Delaying DLA-Haploidentical Hematopoietic Cell Transplantation after Total Body Irradiation

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation (Impact Factor: 3.4). 10/2009; 15(10):1244-50. DOI: 10.1016/j.bbmt.2009.06.004
Source: PubMed


Exposure to accidental or deliberate radiation poses a threat to public health, proving lethal at higher doses in large part because of deleterious effects on marrow. In those cases, allogeneic hematopoietic cell transplantation (HCT) might be required to restore marrow function. Most radiation accident victims will have HLA-haploidentical relatives who could serve as HCT donors. Here, we assessed in a canine HCT model the total body irradiation (TBI) doses after which transplants might be required and successful engraftment would be possible. In an attempt at mimicking the logistical problems likely to exist after radiation accidents, 4-, 8- or 10-day intervals were placed between TBI and HCT. To keep the experimental readout simple, no graft-versus-host disease (GVHD) prevention was administered. All dogs transplanted after a 4-day delay following 700 or 920 cGy TBI successfully engrafted, whereas virtually all those given 450 or 600 cGy rejected their grafts. Transplant delays of 8 and 10 days following 920 cGy TBI also resulted in successful engraftment in most dogs, whereas a delay of 8 days after 700 cGy resulted in virtually uniform graft failure. The time courses of acute GVHD (aGVHD) and rates of granulocyte recovery in engrafting dogs were comparable among dogs regardless of the lengths of delay. In other studies, we showed that most dogs not given HCT survived 700 cGy TBI with intensive supportive care, whereas those given 800 cGy TBI and higher died with marrow aplasia. Thus, DLA-haploidentical HCT was successful even when carried out 4, 8, or 10 days after TBI at or above radiation exposures where dogs survived with intensive care alone.

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Available from: Scott S Graves, Jun 20, 2014
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    • "In this scenario, hematopoietic stem cell transplantation (HSCT) has been used for several years in the hematopoietic system recovery after radiation exposure (Bishop 1997; Hirama et al. 2003; Ding et al. 2009). The transplantation induces stem cell repopulation, reducing the immunosuppression window associated with radiation exposure or radiotherapy (Hirama et al. 2003; Ding et al. 2009). Then, in line with the investigation of novel therapies for IBD, our group has previously demonstrated that high dose cyclophosphamide associated with HSCT is effective in the modulation of mucosal immunity and in accelerating immune reconstitution in an experimental model of intestinal inflammation (Godoi et al. 2010). "
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