TY - JOUR
T1 - Dose Escalation of Total Marrow Irradiation in High-Risk Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
AU - Hui, Susanta
AU - Brunstein, Claudio
AU - Takahashi, Yutaka
AU - DeFor, Todd
AU - Holtan, Shernan G.
AU - Bachanova, Veronika
AU - Wilke, Christopher
AU - Zuro, Darren
AU - Ustun, Celalettin
AU - Weisdorf, Daniel
AU - Dusenbery, Kathryn
AU - Verneris, Michael R.
N1 - Publisher Copyright:
© 2017 The American Society for Blood and Marrow Transplantation
PY - 2017/7
Y1 - 2017/7
N2 - Patients with refractory leukemia or minimal residual disease (MRD) at transplantation are at increased risk of relapse. Augmentation of irradiation, especially to sites of disease (ie, bone marrow) is one potential strategy for overcoming this risk. We studied the feasibility of radiation dose escalation in high-risk patients using total marrow irradiation (TMI) in a phase I dose-escalation trial. Four pediatric and 8 adult patients received conditioning with cyclophosphamide and fludarabine in conjunction with image-guided radiation to the bone marrow at 15 Gy and 18 Gy (in 3-Gy fractions), while maintaining the total body irradiation (TBI) dose to the vital organs (lungs, hearts, eyes, liver, and kidneys) at <13.2 Gy. The biologically effective dose of TMI delivered to the bone marrow was increased by 62% at 15 Gy and by 96% at 18 Gy compared with standard TBI. Although excessive dose-limiting toxicity, defined by graft failure or excessive specific organ toxicity, was not encountered, 3 of 6 patients experienced treatment-related mortality at 18 Gy. Thus, we halted enrollment at this dose level and treated an additional 4 patients at 15 Gy. The 1- year overall survival was 42% (95% confidence interval [CI], 15%-67%) and disease-free survival was 22% (95% CI, 4%-49%). The rate of relapse was 36% (95% CI, 10%-62%), and nonrelapse mortality was 42% (95% CI, 14%-70%). This study shows that TMI dose escalation to 15 Gy is feasible with acceptable toxicity in pediatric and adult patients with high-risk leukemia undergoing umbilical cord blood and sibling donor transplantation.
AB - Patients with refractory leukemia or minimal residual disease (MRD) at transplantation are at increased risk of relapse. Augmentation of irradiation, especially to sites of disease (ie, bone marrow) is one potential strategy for overcoming this risk. We studied the feasibility of radiation dose escalation in high-risk patients using total marrow irradiation (TMI) in a phase I dose-escalation trial. Four pediatric and 8 adult patients received conditioning with cyclophosphamide and fludarabine in conjunction with image-guided radiation to the bone marrow at 15 Gy and 18 Gy (in 3-Gy fractions), while maintaining the total body irradiation (TBI) dose to the vital organs (lungs, hearts, eyes, liver, and kidneys) at <13.2 Gy. The biologically effective dose of TMI delivered to the bone marrow was increased by 62% at 15 Gy and by 96% at 18 Gy compared with standard TBI. Although excessive dose-limiting toxicity, defined by graft failure or excessive specific organ toxicity, was not encountered, 3 of 6 patients experienced treatment-related mortality at 18 Gy. Thus, we halted enrollment at this dose level and treated an additional 4 patients at 15 Gy. The 1- year overall survival was 42% (95% confidence interval [CI], 15%-67%) and disease-free survival was 22% (95% CI, 4%-49%). The rate of relapse was 36% (95% CI, 10%-62%), and nonrelapse mortality was 42% (95% CI, 14%-70%). This study shows that TMI dose escalation to 15 Gy is feasible with acceptable toxicity in pediatric and adult patients with high-risk leukemia undergoing umbilical cord blood and sibling donor transplantation.
KW - BMT
KW - Cord blood
KW - Total marrow irradiation
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U2 - 10.1016/j.bbmt.2017.04.002
DO - 10.1016/j.bbmt.2017.04.002
M3 - Article
C2 - 28396164
AN - SCOPUS:85019357690
SN - 1083-8791
VL - 23
SP - 1110
EP - 1116
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 7
ER -