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

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 × 107/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 γ-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 × 109/l on day 15, the reticulocyte count rose above 1% on day 23, and the platelet count was over 50 × 109/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.Bone Marrow Transplantation (2002) 29, 197–204. doi:10.1038/sj.bmt.1703356

[1]  C. Chastang,et al.  Outcome of cord-blood transplantation from related and unrelated donors , 1997 .

[2]  J. Klein,et al.  Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources. , 2000, The New England journal of medicine.

[3]  J. Adamson,et al.  Outcomes among 562 recipients of placental-blood transplants from unrelated donors. , 1998, The New England journal of medicine.

[4]  J. Kurtzberg,et al.  Hematopoietic reconstitution in a patient with Fanconi's anemia by means of umbilical-cord blood from an HLA-identical sibling. , 1989, The New England journal of medicine.

[5]  J. Wagner,et al.  Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease. , 1996, Blood.

[6]  Y. Suen,et al.  Immunological reconstitution and correlation of circulating serum inflammatory mediators/cytokines with the incidence of acute graft-versus-host disease during the first 100 days following unrelated umbilical cord blood transplantation , 1999, Bone Marrow Transplantation.

[7]  H. Chambost,et al.  Immune reconstitution and outcome after unrelated cord blood transplantation: a single paediatric institution experience , 2000, Bone Marrow Transplantation.

[8]  Kath Bhanot,et al.  Preliminary fact finding mission following the accident at the nuclear fuel processing facility in Tokaimura, Japan (Vienna: IAEA) , 2000, Journal of radiological protection : official journal of the Society for Radiological Protection.

[9]  H. Deeg,et al.  Effect of mixed chimerism on graft-versus-host disease, disease recurrence and survival after HLA-identical marrow transplantation for aplastic anemia or chronic myelogenous leukemia. , 1996, Bone marrow transplantation.

[10]  H. Deeg,et al.  Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. , 1997, Blood.

[11]  K. Sato,et al.  Aberrant CD3- and CD28-mediated signaling events in cord blood T cells are associated with dysfunctional regulation of Fas ligand-mediated cytotoxicity. , 1999, Journal of immunology.

[12]  Hal E. Broxmeyer,et al.  Analysis of engraftment, graft-versus-host disease, and immune recovery following unrelated donor cord blood transplantation. , 2000 .

[13]  H. Deeg,et al.  Stable mixed hematopoietic chimerism in dog leukocyte antigen-identical littermate dogs given lymph node irradiation before and pharmacologic immunosuppression after marrow transplantation. , 1999, Blood.

[14]  Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients. , 1996, The New England journal of medicine.

[15]  S. Asano,et al.  Immunological reconstitution after cord blood transplantation for an adult patient , 1999, Bone Marrow Transplantation.

[16]  G Selidovkin,et al.  Bone marrow transplantation after the Chernobyl nuclear accident. , 1989, The New England journal of medicine.

[17]  H. Deeg,et al.  Stable mixed hematopoietic chimerism in dogs given donor antigen, CTLA4Ig, and 100 cGy total body irradiation before and pharmacologic immunosuppression after marrow transplant. , 1999, Blood.

[18]  J. Wagner,et al.  Placental and/or umbilical cord blood: an alternative source of hematopoietic stem cells for transplantation. , 1997, Blood.

[19]  H. Deeg,et al.  Synergism between mycophenolate mofetil and cyclosporine in preventing graft-versus-host disease among lethally irradiated dogs given DLA-nonidentical unrelated marrow grafts. , 1998, Blood.

[20]  J. Gribben,et al.  Transplantation of anergic histoincompatible bone marrow allografts. , 1999, The New England journal of medicine.

[21]  R. Storb,et al.  Mixed Hematologic Chimerism After Allogeneic Marrow Transplantation for Severe Aplastic Anemia Is Associated With a Higher Risk of Graft Rejection and a Lessened Incidence of Acute Graft-Versus-Host Disease , 1986 .