REMM Bibliography -
Medical Management of Radiation Injury (Exposure)

• General information
• Acute Radiation Syndrome (ARS)
• Pregnancy and fetal issues in radiation incidents
• Infants' and children's issues in radiation incidents
• Hematopoietic stem cell transplantation
• Gastrointestinal Subsyndrome of ARS
• Use of myeloid cytokines
• Use of platelet cytokine
• Use of antiemetics
• Management of febrile neutropenia
• Platelet transfusion
• Use of blood products
• Radiation skin effects

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General information

• Overview
  • Medical Management of Radiation Injuries (IAEA, PAHO, IFRC, 2020)
  • Kim JH, Jenrow KA, Brown SL. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials. Radiat Oncol J. 2014 Sep;32(3):103-15. [PubMed Citation]
  • Rios CI, Cassatt DR, Hollingsworth BA, Satyamitra MM, Tadesse YS, Taliaferro LP, Winters TA, DiCarlo AL. Commonalities Between COVID-19 and Radiation Injury. Radiat Res. 2021 Jan 1;195(1):1-24. [PubMed Citation]
  • Mettler FA Jr, Upton AC: Medical Effects of Ionizing Radiation, 3rd ed. Philadelphia, Pa: Saunders Elsevier, 2008.
  • Bushberg JT, Radiation Exposure and Contamination, Merck Manual for Health Care Professionals (online version, last updated July, 2019)
  • Christensen DM, Iddins CJ, Sugarman SL. Ionizing radiation injuries and illnesses. Emerg Med Clin North Am. 2014 Feb;32(1):245-65.
• Emergency medical response
  • See: Practical Guidance
  • Wolbarst AB, Wiley AL Jr, Nemhauser JB, Christensen DM, Hendee WR. Medical response to a major radiologic emergency: a primer for medical and public health practitioners. Radiology. 2010 Mar;254(3):660-77. [PubMed Citation]
  • Bushberg JT, Kroger LA, Hartman MB, Leidholdt EM Jr, Miller KL, Derlet R, Wraa C. Nuclear/radiological terrorism: Emergency department management of radiation casualties. J Emerg Med. 2007 Jan;32(1):71-85. [PubMed Citation]
  • Flynn DF, Goans RE. Nuclear terrorism: triage and medical management of radiation and combined-injury casualties. Surg Clin North Am. 2006 Jun; 86(3):601-36 [PubMed Citation]
    
  • Musolino SV, Harper FT. Emergency response guidance for the first 48 hours after the outdoor detonation of an explosive radiological dispersal device. Health Phys. 2006 Apr;90(4):377-85 [PubMed Citation]
  • Mettler FA Jr, Voelz GL. Major radiation exposure--what to expect and how to respond. N Engl J Med. 2002 May 16;346(20):1554-61. [PubMed Citation]
• Medical management
  • López M, Martín M. Medical management of the acute radiation syndrome. Rep Pract Oncol Radiother. 2011 Jul 13;16(4):138-46. [PubMed Citation]
  • Berger ME, Christensen DM, Lowry PC, Jones OW, Wiley AL. Medical management of radiation injuries: current approaches. Occup Med (Lond). 2006 May;56(3):162-72 [PubMed Citation]
    
  • Mettler FA. Medical resources and requirements for responding to radiological terrorism. Health Physics 2005; 89(5):488-493 [PubMed Citation]
  • Goans RE, Waselenko JK. Medical management of radiological casualties. Health Phys. 2005 Nov;89(5):505-12 [PubMed Citation]
  • De Lorenzo RA. When it's hot, it's hot. Ann Emerg Med. 2005 Jun;45(6):653-4 [PubMed Citation]
  • Koenig KL, Goans RE, Hatchett RJ, Mettler FA Jr, Schumacher TA, Noji EK, Jarrett DG. Medical treatment of radiological casualties: current concepts. Ann Emerg Med. 2005 Jun;45(6):643-52 [PubMed Citation]
  • Meineke V, van Beuningen D, Sohns T, Fliedner TM. Medical management principles for radiation accidents. Mil Med. 2003 Mar;168(3):219-22 [PubMed Citation]

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Acute Radiation Syndrome (ARS)

