Acute and Myeloid leukemia (AML), chapter 20.6, Rudolph’s Pediatrics

Known risk factors include exposure to high-dose ionizing radiation, previous chemotherapy (especially with alkylating agents and epipodophyllotoxins), Down syndrome, congenital bone marrow failure syndromes (Diamond-Blackfan anemia and Kostmann agranulocytosis [see Chap. 19]), and several other genetic disorders, such as Fanconi anemia and neurofibromatosis.

The clonal origin of AML has been demonstrated with several methods, including cytogenetic analysis and assays with X-linked polymorphisms. The transforming event in AML could occur at any point in hematopoiesis from the pluripotent stem cell to a committed precursor, such as the myeloblast or erythroblast. Unlike the situation for myeloproliferative disorders, little evidence suggests that the target of leukemic transformation in AML is the pluripotent stem cell. Both animal and human data, however, implicate a primitive myeloid stem cell or progenitor as the likely target.

The initial signs and symptoms among most children with AML reflect anemia, thrombocytopenia, and neutropenia caused by bone marrow infiltration with leukemic blasts and decreased production of normal cells. These include pallor, fatigue, epistaxis or gum bleeding, petechiae or purpura, and fever or infection that has not responded to antibiotic therapy. Approximately 15 to 20% of children have an initial leukocyte count greater than 100,000/uL.

The characteristic bone marrow findings include a hypercellular specimen with more than 30% blasts (usually 70 to 90% blasts). Bone marrow biopsy infrequently shows myelofibrosis (except for M7), and occasionally dysplastic changes in the myeloid precursors are present. In most cases of AML, the diagnosis is straightforward after examination of the peripheral blood sample and a bone marrow aspirate.

Other Diagnostic techniques

With a combination of monoclonal antibodies that recognize myeloid antigens, several immunophenotype-based classifications of AML have been proposed.

High-resolution banding techniques have helped identify nonrandom chromosomal abnormalities among more than 70% of children with AML. Many of these abnormalities are unique to AML and are sometimes specific for a particular FAB subtype. The most common chromosomal abnormalities among children and young adults with AML include inv16, t(15;17), t(8;21), and t(9;11). Monosomy of chromosomes 5 and 7 and trisomy 8 are generally not associated with a specific FAB type and are considerably more frequent among older patients with AML.

Treatments

The most widely used remission-induction regimen includes treatment with an anthracycline (chemotherapy), - inhibit DNA rep. The long-term survival rate is approximately 40% among children treated with chemotherapy alone.

Bone marrow transplantation.