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The association of age and outcome is nowhere more evident than between infants and older patients. Infants (less than 1 year of age) often possess a poor prognostic genotype represented by the presence of the MLL gene rearrangement. The MLL gene is capable of partnering with many genes, and in virtually every instance the result is a markedly poor prognosis. All cells that have the MLL gene rearrangement are highly resistant to the key antileukemic drugs such as glucocorticoids and L-asparaginase. Thus, investigators are now focusing on protocols specifically aimed at infant ALL.

Like age, the WBC at presentation is a reliable indicator of CR rate and outcome. The WBC is indicative of tumor burden, although the underlying biological mechanisms that account for the unfavorable outcomes associated with an elevated WBC are

unclear. Patients with WBCs of less than 50 x 10 /mm (50 x 10 /L) are considered standard risk and have a better outcome than those with a higher WBC at presentation, which is associated with higher risk of treatment failure (Table 95-6).

Specific chromosomal abnormalities in leukemic cells also possess prognostic significance. Blast cells with a translocation of parts of chromosome 12 and 21 (the TEL-AML1 fusion) or trisomies of 4, 10, and 17 are considered to have favorable genetic features. The presence of specific translocations between chromosome 9 and 22 (Ph+)

is a high-risk feature, which is present in about 5% of patients with ALL.

The DNA content of blast cells, hyper-, hypo-, or diploid, corresponding to increased-, decreased-, or normal-chromosome numbers, has been considered prognostic. Lower-risk patients with hyperdiploidy (greater than 50 chromosomes per leukemic cell) generally include approximately 25% of children who have B lineage ALL.7 These children are between the ages of 1 and 9 years, whereas the higher-risk patients with normal diploidy (50 chromosomes) generally are older.

Patients with cell-surface markers indicating that the blasts are early in the B-cell lineage (CD markers) are considered favorable and standard risk, whereas those with mature B-cell and T-cell blasts are considered high risk. T-cell ALL is found in approximately 15% of childhood ALL. Compared to B-lineage ALL, T-cell ALL is relatively resistant to different classes of drugs including methotrexate and cytarabine.

Patients completing induction treatment and in apparent remission still harbor malignant cells in their bone marrow, even though they appear disease-free by peripheral blood and bone marrow morphology. Assuming that most patients present with about a 1012 leukemic cell burden at diagnosis, at least 1010 or 1% residual disease remains after induction. These residual leukemic cells are below the limits of detection using standard morphologic examination. Measurement of this population of cells has become an increasingly significant prognostic factor and a determinant of the aggressiveness of postinduction therapy. Through flow cytometric analysis and polymerase chain reaction, it is possible to detect one leukemic cell among 104 normal cells, representing a 100-fold greater sensitivity than morphological examination.

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 ofpostinduction leukemia therapy.14 Several studies in children, in whom ALL is common, have evaluated disease levels at the end of induction and correlated these values with EFS. For example, a patient with detectable MRD less than 0.1% at the end of induction has a EFS greater than 90% at 3 years. Conversely, a patient with high MRD (1%) has a 3-year EFS of only about 25%.15 Assessment of MRD is also emerging as an important indicator of disease recurrence in the adult population and in patients with AML.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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