Myeloablative Fractionated Busulfan for Allogeneic Stem Cell Transplant in Older Patients or Patients with Comorbidities.

Traditional conditioning regimens for patients undergoing allogeneic hematopoietic stem cell transplantation (alloHCT) provide suboptimal outcomes, especially for older patients and those with comorbidities. We hypothesized that a fractionated myeloablative busulfan dose delivered over an extended period would reduce non-relapse mortality (NRM), while retaining anti-leukemic effects. Here, we performed a phase II trial for adults with hematological malignancies receiving matched related or unrelated alloHCT. Participants received busulfan 80mg/m2 outpatient on days -20 and -13 before transplant. Fludarabine 40mg/m2 was given on days -6 to -2 followed by busulfan dosed to achieve a target area under the curve of 20,000mol/min for the whole course. The primary endpoint was day 100 NRM. Seventy-eight patients were included, with a median age of 61 (range 39-70) years, transplanted for acute leukemia (24%), MDS (27%), or MPD/CML (44%). HCT specific comorbidity index (HCT-CI) was >3 in 34 (44%). With a median follow-up of 36.4 (range 2.9-51.5) months, 100-day, 1-year and 3-year NRM was 3.8% (95%CI, 0-8.1%), 8% (95%CI, 2-14%), and 9.3% (95%CI, 2.6-15.9%), without a significant difference by age or HCT-CI score. One-year and 3-year relapse incidence was 10% (95%CI, 4-17%) and 18% (95%CI, 9-27%), respectively. Three-year overall survival was 80% (95%CI, 72-90%) and was similar for patients >60 and <60 years of age, as well as those with HCT-CI>3 and HCT-CI<3. Overall, we found that a myeloablative fractionated busulfan regimen has low NRM without an increase in relapse rate, resulting in promising survival, even in older patients or in patients with comorbidities.