Untreated Childhood Acute Lymphoblastic Leukemia
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ Pediatric and Adult Treatment Editorial Boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
Induction Chemotherapy
Three-drug induction therapy using vincristine, prednisone/dexamethasone, plus L-asparaginase in conjunction with intrathecal therapy (IT), results in complete remission rates of greater than 95%.[1] For patients at high risk of treatment failure, a more intense induction regimen (four or five agents) may result in improved event-free survival (EFS),[2,3,4] and high-risk patients generally receive induction therapy that includes an anthracycline (e.g., daunomycin) in addition to vincristine, prednisone/dexamethasone, plus L-asparaginase. For patients who are at standard risk or low risk of treatment failure, four-drug induction therapy does not appear necessary for favorable outcome provided that adequate postremission intensification therapy is administered.[2,5,6] Because of the likelihood of increased toxicity with four-drug induction therapy, Children's Oncology Group (COG) protocols for National Cancer Institute (NCI) standard-risk precursor B-cell ALL currently utilize dexamethasone, vincristine, and L-asparaginase. Induction regimens using four or more agents are reserved for higher risk patients.[2,5,7]
Many current regimens utilize dexamethasone instead of prednisone during remission induction and later phases of therapy. The Children's Cancer Group (CCG) conducted a randomized trial comparing dexamethasone and prednisone in standard-risk patients, and reported that dexamethasone was associated with a superior EFS.[8] Results from another randomized trial conducted by the United Kingdom Medical Research Council (MRC) demonstrated that dexamethasone was associated with a more favorable outcome than prednisolone in all patient subgroups.[9] In the MRC trial, patients who received dexamethasone had a significantly lower incidence of both central nervous system (CNS) and non-CNS relapses than patients who received prednisolone.[9] However, a third randomized trial (conducted in Japan) did not confirm a survival advantage with dexamethasone.[10] This discrepant result might have been due to the use of a higher dose of prednisolone during induction therapy, the use of a more intensive backbone chemotherapy regimen, and/or the smaller number of patients included in that trial.
While dexamethasone may be more effective than prednisone, data also suggest that dexamethasone may also be more toxic, especially in the context of more intensive induction regimens. Several reports indicate that dexamethasone may increase the frequency and severity of infections and/or other complications in patients receiving intensive (more than three drugs) induction regimens.[11,12] The Berlin-Frankfurt-Muenster (BFM) group observed increased mortality in adolescent patients who received dexamethasone instead of prednisone during a four-drug induction regimen. However, the MRC group did not observe any toxicity or mortality differences between dexamethasone and prednisone during a four-drug induction regimen.[3] Dexamethasone appears to have a greater suppressive effect on short-term linear growth than prednisone,[13] and has been associated with a higher risk of osteonecrosis, especially in adolescent patients.[14]
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