An intensified reduced-intensity conditioning (RIC) regimen does not improve transplant outcomes in patients with acute myeloid leukemia (AML) or myelodysplasia (MDS), according to research published in the Journal of Clinical Oncology.

Adults with AML or MDS who are unable to have myeloablative conditioning before allogeneic stem cell transplantation undergo RIC; however, RIC is linked to higher rate of disease relapse.

The FIGARO trial, a phase 2 randomized trial, compared a sequential transplant regimen of fludarabine, amsacrine, and cytarabine-busulphan (FLAMSA-Bu) with a conventional fludarabine-based RIC regimen in patients with high-risk AML or MDS. The FLAMSA-Bu protocol included additional cytoreductive chemotherapy before a fludarabine-based RIC regimen. Previous studies have shown this regimen to reduce relapse and improve outcomes in patients with high-risk AML or MDS.

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A total of 244 patients (median age, 59 years) with either high-risk AML (n=164) or MDS (n=80) were randomly assigned (1:1) to receive FLAMSA-Bu or an investigator’s choice of 1 of 3 conventional RIC regimens; 108 patients in each arm underwent transplantation.

The median follow-up was 35 months. The 2-year overall survival (OS) for the conventional RIC group vs the FLAMSA-bu group was 58.8% vs 60.9%, respectively (hazard ratio [HR], 1.05; log-rank P =.81).

In addition, the 2-year event-free survival (EFS) was slightly higher for the FLAMSA-Bu (54.2%) arm compared with the conventional RIC arm (48.7%), but the difference was also not statistically significant (HR, 0.96; long-rank P =.82).

No difference in outcomes was determined in subgroup analyses based on age, AML or MDS diagnosis. There were also no significant differences in treatment-related mortality, graft-vs-host disease, or relapse risk between the 2 arms.

The study also evaluated measurable residual disease (MRD) status and transplant outcomes. MRD positivity before transplant was associated with an increased relapse risk.

Despite the predictive value of MRD, the authors did not find a benefit to intensifying RIC for patients with MRD positivity; however, the authors noted that approximately 50% of patients with evidence of MRD before transplant did not relapse. An RIC regimen may have a graft-vs-leukemia effect in high-risk AML, including patients with detectable MRD.

In this trial, the authors did not find a beneficial effect on outcomes with the FLAMSA-Bu regimen in the overall study population.

Disclosure: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Craddock C, Jackson A, Loke J, et al. Augmented reduced-intensity regimen does not improve postallogeneic transplant outcomes in acute myeloid leukemia. J Clin Oncol. Published online December 29, 2020. doi:10.1200/JCO.20.02308