Hostname: page-component-745bb68f8f-mzp66 Total loading time: 0 Render date: 2025-01-24T00:54:06.310Z Has data issue: false hasContentIssue false
  • English
  • Français

First Global Consensus for Evidence-Based Management of the Hematopoietic Syndrome Resulting From Exposure to Ionizing Radiation

Published online by Cambridge University Press:  08 April 2013

Nicholas Dainiak ,
Robert Nicolas Gent ,
Zhanat Carr ,
Rita Schneider ,
Judith Bader ,
Elena Buglova ,
Nelson Chao ,
C. Norman Coleman ,
Arnold Ganser  and
Claude Gorin
...Show all authors
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective: Hematopoietic syndrome (HS) is a clinical diagnosis assigned to people who present with ≥1 new-onset cytopenias in the setting of acute radiation exposure. The World Health Organization convened a panel of experts to evaluate the evidence and develop recommendations for medical countermeasures for the management of HS in a hypothetical scenario involving the hospitalization of 100 to 200 individuals exposed to radiation. The objective of this consultancy was to develop recommendations for treatment of the HS based upon the quality of evidence.

Methods: English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to panel members before the meeting and updated during the meeting. Published case series and case reports of individuals with HS, published randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation (GRADE) system. In cases in which data were limited or incomplete, a narrative review of the observations was made. No randomized controlled trials of medical countermeasures have been completed for individuals with radiation-associated HS. The use of GRADE analysis of countermeasures for injury to hematopoietic tissue was restricted by the lack of comparator groups in humans. Reliance on data generated in nonirradiated humans and experimental animals was necessary.

Results: Based upon GRADE analysis and narrative review, a strong recommendation was made for the administration of granulocyte colony-stimulating factor or granulocyte macrophage colony-stimulating factor and a weak recommendation was made for the use of erythropoiesis-stimulating agents or hematopoietic stem cell transplantation.

Conclusions: Assessment of therapeutic interventions for HS in humans exposed to nontherapeutic radiation is difficult because of the limits of the evidence.

(Disaster Med Public Health Preparedness. 2011;5:202-212)

