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
Describe the classification of the myeloproliferative disorders on the basis of molecular pathogenetic chracteristics?
Describe acute leukaemia
- originally “too many white cells”
- now defined: >20% blasts in the bone marrow
- considered a neoplasia of the bone marrow stem cell
What are the clinical features of acute leukaemias?
- Acute lymphoid leukaemia 7x more in children than actue myeloid leukaemia
- Typical rpesentations:
- recurrent infections
- bone pain
- bleeding
- WCC can be low, normal or high
Explain the treatment of acute myeloid leukaemia and acute lymphoblastic leukaemia
Acute myeloid leukaemia:
- Cytosine arabinoside
- Daunorubicin/Idarubicin
- Etoposide
Remission induction x 2, Consolidation x 2
For High risk patients: bone marrow transplant
Adult cure = 40%
Acute lymphoblsatic leukaemia:
- Prednisolone
- Ara-C
- Vincristine
- Methotrexate
Remission induction x 2, Consolidation x 2
For High risk patients: bone marrow transplant, maintenance, CNS prohpylaxis
Adult cure = 25%
Explain acute promyelocytic leukaemia
- Abnormal promyelocytes with excess granules
- Strongly associated with t(15;17) PML-RARalpha
- Treatment is URGENT - risk of bleeding
- Treatment: all-trans-retinoic acid, idarubicin, arsenic
