TY - JOUR
T1 - Combination of linear accelerator-based intensity-modulated total marrow irradiation and myeloablative fludarabine/busulfan
T2 - A phase i study
AU - Patel, Pritesh
AU - Aydogan, Bulent
AU - Koshy, Matthew
AU - Mahmud, Dolores
AU - Oh, Annie
AU - Saraf, Santosh L.
AU - Quigley, John G.
AU - Khan, Irum
AU - Sweiss, Karen
AU - Mahmud, Nadim
AU - Peace, David J.
AU - DeMasi, Vincenzo
AU - Awan, Azhar M.
AU - Weichselbaum, Ralph R.
AU - Rondelli, Damiano
N1 - Funding Information:
Conflict of interest statement: D.R. was the recipient of a research grant from Otsuka Pharmaceuticals . B.A. was the recipient of a research grant from Varian Medical Systems Inc.
Publisher Copyright:
© 2014 American Society for Blood and Marrow Transplantation.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - 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 3Gy (n=3), 6Gy (n=3), 9Gy (n=6), and 12Gy (n=2) in combination with intravenous (i.v.) fludarabine 160mg/m2 and targeted busulfan (area under the curve, 4800μM*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 1126days (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 9Gy 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.
AB - 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 3Gy (n=3), 6Gy (n=3), 9Gy (n=6), and 12Gy (n=2) in combination with intravenous (i.v.) fludarabine 160mg/m2 and targeted busulfan (area under the curve, 4800μM*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 1126days (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 9Gy 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.
KW - Allogeneic stem cell transplantation
KW - Total marrow irradiation
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U2 - 10.1016/j.bbmt.2014.09.005
DO - 10.1016/j.bbmt.2014.09.005
M3 - Article
C2 - 25234438
AN - SCOPUS:84912131451
SN - 1083-8791
VL - 20
SP - 2034
EP - 2041
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 12
ER -