Keywords

countermeasures for ARScytokines and radiation injurytransplantation for ARSacute radiation syndrome managementradiation effectshematologic diseasesbone marrow transplantationstem cell transplantationreviewsgranulocyte colony-stimulating factorgranulocyte-macrophage colony-stimulating factor
Type
Review Article
Information
Disaster Medicine and Public Health Preparedness , Volume 5 , Issue 3 , October 2011 , pp. 202 - 212
Copyright
Copyright © Society for Disaster Medicine and Public Health, Inc. 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Fliedner, TM, Friesecke, I, Beyrer, KMedical Management of Radiation Accidents: Manual on Acute Radiation Syndrome.Oxford, UK: British Institute of Radiobiology; 2001.Google Scholar
2.Goans, RE, Holloway, EC, Berger, ME, Ricks, RC.Early dose assessment following severe radiation accidents. Health Phys. 1997;72 (4):513–518.CrossRefGoogle ScholarPubMed
3.Parker, DD, Parker, JC.Estimating radiation dose from time to emesis and lymphocyte depletion. Health Phys. 2007;93 (6):701–704.CrossRefGoogle ScholarPubMed
4.Waselenko, JK, MacVittie, TJ, Blakely, WFStrategic National Stockpile Radiation Working Group. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann Intern Med. 2004;140 (12):1037–1051.CrossRefGoogle ScholarPubMed
5.Gorin, NC, Fliedner, TM, Gourmelon, P.Consensus conference on European preparedness for haematological and other medical management of mass radiation accidents. Ann Hematol. 2006;85 (10):671–679.CrossRefGoogle ScholarPubMed
6.Mettler, FA, Upton, ACDeterministic effects of ionizing radiation.In: Mettler FA, Upton AC, eds. Medical Effects of Radiation. 3rd ed. Philadelphia: Saunders Elsevier; 2008.Google Scholar
7.Dainiak, N, Waselenko, JK, Armitage, JO, MacVittie, TJ, Farese, AMThe hematologist and radiation casualties. Hematol Am Soc Hematol Educ Program ; 2003:473-496.Google Scholar
8.Schünemann, HJ, Oxman, AD, Brozek, JGRADE Working Group. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ. 2008;336 1106–1110.CrossRefGoogle ScholarPubMed
9.Richardson, WS, Wilson, MC, Nishikawa, J, Hayward, RS.The well-built clinical question: a key to evidence-based decisions. ACP J Club. 1995;123 (3):A12–A13.CrossRefGoogle ScholarPubMed
10.Guyatt, GH, Oxman, AD, Kunz, RGRADE Working Group. Going from evidence to recommendations. BMJ. 2008;336 1049–1051.CrossRefGoogle ScholarPubMed
11.Guyatt, GH, Oxman, AD, Vist, GEGRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336 924–926.CrossRefGoogle ScholarPubMed
12.Butturini, A, De Souza, PC, Gale, RP.Use of recombinant granulocyte-macrophage colony stimulating factor in the Brazil radiation accident. Lancet. 1988;2 471–475.CrossRefGoogle ScholarPubMed
13.Neelis, KJ, Dubbelman, YD, Qingliang, L, Thomas, GR, Eaton, DL, Wagemaker, G.Simultaneous administration of TPO and G-CSF after cytoreductive treatment of rhesus monkeys prevents thrombocytopenia, accelerates platelet and red cell reconstitution, alleviates neutropenia, and promotes the recovery of immature bone marrow cells. Exp Hematol. 1997;25 (10):1084–1093.Google ScholarPubMed
14.Asano, S.Multi-organ involvement: lessons from the experience of one victim of the Tokai-mura criticality accident. BJR Suppl. 2005;27(Suppl)9–12.CrossRefGoogle Scholar
15.Liu, Q, Jiang, B, Jiang, LP.Clinical report of three cases of acute radiation sickness from a (60)Co radiation accident in Henan Province in China. J Radiat Res (Tokyo). 2008;49 (1):63–69.CrossRefGoogle ScholarPubMed
16.Dainiak, N.Rationale and recommendations for treatment of radiation injury with cytokines. Health Phys. 2010;98 (6):838–842.CrossRefGoogle ScholarPubMed
17.Baranov, AE, Guskova, AK, Nadejina, NM, Nugis, VYu.Chernobyl experience: biological indicators of exposure to ionizing radiation. Stem Cells. 1995;13(Suppl 1)69–77.Google ScholarPubMed
18.Patchen, ML, MacVittie, TJ, Solberg, BD, Souza, LM.Therapeutic administration of recombinant human granulocyte colony-stimulating factor accelerates hemopoietic regeneration and enhances survival in a murine model of radiation-induced myelosuppression. Int J Cell Cloning. 1990;8 (2):107–122.CrossRefGoogle Scholar
19.Neelis, KJ, Hartong, SC, Egeland, T, Thomas, GR, Eaton, DL, Wagemaker, G.The efficacy of single-dose administration of thrombopoietin with coadministration of either granulocyte/macrophage or granulocyte colony-stimulating factor in myelosuppressed rhesus monkeys. Blood. 1997;90 (7):2565–2573.CrossRefGoogle ScholarPubMed
20.Brandao-Mello, CE, Oliveira, AR, Valverde, NJ, Farina, R, Cordeiro, JM.Clinical and hematological aspects of 137Cs: the Goiãnia radiation accident. Health Phys. 1991;60 (1):31–39.CrossRefGoogle ScholarPubMed
