Clinical Management - Leukaemia Flashcards
Name four Leukmias
- Acute Myeloid Leukaemia
- Chronic Myeloid Leukaemia
- Acute Lymphoblastic Leukaemia
- Chronic Lymphocytic leukaemia
What is leukaemia
Malignant proliferation of haemopoietic cells
Blood test for leukaemia
- Haemoglobin ia low
- WBC count raised
- Low platelet count
What would a blood film show for leukaemia
- Blast cells seen
What about a bone marrow biopsy indicate
- Reduced erythropoiesis
- Reduced Megakaryocytic
- Blast cell replacement
What would the CXR show
Mediastinal widening - shows T-lymphoblastic leukaemia
What examination is specific to Acute Lymphocytic Leukaemia
Cerebrospinal Fluid examination - risk of CNS involvement is high
What is immunophenotyping
Classifying tumour cells by antigen expression profile
Genetic diagnosis for leukaemia
- Cytogenetics:
Karyotyping
FISH - Molecular Genetics:
PCR
How does the incidence of Acute Myeloid Leukaemia be effected with age
Increases
What risks increase the chances of Acute Myeloid Leukaemia
- Previous haematological disorders
- Prior Chemotherapy
- Exposure to ionising radiation
Supportive care for Acute Myeloid Leukaemia
- HML
- Blood product support
- Prompt treatment of infections
- Recognition of atypical/unusual infections
Chemotherapy/Transplantation
What is the approximate cure rates for AML
60% children
50% younger adults
Less than 20% older adults
What causes Acute Promyelocytic Leukaemia
PML/PARA gene blocks differentiation of promyelocyte to mature granulocyte
Consequence of Acute Promyelocytic Leukaemia
Haematological Emergency - DIC
How is Acute Promyelocytic Leukaemia treated
targeted ATRA
What age does Chronic Myeloid Leukaemia effect
40-60 yrs age
Sign of Chronic Myeloid Leukaemia
Splenomegaly
Pallor
What would show in a blood test for Chronic Myeloid Leukaemia
High WBC
What is seen on the blood film on CML
Left shift + Basophilia
Key diagnostic features of CML
- Philadelphia Chromosome
- t(9;22)
- Resulting in 210-kDa fusion protein (activated tyrosine Kinase)
How is t(9;22) diagnosed
A signal pattern found when doing BCR/ABL dual colour dual-fusion probe
(Normal should have four dots on the circumference, CML should have four dots circular and central)
What is philedelphia chromosome
Where the q-arm of chromosome 22 has been shortened by translocation with 9 t(22;9)!
How is BCR-ABL signalling activated
ATP phosphorylates tyrosine which is bound to membrane-bound substrate on the same cell
How is Chronic Myeloid Leukaemia treated
Tyrosine Kinase inhibitors
All end in -tinib
Nilotinib, Imatinib
Survival rate of CML
More than 90% survive first 5 years
How can CML be worsened
Accelerated phase due to TKI binding site mutations
Where is Acute lymphoblastic Leukaemia common (ALL)
Common in paediatric malignancy (not in adults)
Presentation of ALL
- Bone Marrow Failure
2. Organ Infiltration (CNS)
How is ALL diagnosed
Same as AML
Cytogenetics of ALL
Philadelphia chromosome (poor prognosis if present)
Treatment phases for ALL
- Induction
- Consolidation
- Delayed intensification
- Maintenance
CNS directed therapy
Stem Cell transplant
Can most children be cured of ALL
Yes
Cure rate in adults for ALL
50%
What is the biggest influential factor for ALL
CYtogenetics
What is the most common type of leukaemia
Chronic Lymphocytic Leukaemia
What is CLL
Gradual accumulation of B lymphocyte
Where do B lymphocytes accumulate
Blood
Spleen
Lymph
When is CLL usually diagnosed
FBC
What age group does CLL commonly effect
Elderly
Sometimes <55 (20%)
Signs of CLL
- Progressive Lymphadenopathy/Hepatosplenomegaly
- Haemolysis (anaemia)
- Marrow failure as marrow replacement occurs
- Hypogammaglobulinaemia + infection
What is stage A CLL
Lymphocytosis
How long does stage A CLL last for
10-15 yrs
What is stage B CLL
Nodal spread
How long does Stage B CLL last
5-7 years
What is stage C CLL
Anaemia + Thrombocytopaenia
How long does stage C CLL last for
2-3 yrs
CLL treatment
Chemotherapy Monoclonal antibodies (rituximab) Target therapy (ibrutinib)Marrow tranplsant
What is Autologous transplantation
Transplant of bone marrow from own host
What is Allogenic transplantation
From someone else
Danger of allogenic transplantation
Toxic
15-30% mortality
Stem cells recipient cells as well as tumour
When is Allogenic transplantation done
Acute and Chronic leukaemias
Benefits of autologous transplantation of stem cells
Allows escalation of chemo
Low mortality