TY - JOUR
T1 - Myeloablative fractionated busulfan for allogeneic stem cell transplant in older patients or patients with comorbidities
AU - Popat, Uday R.
AU - Pasvolsky, Oren
AU - Bassett, Roland
AU - Mehta, Rohtesh S.
AU - Olson, Amanda
AU - Chen, Julianne
AU - Alousi, Amin M.
AU - Al-Atrash, Gheath
AU - Bashir, Qaiser
AU - Gulbis, Alison M.
AU - Hosing, Chitra M.
AU - Im, Jin S.
AU - Kebriaei, Partow
AU - Khouri, Issa
AU - Marin, David
AU - Nieto, Yago
AU - Oran, Betul
AU - Saini, Neeraj
AU - Shigle, Terri Lynn
AU - Srour, Samer A.
AU - Ramdial, Jeremy L.
AU - Rezvani, Katayoun
AU - Qazilbash, Muzaffar H.
AU - Andersson, Borje S.
AU - Champlin, Richard E.
AU - Shpall, Elizabeth J.
N1 - Publisher Copyright:
© 2023 by The American Society of Hematology.
PY - 2023/10/24
Y1 - 2023/10/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85175487020&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85175487020&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2023010850
DO - 10.1182/bloodadvances.2023010850
M3 - Article
C2 - 37611156
AN - SCOPUS:85175487020
SN - 2473-9529
VL - 7
SP - 6196
EP - 6205
JO - Blood Advances
JF - Blood Advances
IS - 20
ER -