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

Authors

Uday R Popat
Oren Pasvolsky
Roland Bassett
Rohtesh S Mehta
Amanda Olson
Julianne Chen
Amin M Alousi
Gheath Al-Atrash
Qaiser Bashir
Alison M Gulbis
Chitra M Hosing
Jin S Im
Partow Kebriaei
Issa Khouri
David Marin
Yago Nieto
Betul Oran
Neeraj Saini
Terri Lynn Shigle
Samer A Srour
Jeremy L Ramdial
Katayoun Rezvani
Muzaffar H Qazilbash
Borje S Andersson
Richard E Champlin
Elizabeth J Shpall

Publication Date

10-24-2023

Journal

Blood Advances

Abstract

Traditional conditioning regimens for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) 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 nonrelapse mortality (NRM) while retaining antileukemic effects. Here, we performed a phase 2 trial for adults with hematological malignancies receiving matched related or unrelated allo-HCT. Participants received busulfan 80 mg/m2 as outpatients on days -20 and -13 before transplant. Fludarabine 40 mg/m2 was administered on days -6 to -3, followed by busulfan dosed to achieve a target area under the curve of 20 000 mol/min for the whole course. The primary end point was day-100 NRM. Seventy-eight patients were included, with a median age of 61 years (range, 39-70 years), who received transplantation for acute leukemia (24%), myelodysplastic syndrome (27%), or myeloproliferative disease/chronic myeloid leukemia (44%). HCT-specific comorbidity index (HCT-CI) was ≥3 in 34 (44%). With a median follow-up of 36.4 months (range, 2.9-51.5), the 100-day, 1-year, and 3-year NRM rates were 3.8%, 8%, and 9.3%, respectively, without a significant difference in age or HCT-CI score. The 1-year and 3-year relapse incidence was 10% and 18%, respectively. The 3-year overall survival was 80%, without a significant difference in age or HCT-CI score and was similar for patients aged >60 years and those aged <60 years as well as for those with HCT-CI ≥3 and HCT-CI <3. Overall, 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. This trial was registered at www.clinicaltrials.gov as #NCT02861417.

Keywords

Adult, Aged, Humans, Middle Aged, Busulfan, Comorbidity, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Recurrence

Comments

Supplementary Materials

PMID: 37611156