• Guidelines
  • RITN Guidance about ARS and Cytokines
    • RITN Acute Radiation Syndrome Treatment Guidelines (PDF - 2.53 MB) (RITN, October 2020)
    • Cytokine Administration Triage Guidelines for Acute Radiation Syndrome (Adult and Pediatric)
      • The purpose of these guidelines are to give physicians, advanced practitioners and nurses (medical providers) simple myeloid cytokine triage guidelines to assist with the administration of these pharmaceuticals to adult and pediatric casualties in the immediate aftermath of a radiological disaster.
      • Formats available
        • 4x6 card (PDF - 635 KB)
        • 8.5x11 size (PDF - 678 KB)
        • 24x36 poster size (PDF - 129 KB)
  • Dainiak N. Medical management of acute radiation syndrome and associated infections in a high-casualty incident. J Radiat Res. 2018 Apr 1;59(suppl_2):ii54-ii64. [PubMed Citation]
  • Dainiak N, Gent RN, et al. Literature Review and Global Consensus on Management of Acute Radiation Syndrome Affecting Nonhematopoietic Organ Systems. Disaster Med Public Health Prep. 2011 Oct;5(3):183-201. [PubMed Citation]
  • Dainiak N, Gent RN, et al. First Global Consensus for Evidence-Based Management of the Hematopoietic Syndrome Resulting From Exposure to Ionizing Radiation. Disaster Med Public Health Prep. 2011 Oct;5(3):202-212. [PubMed Citation]
  • DOE/ORISE/ORAU/REAC/TS
    • The Medical Aspects of Radiation Incidents, 4th Edition, Revised 07/2017 (PDF - 2.46 MB) (REAC/TS/ORAU/DOE)
    • Prehospital Radiological Triage, Version 1.1 (PDF - 2.51 MB) (DOE/ORISE/ORAU/REAC/TS, March 2020)
    • Radiation Patient Treatment, Version 3.1 (PDF - 1.75 MB) (DOE/ORISE/ORAU/REAC/TS, March 2020)
    • Dant JT, Reeves G, Stricklin D. Automated Translation of Clinical Parameters in Evaluating Acute Radiation Injury: Results From a Mass Casualty Exercise. Disaster Med Public Health Prep. 2018 Oct;12(5):569-573. [PubMed Citation] (Note: This compares METREPOL and REAC/TS triage options.)
    • Early Internal and External Dose Magnitude Estimation (REAC/TS, 07/2017)
      • Focuses on external and internal contamination and compares ALI and CDG.
      • Describes methods for rapidly estimating internal and external radiation dose magnitudes that can be used to help guide early medical management.
      • Includes quick reference tables and examples of how to apply the mathematical formulas.
    • Ground and Air Medical Transport of Radiologically Contaminated Patients (Vimeo - 8:18 min) (DOE/ORISE/REAC/TS, 2019)
      • Appropriate patient packaging for transport of a radiologically contaminated patient,
      • Simple contamination control techniques to help ensure contamination is appropriately mitigated and not spread to care providers or equipment.
    • Quick Reference Information – Radiation (DOE/ORISE/REAC/TS, March 2019)
  • Weisdorf D, Apperley J, Gourmelon P, Gorin NC, Wingard J, Chao N. Radiation Emergencies: Evaluation, Management, and Transplantation. Biol Blood Marrow Transplant. 2007;13:103-6. (PDF - 82 KB)
  • Manage ARS with scarce resources after an IND detonation
    • Interactive tool
    • Video explaining how to use the tool
• Complete blood count (CBC) as predictor of hematopoietic ARS severity
  • Port M, Abend M. Clinical Triage of Radiation Casualties - the Hematological Module of the Bundeswehr Institute of Radiobiology. Radiat Prot Dosimetry. 2018 Dec 1;182(1):90-92. [PubMed Citation]
  • Port M, Pieper B, Knie T, Dorr H, Ganser A, Graessle D, Meineke V, Abend M. Rapid Prediction of Hematologic Acute Radaition Syndrome in Radiation Injury Patients Using Peripheral Blood Cell counts. Radiat Res. 2017 Aug;188(2):156-168. [PubMed Citation]
  • Port M, Pieper B, Dorr HD, Hubsch A, Majewski M, Abend M, Correlation of Radiation Dose Estimates by DIC with METRPOL Hematological Classes of Disease Severity. Radiat Res. 2018 May;189(5):449-455. [PubMed Citation]
• Other guidance
  • Manthous CA, Jackson WL Jr. The 9-11 Commission's invitation to imagine: a pathophysiology-based approach to critical care of nuclear explosion victims. Crit Care Med. 2007 Mar;35(3):716-23. [PubMed Citation]
  • Fliedner TM. Nuclear terrorism: the role of hematology in coping with its health consequences. Curr Opin Hematol. 2006 Nov;13(6):436-44. [PubMed Citation]
  • Gorin NC, Fliedner TM, Gourmelon P, Ganser A, Meineke V, Sirohi B, Powles R, Apperley J. Consensus conference on European preparedness for haematological and other medical management of mass radiation accidents. Ann Hematol. 2006 Oct;85(10):671-9. [PubMed Citation]
  • Jackson WL Jr, Gallagher C, Myhand RC, Waselenko JK. Medical management of patients with multiple organ dysfunction arising from acute radiation syndrome. BJR Suppl. 2005;27:161-8
  • Waselenko JK, et al. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann Intern Med. 2004 Jun 15;140(12):1037-51 [PubMed Citation]
  • Dainiak N, Waselenko JK, Armitage JO, MacVittie TJ, Farese AM. The hematologist and radiation casualties. Hematology, (Am Soc Hematol Educ Program). 2003;:473-96 [PubMed Citation]
  • Dainiak N. Hematologic consequences of exposure to ionizing radiation. Exp Hematol. 2002 Jun;30(6):513-28 [PubMed Citation]
• Insights from research
  • MacVittie TJ, Farese AM, Parker GA, Bennett AW, Jackson WE 3rd. Acute Radiation-induced Lung Injury in the Non-human Primate: A Review and Comparison of Mortality and Co-morbidities Using Models of Partial-body Irradiation with Marginal Bone Marrow Sparing and Whole Thorax Lung Irradiation. Health Phys. 2020 Nov;119(5):559-587. [PubMed Citation]
  • Satyamitra MM, Cassatt DR, Hollingsworth BA, Price PW, Rios CI, Taliaferro LP, Winters TA, DiCarlo AL. Metabolomics in Radiation Biodosimetry: Current Approaches and Advances. Metabolites. 2020 Aug 11;10(8):328. [PubMed Citation]
  • Ostheim P, Haupt J, Herodin F, et al. miRNA Expression Patterns Differ by Total- or Partial-Body Radiation Exposure in Baboons. Radiat Res. 2019;192(6):579-588. [PubMed Citation]
  • Port M, Majewski M, Abend M. Radiation dose is of limited clinical usefulness in persons with acute radiation syndrome. Radiat Prot Dosimetry. 2019 Apr 25. [PubMed Citation]
  • Doerr H, Lamkowski A, Graessle DH, Bennett A, Shapiro A, Farese AM, Garofalo M, MacVittie TJ, Meineke V. Linking the human response to unplanned radiation and treatment to the nonhuman primate response to controlled radiation and treatment. Health Phys. 2014 Jan;106(1):129-34. [PubMed Citation]
  • MacVittie TJ, Farese AM, Jackson W 3rd. The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship. Health Phys. 2015 Nov;109(5):342-66. [PubMed Citation]
  • Paul S, Smilenov LB, Amundson SA. Widespread decreased expression of immune function genes in human peripheral blood following radiation exposure. Radiat Res. 2013 Dec;180(6):575-83. [PubMed Citation]
• Issues related to neutron and mixed neutron/gamma radiation
  • MacVittie TJ, Farese AM, Jackson WE 3rd. A Systematic Review of the Hematopoietic Acute Radiation Syndrome (H-ARS) in Canines and Non-human Primates: Acute Mixed Neutron/Gamma vs. Reference Quality Radiations. Health Phys. 2020 Nov;119(5):527-558. [PubMed Citation]

