Advertisement

International Journal of Hematology

, Volume 76, Issue 2, pp 157–164 | Cite as

Severe Immune Dysfunction after Lethal Neutron Irradiation in a JCO Nuclear Facility Accident Victim

  • Hitomi Nagayama
  • Jun Ooi
  • Akira Tomonari
  • Tohru Iseki
  • Arinobu Tojo
  • Kenzaburo Tani
  • Tsuneo A. Takahashi
  • Naohide Yamashita
  • Shigetaka Asano
Case Report

Abstract

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 γ-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 γ-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.

Key words

Neutron irradiation Umbilical cord blood transplantation Autologous hematopoietic recovery Immune dysfunction 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Baranov A, Gale RP, Guskova A, et al. Bone marrow transplantation after the Chernobyl nuclear accident.N Engl J Med. 1989;321:205–212.CrossRefGoogle Scholar
  2. 2.
    Diagnosis and Treatment of Radiation Injuries. Safety reports series no. 2. Vienna: International Atomic Energy Agency, 1998.Google Scholar
  3. 3.
    Gluckman E, Broxmeyer HE, Auerbach AD, et al. Hematopoietic reconstitution in a patient with Fanconi’s anemia by means of umbilical cord blood from a HLA identical sibling.N Engl J Med. 1989;321:1174–1178.CrossRefGoogle Scholar
  4. 4.
    Rubinstein P, Dobrila L, Rosenfield RE, et al. Processing and cryopreservation of placental/umbilical cord blood for unrelated marrow reconstitution.Proc Natl Acad Sci U S A. 1995;92:10119–10122.CrossRefGoogle Scholar
  5. 5.
    Kurtzberg J, Laughlin M, Graham ML, et al. Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients.N Engl J Med. 1996;335:157–166.CrossRefGoogle Scholar
  6. 6.
    Wagner JE, Rosenthal J, Sweetman R, 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.Blood. 1996;88:795–802.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Cairo MS, Wagner JE. Placental and/or umbilical cord blood: an alternative source of hematopoietic stem cells for transplantation.Blood. 1997;90:4665–4678.PubMedGoogle Scholar
  8. 8.
    Gluckman E, Rocha V, Boyer-Chammard A, et al. Outcome of cord-blood transplantation from related and unrelated donors.N Engl J Med. 1997;337:373–381.CrossRefGoogle Scholar
  9. 9.
    Rubinstein P, Carrier C, Scaradavou A, et al. Outcomes among 562 recipients of placental-blood transplants from unrelated donors.N Engl J Med. 1998;339:1565–1577.CrossRefGoogle Scholar
  10. 10.
    Rocha V, Wagner JE, Sobocinski KA, et al. Graft-versus-host diseases in children who have received a cord blood or bone marrow transplantation from an HLA-identical sibling.N Engl J Med. 2000;342:1846–1854.CrossRefGoogle Scholar
  11. 11.
    Barker JN, Davies SM, DeFor T, et al. Survival after transplantation of unrelated donor umbilical cord blood is comparable to that of human leukocyte antigen-matched unrelated donor marrow: results of a matched-pair analysis.Blood. 2001;97:2957–2961.CrossRefGoogle Scholar
  12. 12.
    Rocha V, Cornish J, Sievers EL, et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia.Blood. 2001;97:2962–2971.CrossRefGoogle Scholar
  13. 13.
    Laporte JP, Gorin NC, Rubinstein P, et al. Cord-blood transplantation from an unrelated donor in an adult with chronic myelogenous leukemia.N Engl J Med. 1996;335:167–170.CrossRefGoogle Scholar
  14. 14.
    Laughlin MJ, Barker J, Bambach B, et al. Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors.N Engl J Med. 2001;344:1815–1822.CrossRefGoogle Scholar
  15. 15.
    Sanz GF, Saavedra S, Jimenez C, et al. Unrelated donor cord blood transplantation in adults with chronic myelogenous leukemia: results in nine patients from a single institution.Bone Marrow Transplant. 2001;27:693–701.CrossRefGoogle Scholar
