ACUTE MYELOGENOUS LEUKEMIA

Acute myelogenous or non-lymphoblastic leukemia (AML or ANLL) accounts for ~ 15-20% of childhood leukemia.

Many of these cases are associated with genetic disorders, e.g. Down syndrome, Fanconi anemia, Bloom syndrome or neurofibromatosis, or develop as secondary malignancy after chemotherapy or radiotherapy for other malignancies.

Clinical presentation is similar to ALL, though most cases have more acute and severe course with higher incidence of severe anemia, bleeding and chloroma-a localized mass of leukemic cells on choroid and epidural region.

Acute promyelocytic type of AML is specifically associated with gum hypertrophy, gum bleeding or severe DIC, due to release of procoagulant substances

TABLE 20.6: WHO classification* for acute myelogenous leukemia

AML/APL with recurrent genetic abnormalities

AML with myelodysplasia-related changes

Therapy-related myeloid neoplasms

AML, not otherwise specified

• With minimal differentiation

• With/without maturation

• Acute myelomonocytic leukemia

• Acute monoblastic/monocytic leukemia

• Acute erythroid leukemia

• Pure erythroid leukemia

• Erythroleukemia, erythroid/myeloid

• Acute megakaryoblastic leukemia

• Acute basophilic leukemia

• Acute panmyelosis with myelofibrosis

Myeloid sarcoma

Myeloid proliferations related to Down syndrome Blastic plasmacytoid dendritic cell neoplasm *Modified and abridged.

AML: Acute myelogenous leukemia; APL: Acute promyelocytic leukemia

from leukemic blast cells. Subcutaneous nodules (blueberry muffins) are common in infants.

Diagnosis depends on presence of gt;20% myeloblasts in the bone marrow, though further differentiation is required from lymphoblasts on the basis of morphologic, immunophenotype and cytogenetic characters.

WHO recommends the classification for AML based on the morphology and chromosomal or genetic abnormalities (Table 20.6).

Treatment regimens for AML are not as standardized as for ALL, though risk-stratification is possible on the basis of selected genetic abnormalities. Most protocols use an anthracycline (e.g. daunamycin) and cytosine arabinoside with/without other agents, e.g. etoposide. Addition of retinoic acid (tretinoin) to these protocols during induction phase has shown promising results in acute promyelocytic leukemia.

With current chemotherapeutic regimens, initial remission may be achieved in gt;80% cases, though relapses are common and bone marrow transplant is indicated majority of cases for best results.

Supportive therapy is very important in AML, as most cases are seriously sick on presentation and may die soon after hospitalization due to hemorrhage or overwhelming infections.

Prognosis: Overall cure rate is ~50% with chemotherapy alone and ~70% on chemotherapy with bone marrow transplant. AML with Down syndrome has more favorable prognosis, while bad prognostic factors include—(a) severe sepsis/bleeding on presentation, (b) secondary AML, and (c) early relapse. Cases with certain gene mutations in their leukemic cells, e.g. FLT3, NPM, etc. may have better or worse outlook.

20.2.3