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Pregnancy and fetal issues in radiation incidents

See REMM At-Risk / Special Needs Populations:

• Infants and Young Children
• Pregnant Woman and Fetus

• Possible health effects of radiation exposure on unborn babies (HHS/CDC)
• Prenatal radiation exposure: a fact sheet for physicians (HHS/CDC)
• Donnelly EH, Smith JM, Farfan EB, Ozcan I. Prenatal Radiation Exposure: Background Material for Counseling Pregnant Patients Following Exposure to Radiation. Disaster Med Public Health Prep. 2011 Mar;5(1):62-8. [PubMed Citation]
• Protection of pregnant patients during diagnostic medical exposures to ionising radiation, RCE 9 (Public Health England [PHE], formerly Health Protection Agency [HPA], March 2009)
• Guidance on the application of dose coefficients for the embryo, fetus and breastfed infant in dose assessments for members of the public (RCE-5) (Public Health England [PHE], formerly Health Protection Agency [HPA], 2008)
• Kal HB, Struikmans H. Radiotherapy during pregnancy: fact and fiction. Lancet Oncol. 2005 May;6(5):328-33 [PubMed Citation]
• Prasad KN, Cole WC, Hasse GM. Health risks of low dose ionizing radiation in humans: a review. Exp Biol Med (Maywood). 2004 May;229(5):378-82 [PubMed Citation]
• Doses to infants from radionuclides ingested in mothers' milk, ICRP Publication 95, Ann. ICRP 34(3-4), 2004. Errata published (PDF - 62 KB) (International Commission on Radiological Protection)
• Biological effects after prenatal irradiation (embryo and fetus), ICRP Publication 90, Ann. ICRP 33(1-2), 2003. (International Commission on Radiological Protection)
• Doses to the embryo and fetus from intakes of radionuclides by the mother, ICRP Publication 88, Ann. ICRP 31(1-3), 2001. (International Commission on Radiological Protection)
• Pregnancy and medical radiation, ICRP Publication 84, Ann. ICRP 30(1), 2000. (International Commission on Radiological Protection)
• Brent RL. Utilization of developmental basic science principles in the evaluation of reproductive risks from pre- and postconception environmental radiation exposures. Teratology. 1999 Apr;59(4):182-204 [PubMed Citation]
• Pregnancy and radiation exposure (Health Physics Society)
• Pregnancy and radiation exposure (Health Physics Society)
• Radiation exposure and pregnancy - fact sheet for patients (PDF - 480 KB) (Health Physics Society)

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Infants' and children's issues in mass casualty incidents including radiation incidents

Policy issues

• National Advisory Committee on Children and Terrorism (NACCT) (HHS/CDC)
  • NACCT Recommendations to Secretary of HHS (PDF - 704 KB) (June 12, 2003)
  • Schools and Terrorism: A Supplement to the National Advisory Committee on Children and Terrorism. J Sch Health. 2004 Feb;74(2):39-51. [PubMed Citation]

• Pediatric disaster and terrorism preparedness, A national consensus conference and the pediatric expert advisory panel (PDF - 1,218 KB) David Markenson, MD, Columbia University

