Christopher Wilke1, Shernan G Holtan2, Leslie Sharkey3, Todd DeFor4, Mukta Arora2, Priya Premakanthan5, Sophia Yohe6, Stefano Vagge7, Daohong Zhou8, Jennifer L Holter Chakrabarty9, Marc Mahe10, Renzo Corvo7, Kathryn Dusenbery1, Guy Storme11, Daniel J Weisdorf2, Michael R Verneris12, Susanta Hui13. 1. Dept. of Therapeutic Radiology, University of Minnesota, Minneapolis, USA. 2. Dept. of Medicine, University of Minnesota, Minneapolis, USA. 3. Veterinary Clinical Sciences, University of Minnesota, Minneapolis, USA. 4. Biostatistics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, USA. 5. Masonic Cancer Center, University of Minnesota, Minneapolis, USA. 6. Laboratory Medicine/Pathology, University of Minnesota, Minneapolis, USA. 7. Dept. of Radiation Oncology, IRCCS San Martino-National Institute for Cancer Research and University of Genoa Largo R, Italy. 8. College of Pharmacy, University of Arkansas for Medical Sciences, USA. 9. College of Medicine, Oklahoma Health Sciences Center, USA. 10. Dept. of Radiation Oncology, Saint-Herblain Cédex, France. 11. Dept. of Radiotherapy, Universitair Ziekenhuis Brussel, Belgium. 12. Div. of Hematology, Oncology and Bone Marrow Transplantation, Dept. of Pediatrics, University of Minnesota, Minneapolis, USA. 13. Dept. of Therapeutic Radiology, University of Minnesota, Minneapolis, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, USA. Electronic address: huixx019@umn.edu.
Abstract
BACKGROUND AND PURPOSE: Total body irradiation (TBI) is a common component of hematopoietic cell transplantation (HCT) conditioning regimens. Preclinical studies suggest prolonged bone marrow (BM) injury after TBI could contribute to impaired engraftment and poor hematopoietic function. MATERIALS AND METHODS: We studied the longitudinal changes in the marrow environment in patients receiving allogeneic HCT with myeloablative (MA, n=42) and reduced intensity (RIC, n=56) doses of TBI from 2003-2013, including BM cellularity, histologic features of injury and repair, hematologic and immunologic recovery. RESULTS: Following MA conditioning, a 30% decrease in the marrow cellularity persisted at 1 year post-transplant (p=0.03). RIC HCT marrow cellularity transiently decreased but returned to baseline by 6 months even though the RIC group received mostly umbilical cord blood (UCB) grafts (82%, vs. 17% in the MA cohort, p<0.01). There was no evidence of persistent marrow vascular damage or inflammation. Recipients of more intensive conditioning did not show more persistent cytopenias with the exception of a tendency for minimal thrombocytopenia. Immune recovery was similar between MA and RIC. CONCLUSIONS: These findings suggest that TBI associated with MA conditioning leads to prolonged reductions in marrow cellularity, but does not show additional histological evidence of long-term injury, which is further supported by similar peripheral counts and immunologic recovery.
BACKGROUND AND PURPOSE: Total body irradiation (TBI) is a common component of hematopoietic cell transplantation (HCT) conditioning regimens. Preclinical studies suggest prolonged bone marrow (BM) injury after TBI could contribute to impaired engraftment and poor hematopoietic function. MATERIALS AND METHODS: We studied the longitudinal changes in the marrow environment in patients receiving allogeneic HCT with myeloablative (MA, n=42) and reduced intensity (RIC, n=56) doses of TBI from 2003-2013, including BM cellularity, histologic features of injury and repair, hematologic and immunologic recovery. RESULTS: Following MA conditioning, a 30% decrease in the marrow cellularity persisted at 1 year post-transplant (p=0.03). RIC HCT marrow cellularity transiently decreased but returned to baseline by 6 months even though the RIC group received mostly umbilical cord blood (UCB) grafts (82%, vs. 17% in the MA cohort, p<0.01). There was no evidence of persistent marrow vascular damage or inflammation. Recipients of more intensive conditioning did not show more persistent cytopenias with the exception of a tendency for minimal thrombocytopenia. Immune recovery was similar between MA and RIC. CONCLUSIONS: These findings suggest that TBI associated with MA conditioning leads to prolonged reductions in marrow cellularity, but does not show additional histological evidence of long-term injury, which is further supported by similar peripheral counts and immunologic recovery.
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