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.
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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 |
Journal | Transplantation and cellular therapy
(Transplant Cell Ther)
Vol. 28
Issue 8
Pg. 501.e1-501.e7
(08 2022)
ISSN: 2666-6367 [Electronic] United States |
PMID | 35618218
(Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article)
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Copyright | Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Vorinostat
- Clofarabine
- Vidarabine
- Busulfan
- fludarabine
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Topics |
- Acute Disease
- Busulfan
(therapeutic use)
- Clofarabine
(therapeutic use)
- Drug Therapy, Combination
- Graft vs Host Disease
(prevention & control)
- Hematopoietic Stem Cell Transplantation
(adverse effects)
- Humans
- Leukemia, Myeloid, Acute
(therapy)
- Recurrence
- Vidarabine
(analogs & derivatives)
- Vorinostat
(therapeutic use)
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