Resources

• American Academy of Pediatrics Committee on Pediatric Emergency Medicine; American Academy of Pediatrics Committee on Medical Liability; Task Force on Terrorism. The pediatrician and disaster preparedness. Pediatrics. 2006 Feb;117(2):560-5. [PubMed Citation]
• American Academy of Pediatrics Committee on environmental health. Radiation disasters and children. Pediatrics. 2003 Jun;111(6 Pt 1):1455-66 [PubMed Citation]
• American Academy of Pediatrics, Committee on Pediatric Emergency Medicine and American College of Emergency Physicians, and Pediatric Committee. Care of Children in the Emergency Department: Guidelines for preparedness. Pediatrics. 2001 Apr;107(4):777-81 [PubMed Citation]
• Strategies and tools for meeting the needs of children: public health emergencies (HHS/AHRQ, a free Web conference, 4 Web lectures, broadcast January 11, 2006)
• Talking to Children About War and Terrorism (National Child Traumatic Stress Network)
• Pediatric disaster and terrorism preparedness, by David Markenson, M.D., Columbia University, July 13, 2004 (PowerPoint® - 1135 KB) (Text version)
• ICRP Publication 95: Doses to infants from ingestion of radionuclides in mother's milk, 95 (International Commission of Radiological Protection, ICRP Publication 95, 2004)
• Guidance on the application of dose coefficients for the embryo, fetus and breastfed infant in dose assessments for members of the public (RCE-5) (Public Health England [PHE], formerly Health Protection Agency [HPA], 2008)
• See At-Risk / Special Needs Populations — Infants and Young Children for more references.

Techniques for pediatric incident mass casualty triage

• JumpSTART pediatric multiple casualty incident triage (Dr. Lou E. Romig, MD, Team Life Support, Inc.)
  • JumpSTART pediatric multiple casualty incidents triage tool (Dr. Lou E. Romig, MD, Team Life Support, Inc.)

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Hematopoietic stem cell transplantation

• See: Radiation Injury Treatment Network (RITN) bibliography
• Egan G, Robinson PD, Martinez JPD, Alexander S, Ammann RA, Dupuis LL, Fisher BT, Lehrnbecher T, Phillips B, Cabral S, Tomlinson G, Sung L. Efficacy of antibiotic prophylaxis in patients with cancer and hematopoietic stem cell transplantation recipients: A systematic review of randomized trials. Cancer Med. 2019 Aug;8(10):4536-4546. [PubMed Citation]
• Confer DL, Weisdorf D, Weinstock D, Case C, Chao N. Radiation disasters: role of the BMT team. Biol Blood Marrow Transplant. 2012 Jan;18(1 Suppl):S189-92. [PubMed Citation]
• Dainiak N, Gent RN, Carr Z, et al. First global consensus for evidence-based management of the hematopoietic syndrome resulting from exposure to ionizing radiation.. Disaster Med Public Health Prep. 2011 Oct;5(3):202-12. [PubMed Citation]
• Ross JR, Case C, Confer D, Weisdorf DJ, Weinstock D, Krawisz R, Chute J, Wilhauk J, Navarro W, Hartzman R, Norman Coleman C, Hatchett R, Chao N. Radiation injury treatment network (RITN): healthcare professionals preparing for a mass casualty radiological or nuclear incident. Int J Radiat Biol. 2011 Aug;87(8):748-53. [PubMed Citation]
• Davids MS, Case C Jr, Confer DL, Weisdorf DJ, Weinstock DM. Medical management of radiation victims in the United States. Health Phys. 2010 Jun;98(6):833-7. [PubMed Citation]
• Weinstock DM, Case C Jr, Bader JL, Chao NJ, Coleman CN, Hatchett RJ, Weisdorf DJ, Confer DL. Radiologic and nuclear events: contingency planning for hematologists/oncologists. Blood. 2008 Jun 15;111(12):5440-5. [PubMed Citation]
• Weisdorf D, Chao N, Waselenko JK, Dainiak N, Armitage JO, McNiece I, Confer D. Acute radiation injury: contingency planning for triage, supportive care, and transplantation. Biol Blood Marrow Transplant. 2006 Jun;12(6):672-82. [PubMed Citation]
• Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006 Apr 27; 354(17):1813-26. [PubMed Citation]
• Dainiak N, Ricks RC. The evolving role of haematopoietic cell transplantation in radiation injury: potentials and limitations. BJR Suppl. 2005; 27:169-74.
• Waselenko JK, MacVittie TJ, Blakely WF, Pesik N, Wiley AL, Dickerson WE, Tsu H, Confer DL, Coleman CN, Seed T, Lowry P, Armitage JO, Dainiak N; Strategic National Stockpile Radiation Working Group. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Annals of Internal Medicine 2004; Vol. 140:1037-51. [PubMed Citation]

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Gastrointestinal Subsyndrome of ARS

• MacVittie TJ, Farese AM, Parker GA, Jackson W 3rd, Booth C, Tudor GL, Hankey KG, Potten CS. The Gastrointestinal Subsyndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose-response Relationship With and Without Medical Management. Health Phys. 2019 Mar;116(3):305-338. [PubMed Citation]