21.International Atomic Energy Agency. The Radiological Accident in Goiãnia.Vienna: IAEA; 1998.Google Scholar
22.Hirama, T, Tanosaki, S, Kandatsu, S.Initial medical management of patients severely irradiated in the Tokai-mura criticality accident. Br J Radiol. 2003;76 (904):246–253.CrossRefGoogle ScholarPubMed
23.International Atomic Energy Agency. The Radiological Accident in Gilan.Vienna: IAEA; 2002.Google Scholar
24.International Atomic Energy Agency. The Radiological Accident in Istanbul.Vienna: IAEA; 2000.Google Scholar
25.Grimes, DA, Schulz, KF.An overview of clinical research: the lay of the land. Lancet. 2002;359 (9300):57–61.CrossRefGoogle ScholarPubMed
26.Grimes, DA, Schulz, KF.Descriptive studies: what they can and cannot do. Lancet. 2002;359 (9301):145–149.CrossRefGoogle Scholar
27.FitzGerald, TJ, McKenna, M, Rothstein, L, Daugherty, C, Kase, K, Greenberger, JS.Radiosensitivity of human bone marrow granulocyte-macrophage progenitor cells and stromal colony-forming cells: effect of dose rate. Radiat Res. 1986;107 (2):205–215.CrossRefGoogle ScholarPubMed
28.Oriya, A, Takahashi, K, Inanami, O.Individual differences in the radiosensitivity of hematopoietic progenitor cells detected in steady-state human peripheral blood. J Radiat Res (Tokyo). 2008;49 (2):113–121.CrossRefGoogle ScholarPubMed
29.International Atomic Energy Agency. Diagnosis and Treatment of Radiation Injuries. Safety Reports Series No. 2.Vienna: IAEA; 1998.Google Scholar
30.Alexander, GA, Swartz, HM, Amundson, SA.BiodosEPR-2006 Meeting: acute dosimetry consensus committee recommendations on biodosimetry applications in events involving uses of radiation by terrorists and accidents. Radiat Meas. 2007;42(Suppl)972–996.CrossRefGoogle Scholar
31.Fliedner, TM, Meineke, V, Akashi, M, Dainiak, N, Gourmelon, PProceedings of the Advanced Research Workshop on Radiation-Induced Multi-Organ Involvement and Failure: A Challenge for Pathogenetic, Diagnostic, and Therapeutic Approaches and Research.London: British Institute of Radiology; 2003.Google Scholar
32.Jammet, H, Mathe, G, Pendic, B.Study of six cases of accidental acute total irradiation. Rev Fr Etud Clin Biol. 1959;4 (3):210–225.Google ScholarPubMed
33.Baranov, A, Gale, RP, Guskova, A.Bone marrow transplantation after the Chernobyl nuclear accident. N Engl J Med. 1989;321 (4):205–212.CrossRefGoogle ScholarPubMed
34.International Atomic Energy Agency. The Vinca Dosimetry Experiment, Tech Rep Ser No. 6.Vienna: IAEA; 1962.Google Scholar
35.Gilbert, MVThe 1967 radiation accident near Pittsburgh, Pennsylvania, and a follow up report.In: Hubner KF, Fry SA, eds. The Medical Basis for Radiation Accident Preparedness. Amsterdam: Elsevier-North Holland; 1980:131-140.Google Scholar
36.Maekawa, KOverview of medical care for highly exposed victims in Tokaimura accident.In: Ricks RC, Berger ME, O’Hara FM, eds. The Medical Basis for Radiation-Accident Preparedness: The Clinical Care of Victims. Boca Raton, FL: Partheon Publishing Group; 2002:313-318.Google Scholar
37.Drouet, M, Mourcin, F, Grenier, N.Single administration of stem cell factor, FLT-3 ligand, megakaryocyte growth and development factor, and interleukin-3 in combination soon after irradiation prevents nonhuman primates from myelosuppression: long-term follow-up of hematopoiesis. Blood. 2004;103 (3):878–885.CrossRefGoogle ScholarPubMed
38.Hérodin, F, Grenier, N, Drouet, M.Revisiting therapeutic strategies in radiation casualties. Exp Hematol. 2007;35 4(Suppl 1)28–33.CrossRefGoogle ScholarPubMed
39.Smith, TJ, Khatcheressian, J, Lyman, GH.2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006;24 (19):3187–3205.CrossRefGoogle ScholarPubMed
40.Greil, R, Thödtman, R, Roila, FESMO Guidelines Working Group. Erythropoietins in cancer patients: ESMO recommendations for use. Ann Oncol. 2008;19(Suppl 2)ii113–ii115.CrossRefGoogle ScholarPubMed
41.Hughes, WT, Armstrong, D, Bodey, GP.2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002;34 (6):730–751.CrossRefGoogle ScholarPubMed
42.Food and Drug Administration. Information on erythropoiesis-stimulating agents (ESAs) epoetin alfa (marketed as Procrit, Epogen) darbepoetin alfa (marketed as Aranesp). http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM109375. Accessed August 29, 2011.Google Scholar
43.Dainiak, N, Ricks, RC.The evolving role of haematopoietic cell transplantation in radiation injury: potentials and limitations. BJR Suppl. 2005;27(Suppl)169–174.CrossRefGoogle Scholar
44.Densow, D, Kindler, H, Baranov, AE, Tibken, B, Hofer, EP, Fliedner, TM.Criteria for the selection of radiation accident victims for stem cell transplantation. Stem Cells. 1997;15(Suppl 2)287–297.CrossRefGoogle ScholarPubMed