancer histologically aggressive

Answer 21

large cells with high nuclear cytoplasmic ration
prominent nucleoli
rapid proliferation

Question 22

what makes a cancer clinically aggressive

Answer 22

rapid progression of symptoms

Question 23

how do acute leukaemias present

Answer 23

failure of normal bone marrow function

Question 24

define acute leukaemia

Answer 24

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

Question 25

what are the types of acute leukaemia

Answer 25

acute myeloid | acute lymphoblastic

Question 26

what is the most common childhood cancer

Answer 26

acute lymphoblastic leukaemia

Question 27

what is acute lymphoblast leukaemia

Answer 27

malignancy of primitive lymphoid cells (lymphoblasts)

Question 28

what is the presentation of acute lymphoblastic leukaemia

Answer 28

usually in children marrow failure= anaemia, infections, bleeding leukaemic effects: high count with obstruction of circulation (DVT/PE), extramedullary involvement (CNS, testis) bone pain

Question 29

what is the presentation of acute myeloid leukaemia

Answer 29

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

Question 30

what Ix for acute leukaemia

Answer 30

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

Question 31

what is seen on a blood film in leukaemia IMPORTANT

Answer 31

reduction in normal cells presence of abnormal cells: blasts with high nuclear: cytoplasmic ratio ANUER rod in acute myeloid leukaemia

Question 32

how is immunophenotyping done

Answer 32

by flow cytometry (looks for lineage specific proteins on the cell surface)

Question 33

what is required for a definitive diagnosis of acute leukaemia

Answer 33

immunophenotyping

Question 34

what is the curative Tx for acute leukaemia

Answer 34

``` 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 ```

Question 35

what is a hickman line

Answer 35

central venous catheter used for the administration of chemo therapy

Question 36

what problems can arise from marrow suppression

Answer 36

anaemia neutropenia: infections thrombocytopenia: bleeding

Question 37

what organisms pose a high risk to neutropenic patients

Answer 37

gram -ve bacteria (cause fulminant life threatening sepsis)

Question 38

what are the complications of chemotherapy

Answer 38

``` 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

Question 39

how do you manage infections in chemo patients

Answer 39

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)

Question 40

what are the usualy outcomes of AL treatment

Answer 40

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 ```

Question 41

what options other than chemo exists for AL

Answer 41

``` targeted Txs (molecular targeting with kinase inhibitors) allogenic stem cell transplantation ```