Bone Marrow Transplantation (2002) 29, 197–204  2002 Nature Publishing Group All rights reserved 0268–3369/02 $25.00 www.nature.com/bmt Cord blood stem cells Transient hematopoietic stem cell rescue using umbilical cord blood for a lethally irradiated nuclear accident victim H Nagayama 1,2 , K Misawa 1 , H Tanaka 4 , J Ooi 1 , T Iseki 1 , A Tojo 1 , K Tani 1 , Y Yamada 1 , H Kodo 3 , TA Takahashi 1 , N Yamashita 1 , S Shimazaki 4 and S Asano 1 1 Institute of Medical Science, University of Tokyo, Tokyo, Japan; 2 Keio University School of Medicine, Tokyo, Japan; 3 Fuchu Metropolitan Hospital, Tokyo, Japan; and 4 Kyorin University, Tokyo, Japan Summary: We performed stem cell rescue and allogeneic skin transplantation on a lethally neutron-irradiated nuclear accident victim. HLA-DRB1 mismatched unrelated umbilical cord blood cells (2.08  10 7 /kg recipient body weight) were transplanted to an 8–10 Gy equivalent neutron-irradiated patient because of a lack of a suit- able bone marrow or peripheral blood donor. Pre-trans- plant conditioning consisted of anti-thymocyte -globu- lin alone, and GVHD prophylaxis was a combination of cyclosporine (CYA) and methylprednisolone (mPSL). Granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), and thrombopoietin (TPO) were concurrently administered after transplantation. The absolute neutrophil count reached 0.5  10 9 /l on day 15, the reticulocyte count rose above 1% on day 23, and the platelet count was over 50  10 9 /l on day 27, respect- ively. Cytogenetic studies of blood and marrow showed donor/recipient mixed chimerism. Rapid autologous hematopoietic recovery was recognized after with- drawal of CYA and mPSL. Repeated pathological examinations of the skin revealed no evidence of acute GVHD. Eighty-two days after the irradiation, skin transplantation was performed to treat radiation burns. Almost 90% of the transplanted skin engrafted. Immunological examination after autologous hematopo- ietic recovery revealed an almost normal T cell count. However, immune functions were severely impaired. The patient died from infectious complication 210 days after the accident. Bone Marrow Transplantation (2002) 29, 197–204. DOI: 10.1038/sj/bmt/1703356 Keywords: umbilical cord blood; hematopoietic stem cell; skin transplantation; neutron irradiation; acute radi- ation syndrome Correspondence: Dr H Nagayama, Department of Hematology, Keio Uni- versity School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160- 8582, Japan Received 19 April 2001; accepted 23 August 2001 The feasibility and efficacy of allogeneic hematopoietic stem cell transplantation for accidentally irradiated individ- uals remain unclear because of the high incidence of trans- plant-related mortality including acute graft-versus-host disease (GVHD) and ensuing complications, that are exacerbated by coincident radiation injury. 1 Target organs of acute GVHD are mainly the skin, gastro-intestinal tract, and liver, which are also susceptible to acute radiation syn- drome (ARS). 2 Main causes of death after allogeneic bone marrow transplantation for irradiated individuals are burns, acute GVHD and interstitial pneumonitis with or without adult respiratory distress syndrome (ARDS). 1,2 Umbilical cord blood is a useful stem cell source because the incidence and extent of acute GVHD associated with its use are low as compared to conventional bone marrow, 3–10 allowing for three HLA loci donor/recipient mis- matching. 4,7,8 In addition, umbilical cord blood can be used for urgent triage for numerous victims without donor acqui- sition delay, because it has already been screened and cryo- preserved. Thus, umbilical cord blood is an ideal stem cell source for accidentally irradiated individuals. Neutrons cause severe cutaneous blistering and desquam- ative changes on irradiated skin fields several weeks after irradiation. 2 Systemic neutron irradiation induces fatal sys- temic destruction of the skin barrier that plays an important role in host defense against exogenous pathogens. In the present study, we examined the feasibility and efficacy of unrelated HLA-disparate umbilical cord blood and cadaver skin transplantation for the rescue of a lethally irradiated recipient. We also examined donor/recipient chimerism and immunological reconstitution in the early phase of umbilical cord blood transplantation (CBT) for ARS. Case report A 39-year-old male, who had been lethally irradiated with neutrons at 8–10 Gy equivalent (Eq) in a nuclear accident, 11 was referred to our hospital on 4 October 1999 for hemato- poietic stem cell transplantation. He had been irradiated by a critical fission reaction at the uranium-processing plant by JCO, Co., Ltd, in the village of Tokai in the Ibaraki Prefecture, Japan, on 30 September 1999. Symptoms