Indications for Testing

Many of these genetic alterations have important prognostic implications that can guide the selection of therapy. Treatment of the acute leukemias has progressed from uniform strategies devised for large groups of patients to more-refined protocols tailored to the risk of relapse in discrete subgroups.1,2 Although routinely recorded features, such as the blast cell immunophenotype and the presenting white blood cell count, provide useful criteria for risk assessment, molecular genetic changes appear to offer the most sensitive markers of potential leukemia cell aggressiveness and hence are the best guides to treatment. IG and TCR gene rearrangement studies are useful both for the diagnosis of childhood ALL and for MRD assessment because these rearrangements occur in the vast majority of ALL patients.13-17,44-46

Molecular detection of chromosomal abnormalities in blast cells of leukemia patients, as described above, have important prognostic implications that can guide staging and selection of treatment for these patients. In addition, detection of specific translocations is used to assess MRD in leukemia patients.47 The term "minimal residual disease" (MRD) has been used to define the lowest level of disease detected in patients in complete continuous remission by conventional methods of analyses.

At clinical presentation, the number of leukemic cells is approximately 1011 to 1012; if the patient is not treated, the clone continues to expand, and death occurs with approximately 1013 total leukemic cells. With cytotoxic treatment, the number of neoplastic cells is diminished and when less than 5% of leukemia blasts are identified in the bone marrow by conventional cytology, the disease is considered in complete remission. Thus, patients considered in complete remission have from zero to 1010 leukemic cells. The detection of MRD when clinical remission is achieved or during the treatment can help direct adjustments to therapeutic strategies and identify patients with a higher risk of relapse.44-46,48,49 In patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), detection of MRD may lead to tapering of immunosuppressive treat-ment50,51 to prevent clinical relapse. MRD detection is also used to assess the effectiveness of purging procedures in the context of autologous HSC rescue.52

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