Vorinostat Combined with Busulfan, Fludarabine, and Clofarabine Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Leukemia: Long-Term Study Outcomes

Authors

Gheath Alatrash
Chantal Saberian
Roland Bassett
Peter F Thall
Celina Ledesma
Yoshimi Lu
May Daher
Benigno C Valdez
Jitesh Kawedia
Uday Popat
Rohtesh Mehta
Betul Oran
Yago Nieto
Amanda Olson
Paolo Anderlini
David Marin
Chitra Hosing
Amin M Alousi
Elizabeth J Shpall
Gabriela Rondon
Julianne Chen
Muzaffar Qazilbash
Richard E Champlin
Partow Kebriaei

Publication Date

8-1-2022

Journal

Transplantation and Cellular Therapy

DOI

10.1016/j.jtct.2022.05.021

PMID

35618218

Abstract

Conditioning regimens play a major role in determining disease outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The use of i.v. busulfan (Bu) as part of conditioning chemotherapy has been shown to be effective in controlling disease relapse; however, disease relapse remains a major cause of death following allo-HSCT. This study was conducted to determine the long-term outcomes of vorinostat with i.v. Bu plus dual nucleoside analogs clofarabine (Clo) and fludarabine (Flu) in the conditioning regimen for patients undergoing allo-HSCT. This was a rapid dose escalation phase I/II study designed to determine whether the addition of vorinostat would improve the efficacy of standard i.v. Bu/Flu/Clo conditioning regimen. This report presents the long-term disease outcomes of this combination in 68 patients with high-risk leukemia, including 31 (46%) with acute lymphoblastic leukemia (ALL) and 37 (54%) with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Fifty-eight patients (85%) were in morphologic complete remission at time of transplantation, and 38 (56%) received a matched unrelated donor graft. Over the median follow-up of 37.6 months, 29 of the 68 patients died (43%), and the nonrelapse mortality (NRM) rate was 22% (n = 15). The median overall survival and median NRM were not reached. Nineteen patients (28%) experienced disease progression. The median progression-free survival was 36.8 months. Thirty-seven patients (57%) developed grade II-IV acute graft-versus-host disease (GVHD), and 20 patients (31%) developed chronic GVHD. Our results suggest a lack of benefit from adding a short course of vorinostat to i.v. Bu/Flu/Clo conditioning regimens for leukemia patients undergoing allo- HSCT.

Keywords

Acute Disease, Busulfan, Clofarabine, Drug Therapy, Combination, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Myeloid, Acute, Recurrence, Vidarabine, Vorinostat

Published Open-Access

yes

Recommended Citation

Alatrash, Gheath; Saberian, Chantal; Bassett, Roland; et al., "Vorinostat Combined with Busulfan, Fludarabine, and Clofarabine Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Leukemia: Long-Term Study Outcomes" (2022). Faculty, Staff and Student Publications. 4322.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4322