Prospective Randomized Comparison of High Dose AraC and Autologous Peripheral Blood Stem Cell Transplantation as Late Consolidation for Patients ≤60 Years with Standard Risk AML.

484 patients aged ≤60 years with de novo (n=385) or secondary (n=99) acute myeloid leukemia (AML) were treated with risk-adapted therapy. Patients with t(8;21), inv(16) or normal karyotype and good response (GR) to induction I (≤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 etoposide (IVA-I). Patients with GR to IVA-I continued with IVA-II on day 21 as double induction. Patients with bad response (>5% blasts in day 15 BM) received FlAG/Ida as second cycle. Double induction was followed by early consolidation with intermediate dose araC. As late consolidation, SR patients with normal karyotype and an HLA-matched sibling received matched related donor (MRD) transplantation. The remaining SR patients were randomized between high dose araC (HD-araC; 12 x 3g/m²)/daunorubicine or an autologous peripheral blood stem cell transplantation (autoPBCSCT) with PBSC mobilized after early consolidation. 90% of SR patients (n=250) achieved complete remission (CR) in contrast to 58% of HR patients (n=234) (overall CR rate 75%). 4% of the SR patients died during induction. At 70 months, overall survival (OS) was significantly better for SR (51%) than for HR patients (28%). Within the SR group, relapse free survival at 50 months was not different between patients with normal karyotype (n=165), inv(16) (n=30) or t(8;21) (n=30). 55 SR patients were randomized to receive HD-araC and 59 to autoPBSCT. Distribution of the main characteristics were well balanced (age, performance status, cytogenetics, FLT3 mutation status, de novo or secondary AML). At 63 months, OS was 62% for patients treated with autoPBSCT and 59% for those receiving HD-araC (p=0.91, intent-to-treat). Median duration of neutropenia (<500/μl) was 8 days for autoPBSCT and 20 days for HD-araC (p<0.05). This corresponded to a significantly higher rate of septicemia (20% vs. 10%) and pneumonia (13% vs. 3%) after HD-araC. The duration of thrombocytopenia was 22 days after HD-araC and 11 days after autoPBSCT (p<0.01). 14 patients died in the HD-araC group (4 in CR and 10 from relapse) and 14 patients died after autoPBSCT (1 in CR and 13 from relapse). In patients with normal karyotype, OS at 67 months for the SR patients receiving MRD transplantation (n = 37) was 61% with no significant difference to HD-araC or autoPBSCT. In conclusion, OS is similar in SR AML patients after autoPBSCT, HD-araC or MRD transplantation. In SR patients without an HLA-identical sibling donor, autoPBSCT instead of HD-araC is recommended for late consolidation due to the reduced treatment related toxicity.