Combination of linear accelerator-based intensity-modulated total marrow irradiation and myeloablative fludarabine/busulfan: a phase I study
Pritesh Patel, Bulent Aydogan, Matthew Koshy, Dolores Mahmud, Annie Oh, Santosh L Saraf, John G Quigley, Irum Khan, Karen Sweiss, Nadim Mahmud, David J Peace, Vincenzo DeMasi, Azhar M Awan, Ralph R Weichselbaum, Damiano Rondelli, Pritesh Patel, Bulent Aydogan, Matthew Koshy, Dolores Mahmud, Annie Oh, Santosh L Saraf, John G Quigley, Irum Khan, Karen Sweiss, Nadim Mahmud, David J Peace, Vincenzo DeMasi, Azhar M Awan, Ralph R Weichselbaum, Damiano Rondelli
Abstract
Here we examined the addition of intensity-modulated total marrow irradiation (TMI) delivered using a linear accelerator to a myeloablative chemotherapy conditioning regimen before allogeneic hematopoietic stem cell transplantation (HSCT). In this phase I study, we enrolled 14 patients with high-risk hematologic malignancies who received escalating doses of TMI at 3 Gy (n = 3), 6 Gy (n = 3), 9 Gy (n = 6), and 12 Gy (n = 2) in combination with intravenous (i.v.) fludarabine 160 mg/m(2) and targeted busulfan (area under the curve, 4800 μM*minute). Peripheral blood mobilized stem cells were obtained from HLA-matched related (n = 9) or unrelated (n = 4) or 1 antigen-mismatched unrelated (n = 1) donors. All patients rapidly engrafted and recovered their immune cells. Overall, Bearman extrahematologic toxicity were limited to grades 1 or 2, with oral mucositis grade 1 in 64% and grade 2 in 36% of the patients. With a median follow-up of 1126 days (range, 362 to 1469) for living patients, the overall survival was 50% and relapse-free survival was 43%. Of 7 deaths, 3 were due to relapse and 4 to transplantation-related complications. We conclude that 9 Gy TMI can be combined with myeloablative chemotherapy in the design of new preparative regimens for HSCT. This study was registered at clinicaltrials.gov as NCT00988013.
Keywords: Allogeneic stem cell transplantation; Total marrow irradiation.
Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
Source: PubMed