Acute Myelogenous Leukemia

AML is more common in patients with DNA repair defects syndromes; it can also occur as a secondary neoplasm after chemotherapy with alkylating agents and epipodophyllotoxins.  At least one of the following cell surface determinants is usually positive: CD 11b, 13, 14, 15, 33, 36.  Cytogenetic abnormalities are present in almost all cases of AML.

Symptoms:  The presenting signs of AML usually relate to bone marrow replacement, anemia, and accumulation of cells in the reticuloendothelial system.  Bone marrow failure and infiltration can result in variable anemia, granulocytopenia, and thrombocytopenia. In about half of the cases, hepatosplenomegaly is present, and lymphadenopathy may also occur.  In some variants, coagulopathy/DIC is common such as M3, M4, and M5.  The M4 and M5 variants are also associated with solid masses of leukemic cells termed chloromas or granulocytic sarcomas.  If leukemia occurs in the skin, it is termed leukemia cutis; leukemia of the meninges is also known.  CNS involvement is more common in AML than ALL, particularly in patients less than two years of age, those with high white counts at presentation, and in M4 and M5 variants.

Prognosis:  The long term event free survival of AML patients in general is about 3-45%.  Poor prognostic factors include high white counts, the presence of monosomy 7, the development of AML after a myelodysplastic syndrome or chemotherapy treatment, and the presence of the multidrug resistance glycoprotein.  Good prognosis is associated with the t(8;21) and inv(16) karyotypes associated with M4Eo, and with t(15;17) and t(9;11).

Treatment:  The initial treatment of AML may involve stabilization: correction of coagulopathy, treatment of hyperviscosity (by leukophoresis, hydroxyurea, exchange transfusion), and correction of electrolyte disturbances.  Patients are then placed on hydration and allopurinol to prevent tumor lysis syndrome and started on chemotherapy as quickly as possible.  Treatment of AML uses multidrug regimens which are more toxic and myeloablative than the ALL protocols.  About 75-80% of patients achieve a complete remission (no peripheral blasts and marrow < 5% blasts).  Toxic deaths in the induction period range 5-10%.  The patients then proceed to an intensification regimen, without which 90% would spontaneously relapse.  When a matched sibling is available, allogeneic stem cell transplant is preferable.  Unmatched transplants may be considered for treatment-related AML and in cases of monosomy 7 where the natural history of the disease is worse.