Consolidation Therapy

The choice of appropriate postremission therapy will depend on the patient's risk of relapse, which can be estimated based on presenting WBC and platelet counts.4 APL patients in low- and intermediate-risk groups can generally be successfully consolidated with anthracyclines alone. In recent trials published by the PETHEMA and GIMEMA groups, relapse rates of patients in low and intermediate risk groups were less than 10%, following consolidation with anthracyclines plus ATRA or anthracycline alone (patients generally received induction with idarubicin and ATRA, and 2 years of ATRA-based maintenance).26'32 However, in the PETHEMA LPA99 trial,32 patients with high WBC counts continued to have a high risk of relapse (21%), despite addition of ATRA during each course of consolidation, and increased intensity (by approximately twofold) of anthracyclines. High-risk patients appear to be faring somewhat better in the recent AIDA2000 trial,26 with a relapse rate (at 2 years) of only 2%. Consolidation therapy in this patient group was intensified by addition of ara-C during cycle 1, VP-16 during cycle 2, and ara-C and 6-TG during cycle 3. (All patients also received 15 days of ATRA with each course.) High-risk patients in the APL2000 trial, all of whom received ara-C during consolidation, also have excellent early outcomes, with rates of relapse below 5%.20 To summarize, consolidation therapy in APL should include, at a minimum, two cycles of ATRA plus anthracyclines; however, APL patients who present with WBC counts of more than 10,000/^L, and perhaps APL patients who express CD56, require additional, or alternative, therapy in addition to standard ATRA and anthracyclines. While further dose escalation of anthracyclines may be possible, current evidence suggests that a significant percentage of high-risk patients may be cured by incorporating ara-C into the induction and/or consolidation regimens. Whether other agents (e.g., arsenic trioxide and gemtuzumab ozogamicin) could substitute for ara-C in this role is not yet known, but this question, at least for arsenic trioxide, is being addressed in the current North American Intergroup trial.

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