Front-Line Treatment of Acute Promyelocytic Leukemia with AIDA Induction Followed by Risk-Adapted Consolidation: Results of the AIDA-2000 Trial of the Italian GIMEMA Group.

Following the identification, in collaboration with the Spanish PETHEMA group, of distinct prognostic categories among APL patients receiving AIDA-like therapies (Sanz et al. Blood 2000) the Italian GIMEMA group designed a protocol for newly diagnosed APL (AIDA-2000) in which the intensity of post-remission treatment was adapted to the relapse risk. A total of 298 PML/RARa-positive patients with median age 40 yrs (range 1–60) were enrolled during the period January 2000 – February 2003 from 64 Italian institutions. After the standard AIDA-0493 induction (Mandelli et al, Blood 1997), patients with low- and intermediate-risk received 3 anthracycline-based consolidation courses with idarubicin, mitoxantrone, and idarubicin as in the PETHEMA LPA-96 (Sanz et al. Blood 1999), whereas patients with high-risk disease (WBC > 10 x 10⁹/L) received the same 3 anthracycline courses with the addition of cytarabine, etoposide and cytarabine plus 6-thioguanine during the first, second and third course, respectively, as in the original AIDA. In addition, distinct from those in the AIDA-0493, all patients enrolled in the AIDA-2000 received concomitant ATRA 45 mg/m² for 15 d during each consolidation course. The results of the AIDA-2000 series were compared to those obtained in 346 consecutive patients (median age 36 yrs, range 1–60) enrolled in the AIDA-0493 study during the period May 1997 – May 2000. All patients in either studies who tested PCR-negative post-consolidation received ATRA maintenance for a total of two years. After induction, 323/338 (96%) and 276/294 (94%) evaluable patients achieved CR in the AIDA-0493 and AIDA-2000, respectively (P=0.34). Molecular remission was obtained after consolidation in 291/296 (98%) and 235/238 (99%) patients (P=0.69). With a median follow-up of 4.5 and 2.0 yrs in the two studies, the DFS at 2.0 yrs for patients in the AIDA-0493 and AIDA-2000 was 84% and 90%, respectively (P=0.09), whereas the CIR rate at 2.0 yrs was 14% and 5%, respectively (P=0.04). Five and 9 patients died in CR in the two series and were equally distributed among risk groups. By comparing separately the distinct risk groups in the AIDA-0493 and AIDA-2000, there was no significant difference in the CIR rate for low- (3% vs. 2%) and intermediate-risk (11% vs. 9%) groups, while a significantly higher CIR was observed in the AIDA-0493 for high-risk (29% vs. 2%, P=0.0004). In line with recent PETHEMA results, our data confirm that anthracycline-based consolidation is equally effective as cytarabine-containing regimens for patients with low- and intermediate-risk and suggest that a risk-adapted strategy including ATRA for consolidation provides an outcome improvement in newly diagnosed APL. In addition, our results suggest a benefit in terms of relapse rate reduction using cytarabine coupled to anthracyclines and ATRA during consolidation in the high-risk group.