Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that build up in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute leukemia affecting adults, and its incidence increases with age.
Definition
Leukaemia is a type of cancer of the blood. There are different forms of leukaemia depending on the type of blood cell affected. "Acute" describes a rapid progression, and "myeloblastic" denotes the origin from myeloid cells. Myeloid cells are immature cells that normally become mature red blood cells, white blood cells, or platelets. In acute myeloid leukaemia, the bone marrow produces too many early (immature) blood cells which do not go on to become mature blood cells. Platelets play a critical role in stopping bleeding and red blood cells are important in delivering oxygen to all cells in the body. Excess production of immature myleloid blood cells in the bone marrow ultimately prevents the normal production of red blood cells, resulting in anaemia and decreased production of platelets or thrombocytompenia. Patients with AML seek medical care due to lack of energy and fatigue from anaemia or bleeding and bruising from insufficient platelets. Without enough normally functioning white blood cells the body"s immune system also becomes weak and susceptible to infection. Other symptoms include fever, shortness of breath and bone pain. At diagnosis, most patients - though not all - have a white blood cell count (the number of white blood cells circulating in the blood) that is above normal.
Causes
The cause of acute myeloblastic leukaemia (AML) is not understood. A small number of predisposing risk factors have been identified due to catastrophic events, including the atomic bombing of Hiroshima and the nuclear reactor accident in Chernobyl. A risk factor increases the chance of cancer occurring, but it in itself does not cause cancer. If you have a risk factor it does not necessarily mean you will develop cancer. A risk factor is not a cause in itself.
Risk factors
- Exposure to radiation
- Exposure to chemicals
- Chemotherapy
- Genetic abnormalities and mutations in the DNA of the cancer cell commonly occur in AML
- Trisomy
- Hereditary syndromes
Diagnosis
Bone marrow aspiration is the diagnostic procedure. The WHO classification requires more than 20% blasts in the peripheral blood, to make a diagnosis of AML. Patients potentially suitable for allogeneic stem cell transplantation (alloSCT) should be HLA typed at diagnosis, as should their available first-degree family members. In high-risk disease (eg, poor karyotype), early matched unrelated donor allogeneic transplantation must be considered, and a donor search should be performed as early as possible. Cytochemical stains allow classification into seven of the subtypes M1 to M7. These stains may not be useful for M0 (acute undifferentiated leukaemia) or M7 (acute megakaryocytic leukaemia) and so flow cytometry is used. Cytogenetic studies are also performed to provide important information about prognosis. They are also useful to confirm acute promyelocytic leukaemia (APL), which shows the t(15;17) and is treated differently. Chromosomal analyses are performed on children with AML to identify subgroups for prognostic assessment and to tailor therapy. Techniques such as gene expression profiling are increasingly used.
- Previously >30% blasts on BM aspirate (per FAB criteria)
- Recently changed to > 20% blasts on BM aspirate (per WHO criteria)
- patients with certain cytogenic abnormalities are considered to have AML regardless of blast percentage
- t(8;21)(q22;q22), inversion (16)(p13q22)
- t(16;16)(p13;q22), and t(15;17)(q22;q12)
- patients with certain cytogenic abnormalities are considered to have AML regardless of blast percentage
Signs and symptoms
Due to the excessive proliferation of myeloid precursor cells in bone marrow, certain symptoms/lab findings are expected (e.g. as a result of pancytopenia)
- Functional neutropenia – fever, chills (INFECTION)
- Thrombocytopenia – bleeding, bruising
- Anemia – weakness, fatigue
- Other findings
- Bone pain (sternum, lower extremities) – infrequent but thought to be secondary to expansion of medullary cavity
- Gingival involvement (especially in the monocytic variants (M4 or M5))
- Rare hepatosplenomegaly or LAD
- Pallor, petechiae, ecchymoses
- Bone tenderness
- Retinal hemorrhage
- CNS infiltration (more common in M4 and M5)
- Skin, soft tissue infiltration
Treatment
- Goal for complete remission
- platelet count greater than 100
- neutrophil count greater than 1000
- BM with 5% or less blasts
- Molecular complete remission : no evidence of leukemic cells in BM even with sensitive tests (eg, PCR, flow cytometry)
- If in complete remission for more than 3 yrs without relapse → potentially cured (less than 10% chance of relapse)
- Remission induction therapy
- Commonly anthracycline (ie, daunorubicin, idarubicin) and cytarabine → ("3+7 regimen")
- Cytarabine has ample CNS penetration so no need for prophylactic intrathecal chemotx (also, ↓ risk in patients with AML compared to ALL)
- 60-80% achieve complete remission
- Commonly anthracycline (ie, daunorubicin, idarubicin) and cytarabine → ("3+7 regimen")
- Postremission therapy
- Consolidation
- longer survival than maintence alone
- typically high dose cytarabine
- Maintenance – continue chemotx monthly for 4-12 months
- nonmyelosuppressive doses
- Consolidation
- Increasingly, hematopoietic cell transplantation is used in patients with AML after 1st remission in those with poor/intermediate prognostic factors.
- Also allogenic/autologous transplant in those with relapse or 2nd remission
- autologous with higher relapse rates. Used in those without HLA matched donor