Among elderly patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic stem cell transplantation (HSCT), fractionated busulfan myeloablative conditioning yields improved survival without an increased risk of non-relapse mortality (NRM), according to research published in Cancer.

HSCT is a standard curative treatment among patients with AML and MDS, although conditioning regimen intensity has a large effect on treatment efficacy. While younger and more healthy patients are better able to tolerate an intense myeloablative conditioning regimen (MAC), reduced-intensity conditioning regimens are often used in elderly and less healthy patients, as NRM can be high when MAC is used, counterbalancing the efficacy of treatment.

An important aim in AML and MDS, therefore, is to identify an intense, effective MAC that does not increase NRM. For this open-label phase 2 study, researchers evaluated the safety and efficacy of a myeloablative fractionated busulfan dose vs that of a standard non-fractionated lower busulfan dose regimen. The fractionated busulfan dose was designed to reach an area under the curve of 20,000 μmol per minute (f-Bu20K) over 2 weeks vs 16,000 μmol per minute (Bu16K) over 4 days in the non-fractionated dose group.

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Overall, 84 patients were randomly assigned to the f-Bu20K group and 78 were assigned to the Bu16K group. In the f-Bu20K group vs the Bu16K group, the median ages were 65 vs 66 years, respectively, 46 (55%) vs 38 (49%) patients had AML, 24 (30%) vs 25 (32%) patients had MDS, and 11 (13%) vs 11 (14%) patients had AML with preceding MDS. About 40% of patients in both groups had poor-risk cytogenetics.

After 2 years, patients in the f-Bu20K group had improved progression-free survival vs those in the Bu16K group (45% vs 24%, respectively; hazard ratio [HR], .5; P =.004). There was, furthermore, no noted increase in NRM in the f-Bu20K group (21% vs 15% in the Bu16K group; HR, 1.4; P =.3).

Overall survival was also significantly better in the f-Bu20K group (51% vs 31% in the Bu16K group; HR, .6; P =.01).

“To conclude, our observational study supports the notion that a MAC regimen administered in a fractionated manner to an older patient population is safe and efficacious,” the authors wrote. “These data, which need to be confirmed in future, larger, prospective studies, may indicate a paradigm shift toward the use of MAC regimens given over a longer period in older transplantation recipients with AML and MDS.”

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


Oran B, Saliba RM, Mehta RS, et al. Fractionated busulfan myeloablative conditioning improves survival in older patients with acute myeloid leukemia and myelodysplastic syndrome. Cancer. Published online January 20, 2021. doi:10.1002/cncr.33383