Leukaemia Part II Flashcards
What is the incidence rate of Acute Myeloid Leukaemia?
4.1/100000 and is more common in adults
What causes Acute Myeloid Leukaemia? (Etiology)
Genotoxic exposures such as radiation and chemotherapy
History of other myeloid cancers
Genetic predisposition syndrome (Fanconi anaemia)
Idiopathic (Acquired genetic abnormalities)
What are the symptoms of acute myeloid leukaemia?
Anaemia,
lethargy,
leucopenia,
Thrombocytopaenia, infections, fevers and bleeding, (more common in AML than ALL)
bruising,
“blast” cells,
bone pain (more common in ALL than in AML),
weight loss, loss of appetite
What are the signs of acute myeloid leukaemia?
Leukaemic cutis (Skin lesion that is not tender and contains collection of blast cells) [not expected in ALL]
Gingival hyperplasia (Swelling of gums due to infiltration of blast cells here)
Conjunctival pallor (White under eyelids)
Bruises
Hepatosplenomegaly and lymphadenopathy are less common than in ALL
What is seen in FBC of acute myeloid leukaemia?
Pancytopaenia + blast cells
What is seen on blood film in acute myeloid leukaemia?
Pancytopaenia
Myeloblasts
What are the 4 types of myeloblastic leukaemia?
Acute myeloblastic leukaemia (know how this blood slide looks)
Acute promyelocytic leukaemia (know how this blood slide looks)
Acute monoblastic leukaemia
Acute erythroblastic leukaemia
What is the defining feature of acute myeloblastic leukaemia?
presence of granules and a large nucleolus
What is the defining feature of acute promyelocytic leukaemia?
Double lobed nucleus and denser granules and darker coloured nucleus and granules
What is the defining feature of acute monoblastic leukaemia?
Huge nucleus which is folded in an irregular manner and fine granules.
Grey coloured cytoplasm compared to more pink colour in normal blood slide
What is the defining feature of acute erythroblastic leukaemia?
Big nucleus big cell and lots of cytoplasm.
What does trephine look like for AML?
Hypercellular
What does bone marrow aspirate show in AML?
Myeloblasts (nucleoli, variable cytoplasm volume, numerous granules + Auer rods)
What are Auer rods?
Granules that line up
What is expected on Acute Myeloid Leukaemia cytometry?
CD13, CD14, CD117, HLA-DR, and CD34
Which karyotype images indicate a good prognosis for AML?
t (15, 17), t (8,21), t(16/16)
Which karyotype images indicate a good prognosis for AML?
t (15, 17), t (8,21), t(16/16)
t=translocation
Which karyotype is associated with a bad prognosis?
Monosomy 3, 5, and 7
What is the prognosis of a normal karyotype in AML?
Intermediate
What do molecular studies tell us about intermediate risk patients?
Whether their risk is more or less favourable
Does NPM1 have a good or bad prognosis?
Good
Does FLT3 have a good or bad prognosis?
Poor
How is AML treated?
Multiagent chemotherapy (induction and consolidation)
Allogeneic Stem Cell Transplant
Transfusion and Antimicrobial Support
What is the 5-year survival rate of AML?
25%, however if acute promyelocytic leukaemia is treated it has a 90% 5-year survival rate
Why is only consolidation and induction chemotherapy used in AML?
Because no evidence shows that maintenance chemo helps. (Induction 2 months, consolidation 4 months due to higher toxicity)
How does Acute promyelocytic Leukaemia present?
Pancytopaenia and coagulopathy where patients blood excessively)
Blood film and Bone Marrow Analysis show excessive promyelocytes
How is acute promyelocytic leukaemia treated?
Arsenic and ATRA (a vitamin A derivative)
What does arsenic and ATRA do?
Forces promyelocytes to undergo maturation causing them to lyse
What is the incidence rate of chronic myeloid leukaemia?
1 - 2/100000 in middle aged patients (slight male predominance)
What are the symptoms of chronic myeloid leukaemia?
Often asymptomatic (incidental finding on blood tests) but sometimes presents as leucocytosis and thrombocytosis as well as fatigue, malaise, bleeding, and bruising.
What are the signs of chronic myeloid leukaemia?
Enlarged liver and spleen
What does full blood count show in CML?
Increase in number of most WBCs (neutrophils, eosinophils, monocytes, basophils, and myeloid cells at differnet stages of maturation)
What does trephine show in CML?
Hypercellularity
What translocation is characteristic in CML karyotype?
t (9,22) [philadelphia chromosome]
What is labelled in FISH study to diagnose CML? How is the diagnosis confirmed?
ABL1 on chromosome 9
BCR on chromosome 22
Seeing a fusion between these 2 chromosomes indicates presence of a Philadelphia chromosome
What happens when the Philadelphia chromosome expresses the gene in between both chromosomes?
A fusion protein Bcr-Abl is made which binds to ATP and can increase number of leukaemic cells indefinitely
How is CML treated?
Tyrosine Kinase Inhibitor (Imatinib, Dasatinib, Nilotinib, and Ponatinib)
Allogenic Stem Cell Transplant
What is the 5-year survival rate of CML before and after using tyrosine kinase inhibitor?
Pre-TKI 5 -year survival rate = 45%
Post-TKI 5-year survival rate = 90%
How do the “-tinib” drugs treat CML?
They block ATP binding to Bcr-Abl protein which results in gene being switched off which switches off the entire leukaemia project. This drug must be used permanently.
What is the incidence rate of Chronic Lymphocytic leukaemia?
6.75/100000 (most common in elderly that are >60 years old and slgihtly more predominant in males)
[occurs in 3% of elderly population]
Which cells typically causes Chronic Lymphocytic Leukaemia?
B lymphocytes
What are the symptoms of CLL?
Anaemia
Lymphocytosis (B symptoms)
Neutropenia
Thrombocytopaenia
Fevers, night sweats, and weight loss
Bleeding, bruising
Infections, fevers
Lethargy
What are the signs of CLL?
Hepato+splenomegaly
Lymphadenopathy (large lymph nodes)
May affect tonsils and salivary glands
What shows up on FBC of CLL?
Lymphocytosis with or without cytopaenia
What shows up on blood film in CLL?
Lymphocytosis + smear cells
What is a smear cell?
Cell in process of apoptosis
What is seen in trephine of CLL?
Nodular infiltration
What is seen in bone marrow aspirate of CLL?
a large number of mature lymphocytes
How can ALL and CLL be told apart on a blood film?
ALL has granule
Nucleoli in ALL (immature formed cells)
Mature cells in CLL compared to immature in ALL
How can ALL and CLL be told apart on a blood film?
ALL has granule
Nucleoli in ALL (immature formed cells)
Mature cells in CLL compared to immature in ALL
More closely packed in CLL compared to ALL
More pancytopaenia in ALL compared to CLL
What is seen in flow cytometry of CLL?
Since mostly B cells we see B cell markers such as CD19, CD20, CD45. HLA-DR
Aberrant T-lymphocyte expresion: CD5
Special expressions: CD23, CD200
What are cytogenetic studies used for in CLL?
For prognosis:
trisomy 12, del 13q = good prognosis
del 11q and del 17p = bad prognosis
When is treatment used for CLL?
Treatment might not be needed at diagnosis unless there are symptoms and cytopaenia.
How is CLL treated?
Multiagent chemo
Anti-CD20 antibodies (rituximab)
Small molecule inhibitors (venetoclax)
What is the 5 year survival rate of CLL?
85%
What does venetoclax act on?
Inhibits Bcl2 which is an antiapoptotic peptide