Haematology Flashcards
Translocation in APML
t(15:17) (q22;q12)
Translocation involving the retinoic acid receptor alpha (RARA)
Strongest advserse clinical predictors for AML
Risk of death:
Advanced Age
Poor performance status
Risk of treatment resistance or early recurrence:
Cytogenetic and molecular factors - (deletion of chromosome 5 or 7)
History of exposure to cytotoxic agents or radiation
History of myledysplasia or myeloproliferative neoplasms (ie secondary AML)
Cytogenetics indicating poor prognosis in AML
Any deletion of chromosome 5 or 7
Complex karyotype
Monosomy karyotype (monosomy 17)
Most common mutation in AML?
FLT3
- transmembrane tyrosine kinase receptor that stimulates cellular proliferation.
Induction treatment for AML
7+3 induction
7 days of cytarabine
3 days of anthracycline (daunorubacin)
If patients have a FLT mutation - the addition of midostaurin
Aplastic Anaemia cause
Decrease in haematopoitic stem cells. Many causes:
- Autoimmunity
- Medications - carbimazole, PTU, B lactams, sulfonamides.
- Infections
Whilst its called aplastic anaemia. Usually affects all cell lines.
Aplastic Anaemia treatment
Age > 50: immunosupression with ATG, cyclosporine and prednisolone.
Age <50: allogeneic stem cell transplant
Pure Red cell aplasia
Normocytic or red cell aplasia with decreased reticulocytes and decreased red cell precursors in the blood. However normal leukocytes and platelets.
Causes:
- Infections - Parvovirus B19 (worse in immunocomprompromised patients who may need IVIg, and in patients with chronic haemolysis who depend on haemolysis.
- Thymoma
- Lympoid malignancy
- Ant-EPO antibodies in patients having EPO therapy
- Pregnancy
-
Pathology of Mylodysplastic syndrome
Clonal stem cell disorder with ineffective haematopoiesis leading to dysplastic and hypercellular bone marrow and peripheral blood cytopenias.
Mostly idiopathic, but can be secondary to chemo, radiation or chemical exposure.
Need to rule out reversible causes of dysplasa: B12, folate, and copper deficiency; alcohol consumption, medications, infections (HIV).
Classification of MDS:
WHO Classification:
<5% blasts - dividedd into unilingeage, multilineage + special category for isolated 5q-
5-10% blasts - excess blasts 1 (EB1)
10-19% blasts - excess blasts 2 (EB2)
MDS associated with 5q-
subset of MDS. Features increased hypolobulated megakaryocytes. Separated as is low risk and can be treated with lenalidomide if they are transfusion dependent (decreased transfusion requirements).
Management of MDS:
Low Risk - monitor, transfuse or EPO if required.
High risk MDS - treatment with hypomethylating agents has been shown to decrease risk of conversion to AML.
5q- can be treated with lenalidomide.
Myeloproliferative neoplasms
Clonal stem cell disorder characterised by proliferation of the components of the myeloid, erythroid, or megakaryocyte lineage:
- Polycythemia
- Essential thrombocythemia
- Chronic myeloid leukaemia
- Myelofibrosis
Chronic Myeloid Leukaemia phases
Chronic Phase - <10% blasts
Accelerated Phase 10-20% blasts
Blast crisis / Secondary AML - >20% blasts
Diagnosis of CML
Identification of the Philadelphia chromosome, either by:
- BCR-ABL gene transcript by PCR
- t(9,22) via FISH
Treatment of CML
Tyrosine Kinase Inhibitors:
- Imatinib
-dasatinib
- nilotinib
Side effects of TKIs in CML:
Imatinib, dasatinib, nilotinib.
Fluid retention
QTc prolongation
Polycythemia Vera Pathology:
Activating mutation of the JAK2 gene in 97% of cases. (JAK V617F).
Causes of secondary polycythemia:
Hypoxia: Lung disease, sleep apnoea, congenital heart disease / shunting
Ectopic EPO production - RCC, HCC, uterine fibroids.
Unusual - high oxygen affinity Hb
Treatment of Polycythemia vera
Phlebotomy with goal of Hct <45%
Aspirin.
Hydroxyurea if high risk for thrombosis: age >60, previous thrombosis.
Jak1/2 inhibitor Rutolitinib - for refractory PV, intolerant to hydroxyurea.
Pathology of essential thrombocythema
Jak2 mutation in 50%
- Calreticulin
- MPL
Treatment of ET
Monitor
Treat if high risk:
- Age >60
- Previous thrombosis
- Platelet count > 1500 (high risk for bleeding)
Treatment if high risk:
- Hydroxyurea
- Aspirin
Lower risk of transformation than other MPNs
Primary Myelofibrosis pathology
Worst prognosis of all of the MPNs
Clonal myloid stem cell disorder characterised by marrow fibrosis and extramedullary haematopoiesis.
Path:
- JAk2 mutation in 50%
- proliferation of megakeryocytes, secretion of FGF
- marrow fibrosis, often dry tap on biopsy
- leukoerythroblastic blood picture
Myelofibrosis presentation
Cytokine related hypercatabolic state - weight loss, fatigue, fever chills. Massive hepatosplenomegally.
