ACUTE MYELOID LEUKAEMIA Flashcards
(13 cards)
What are Leukaemias? How are they classified?
Leukaemias are a group of clonal disorders characterized by the accumulation of malignant white cells in the bone marrow and blood.
Depending on duration of onset, they are classified as Acute or Chronic leukaemias.
Depending on cell of origin, each class is further sub-classified into myeloid or lymphoid leukaemias
The acute leukaemias are ACUTE MYELOID LEUKAEMIA (AML) and ACUTE LYMPHOBLASTIC LEUKAEMIA (ALL).
What is AML?
An acute leukaemia characterized by the accumulation of immature white cells (blasts) of the myeloid series in the bone marrow and peripheral blood
Epidemiology
Acute leukaemias can occur at any age.
Typically, AML is a disease of adults and incidence increases with age.
No particular sex predilection.
10-15% of cases are however found in childhood
What is the AETIOPATHOGENESIS of AML? The genetic damage results in what?
Leukaemias are clonal diseases that involve haemopoietic tissues
They derive from a single cell in the bone marrow or peripheral lymphoid tissues
Most times, the cell of origin has undergone prior genetic alteration
Overall, the genetic damage results in:
An increased rate of cellular proliferation
Reduced apoptosis
A block in cellular differentiation
What is the FAB (French American British) Classification for AML? Q
M0 AML with minimal differentiation
M1 AML without maturation
M2 AML with maturation
M3 Acute promyelocytic leukaemia (APL)
M4 Acute myelomonocytic leukaemia
M5a Acute monoblastic leukaemia
M5b Acute monocytic leukaemia
M6 Acute erythroid leukaemia
M7 Acute megakaryoblastic leukaemia
M8 Acute basophilic leukaemia
M9 Acute panmyelosis with myelofibrosis
Symptoms are essentially due to:
MCQ which blasts infiltrate the gums
- Bone marrow suppression
* Symptoms and signs of anaemia
* Recurrent infection due to neutropenia
Bleeding caused by thrombocytopaenia or DIC (APL) - Organ infiltration
* Gum hypertrophy ( due to infiltration of M4/M5 blasts)
* Skin infiltration (Sweet syndrome or leukaemia cutis)
* Chloromas/ myeloid sarcoma: Isolated mass of leukaemic cells in an extramedullary site, commonly in soft tissues of head and neck.
* Bone pain, hepatomegaly and splenomegaly are less common.
Diagnostic Investigations and findings
- Full blood count and differentials:
Normocytic normochromic anaemia
White cell count may be low, normal or high
Thrombocytopaenia - Blood film
Immature white blood cells (blasts) comprising >20% of total white cells seen.
Blasts of myeloid origin: Myeloblasts
Total WBC count normal or low with blasts in peripheral blood: Subleukaemic leukaemia
Total WBC count normal or low and blasts not demonstrable in peripheral blood but present in bone marrow: Aleukaemic leukaemia - Bone marrow aspiration
Complements peripheral blood film findings
Reveals the white cell subtype implicated (myeloid or lymphoid)
Reveals the state of erythropoiesis (RBC production) and thrombopoiesis (platelet production). - Cytochemistry
Using special stains to differentiate lymphoblasts (ALL) from myeloblasts (AML).
Stains specific for AML: Sudan black B, Myeloperoxidase, Non specific esterases
Other Investigations
Cytogenetics: To detect translocations, inversions, deletions etc. Common translocations in AML include t(8;21) in M2 and t(15;17) in M3.
Immunophenotyping: To detect CD markers on cells for proper identification of lineage. The typical myeloid markers are CD13, CD33 and CD117.
Molecular Genetics
Supportive Investigations
Clotting profile (PT, APTT)
Serum U/E, Cr
Blood sugar
Liver function tests
Uric acid, Ca2+, Phosphate
Background viral serology (medico-legal implications)
Sepsis work up
Radiological evaluation (X-ray, USS, CT, PET scan)
Supportive Treatment
Counselling
Reproductive issues
Nutritional support
Determine baseline performance status of patient
Insertion of a central venous catheter
Intravenous fluid administration
Blood and blood product support
Anti-infective agents (prophylaxis)
Anti-uric acid agents
Analgesics
Definitive Treatment
Combination cytotoxic chemotherapy: Administered in courses and cycles.
Phases:
1. Induction of remission- to ↓blast count to <5%. Agents used include Daunorubicin, Cytosine arabinoside (Ara-C)
- Consolidation- with the hope of eliminating the disease. Agents include Daunorubicin, Ara-C, Thioguanine, Etoposide
- Maintenance therapy – mainly used for APL. Agents used include All-Trans Retinoic Acid (ATRA).
Use anti-emetics and steroids for pre-medication.
Follow up patient with investigation results per cycle.
Counselling is continuous through out the treatment process
Targeted therapy can be used in AML (e.g. ATRA, Mylotarg – anti CD 33)
Definitive treatment is Haemopoietic Stem Cell Transplantation
ACUTE PROMYELOCYTIC LEUKAEMIA (APL)
M3 variant of AML
Caused by t(15;17) translocation. PML gene on chromosome 15 is fused with retinoic acid receptor α gene on chromosome 17.
This leads to a PML-RARα fusion protein which causes arrested differentiation
The primary granules within the abnormal promyelocytes contain thromboplastin-like material and can cause a haemorrhagic syndrome of DIC
Treatment is with platelet concentrates, fresh frozen plasma (or fresh whole blood) and ATRA. Arsenic trioxide is given in patients who are refractory to ATRA
Prognosis
