Severe immune dysfunction after lethal neutron irradiation in a JCO nuclear facility accident victim

The optimal treatment for the hematological toxicity of acute radiation syndrome (ARS) is not fully established, especially in cases of high-dose nonuniform irradiation by mixed neutrons and gamma-rays, because estimation of the irradiation dose (dosimetry) and prediction of autologous hematological recovery are complicated. For the treatment of ARS, we performed HLA-DRB1-mismatched unrelated umbilical cord blood transplantation (CBT) for a nuclear accident victim who received 8 to 10 GyEq mixed neutron and gamma-ray irradiation at the JCO Co. Ltd. nuclear processing facility in Tokaimura, Japan. Donor/ recipient mixed chimerism was attained; thereafter rapid autologous hematopoietic recovery was achieved in concordance with the termination of immunosuppressants. Immune function examined in vitro showed recovery of the autologous immune system was severely impaired. Although the naive T-cell fraction and the helper T-cell subtype 1 fraction were increased, the mitogenic responses of T-cells and the allogeneic mixed leukocyte reaction were severely suppressed. Endogenous immunoglobulin production was also suppressed until 120 days after the accident. Although skin transplantation for ARS was successful, the patient died of infectious complications and subsequent acute respiratory distress syndrome 210 days after the accident. These results suggest that fast neutrons in doses higher than 8 to 10 Gy cause complete abrogation of the human immune system, which may lead to fatal outcome even if autologous hematopoiesis recovers. The roles of transplantation, autologous hematopoietic recovery, chimerism, immune suppression, and immune function are discussed.