Acute Leukemia Flashcards
What are the symptoms of Acute Leukemia?
(Note these are also for chronic leukemia)
What is leukemia?
Haematological malignancy characterised by abnormal proliferation of myeloid or lymphoid precursor cells resulting in BM failure and pancytopenia
Acute leukaemia is a haematological emergency and requires urgent evaluation. Whatre the 2 types of acute leukaemia?
AML = Clonal proliferation of myeloid precursors
ALL = Malignancy of lymphoid cells affecting T and B cells
Most adult ALL affect B or T cells?
Whatre the genetics behind this leukemia?
What is the main therapeutic target for this? + Give name of drug
Most adult ALL fall into B-lymphoblastic leukemia/lymphoma
Philadelphia chromosome coding BCR-ABL1
Tyrosine Kinase Inhibitors (TKI) target this - Imatinib
What is the philadelphia chromosome?
Common translocation of chromosomes 9 and 22 => t(9;22)
What classification is used for Leukemia?
2016 WHO classification of myeloid and acute leukemias
It is not required knowledge but it does demonstrate the importance of clinical, morphological, immunophenotypic and genetic features in the diagnosis, treatment and planning for patients
What is the most common acute leukemia in childhood? What about adults?
Childhood = ALL
Adult = AML
What percent of adult leukemias are ALL vs AML
AML 80%
ALL 20%, the most common of which is B-cell
Give the basic pathophysiology of of Leukaemia
1) Genetic damage to progenitor cells (=blast cells) leads to uncontrolled proliferation, reduced apoptosis, and a block in cellular differentiation
2) This leads to an accumulation of blast cells => replacing normal haematopoiesis => pancytopenia
3) Organ infiltration and tumour masses
Tumour masses in leukemia are caled?
Sarcomas
Testicular infiltration is characteristic of AML or ALL?
how would it present?
ALL
Painless testicular enlargement
Give the symptoms of acute leukemia
+ bone pain
+ Extramedullary disease (=> screen organ systems such as CNS!!)
e.g. in ALL, Testicular infiltration (=> US)
What is Fanconi syndrome
Rare disorder in DNA repair => BM failure and predisposition to anaemia
+ Congenital abnormalities
Give 4 RF for AML
Give 4 RF for ALL
What are the main diagnostic investigations for leukemia?
BM aspirate and BM trephine biopsy
What finding on BM aspirate/biopsy would indicate it to be AML instead of ALL?
Auer rods
They are needle-shaped cytoplasmic inclusions of abnormally fused granules in myeloblastic cells
What will you find in BM aspirate/biopsy to confirm the diagnosis of leukemia? (for AML and ALL)
What else should be done with the sample other than microscopy as part of the workup?
Presence of >20% blast cells at clinical presentation.
ALL - Lymphocytic Blast cells
AML - Hypercellular BM due to infiltration of myeloblasts + !!!Auer rods
Sample should also be sent for immunophenotyping (to determine cell lineage) and Genetic studies such as FISH or PCR to identify mutations and chromosomal abnormalities to guide treatment
What would you expect to see on an FBC of leukemia?
Pancytopenia but WCC may be raised or low => always roder with differentials to see which cell specifically is raised
How would a blood film result differ between ALL and AML
ALL: Blast cells
AML: Immature blast-like cells called Leukemic cells and Auer rods
What imaging would you perform for leukemia?
Discuss the necessary diagnostic and supportive investigations for a patient presenting with leukemia.
This is a stupid question but give 1 prevention strategy for ALL and 1 for AML
Before getting chemo, patients should get an all around check including renal, hepatic, Resp (PFTs) and heart (ECHO, ECG)
Before starting chemo, patients should get an all around check of all system functioning including renal, hepatic, Resp (PFTs) and heart (ECHO, ECG)
What medication should they be started on before chemotherapy?
What is the regimen for ALL and AML?
Allopurinol or Rasburicase for tumour lysis syndrome before chemotherapy
Regimen should include at least 2 drugs of differing MOAs
ALL - Vincristine, Cyclophosphamide, steroids, Daunorubicin
If Philadelphia chromosome + Imatinib
AML - Cytarabine + Anthracyclin
When receiving a BM transplant, is it implanted in the BM? how?
No it is not
It is infused IV and the stem cells naturally migrate to the BM
How is a BM transplant performed?
Collection: Stem cells harvested from donor BM and processed to concentrate stem cells
Patient recieves high dose chemotherapy +/- radiotherapy before IV infusion of the stem cells
Acute leukaemia is a haematological emergency and requires urgent evaluation. What is the most common cause of an acute presentation of leukaemia?
How will you manage leukaemia acutely?
Neutropenic sepsis
1) Manage as you would sepsis => sepsis 6 with very aggressive AB
+ Place patient in an isolated room!
2) G-CSF (granulocyte colony stimulating factor)
3) Allopurinol or Rasburicase for tumour lysis syndrome
4) Chemotherapy:
ALL - Vincristine, Cyclophosphamide, steroids, Daunorubicin
AML - Cytarabine + Anthracyclin
5)
Collection: Stem cells harvested from donor BM and processed to concentrate stem cells
Patient recieves high dose chemotherapy +/- radiotherapy before IV infusion of the stem cells
What endocrinopathies are seen in leukaemia tx?
Impaired glucose + Insulin metabolism
Thyroid dysfunction
Adrenal insufficiency due to high dose steroids (rest from chemo)
What are the complications of receiving chemotherapy?
Febrile neutropenia
Tumour lysis syndrome
Alopecia
Cardiotoxicity
Infertility
Risk for secondary malignancy
Endocrinopathies (impaired glucose and insulin metabolism, thyroid dysfunction)
State the complications (4) of Leukemia itself
Then state 5 complications from treatment (total =7)
Leucopenia - Recurrent infections/sepsis
Thrombocytopenia - Major bleeding
Whichever cell is overproduced => Hyper viscosity syndrome
Ascites (not due to portal HTN)
Complications from treatment:
Febrile neutropenia
Tumour lysis syndrome
Alopecia
Cardiotoxicity
Infertility
Risk for secondary malignancy
Endocrinopathies (impaired glucose and insulin metabolism, thyroid dysfunction + !!Adrenal insufficiency)