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Use of myeloid cytokines

Use in adults

• Gale RP, Armitage JO. Use of molecularly-cloned haematopoietic growth factors in persons exposed to acute high-dose, high-dose rate whole-body ionizing radiations. Blood Rev. 2020 Apr 2:100690. doi: 10.1016/j.blre.2020.100690. [PubMed Citation]
• DiCarlo AL, Horta ZP, Aldrich JT, Jakubowski AA, Skinner WK, Case CM Jr. Use of Growth Factors and Other Cytokines for Treatment of Injuries During a Radiation Public Health Emergency. Radiat Res. 2019 Jul;192(1):99-120. [PubMed Citation]
• Horta ZP, Case CM Jr, DiCarlo AL. Use of Growth Factors and Cytokines to Treat Injuries Resulting from a Radiation Public Health Emergency. Radiat Res. 2019 Jul;192(1):92-97. [PubMed Citation]
• Hofer M, Pospíšil M, Komůrková D, Hoferová Z. Granulocyte colony-stimulating factor in the treatment of acute radiation syndrome: a concise review. Molecules. 2014 Apr 16;19(4):4770-8. [PubMed Citation]
• Weycker D, Li X, Barron R, Li Y, Reiner M, Kartashov A, Figueredo J, Tzivelekis S, Garcia J. Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis in US clinical practice. Support Care Cancer. 2015 Dec 15. [PubMed Citation]
• Smith TJ, Bohlke K, Lyman GH, Carson KR, Crawford J, Cross SJ, Goldberg JM, Khatcheressian JL, Leighl NB, Perkins CL, Somlo G, Wade JL, Wozniak AJ, Armitage JO. Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. (2015 ASCO guideline) J Clin Oncol. 2015 Oct 1;33(28):3199-212. [PubMed Citation] (This 2015 ASCO guideline updates the 2006 myeloid cytokine guideline)
• NCCN Clinical Practice Guidelines in Oncology, Myeloid Growth Factors, Version 1.2017, April 28, 2017 See section entitled "NCCN Guidelines for Supportive Care" > "Myeloid Growth Factors". (Registration required.)
• Dainiak N, Gent RN, et al. First Global Consensus for Evidence-Based Management of the Hematopoietic Syndrome Resulting From Exposure to Ionizing Radiation. Disaster Med Public Health Prep. 2011 Oct;5(3):202-212. [PubMed Citation] (Full text)
• Kaushansky K. Lineage-specific hematopoietic growth factors. N Engl J Med. 2006 May 11;354(19):2034-45 [PubMed Citation]
• Smith TJ, Khatcheressian J, Lyman GH, et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006 Jul 1;24(19):3187-205. Epub 2006 May 8 [PubMed Citation]
• Kuderer NM, Dale DC, Crawford J, Lyman GH. Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review. J Clin Oncol. 2007 Jul 20;25(21):3158-67. [PubMed Citation]
• Herbst C, Naumann F, Kruse EB, Monsef I, Bohlius J, Schulz H, Engert A. Prophylactic antibiotics or G-CSF for the prevention of infections and improvement of survival in cancer patients undergoing chemotherapy. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD007107. [PubMed Citation]

Use in non-human primates

• Clayton NP, Khan-Malek RC, Dangler CA, Zhang D, Ascah A, Gains M, Gardner B, Mockbee C, Keutzer JM, McManus J, Authier S. Sargramostim (rhu GM-CSF) Improves Survival of Non-Human Primates with Severe Bone Marrow Suppression after Acute, High-Dose, Whole-Body Irradiation. Radiat Res. 2020 Dec 10. doi: 10.1667/RADE-20-00131.1. [PubMed Citation]
• Zhong Y, Pouliot M, Downey AM, Mockbee C, Roychowdhury D, Wierzbicki W, Authier S. Efficacy of delayed administration of sargramostim up to 120 hours post exposure in a nonhuman primate total body radiation model. Int J Radiat Biol. 2020 Sep 22:1-17. doi: 10.1080/09553002.2019. [PubMed Citation]
• Wong K, Chang PY, Fielden M, Downey AM, Bunin D, Bakke J, Gahagen J, Iyer L, Doshi S, Wierzbicki W, Authier S. Pharmacodynamics of romiplostim alone and in combination with pegfilgrastim on acute radiation-induced thrombocytopenia and neutropenia in non-human primates. Int J Radiat Biol. 2020 Jan;96(1):155-166. [PubMed Citation]
• MacVittie TJ, Farese AM, Parker GA, Jackson W 3rd. The Time Course of Radiation-induced Lung Injury in a Nonhuman Primate Model of Partial-body Irradiation With Minimal Bone Marrow Sparing: Clinical and Radiographic Evidence and the Effect of Neupogen Administration. Health Phys. 2019;116(3):366‐382. [PubMed Citation]
• Farese AM, Bennett AW, Gibbs AM, Hankey KG, Prado K, Jackson W 3rd, MacVittie TJ. Efficacy of Neulasta or Neupogen on H-ARS and GI-ARS Mortality and Hematopoietic Recovery in Nonhuman Primates After 10-Gy Irradiation With 2.5% Bone Marrow Sparing. Health Phys. 2019 Mar;116(3):339-353. [PubMed Citation]
• Hankey KG, Farese AM, Blaauw EC, Gibbs AM, Smith CP, Katz BP, Tong Y, Prado KL, MacVittie TJ. Pegfilgrastim Improves Survival of Lethally Irradiated Nonhuman Primates. Radiat Res. 2015 Jun;183(6):643-55. [PubMed Citation]
• MacVittie TJ. The MCART Consortium Animal Model Series: MCART Animal Model Refinement and MCM Development: Defining organ dose, organ-specific tissue imaging, model validation and the natural history between the acute radiation syndrome (ARS) and the delayed effects of acute radiation exposure (DEARE). Health Phys. 2015 Nov;109(5):335-41. [PubMed Citation]
• MacVittie TJ, Bennett AW, Farese AM, Taylor-Howell C, Smith CP, Gibbs AM, Prado K, Jackson W 3rd. The Effect of Radiation Dose and Variation in Neupogen® Initiation Schedule on the Mitigation of Myelosuppression during the Concomitant GI-ARS and H-ARS in a Nonhuman Primate Model of High-dose Exposure with Marrow Sparing. Health Phys. 2015 Nov;109(5):427-39. [PubMed Citation]
• Farese AM, Brown CR, Smith CP, Gibbs AM, Katz BP, Johnson CS, Prado KL, MacVittie TJ. The ability of filgrastim to mitigate mortality following LD50/60 total-body irradiation is administration time-dependent. Health Phys. 2014 Jan;106(1):39-47. [PubMed Citation]
• Farese AM, Cohen MV, Katz BP, Smith CP, Gibbs A, Cohen DM, MacVittie TJ. Filgrastim improves survival in lethally irradiated nonhuman primates. Radiat Res. 2013 Jan;179(1):89-100. [PubMed Citation]
• Farese AM, Cohen MV, Katz BP, Smith CP, Jackson W 3rd, Cohen DM, MacVittie TJ. A nonhuman primate model of the hematopoietic acute radiation syndrome plus medical management. Health Phys. 2012 Oct;103(4):367-82. [PubMed Citation]
• Farese AM, Cohen MV, Stead RB, Jackson W 3rd, Macvittie TJ. Pegfilgrastim administered in an abbreviated schedule, significantly improved neutrophil recovery after high-doseradiation-induced myelosuppression in rhesus macaques. Radiat Res. 2012 Nov;178(5):403-13. [PubMed Citation]

