title: Marrow damage and hematopoietic recovery following allogeneic bone marrow transplantation for acute leukemias: Effect of radiation dose and conditioning regimen.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Dept. of Therapeutic Radiology, University of Minnesota, Minneapolis, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Wilke
authors.affiliation: Dept. of Medicine, University of Minnesota, Minneapolis, USA.
authors.forename: Shernan G
authors.initials: SG
authors.lastname: Holtan
authors.affiliation: Veterinary Clinical Sciences, University of Minnesota, Minneapolis, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Sharkey
authors.affiliation: Biostatistics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: DeFor
authors.affiliation: Dept. of Medicine, University of Minnesota, Minneapolis, USA.
authors.forename: Mukta
authors.initials: M
authors.lastname: Arora
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Premakanthan
authors.affiliation: Laboratory Medicine/Pathology, University of Minnesota, Minneapolis, USA.
authors.forename: Sophia
authors.initials: S
authors.lastname: Yohe
authors.affiliation: Dept. of Radiation Oncology, IRCCS San Martino-National Institute for Cancer Research and University of Genoa Largo R, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Vagge
authors.affiliation: College of Pharmacy, University of Arkansas for Medical Sciences, USA.
authors.forename: Daohong
authors.initials: D
authors.lastname: Zhou
authors.affiliation: College of Medicine, Oklahoma Health Sciences Center, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Holter Chakrabarty
authors.affiliation: Dept. of Radiation Oncology, Saint-Herblain Cédex, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Mahe
authors.affiliation: Dept. of Radiation Oncology, IRCCS San Martino-National Institute for Cancer Research and University of Genoa Largo R, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Corvo
authors.affiliation: Dept. of Therapeutic Radiology, University of Minnesota, Minneapolis, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Dusenbery
authors.affiliation: Dept. of Radiotherapy, Universitair Ziekenhuis Brussel, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Storme
authors.affiliation: Dept. of Medicine, University of Minnesota, Minneapolis, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.affiliation: Div. of Hematology, Oncology and Bone Marrow Transplantation, Dept. of Pediatrics, University of Minnesota, Minneapolis, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
authors.affiliation: Dept. of Therapeutic Radiology, University of Minnesota, Minneapolis, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, USA. Electronic address: huixx019@umn.edu.
authors.forename: Susanta
authors.initials: S
authors.lastname: Hui
mesh_terms: D000208:Acute Disease; D001853:Bone Marrow / Q000473:pathology*; D016026:Bone Marrow Transplantation; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007938:Leukemia / Q000628:therapy*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000473:pathology; D011829:Radiation Dosage; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
keywords: Bone marrow transplantation; Marrow cellularity; Total body irradiation