Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia. Final results of a prospective randomized European Intergroup Trial

Abstract

Background: Allogeneic stem cell transplantation is usually considered the only curative treatment option for patients with advanced or transformed myelodysplastic syndromes in complete remission, but post-remission chemotherapy and autologous stem cell transplantation are potential alternatives, especially in patients over 45 years old.

Design and methods: We evaluated, after intensive anti-leukemic remission-induction chemotherapy, the impact of the availability of an HLA-identical sibling donor on an intention-to treat basis. Additionally, all patients without a sibling donor in complete remission after the first consolidation course were randomized to either autologous peripheral blood stem cell transplantation or a second consolidation course consisting of high-dose cytarabine.

Results: The 4-year survival of the 341 evaluable patients was 28%. After achieving complete remission, the 4-year survival rates of patients under 55 years old with or without a donor were 54% and 41%, respectively, with an adjusted hazard ratio of 0.81 (95% confidence interval [95% CI], 0.49-1.35) for survival and of 0.67 (95% CI, 0.42-1.06) for disease-free survival. In patients with intermediate/high risk cytogenetic abnormalities the hazard ratio in multivariate analysis was 0.58 (99% CI, 0.22-1.50) (P=0.14) for survival and 0.46 (99% CI, 0.22-1.50) for disease-free survival (P=0.03). In contrast, in patients with low risk cytogenetic characteristics the hazard ratio for survival was 1.17 (99% CI, 0.40-3.42) and that for disease-free survival was 1.02 (99% CI, 0.40-2.56). The 4-year survival of the 65 patients randomized to autologous peripheral blood stem cell transplantation or a second consolidation course of high-dose cytarabine was 37% and 27%, respectively. The hazard ratio in multivariate analysis was 1.22 (95% CI, 0.65-2.27) for survival and 1.02 (95% CI, 0.56-1.85) for disease-free survival.

Conclusions: Patients with a donor and candidates for allogeneic stem cell transplantation in first complete remission may have a better disease-free survival than those without a donor in case of myelodysplastic syndromes with intermediate/high-risk cytogenetics. Autologous peripheral blood stem cell transplantation does not provide longer survival than intensive chemotherapy.

Trial registration: ClinicalTrials.gov NCT00002926.

Figure 1.

Overview of treatment allocation of all 341 eligible patients.*Reasons for not administering the scheduled consolidation course were: early relapse (n=2), protocol violation (n=4), toxicity (n=10), refusal (n=1), and other reasons (n=2). Seven of these patients had an HLA-identical sibling and five of them received an allograft in first complete remission without the consolidation course. **Reasons for not randomizing the patients were: early relapse (n=11), toxicity (n=11), refusal (n=3), protocol violation (n=3), allograft (n=1), autograft (n=3), ineligibility for randomization (n=2), other (n=5) #: In total 68 patients were randomized (including 42 patients younger than 55 years who participated in the donor versus no donor comparison), but three patients were considered ineligible because they had relapsed before randomization. CR: complete remission; CR-1: first complete remission; AlloSCT: allogeneic stem cell transplantation; APSCT: autologous peripheral blood stem cell transplantation.

Figure 2.

Survival from registration in study, for all patients, and survival from complete remission for all patients who reached complete remission.

Figure 3.

Survival from complete remission without relapse according to the availability of a HLA identical sibling in patients ≤55 years old.

Figure 4.

Survival (two upper curves) and disease-free survival (two lower curves) from randomization according to the randomization group. N: number of patients; O: observed number of events (death –for survival analysis –, or relapse or death without relapse); P value given by the logrank test. APSCT: autologous peripheral blood stem cell transplantation; HDAC: high-dose cytarabine.