  16. 16.
    Nagayama H, Nakayama K, Yasuo K, et al. Immunological reconstitution after cord blood transplantation for an adult patient.Bone Marrow Transplant. 1999;24:211–213.CrossRefGoogle Scholar
  17. 17.
    Machida U, Tojo A, Ooi J, et al. Refractory facial cellulitis following cosmetic rhinoplasty after cord-blood stem cell transplantation.Int J Hematol. 2000;72:98–100.PubMedGoogle Scholar
  18. 18.
    Report on the Preliminary Fact Finding Mission following the Accident at the Nuclear Fuel Processing Facility in Tokaimura, Japan. Vienna: International Atomic Energy Agency, 1999.Google Scholar
  19. 19.
    Kawachi K. Initial response of NIRS.Proceedings of International Symposium on the Criticality Accident in Tokaimura: Medical Aspects of Radiation Emergency. Chiba, Japan: National Institute of Radiological Science, 2001:24–34.Google Scholar
  20. 20.
    Akashi M. Dose estimation of victims severely exposed based on initial symptoms in the criticality accident in Tokaimura.Proceedings of International Symposium on the Criticality Accident in Tokaimura: Medical Aspects of Radiation Emergency. Chiba, Japan: National Institute of Radiological Science, 2001:72–80.Google Scholar
  21. 21.
    Nagayama H, Takahashi TA, Misawa K, et al. Case presentation of worker B.Proceedings of International Symposium on the Criticality Accident in Tokaimura: Medical Aspects of Radiation Emergency. Chiba, Japan: National Institute of Radiological Science, 2001:154–158.Google Scholar
  22. 22.
    Iseki T, Nagayama H, Ooi J, et al. Unrelated cord blood transplantation for a heavily irradiated patient.Proceedings of International Symposium on the Criticality Accident in Tokaimura: Medical Aspects of Radiation Emergency. Chiba, Japan: National Institute of Radiological Science, 2001:220–227.Google Scholar
  23. 23.
    Nagayama H, Misawa K, Tanaka H, et al. Transient hematopoietic stem cell rescue using umbilical cord blood for a lethally irradiated nuclear accident victim.Bone Marrow Transplant. 2002;29:197–204.CrossRefGoogle Scholar
  24. 24.
    Koike S, Ando K. Relative biological effectiveness of fast neutrons in murine tissues.Proceedings of International Symposium on the Criticality Accident in Tokaimura: Medical Aspects of Radiation Emergency. Chiba, Japan: National Institute of Radiological Science, 2001:66–71.Google Scholar
  25. 25.
    Sato K, Nagayama H, Takahashi TA. Aberrant CD3- and CD28-mediated signaling events in cord blood T cells are associated with dysfunctional regulation of Fas ligand-mediated cytotoxicity.J Immunol. 1999;162:4464–4471.PubMedGoogle Scholar
  26. 26.
    Hill RS, Peterson FB, Storb R, 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.Blood. 1986;67:811–816.PubMedGoogle Scholar
  27. 27.
    Chiba S, Saito A, Ogawa S, et al. Allogeneic peripheral blood stem cell transplantation for a victim of the criticality accident in Tokaimura.Proceedings of International Symposium on the Criticality Accident in Tokaimura: Medical Aspects of Radiation Emergency. Chiba, Japan: National Institute of Radiological Science, 2001:212–218.Google Scholar

Copyright information

© The Japanese Society of Hematology 2002

Authors and Affiliations

  • Hitomi Nagayama
    • 1
    • 2
  • Jun Ooi
    • 1
  • Akira Tomonari
    • 1
  • Tohru Iseki
    • 1
  • Arinobu Tojo
    • 1
  • Kenzaburo Tani
    • 1
  • Tsuneo A. Takahashi
    • 1
  • Naohide Yamashita
    • 1
  • Shigetaka Asano
    • 1
  1. 1.Institute of Medical ScienceUniversity of TokyoTokyoJapan
  2. 2.Division of Hematology, Department of MedicineKeio University School of MedicineTokyoJapan

Personalised recommendations