The Role Of Arac

While ara-C has historically been relegated to a minor role in the treatment of APL,57 more recent data suggest that certain patients, particularly those with high-risk APL, may derive considerable benefit from the addition of ara-C to their treatment. The German AML Cooperative Group,2425 which uses high-dose ara-C during induction, is one of the only groups to report essentially equivalent outcomes in patients with high and low WBC counts, suggesting that high-dose ara-C overcomes the negative prognostic impact of high WBC count. In the recently reported AIDA 2000 trial,26 intensification of consolidation therapy with ATRA and ara-C in high-risk patients led to a cumulative incidence of relapse of 2%, well below the 29% relapse rate seen in the earlier AIDA 0493 trial, and significantly below the 9% relapse rate noted in "intermediate-risk" patients consolidated with anthracyclines and ATRA alone. Finally, the European APL Group20 has reported preliminary results of a randomized trial in which low-risk patients (below the age of 60 and with WBC counts of less than 10,000/^L) were randomized to receive (group A) or not receive (group B) ara-C during induction and consolidation. All high-risk patients (WBC count >10,000) received standard-dose ara-C during induction and high-dose ara-C (1 or 2 g/m2 every 12 h for eight doses) during consolidation. The preliminary results demonstrate significantly improved EFS (93.6% vs 83.4%) and decrease in relapse rate (3.8% vs 11.9%) in low-risk patients randomized to receive ara-C. Perhaps even more striking, in the nonrandomized high-risk patients (groups C and E, WBC counts >10,000/^L), the relapse rates were 2.6 and 0% respectively, and EFS was extremely impressive, at 88.4% (group C, age <60) and 78.3% (group E, age >60). As reported by the Italian26 and Spanish groups,32 cure rates with ATRA- and anthracycline-based therapies are excellent in low-risk patients (WBC count <10,000/^L and platelet count >40,000/^L) and are generally acceptable in intermediate-risk patients (WBC count <10,000/^L and platelet count <40,000/^L), so the need for ara-C in these "low-risk" subgroups remains unclear. However, if longer follow up validates the data from the randomized portion of the APL2000 trial, incorporation of ara-C into the treatment regimen of even low-risk patients may need to be seriously reconsidered. In summary, while the role of ara-C in the treatment of APL remains far from settled, an argument can be made that this agent, particularly at high or intermediate dose, benefits patients with high-risk APL, and as such it should be seriously considered for inclusion into the treatment of all such patients.

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