Myeloid malignancy Flashcards
What groups of blood cancers fall under the myeloid malignancies?
What cells are myeloid cells ie what cells are implicated in myeloid malignancies?
AML - Acute Myeloid Leukaemias
Myeloproliferative disorders
Myeloid malignancies are caused by mutations in what cells?
Haematopoietic stem cells
Rarely in early progenitor cells
Different mutations will cause different myeloid malignancies down the line
What are the main groups of myeloid malignancy?
AML - Acute myeloid leakaemia
CML - Chronic myeloid leukaemia
MDS - Myelodysplastic syndromes
MPN - Myeloproliferative neoplasms
What are the differences between acute and chronic leukaemia, in terms of:
a) differentiation of cells
b) effects on bone marrow
c) speed of onset/decline
a) In Acute leukaemias - there is no differentiation of progenitor cells but in chronic - there is
b) In acute leukaemia - proliferation occurs in and takes over the bone marrow leading to rapid bone marrow failure. In chronic leukaemia, there is proliferation without bone marrow failure
c) Acute leukaemia symptoms develop in a matter of weeks/months whereas Chronic leukaemias develop much slower
What are the clinical features of AML?
Bone marrow failure triad:
Anaemia
Thrombocytopenic bleeding (purpura & mucosal membrane bleeds)
Infection (bacterial and fungal esp)
What are the essential investigations for AML?
Blood count and blood film:
- cytopenia
- anaemia
- thrombocytopenia
- neutropenia
Bone marrow aspirate / trephine:
- AML & ALL - diagnosed if >20% blast cells
Cytogenetic (karyotype) of blast cells
Immunophenotyping of blasts (determine in AML or ALL)
Give an overview of the treatment of AML?
Supportive care
Anti-leukaemic chemotherapy:
- Remission induction (1-2 cycles)
- Consolidation (1-3 cycles)
- Maintenance
How is Acute promyelocytic leukaemia treated?
ATRA & ATO
(All-trans retinoic acid & arsenic trioxide)
Chemo-free and 90% curative
Describe anti-leukaemic chemotherapy for AML
Anti-leukaemic chemotherapy for AML has 3 distinct phases…
1) Remission induction:
- remission = normal blood count & <5% blasts
- 1-2 cycles of chemotherapy
2) Consolidation (1-3 cycles):
- patients recieve chemotherapy and then…
- Allogeneic stem cell transplantation
3) Maintenance:
- targeted therapies
What are the clinical features of Chronic myeloid leukaemia?
Anaemia
Splenomegaly
Weight loss
Hyperleukostasis
Gout
Hyperleukostasis is one of the key clinical features of CML
What does this mean?
This is caused by high white cell counts and is characterised by:
- fundal haemorrhage
- venous congestion
- altered consciousness
- respiratory failure
What features of a blood count might indicate CML?
What cells would be present in the blood that are not normally present?
WBCs - elevated
RBCs - depressed
Platelets - elevated
Presence of bone marrow cells in blood - such as blasts, promyelocytes etc
What key feature is present in bone marrow and blood cells in patients with CML?
CML - bone marrow and blood cells contain the Philadelphia chromosome - t(9;22)
(this is basically a small chromosome 22 due to translocation between part of chromosome 9 and 22)
How is CML treated?
Tyrosine kinase inhibitors (TKIs) of BCR-ABL is first line:
- Imatinib (Glivec)
- Dasatinib (Sprycel)
- Nilotinib (tasigna)
- Bositinib
- Ponatinib
Allogeneic stem cell transplantation is used in patients when TKIs fail
What are the myeloproliferative neoplasms (MPN)?
Polycythaemia vera (PV or PRV)
Essential thrombocythaemia (ET)
Myelofibrosis - often an advanced stage of PV and ET
What are the laboratory features of polycythaemia vera?
Raised haemoglobin and haematocrit concerntrations
Tendancy for elevated WBCs and Platelets
elevated uric acid (& risk of gout)
elevated number of red cells
