Malignancy in Hematology Flashcards
How to identify NORMAL, more mature NON-lymphoid cells?
- morphology
- cell surface Ag (glycoprotein A= RED cells)
- enzyme expression (myeloperoxidase- neutrophils)
How to identify normal, PROGENITOR cells?
- Immunophenotyping (cell surface Ags)
- Cell culture ASSAY
- Animal models
What occurs in Malignant Haemopoiesis?
- incr. no. of ABNORMAL and dysfunctional cells
- LOSS of normal activity
- —-haemopoeisis/ immune function
What causes the prodn of abmormal cells, and thus dysfunctional activity?
- incr. proliferation
- lack of differentiation
- lack of maturation
- lack of apoptosis
What is the pathophysiology of Acute leukemia?
Give an example of an Acute leukemia.
- proliferation of ABNORMAL progenitors
- with BLOCK in DIFFERENTIATION/ MATURATION
- Acute myeloid leukemia
What is the pahtophysiology of Chronic myeloproliferative d.o?
- also PROLIFERATION of abnormal progenitors
- –NO differentiation/ Maturation block
ex: CHRONIC myeloid leukemia
What causes haematological malignancies?
- somatic mutation in regulatory genes (DRIVER mutation vs PASSENGER mutation)
- usually MULTIPLE hits (more than single event)
- genetic, epigenetic, env. interaction
- recurrent cytogenic abnormalities (not causal)
What are driver mutations?
mutations that provide a selective GROWTH advantage
- thus promotes CANCER development
aka CANCER gene
Is malignant haemopoiesis MONOCLONAL or POLYCLONAL?
- MONOCLONAL
Wht is a clone?
popn of cells derived from a SINGLE parent cell
—-parent cell has a driver mutation that is shared with daughter cells
—-clones may diversify; but they contain similar backbone
How to screen kids who develop ACUTE LYMPHOBLASTIC LEUKEMIA?
Guthrie cards
What are the haematological malignancies based on ?
- Lineage (myeloid/ lymphoid)
- Developmental stage
- Anatomical site
What are the diff. malignancies seen developed in lymphoid lineagee?
Acute Lymphoblastic leukemia
>Chronic Lymphocytic Leukemia
>Myeloma
What are the diff. sites of haematological malignancies?
- blood: LEUKAEMIA
2. Lymph node involvement: LYMPHOMA
AT what sites does chronic lymphocytic leukaemia manifest?
in blood and lymph nodes
Where does myeloma manifest?
plasma cell malignancy in MARROW
Which is more CLINICALLY aggressive?
Acute leukemias and HIGH-grade LYMPHOMAS
—-aggressive due to RAPID progression of SX
What are the histological fts of aggression?
- large cells with HIGH nuclear-cytoplasmic ratio
- Prominent nucleoli
- Rapid proliferation
What is Acute lymphoblastic leukaemia a disease of?
- malignant disease of PRIMITIVE lymphoid cell (lymphoblasts)
Name the most common childhood cancer.
Acute lymphoblastic leukaemia
What is the clinical presentation of ALL?
- Marrow failure (anaemia/ infections/ bleeding)
- leukemic efx: high count with OBSTRUCTION of circulation (involves areas OUTSIDE the marrow and blood)—CNS and TESTIS
- Bone pain
What is seen with Acute Myeloid Leukaemia? And in whom?
- SIMILAR presentation to MARROW failure
- >60 y.o
What ivx done for acute leukemia?
- blood film and COUNT
- Coagulation screen
- bone marrow aspirate
What should be observed on blood film?
- reduction in NORMAL
- presence of ABNORMAL
- —note the BLASTS with a HIGH nuclear:cytoplasmic ratio
What could be invx with bone marrow sampling?
- Morphology
- Immunophenotyping
- cyto/molecular genetics (diagnostic UTILITY and PROGNOSTIC significance)
- Trephine
How tell AML apart from ALL?
by immunophenotyping
— replaced cytochemistry as a diagnostic tool
What does immunophenotyping seek?
(by flow-cytometry) —lineage-specific proteins on cell surface
What is trephine?
- the analysis of a PIECE pf a bone
- allows better assessment of cellularity and HELPFUL when aspirate is sub-optimal
What is the treatment for ALL like?
- lasts up to 2-3 years
- diff. phases of rx (varying intensity)
- targeted rx for diff. subsets
What is the rx for AML like?
- normally intensive
- 2-4 cycles of CHEMO (5-10 days of chemo followed by 2-4 weeks of recovery)
- prolonged hospitalisation
- target rx
What is a Hickman-Line?
- long, flexible, plastic tube inserted underneath the CHEST wall skin
> into the large vein draining INTO the heart
—allows the delivery of medication
What are the issues with marrow suppression?
- Anaemia
- Neutropenia (Infections/ severity and duration)
- Thrombocytopenia
What are neutropenic pts predisposed to?
- gram (-)ve bacteria
- –may cause fulminant LIFE threatening sepsis
Risk of thrombocytopenia.
BLEEDING
- purpura
- petechiae (plt <20 x10)
What are the complications of rx?
- N.V
- hair loss
- liver, renal dysfxn
- tumor lysis syndrome (1st course of rx)
- INFECTION
- later: loss of fertility/ cardiomyopathy with anthracyclines)
What is tumor lysis syndrome?
- the mass breakdown of tumor cells, results in a huge spike in K+, uric acid
- drop in calcium levels
What are the symptoms of tumor lysis syndrome?
- palpitations
- seizures
- DARK urine, reduced output and flank pain
- Nausea (with/without vomitting)
- lack of appetite
- numbness/ hallucinations
- muscle cramps/ spasms
—left untreated> KIDNEY FAILURE and DEATH
What should be done as soon as a chemo pt develops a fever?
- neutropenic fever
- give EMPIRICAL treatment with BROAD spectrum antibiotics (cover gram (-)ve)
What does it mean if there is PROLONGED neutropenia with a PERSISTING fever unresponsive to anti-bacterial agents?
FUNGAL infection
What protozoan infection maybe seen with chemo?
PJP
What kind of infections are common in individuals?
bacterial is COMMON
—-but they are v. susceptible to FUNGAL
Define acute leukemia.
- excess of BLASTS (>20%) in either the peripheral blood or bone marrow !
—–rapid, progressive clonal malignancy of the marrow or blood with maturation defects.
Characteristic presentation for AML subgroups.
- gum hypertrophy
- DIC
How effective if rx for leukaemia?
- MANY go into REMISSION (<5% marrow blasts with recovery of NORMAL haemopoiesis)
- —remissions not durable for some types of leukaemia (many RELAPSE)
—some die of rx-related toxicity
What are other options for treamtment of leukaemia?
- targeted rx (Molecular targeting- with KINASE inhibitors; Acute lymphocytic leukaemia wuth PHILADELPHIA chromosome)
- allogenic stem cell transplant
What makes AML (acute promyelocytic leukaemia) associated with another particular disorder.
- specific chromosomal translocation
t(15:17) - a.w DIC
What is immunotherapy about?
- egineering T-cells to ATTACK leukaemic cells
CAR T-CELL therapy
