HAEM: White Cell Disorders I - Myeloid Disorders + Acute Leukaemia Flashcards
What are the 2 choices for a haematopoietic stem cell?
- Renew
- Differentiate into:
- blood cells (myeloid)
- immune (lymphoid) systems
How are growth factors used therapeutically?
-
Granulocyte-colony stimulating factor (G-CSF)
- Boosts neutrophil recovery after chemotherapy
- mobilises stem cells into the blood stream
-
Erythropoietin (Epo)
- win Tour de France! lmao
- increases red cell production in renal and marrow failure
-
Thrombopoietin receptor analogues (e.g. romiplostim):
- new for idiopathic thrombocytopaenia purpura (ITP)
What are the “B” symptoms from pathological cell populations?
- Weight loss >10%
- Fever x 2 >38.5
- Night sweats
Seen in lymphoma, acute leukaemias
Explain the concept of “left shift”
A blood cells mature, they get smaller.
With more severe pathology, the type of cells seens in the blood are more and more immature (“left in the development pathway”)
Myeloblast -> Promyelocyte -> Myelocyte -> Band form -> Neutrophil
What is Joske’s Law?
The more of the 3 cell lineages (WCC, Haemoglobin, Platelets) that are numerically abnormal, the more likely there is an intrinsic marrow disorder.
Mix the pathological process with the haematological term:
- Aplasia
- Dys-or Hypo-plasia
- Normal
- Hyperplasia
- Neoplasia
and
- Aplastic anaemia (When cell not working at all)
- Myelodysplasia (The cells are dysplatic/not growing right)
- Normal
- Myeloproliferative disorders
- Acute leukaemia (full blown cancer - >20% blast cells in bone marrow)
In the order lol
- Aplasia
- Dys-or Hypo-plasia
- Normal
- Hyperplasia
- Neoplasia
and
- Aplastic anaemia (When cell not working at all)
- Myelodysplasia (The cells are dysplatic/not growing right)
- Normal
- Myeloproliferative disorders
- Acute leukaemia (full blown cancer - >20% blast cells in bone marrow)
Provide an overview of “aplastic anaemia”
- Pancytopaenia - not anaemia!
- Blood counts: very low
- Bone marrow: empty
- Treatment:
- immunosuppression
- bone marrow transplantation
Provide an overview of myelodysplasia
- Abnormal morphology:
- hypogranular and figure 8 nucleus neutrophils
- ringed sideroblast
- Blasts 5-20% in marrow
- Blood counts: low
- 20-60% progress into acute myeloid leukaemia
- Treatment:
- supportive - red cell and platelet transufsion, antibiotics
- azacitidine - new, promotes myeloid differetiation, 50% effectiveness
- lenalidomide for 5q-syndrome
What are myeloproliferative disorders and what are common symptoms and complications?
Myeloproliferative disorders = group of disorders characterized by over-production of blood cells
- Usually along one lineage, generally normal cell morphology
Common symptoms:
- fatigue
- headache
- itch
- weight loss
- night sweats
Common complications:
- Progression to myelofibrosis (bone marrow bristling) or AML (5-10%)
- DVT, stroke or haemorrhage
- Splenic infarction (takes over from not working bone marrow)
What are the 3 types of myeloproliferative disorders?
-
Polycythaemia (Rubra) Vera = too many red cells
- high haematocrit: risk of arterial and venous thrombosis
-
Essential thrombocythaemia = too many platelets
- risk of bleeding AND thrombosis
-
Myelofibrosis = too much fibrosis in the bone marrow
- massive splenomegaly, splenic pain, early satiety
Explain polycythaemia (rubra) vera and what dictates a medical emergency?
Features:
- packed blood film
- facial plethora
History:
- symptoms, drugs, cardioresp disease, Epo-secreting tumors
Examination:
- splenomegaly in 2/3, erythromelalgia
Tests:
- JAK2 kinase mutation status
High haemoglobin (e.g. >200g/L) is a medical emergency: Urgent therapeutic venesection and haematology review
How are myeloproliferative syndromes treated?
- Polycythaemia / Rubra vera
- venesection, aspirin, hydroxyurea, anagrelide, interferon
- Essential thrombocythaemia
- aspirin, hydroxyurea, anagrelide, interferon
- Myelofibrosis
- chemotherapy, hydroxyurea, marrow support
Targeted treatment:
- JAK2 kinase inhibitors (e.g. ruxolitinib) in clinical trials and now listed on PBS
Explain Chronic Myeloid Leukaemia
- A myeloproliferative disorder wtih high neutrophil count
- Median age 50 years, 150 a year in WA
- Symptoms: weight loss, fatigue, headache
- Classic signs: massive spegalomegaly
What is the genetic cause of chronic myeloid leukaemia?
“Philadelphia chromosome” - t(9;22)
Creates bcr-abl fusion protein with tyrosine kinase activity
What is the treatment of choice for CML?
Imatinib
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