Reduced-intensity conditioning allogeneic blood stem cell transplantation with fludarabine and oral busulfan with or without pharmacokinetically targeted busulfan dosing in patients with myeloid leukemia ineligible for conventional conditioning.

We prospectively compared outcomes after a fludarabine (Flu) plus oral busulfan (Bu)-containing reduced-intensity conditioning regimen (150 mg/m2 Flu and 10 mg/kg oral Bu), with (n = 32; Flu- T Bu group) or without (n = 30; Flu-Bu group) therapeutic dose monitoring and dose adjustment of Bu. All patients received peripheral blood stem cells from a genoidentical sibling, and study cohorts had similar patient characteristics. Dose adjustments of Bu were required in 20 (63%) patients in the Flu- T Bu group (median final dose, 8.89 mg/kg; range, 6.3-13.34 mg/kg). Donor T-cell and granulocyte engraftments were similar, and early conditioning-related toxicities were mild and similar in both study groups. With a median follow-up of 45 months (51 months in the 37 survivors), posttransplantation outcomes did not differ between cohorts. The strongest predictor of 2-year overall survival and leukemia-free survival was the presence of chronic graft-versus-host disease (77% versus 34% for overall survival and 74% versus 34% for leukemia-free survival; P < .001 for both outcomes). In conclusion, therapeutic dose monitoring of oral Bu in a reduced-intensity conditioning setting does not seem to affect outcome, although further studies may identify very-high-risk patients who benefit from this strategy.