Reduced-dose conditioning prior to allogenic stem cell transplantation (ASCT) in patients with myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML) resulted in similar outcomes including nonrelapse mortality, incidence of relapse, and relapse-free survival compared with standard-dose conditioning. Nicolaus Kröger, MD, University Cancer Center Hamburg, Hamburg, Germany, presented data from the Dose-Reduced Versus Standard Conditioning in MDS/sAML trial [RICMAC; NCT01203228].

Currently, the most effective, potentially curative, treatment for MDS is ASCT. In favor of reducing toxicity, dose-reduced conditioning is being increasingly used; however, some retrospective data suggest that dose-reduced conditioning may lead to higher rates of relapse. The purpose of the RICMAC trial was to evaluate the effect of reduced-dose conditioning on the outcomes of patients with MDS or sAML after ASCT.

In the prospective, open-label, phase 3 RICMAC trial, patients (n = 129) with MDS or sAML were randomly assigned to receive standard-dose busulfan (12.8 mg/kg ideal body weight [IBW] intravenously [IV] or 16 mg/kg body weight [BW] orally) plus cyclophosphamide (120 mg/kg BW IV) or reduced-dose busulfan (6.4 mg/kg IBW IV or 8 mg/kg BW orally) plus fludarabine (5 × 30 mg/m² IV). Patients were considered to have cytologically proven MDS based on refractory anemia or refractory anemia with ring sideroblasts, excess blasts, or excess of blast in transformation. Patients with chronic myelomonocytic leukemia and sAML were also included. All patients had a blast count < 20% regardless of chemotherapy at the time of ASCT. Other eligibility criteria included human leukocyte antigen (HLA)–matched related donors aged 18 to 65 years or unrelated donors aged 18 to 60 years and no major organ dysfunction. One HLA antigen mismatch was also allowed. Patients were excluded if there was central nervous system involvement, a life expectancy < 6 months owing to comorbidities, serious psychiatric or psychological disorder, pregnancy or lactation, or positive serology for HIV.

The primary end point of the study was nonrelapse mortality at 1 year after ASCT. Secondary end points included incidence of acute and chronic graft-vs-host disease, overall survival (OS) at 2 years, event-free survival at 2 years, and incidence of relapse at 2 years. Slow recruitment led to early termination of the study.

There was no significant difference in nonrelapse mortality at 24 months (P = .17). Similarly, there was no significant difference in relapse incidence or relapse-free survival in both arms. There was a higher percentage in survival in the reduced-dose arm compared with the standard-dose arm, but results did not achieve significance (P = .06).

In a subanalysis, patients aged > 51 years had significantly lower rates of relapse-free survival compared with younger patients (HR, 1.93; P = .03). In addition, prior chemotherapy increased the risk of relapse (HR, 3.36; P = .01) and OS was significantly lower in patients with a performance status of 1 to 3 compared with 0 (HR, 2.58; P = .04). Interestingly, patients with a low cytogenetic risk who receive reduced-dose conditioning had significantly higher rates of OS compared with patients who received standard-dose conditioning (HR, 0.14; P = .002). However, there was no benefit in patients with intermediate risk and patients with high risk demonstrated greater rates of OS when treated with standard-dose conditioning (HR, 1.70; P = .39).

In conclusion, Dr Kröger indicated that the data from the RICMAC trial suggest that reduced-dose conditioning results in similar outcomes as standard-dose conditioning; however, he indicated that a longer follow-up period is required to confirm these results.