Transient hematopoietic stem cell rescue using umbilical cord blood for a lethally irradiated nuclear accident victim

Abstract

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 suitable bone marrow or peripheral blood donor. Pre-transplant conditioning consisted of anti-thymocyte ␥-globulin 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, respectively. Cytogenetic studies of blood and marrow showed donor/recipient mixed chimerism. Rapid autologous hematopoietic recovery was recognized after withdrawal 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 hematopoietic 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.

Ghrelin as a Novel Therapy for Radiation Combined Injury

“…This notion of multiple organ dysfunction syndrome became evident in the victims of the recent accidents in Nesvizh and Tokaimura, who showed a mixed pathology involving the liver and kidney rather than the classical target organs such as the hematopoietic tissues and the gut (17,18). Experimental data from a primate model supported the existence of a radiation-induced systemic inflammatory response.…”

Le syndrome hématopoïétique induit par une irradiation accidentelle : évaluation et traitements possibles

“…Ainsi, la reconstruction dosimétrique de l'accident de Mol (Belgique en 1965) où un opérateur s'est appuyé sur un assemblage de combustible, a démontré l'existence de territoires médullaires irradiés à des doses inférieures à 3 Gy à partir desquels une reprise hématopoïétique a été observée (Parmentier et al, 1980). L'existence de cellules souches hématopoïétiques (CSH) survivantes à plus de 10 Gy a été démontrée chez la victime de l'accident de Nesvizh (Biélorussie en 1991 ; Baranov et al, 1994), et le rejet de la greffe de CSH chez l'un des trois irradiés de Tokai-mura est une démonstration de l'existence d'une hématopoïèse rési-duelle, suffisante pour assurer une reconstitution autologue après une irradiation accidentelle à forte dose (Nagayama et al, 2002).…”

“…Malgré ces risques élevés associés à la greffe de CSH, un concept de greffe transitoire a été proposé (Dainiak, 2005) de façon à protéger le patient des hémorragies et des infections avec un apport de cellules fonctionnelles en attendant une reprise endogène. C'est ce qui a été réalisé chez l'une des victimes de l'accident de Tokai-mura (Nagayama et al, 2002). Cependant, le bilan du traitement des victimes d'irradiation accidentelles montre que la greffe de moelle osseuse représente une thérapie à risques.…”

Exposure to a MRI‐type high‐strength static magnetic field stimulates megakaryocytic/erythroid hematopoiesis in CD34+ cells from human placental and umbilical cord blood

“…Despite these guidelines and the study of various biological effects induced by a high-strength SMF [Miyakoshi, 2005], there are still important safety issues regarding such exposure. The hematopoietic system is sensitive to extracellular oxidative stresses, such as radiation or chemotherapy [Hamimovitz-Friedman, 1998;Wright, 1998;Schmidt-Ullrich et al, 2000;Nagayama et al, 2002;Kashiwakura et al, 2007]. However, very few studies so far have described the effects of SMF on the proliferation and differentiation of human hematopoietic stem-progenitor cells in comparison to other cellular investigations.…”