Allogeneic (Allo-) or Autologous (Auto-) Peripheral Blood Stem Cell Transplantation (SCT) Randomized Versus a Second Intensive Consolidation after a Common Induction and Consolidation Course in Patients with Bad Prognosis Myelodysplastic Syndromes and Acute Myelogenous Leukemia Following MDS of More Than 6 Months Duration: The Final Analysis of a Joint Study (CRIANT) of the EORTC, EBMT, SAKK, HOVON and GIMEMA Leukemia Groups.

Allo-SCT is currently considered the only curative treatment option of patients (pts) with advanced stages of MDS. The CRIANT study tested in pts without an HLA-id. sibling the value of auto-SCT versus one additional course of high dose cytarabine (HDAC). Pts with identified HLA-id. sibling(s) were candidates for allo-SCT. All pts received remission-induction therapy consisting of idarubicin, cytarabine and etoposide (ICE). Pts who reached CR received one consolidation course (cons) with intermediate dose of cytarabine and idarubicin. All pts without a HLA-id. sibling received filgrastim during the recovery phase of 1st cons to mobilize stem cells and were randomized between ASCT and 2nd cons. Between November 1996 and September 2003, 345 pts were registered (69% of them ≤ 55 years of age and 77% with MDS). Reviewed cytogenetic data were available of 295 (86%) and FISH data of 167 pts (48%). Out of 341 evaluable pts 256 have died and the median follow-up was 5.3 years. The median survival was 1.3 years and the 4-year survival rate was 29% (SE=3%). Age (> vs ≤ 55 yrs: HR=1.5, p=0.003) and the IPSS cytogenetic/FISH score (intermediate vs low: HR=1.5, p=0.02; high vs low: HR=3.1, p<0.0001) were independent prognostic factors for survival. ICE induced CR in 194 (57%) pts. The median DFS was 1.0 yr and the 4-year DFS rate was 29% (SE=3%). 176 (91%) CR pts received the 1st cons. 34 pts were randomized for auto-SCT and 38 for HDAC. Mobilization of stem cells after the 1st cons was adequate in 48 and failed in 54 pts. In total 19 randomized pts (56%) received auto-SCT and 26 (68%) received HDAC. The 4-year DFS rates of the 2 groups were 30% (SE=8%) and 17% (SE=7%), resp. (p=0.32). The 4-year DFS rate of pts with a failed mobilization was 26% vs 17% for those with a successful harvest (p=0.21; p=0.76 adjusted for cytogenetics). The outcome of pts in CR (≤ 55 yrs) was compared according to the availability of a HLA-id. sibling donor. The 4-year DFS of the 50 pts with a donor was 45% (SE=8%) and of the 85 pts without a donor 27% (SE=7%) (HR=0.62, 95% CI 0.39–0.97, p=0.04, after adjustment for age and IPSS cytogenetic score). In intermediate/high risk pts. the difference was higher (HR=0.43, p=0.009). Cytogenetic analysis in CR was performed in 43 of 73 pts in CR with cytogenetic/FISH aberrations at diagnosis. The 4-year relapse rate was higher in the 13 pts with persisting abnormalities compared to the 30 pts with no cytogenetic abnormalities in CR: 93% versus 74%, resp. (p=0.22). In conclusion: cytogenetic characteristics and age are the major prognostic factors in MDS/sAML pts treated by intensive remission-induction/consolidation chemotherapy, followed by another consolidation course or SCT. Pts with a donor and candidates for allo-SCT in CR-1 have a better outcome than those without a donor. Pts randomized for auto-SCT had a 13% higher 4-yr DFS rate than those randomized for intensive chemotherapy only.