Malignancy Flashcards
What is acute Lymphoblastic leukaemia
Acute malignancy of lymphoid cells
Pathology of ALL
Affecting lymphoid lineages
Increase proliferation
But failure to differentiate
Uncontrolled proliferation of immature blast cells
Who is ALL common in
Children
Clinical features of ALL
V. short Hx/V. Acute:
Marrow failure: Anaemia (Hb) Infection (WCC) Bleeding (platelets) Pallor (due to anaemia) Petechia (due to platelet dysfunction)
Infiltration:
Hepatosplenomegaly
Lymphadenopathy
CNS involvement:
CN palsies
Meningism
Common infections in ALL
Bacterial septicaemia Zoster CMV Measles Candiadisis
Blood film in ALL
Characteristic blast cells
Bone marrow in ALL
Characteristic blast cells
Dx blast cell criteria for ALL
> 20% lymphoblasts present in bone marrow
Ix for ALL
Blood film Bone marrow biopsy FBC Coagulation screen U&E's LFTs CXR CT LP
Prognosis in ALL in children compared to adults
Cure rates in children 70-90%
Adults = poorer prognosis
Describe CAR therapy
Patient/healthy 3rd party T cells harvested
Transfected to express a specific T-cell receptor
Expanded in vitro
Re-infused into the patient
Complications of T cell immunotherapy
Cytokine release syndrome
Neurotoxicity
Chemotherapy regimen for ALL
Induction therapy
Consolidation therapy
Maintenance chemotherapy
Newer therapies used to treat ALL
Bispecific T cell engagers
CAR therapy
CNS directed/prophylaxis Rx in ALL
Intrathecal (or high dose) methotrexate +/- CNS irradiation
What is the commonest acute leukaemia in adults
AML
Pathology of AML
Affects Myeloid cells so that:
Increased proliferation but failure to differentiate or mature
Bone Marrow Failure clinical features in AML
Anaemia
Thrombocytopenia (purpura and mucosal membrane bleeding)
Infection (due to neutropenia -> predominantly bacterial and fungal)
Infiltration clinical features of AML
Hepatomegaly Splenomegaly Gum hypertrophy Infiltration brain Bone pain (bone infiltration)
Blood count features AML
Neutropenia
Thrombocytopenia
Decreased Hb
Ix for AML
FBC
Blood fim
Bone marrow biopsy
What blast count confirms AML
> 20%
When would CSF be Ix in AML
If CNS symptoms present
Rx for AML
Supportive care
Anti-leukaemic chemotherapy
Stem cell Tx
Targeted treatment
Describe stem cell Tx in AML
Allogenic
HLA matched donors
Aim to conoslidate remission/potentially cure
What does myeloid blast cell count <15% mean
Myelodysplastic disorders
Describe remission
State where blood counts have returned to near normal state independent of transfusion
Blast count <5%
New developments in AML treatment
Targeted Ab
Targeted small molecules
New delivery systems
Pathology of chronic myeloid leukaemia
Affects myeloid cells:
Ongoing proliferation
AND
Ongoing differentiation ast a higher rate
Features of CML
Anaemia Splenomegaly Abdo pain Weight loss Gout
Features of hyperleukostasis
Fundal haemorrhage
Venous congestion
Altered consciousness
Resp failure
What is hyperleukostaiss
Medical emergency
Commonly associated with CML
Extremely elevated blast cell counts and symptoms of decreased tissue perfusion
Symptoms of CML
Mostly chronic and insidious
W.t loss Fever
Fatigue
Sweats
Lab features of CMl
Increased WCC
Increased platelets
Decreased Hb (anaemia)
Blood film features of CML
All stages of WCC differentiation are increased
Ix for CML
FBC
Blood film
Bone marrow biopsy Dx
Which chromosomal anomaly is associated with CML
Philadelphia chromosome
Describe philadelphia chromosome
Small chromosome 22
Result of balance translocation between chromosome 9 and 22
Forming fusion BCR-ABL oncogene
Which oncogene is formed in Philadelphia chromosome
BCR-ABL
Why are Tyroskine kinase inhibitors used to treat CML
Because BCR-ABL oncogene (from Philadelphia chromosome) has tyrosine kinase activity
1st line RX for CML
Tyrosine Kinase Inhibitors: e.g Imatinib
Direct inhibitor of BCR-ABL
1st line in all patient’s now
2nd line Rx CML
Allogenic Tx
Few now
Carried sig. morbidity and mortality
When would allogenic Rx be used in CML
Failure of tyrosine kinase inhibitors
Who is the Philadelphia chromosome found in
Most patients with CML
Some patients with AML
Who does CLL mainly affect
Older
What is the commonest leukaemia worldwide
CLL
Aetiology of CLL
Potentially genetic
But relatively unknown
Dx criteria for CLL
Blood > 5 x 10 to 9/L lymphocytes
Bone marrow > 30% lymphocytes
Pathology of CLL
Affects lymphoid cells so that
Ongoing proliferation
AND
Ongoing differentiation at a higher rate
Clinical features of CLL
Bone marrow failure:
Anaemia
Thrombocytopenia
Lymphadenopathy (enlarged, rubbery, non-tender)
Splenomegaly
Fever and sweats
What is the commonest presentation of CLL
Often asymptomatic
Patients picked up on routine bloods for something else e.g anaemia
Ix for CLL
FBC
Blood film
Bone marrow biopsy
Which staging is used for CLL
Binet
Describe Binet stage A
<3 groups LN affected
Increased WCC
Describe Binet stage B
> 3 groups of enlarged LN affected
And increased WCC
Describe Binet Stage C
Enlarged LN or spleen
Increased WCC
Decreased RBC
Decreased platelets
Rx for CLL
Often nothing
1/2 require chemo
1/2 require observation
Potential Rx treatments for CLL
Cytotoxic chemotherapy
Monoclonal antibodies
Novel agents
Radiotherapy
Which monocloncal ab can be used to Rx CLL
Rituximab
Which novel agents cn be used to Rx CLL
Bruton tyrosine kinase inhibtors
PI3K inhibitor
What can radiotherapy be used to Rx in CLL
Splenomegaly
Lymphadenopathy
Indications for RX in CLL
Progressive bone marrow failure Massive lymphadenopathy Progressive splenomegaly Lymphocyte doubling time <6 months Systemic symptoms Autoimmune cytopenias
Poor Prognostic factors CLL
Advanced disease Atypical lymphocyte morphology Rapid lymphocyte doubling time CD38+ expression Loss/mutation p53