Research on using cytokines in non-standard dosing schedules

• Clayton NP, Khan-Malek RC, Dangler CA, Zhang D, Ascah A, Gains M, Gardner B, Mockbee C, Keutzer JM, McManus J, Authier S. Sargramostim (rhu GM-CSF) Improves Survival of Non-Human Primates with Severe Bone Marrow Suppression after Acute, High-Dose, Whole-Body Irradiation. Radiat Res. 2020 Dec 10. doi: 10.1667/RADE-20-00131.1. [PubMed Citation]
• Zhong Y, Pouliot M, Downey AM, Mockbee C, Roychowdhury D, Wierzbicki W, Authier S. Efficacy of delayed administration of sargramostim up to 120 hours post exposure in a nonhuman primate total body radiation model. Int J Radiat Biol. 2020 Sep 22:1-17. doi: 10.1080/09553002.2019. [PubMed Citation]

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Use of platelet cytokine

• DiCarlo AL, Horta ZP, Aldrich JT, Jakubowski AA, Skinner WK, Case CM Jr. Use of Growth Factors and Other Cytokines for Treatment of Injuries During a Radiation Public Health Emergency. Radiat Res. 2019 Jul;192(1):99-120. [PubMed Citation]
• Wong K, Chang PY, Fielden M, Downey AM, Bunin D, Bakke J, Gahagen J, Iyer L, Doshi S, Wierzbicki W, Authier S. Pharmacodynamics of romiplostim alone and in combination with pegfilgrastim on acute radiation-induced thrombocytopenia and neutropenia in non-human primates. Int J Radiat Biol. 2020 Jan;96(1):155-166. [PubMed Citation]
• Bunin DI, Bakke J, Green CE, Javitz HS, Fielden M, Chang PY. Romiplostim (Nplate®) as an effective radiation countermeasure to improve survival and platelet recovery in mice. Int J Radiat Biol. 2020 Jan;96(1):145-154. [PubMed Citation]
• Yamaguchi M, Suzuki M, Funaba M, Chiba A, Kashiwakura I. Mitigative efficacy of the clinical dosage administration of granulocyte colony-stimulating factor and romiplostim in mice with severe acute radiation syndrome. Stem Cell Res Ther. 2020 Aug 3;11(1):339. [PubMed Citation]
• Chiba A, Kawabata N, Yamaguchi M, Tokonami S, Kashiwakura I. Regulation of Antioxidant Stress-Responsive Transcription Factor Nrf2 Target Gene in the Reduction of Radiation Damage by the Thrombocytopenia Drug Romiplostim. Biol Pharm Bull. 2020;43(12):1876-1883. [PubMed Citation]
• Yamaguchi M, Hirouchi T, Yoshioka H, Watanabe J, Kashiwakura I. Diverse functions of the thrombopoietin receptor agonist romiplostim rescue individuals exposed to lethal radiation. Free Radic Biol Med. 2019 May 20;136:60-75. [PubMed Citation]
• Yamaguchi M, Hirouchi T, Yokoyama K, Nishiyama A, Murakami S, Kashiwakura I. The thrombopoietin mimetic romiplostim leads to the complete rescue of mice exposed to lethal ionizing radiation. Sci Rep. 2018 Jul 13;8(1):10659. [PubMed Citation]
• Note: FDA approval or romiplostim was based on animal studies. See cytokines page and romiplostim FDA drug label.

