Host marrow stem cell potential and engraftability at varying times after low-dose whole-body irradiation

High levels of chimerism in syngeneic BALB/c transplants were reported when hosts were exposed to 1 Gy (100 cGy) whole body irradiation (WBI) and infu sed with 40 x 10(6) marrow cells. The recovery of host stem cells and alter ations of enhanced host engraftability at varying times after I Gy WBI have now been evaluated in this study. Male BALB/c marrow (40 x 106 cells) was infused into female BALB/c hosts immediately or at 6, 12, and 24 weeks afte r 1 Gy WBI of host female BALB/c mice; engraftment percentages 8 weeks afte r cell injection at week 0, 6, 12, or 24 were 68% +/- 12%, 45% +/- 15%,51% +/- 12%, or 20% +/- 8%, respectively. Eight-week engraftment levels in noni rradiated hosts average 7.7%. Conversely, engraftable stem cells measured a t 8 weeks postengraftment in I Gy-exposed hosts were reduced to 8.6% +/- 3% of nonirradiated mice at time 0, 35% +/- 12% 6 weeks later, 49% +/- 10% at 3 months, and 21% +/- 7% at 6 months. Engraftment was still increased and stem cell decreased 1 year after I Gy. Furthermore, the primary cells trans planted into I Gy hosts can be serially transplanted, and the predominant e ffect of 1 Gy is directly on engrafting stem cells and not through accessor y cells. These data show that transplantation in I Gy mice may be delayed u ntil recovery of hematopoiesis, suggesting strategies in allogeneic transpl antation to avoid the adverse effects of cytokine storm. The incomplete rec overy of engraftable stem cells out to 12 months indicates that stem cell e xpansion, especially in patients previously treated with radiomimetic drugs , may not be feasible.