Treatment of Patients up to 60 Years with High Risk AML: Final Results of the AML SHG-Hannover 01/99 Trial.

In this prospective multicenter trial, we treated 520 patients with AML ≤60 years (414 with de novo and 106 with secondary AML). Patients with CBF-leukemias [t(8;21) or inv(16)] or normal karyotype and good response (GR) to induction I (≤5% blasts in day 15 BM) were considered standard risk (SR), all other patients as high risk (HR). Patients with t(15;17) were excluded. Induction course I consisted of standard dose araC, idarubicine and etoposide (IVA-I). Patients with GR to IVA-I continued with IVA-II on day 21. In patients with bad response (BR; >5% BM blasts on day 15), 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, HR patients with an HLA-matched sibling were scheduled for a matched related donor (MRD) transplantation; patients without a family donor should undergo autologous peripheral blood stem cell transplantation (autoPBSCT). PBSC were mobilized after early consolidation. An interim analysis showed superior results for allogeneic transplants compared to patients who had undergone autoPBSCT. Therefore, since 2003 all HR patients without a sibling donor were scheduled for matched unrelated donor (MUD) transplantation. 147 of 249 HR patients (59%) achieved complete remission. 33 (13%) of the HR patients died during induction. After 75 months, overall survival (OS) was significantly worse for HR patients (24%) than for SR patients (53%). For HR patients, there was no difference in OS and relapse-free survival (RFS) between patients classified as HR because of BR to IVA-1 (n = 83), unfavourable karyotype (n = 87) or both characteristics (n = 79). RFS was neither different between HR patients with de novo or secondary AML nor between HR patients with normal karyotype, complex karyotype or other high risk cytogenetics. Regarding late consolidation, the “as treated” analysis revealed that OS and RFS was significantly better after an MRD transplantation (n=41, OS 67%, RFS 62%) than after autoPBSCT (n=27, OS 14%, RFS 7%). Patients who received a MUD transplantation (n=32) showed a significantly better RFS (52%) than after autoPBSCT. RFS and OS after MUD transplantation did not differ significantly from MRD transplants. OS of patients after autoPBSCT was not significantly different from patients who received no transplant at all after entering CR. Of the 69 HR patients who did not enter CR after induction, 44 received an MRD or MUD transplantation. 15 of these patients (35%) are alive in CR. In conclusion, HR patients as defined in our study do not benefit from an autologous PBSCT and an allogeneic MRD or MUD transplantation should be performed. Moreover, allogeneic transplants are a viable salvage option for HR patients not entering CR.