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Use of antiemetics

See Guidelines for Use of Antiemetics

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Management of febrile neutropenia

Introduction

• In clinical oncology, diagnosis and treatment of fever and neutropenia is a common problem. Many clinical practice guidelines and evidence reviews have been published, with periodic updates as understanding of the pathophysiology improves, and new drugs and regimens are introduced.
• During a mass casualty radiation emergency, diagnosis and treatment of fever and neutropenia will surely occur among those who receive a high enough dose from exposure to whole- or partial-body radiation.
• REMM clinical guidance focuses mainly on mass casualty radiation emergencies. In the absence of formal, prospective research on optimal guidelines for diagnosis and treatment of fever and neutropenia during large, mass casualty radiation emergencies, REMM citations and links on this topic are largely based on peer-reviewed publications in clinical oncology and expert opinion. These links and citations serve as background information only. No uniformly accepted clinical guidance exists for optimal regimens during large mass casualty radiation emergencies, especially when adequate resources may be inadequate at least initially, and crisis standards of care may be implemented.
• See REMM’s Fever and Neutropenia sections in the Template for Hospital Orders in adults and children. Treatment options are offered by REMM and RITN experts as guidance, but no specific regimen is officially endorsed. Every patient should be managed individually, with the resources and information available at the time the patient is seen.

See REMM information about Acute Radiation Syndrome, Exposure Algorithm, Dose Estimation, Time-Dose Effects, Crisis Standards of Care

Children

• Lehrnbecher T, Averbuch D, Castagnola E, Cesaro S, Ammann RA, Garcia-Vidal C, Kanerva J, Lanternier F, Mesini A, Mikulska M, Pana D, Ritz N, Slavin M, Styczynski J, Warris A, Groll AH; 8th European Conference on Infections in Leukaemia. 8th European Conference on Infections in Leukaemia: 2020 guidelines for the use of antibiotics in paediatric patients with cancer or post-haematopoietic cell transplantation. Lancet Oncol. 2021 Mar 31:S1470-2045(20)30725-7. [PubMed Citation]
• Lekshminarayanan A, Bhatt P, Linga VG, Chaudhari R, Zhu B, Dave M, Donda K, Savani S, Patel SV, Billimoria ZC, Bhaskaran S, Zaid-Kaylani S, Dapaah-Siakwan F, Bhatt NS. National Trends in Hospitalization for Fever and Neutropenia in Children with Cancer, 2007-2014. J Pediatr. 2018 Nov;202:231-237. [PubMed Citation]
• Moody KM, Baker RA, Santizo RO, Olmez I, Spies JM, Buthmann A, Granowetter L, Dulman RY, Ayyanar K, Gill JB, Carroll AE. A randomized trial of the effectiveness of the neutropenic diet versus food safety guidelines on infection rate in pediatric oncology patients. Pediatr Blood Cancer. 2018 Jan;65(1). [PubMed Citation]
• Lehrnbecher T, Robinson P, Fisher B, Alexander S, Ammann RA, Beauchemin M, Carlesse F, Groll AH, Haeusler GM, Santolaya M, Steinbach WJ, Castagnola E, Davis BL, Dupuis LL, Gaur AH, Tissing WJE, Zaoutis T, Phillips R, Sung L. Guideline for the Management of Fever and Neutropenia in Children With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: 2017 Update. J Clin Oncol. 2017 Jun 20;35(18):2082-2094. [PubMed Citation]
• Robinson PD, Lehrnbecher T, Phillips R, Dupuis LL, Sung L. Strategies for Empiric Management of Pediatric Fever and Neutropenia in Patients With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: A Systematic Review of Randomized Trials. J Clin Oncol. 2016 Jun 10;34(17):2054-60. [PubMed Citation]
• Haeusler GM, Sung L, Ammann RA, Phillips B. Management of fever and neutropenia in paediatric cancer patients: room for improvement? Curr Opin Infect Dis. 2015 Dec;28(6):532-8. [PubMed Citation]
• Miedema KG, Tissing WJ, Abbink FC, Ball LM, Michiels EM, van Vliet MJ, de Vries WY, Kamps WA, Norbruis OF, Fiocco M, de Groot-Kruseman HA, van de Wetering MD, de Bont ES. Risk-adapted approach for fever and neutropenia in paediatric cancer patients--a national multicentre study. Eur J Cancer. 2016 Jan;53:16-24. [PubMed Citation]
• Vedi A, Pennington V, O'Meara M, Stark K, Senner A, Hunstead P, Adnum K, Londall W, Maurice L, Wakefield C, Cohn RJ. Management of fever and neutropenia in children with cancer. Support Care Cancer. 2015 Jul;23(7):2079-87. [PubMed Citation]

