Acute lymphoblastic leukemia

The treatment of childhood ALL has been one of the great success stories of modern chemotherapy and cure rates approaching 80% have been achieved in recently reported series. ALL cells usually rearrange either the IgH or TCR genes or both, and these provide markers that can be used to assess the clinical significance of MRD detection in a disease with such a high likelihood of cure. Despite near uniformity in approaches to the management of newly diagnosed ALL, the issue of whether eradication of PCR-detectable MRD is necessary for cure remains highly controversial in this disease. Most studies have suggested that modern aggressive induction regimens are often associated with rapid elimination of PCR-detectable disease. Additional studies have suggested an association between the rate of decrease of detectable disease and subsequent prognosis. However, a significant number of patients have persistence of PCR-detectable disease and yet have not relapsed. One study suggested that, using the most sensitive PCR analysis, it is possible to detect persistent cells bearing the associated antigen receptor rearrangement in the majority of patients, indicating that it is neither possible nor necessary to eradicate PCR-detectable disease for cure. For this reason, many current studies are addressing whether the quantitative assessment of MRD may be required to predict which patients are ultimately fated to relapse. Most studies addressing this issue have suggested that a quantitative increase in tumor burden is almost invariably associated with impending relapse.

The TEL/AML-1 gene rearrangement results from the cryptic reciprocal translocation t(12;21). This is the most common gene rearrangement found in childhood ALL and accounts for 25% of pre-B-cell ALL in children, but is rarely found in adult ALL. Some data are suggestive that the presence of this rearrangement is associated with a good prognosis. However, qualitative and quantitative PCR analysis studies have suggested that the persistence of residual leukemia cells or a slower rate of eradication of the leukemic cells is associated with a poorer prognosis.

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