Key concepts

© The acute leukemias are hematologic malignancies of bone marrow precursors characterized by excessive production of immature hematopoietic cells. This proliferation of "blast" cells eventually replaces normal bone marrow and leads to the failure of normal hematopoiesis and the appearance of leukemia cells in peripheral blood as well as infiltration of other organs.

Acute leukemias are classified according to their cell of origin. Acute lymphocyt-ic leukemia (ALL) arises from the lymphoid precursors. Acute nonlymphocytic leukemia (ANLL) or acute myelogenous leukemia (AML) arises from the myeloid or megakaryocytic precursors.

The goal is to match treatment to risk and minimize over- or undertreatment. Children with ALL are sorted into prognostic categories based on clinical and biological features that mirror their risk of relapse. Risk assessment is an important factor in the selection of treatment.

^^ Minimal residual disease (MRD) is a quantitative assessment of subclinical remnant of leukemic burden remaining at the end of the initial phase of treatment (induction) when a patient may appear to be in a complete morphologic remission. This measure has become one of the strongest predictors of outcome for patients with acute leukemia. The elimination of MRD is a principal objective of postinduction leukemia therapy.

O The initial treatment for acute leukemias is called induction. The purpose of induction is to induce a remission, a state where there is no identifiable leukemic cells in the bone marrow or peripheral blood with light microscopy. This definition may change as more sensitive techniques come into play.

The current induction therapy for ALL typically consists of vincristine, aspar-aginase, and a steroid (prednisone or dexamethasone). An anthracycline is added for higher-risk patients.

^^ Leukemic invasion of the CNS is considered to be an almost universal event in patients, even in those whose cerebrospinal fluid (CSF) cytology shows no apparent disease. Thus, all patients with ALL and AML receive intrathecal chemotherapy. Although this is often referred to as "prophylaxis," it more realistically represents treatment.

® Marrow relapse is a major complication for 15% to 20% of patients with ALL. Current research suggests that this is the result of residual leukemic cells at diagnosis. Thus the importance of MRD.

O The current induction therapy for AML usually consists of a combination of cyta-rabine and an anthracycline daunorubicin or idarubicin, with the frequent addition of a steroid and/or an antimetabolite such as 6-thioguanine. The second phase of treatment for AML is called consolidation. The purpose of this phase is to further enhance remission with more cytoreduction.

<B> Although survival in pediatric cancers has improved dramatically over the last 35 years, 50% to 60% of cancer survivors are estimated to have at least one chronic or late-occurring complication of treatment.

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