3.7Characteristics of and Therapy for AML Subtypes

•Hypertrophy of gingiva and ulceration of mucosa in about 50% of children

•Often infiltration of skin and lymphadenopathy

•Laboratory findings:

–Anemia and thrombocytopenia are common; WBC variable

–DIC: Release of tissue factors/proteases during lysis of monocytes Treatment is the same as for other patients with AML.

3.7.3Erythroleukemia (Di Guglielmo Syndrome, M6)

•The clinical presentation consists of fatigue, fever, petechiae, and often splenomegaly

•Laboratory findings:

–Initial phase: macrocytic anemia, erythroblasts with two or three nuclei and showing a maturation disturbance, anisocytosis and poikilocytosis, elliptocytes

–Variable numbers of reticulocytes; oxyphilic normoblasts and often ellipto- cytes and macrocytes in the peripheral blood; thrombocytopenia variable; megaloblastic hyperplasia of erythropoiesis in the bone marrow; results of glycophorin analysis: low to highly positive

–Intermediate phase: mixed erythromyeloblastic proliferation

–Late phase: similar to AML

–Treatment is the same as for other patients with AML.

3.7.4Acute Megakaryocytic Leukemia (AMKL)

•Clinical presentation and laboratory findings are comparable with other AML subtypes, although this type of AML can be associated with low percentages of bone marrow blasts and hepatic and skeletal involvement.

•This leukemia is most common in children with Down syndrome, in whom prog- nosis is superb with less than standard intensive treatment; in children without

Down syndrome, AMKL has a worse prognosis.

•Immunophenotyping shows leukemia cells to be positive for CD41/61 and CD42 are present.

•Treatment is the same as for other patients with AML.

3.7.5Myelodysplastic Syndrome (MDS) [For Details see Chap. 4]

Occurs in about 3% of children with acute leukemia, the disease begins as preleukemia characterized by:

•Anemia, cytopenia, blasts in peripheral blood, and morphological nuclear abnormalities of blood cells

•Bone marrow: mostly hypercellular, megaloblastic, dyserythropoietic; less than 5% blasts with nuclear anomalies, large or small megakaryocytes; chromosomal abnor- malities in hematopoietic cells (monosomy 7); growth irregular in cultures in vitro

•Clinical course: often develops into AML within 6–24 months

•Prognosis: often therapy-resistant subtypes of AML; bone marrow transplanta- tion can be curative

3.7.6Eosinophilic Leukemia

•Rare subtype of AML

•Symptoms: nausea, fever, sweating, cough, dyspnea, thoracic pain, weight loss, and pruritus

•Clinical findings: cardiac arrhythmia, cardiomegaly, and hepatomegaly are com- mon; in 50% of cases, lymphadenopathy; neurological disturbances (without leukemic CNS disease) are common

•Laboratory findings: often anemia and thrombocytopenia; WBC often high, occasionally more than 100 × 109/l, with predominantly eosinophilic cells with large granules; chromosomal abnormalities sometimes present

•Clinical course: During progression of disease, no difference to AML

•Differential diagnosis: Hypereosinophilia parasitosis (larva migrans, Toxocara canis), tropical eosinophilia

•Therapy: transient response to corticosteroids and hydroxyurea; AML therapy – including the use of tyrosine kinase inhibitors in patients with FGF/PDGF translocations may induce remission

3.7.7Congenital Leukemias

•Associated with Trisomy 21, mosaic trisomy 9 and 7, Turner syndrome

•Differential diagnosis: transient myeloproliferative syndrome in Trisomy 21

•Clinical presentation in infants from birth to 6 weeks of age: nodular, blueish skin infiltration, purpura/petechiae, pallor, hepatomegaly, lethargy, poor feeding, respiratory distress

•Usually monocytic ANLL, possibility of pre-B-ALL

•Infants with AML have outcomes similar to older children when treated according to standard, intensive AML regimens

3.7.8Inherited AML

•Several bone marrow failure syndromes (BMFS) also demonstrated increased risk of developing AML. These include

–Fanconi anenda (defects in DNA repair), Kostmann Syndrome (defects in neutrophil elastase SL42)

–Schwachman-Diamond Syndrome (ribosomal processing SBDS gene)

–Diamond-Blackfan Anemia (defects in ribosomal small and large subunit proteins)