In our prospective multicenter AML 01/99 trial for risk-adapted therapy of patients aged up to 60 years with acute myeloblastic leukemia, patients 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 other patients as high risk (HR). Patients with acute promyelocytic leukemia were excluded. Between January 1999 and May 2004, 421 patients (328 with with de novo and 93 with secondary AML) were treated. 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 as double induction. In patients with bad response (>5% bone marrow blasts on day 15), the second cycle consisted of either IVA-II or FlAG/Ida. Double induction was followed by an early consolidation with intermediate dose araC. As late consolidation, HR patients were allo- [HLA-matched sibling or matched unrelated donor (MUD)] or autotransplanted. Matched sibling allotransplantation was done in all participating centers whereas MUD transplantation was favoured by only two centers. The remaining centers performed autologous PBSCT if there was no sibling donor available. 199 patients were classified as HR, of whom 118 (59%) achieved CR, and 25 (13%) of the HR patients died during induction. After 55 months, overall survival was significantly worse for HR patients (25%) than for SR patients (49%). This was also true for the relapse-free survival (32% vs. 42%; p = 0.049). In the HR group, there was no difference in overall and relapse-free survival between those patients classified as HR because of bad response to IVA-1 (n = 65), unfavourable karyotype (n = 71) or both characteristics (n = 63). Regarding the different regimens for late consolidation, the “as treated” analysis of the HR patients revealed that overall (59% vs. 20%) and relapse-free survival (59% vs. 20%) was significantly better after an allogeneic HLA-matched sibling transplantation (n = 26) than after autoPBSCT (n=24). Overall and relapse-free survival for the 23 patients who underwent MUD transplantation were 59% and 45% respectively.

In conclusion, in HR patients with an HLA-identical sibling donor an allotransplantation should be performed. The results obtained with MUD transplantation in this particular patient group are encouraging. Therefore, in HR patients without an HLA-identical sibling allografting from unrelated donors should be considered in first CR. On the other hand, HR patients as defined by our risk stratification do not seem to benefit from autografting even after intensive induction and consolidation therapy.

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