Late Consolidation for Patients with Standard Risk AML up to 60 Years: Results of a Prospective Randomized Comparison of High Dose AraC and Autologous PBSCT.

421 patients (pts.) up to 60 years with de novo (n=328) or secondary (n=93) AML were treated with risk-adapted therapy. Pts. with CBF-leukemias [t(8;21) or inv(16)] or normal karyotype and good response (GR) to induction I (up to 5% blasts in day 15 BM) were considered standard risk (SR), all others as high risk (HR). Induction I consisted of standard dose araC, idarubicine and VP16 (IVA-I). Pts. with GR to IVA-I continued with IVA-II on day 21. In pts. with bad response, the second cycle consisted of either IVA-II or FlAG/Ida. Double induction was followed by early consolidation with intermediate dose araC. As late consolidation, SR patients were randomized between high dose (HD) araC (12 x 3g/m²)/daunorubicine (3 x 45mg/m²) or an autologous PBSCT with PBSC mobilized after early consolidation except SR pts. with normal karyotype and an HLA-matched sibling who were allotransplanted. 214 pts. were classified as SR and 199 as HR. 91% of the SR and 59% of the HR pts. achieved CR (overall CR rate 75%) and 1% of the SR pts. died during induction. After 55 months, overall survival was significantly better for SR (49%) than for HR pts. (25%). Within the SR group, relapse free survival at 46 months was 63% for 21 pts. with inv(16), 58% for 25 pts. with t(8;21), and 37% for 148 pts. with normal karyotype (p = 0.13). Overall survival at 48 months was significantly better (p=0.014) for pts. with inv(16) (93%) than for those with t(8;21) (60%) or normal karyotype (44%). 48 SR pts. (12 with CBF leukemia) were randomized to receive HDaraC and 53 (14 with CBF leukemia) to undergo autoPBSCT. At 55 months, the overall survival was 52% for the autotransplanted pts. and 65% for those receiving HDaraC (p=0.71, intent-to-treat analysis). Median duration of neutropenia (<500/ μl) was 8 days for autoPBSCT and 19 days for HDaraC. Eleven pts. died in the HDaraC group (4 in CR and 7 from relapse) and 12 autotransplanted pts. died (1 in CR and 11 from relaspe). In pts. with normal karyotype, overall survival at 55 months for the allotransplanted SR pts. (n = 29) was 58% with no significant difference to HDaraC (62%) or autoPBSCT (43%). Relapse free survival for SR pts. with normal karyotype was 56% after allotransplantation, and 36% after autoPBSCT and HDaraC respectively (p = n.s.). In conclusion, overall survival is similar in SR AML pts. after autoPBSCT, HDaraC or allotransplantation. In SR pts. without an HLA-identical sibling donor, the reduced treatment related toxicity recommends autoPBSCT as late consolidation. In standard risk pts. with normal karyotype, allotransplantation from an HLA-identical sibling seems to have the highest antileukemic activity.