Adults

• NCCN Clinical Practice Guidelines in Oncology^®: Prevention and Treatment of Cancer-Related Infections, Version 1.2019 – October 25, 2019.
  • Navigation to the page: Home page > NCCN Guidelines^® > NCCN Guidelines for Supportive Care > Prevention and Treatment of Cancer-Related Infections (Requires registration to access the pdf guideline.)
  • See information on diagnosis as well as antibacterial, antifungal and antiviral agents
• Egan G, Robinson PD, Martinez JPD, Alexander S, Ammann RA, Dupuis LL, Fisher BT, Lehrnbecher T, Phillips B, Cabral S, Tomlinson G, Sung L. Efficacy of antibiotic prophylaxis in patients with cancer and hematopoietic stem cell transplantation recipients: A systematic review of randomized trials. Cancer Med. 2019 Aug;8(10):4536-4546. [PubMed Citation]
• Stern A, Carrara E, Bitterman R, Yahav D, Leibovici L, Paul M. Early discontinuation of antibiotics for febrile neutropenia versus continuation until neutropenia resolution in people with cancer. Cochrane Database Syst Rev. 2019 Jan 3;1:CD012184. [PubMed Citation]
• Taplitz RA, Kennedy EB, Bow EJ, Crews J, Gleason C, Hawley DK, Langston AA, Nastoupil LJ, Rajotte M, Rolston KV, Strasfeld L, Flowers CR. Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update. J Clin Oncol. 2018 Sep 4:JCO1800374. [PubMed Citation]
• Taplitz RA, Kennedy EB, Bow EJ, Crews J, Gleason C, Hawley DK, Langston AA, Nastoupil LJ, Rajotte M, Rolston K, Strasfeld L, Flowers CR. Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update. J Clin Oncol. 2018 May 10;36(14):1443-1453. [PubMed Citation]
• Mellinghoff SC, Panse J, Alakel N, Behre G, Buchheidt D, Christopeit M, Hasenkamp J, Kiehl M, Koldehoff M, Krause SW, Lehners N, von Lilienfeld-Toal M, Löhnert AY, Maschmeyer G, Teschner D, Ullmann AJ, Penack O, Ruhnke M, Mayer K, Ostermann H, Wolf HH, Cornely OA. Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO). Ann Hematol. 2018 Feb;97(2):197-207. [PubMed Citation]
• Patel K, West HJ. Febrile Neutropenia: Information for Patients. JAMA Oncol. 2017 Dec 1;3(12):1751. [PubMed Citation]
• Heinz WJ, Buchheidt D, Christopeit M, von Lilienfeld-Toal M, Cornely OA, Einsele H, Karthaus M, Link H, Mahlberg R, Neumann S, Ostermann H, Penack O, Ruhnke M, Sandherr M, Schiel X, Vehreschild JJ, Weissinger F, Maschmeyer G. Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol. 2017 Nov;96(11):1775-1792. [PubMed Citation]
• van Dalen EC, Mank A, Leclercq E, Mulder RL, Davies M, Kersten MJ, van de Wetering MD. Low bacterial diet versus control diet to prevent infection in cancer patients treated with chemotherapy causing episodes of neutropenia. Cochrane Database Syst Rev. 2016 Apr 24;4:CD006247. [PubMed Citation]
• Klastersky J, de Naurois J, Rolston K, et al. Management of febrile neutropaenia:ESMO Clinical Practice Guidelines. Ann Oncology, 2016;27(suppl 5):v111-v118. (European Society for Medical Oncology, ESMO)
• Krzyzanowska MK, Walker-Dilks C, Atzema C et al., Approach to fever assessment in ambulatory cancer patients receiving chemotherapy: a clinical practice guideline. Curr Oncol 2016; 23(4):280-285. [PubMed Citation]

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Platelet transfusion

• Kaufman RM, Djulbegovic B, Gernsheimer T, Kleinman S, Tinmouth AT, Capocelli KE, Cipolle MD, Cohn CS, Fung MK, Grossman BJ, Mintz PD, Sesok-Pizzini DA, Shander A, Stack GE, Webert KE, Weinstein R, Welch BG, Whitman GJ, Wong EC, Tobian AA. Platelet Transfusion: A Clinical Practice Guideline From the AABB. Ann Intern Med. 2014 Nov 11. [PubMed Citation]
• Kumar A, Mhaskar R, Grossman BJ, Kaufman RM, Tobian AA, Kleinman S, Gernsheimer T, Tinmouth AT, Djulbegovic B; AABB Platelet Transfusion Guidelines Panel. Platelet transfusion: a systematic review of the clinical evidence. Transfusion. 2014 Nov 12. [PubMed Citation]
• Staworth SJ, Estcourt LJ, Powter G. A No-prophylaxis platelet-transfusion strategy for hematologic cancers. N Engl J Med 2013;368(19):1771-80. [PubMed Citation]
• Estcourt LJ, Birchall J, Lowe D, Grant-Casey J, Rowley M, Murphy MF. Platelet transfusions in haematology patients: are we using them appropriately? Vox Sang 2012;103:284-93. [PubMed Citation]
• Estcourt L, Stanworth S, Doree C, et al. Prophylactic platelet transfusion for prevention of bleeding in patients with haematological disorders after chemotherapy and stem cell transplantation. Cochrane Database Syst Rev 2012;5:CD004269. [PubMed Citation]
• Slichter SJ, Kaufman RM, Assmann SF, et al. Dose of prophylactic platelet transfusions and prevention of hemorrhage. N Engl J Med 2010;362:600-13. [PubMed Citation]
• Slichter SJ. Evidence-based platelet transfusion guidelines. Hematology Am Soc Hematol Educ Program 2007:172-8. [PubMed Citation]
• Apelseth TO, Hervig T, Bruserud O. Current practice and future directions for optimization of platelet transfusions in patients with severe therapy-induced cytopenia. Blood Rev. 2011 May;25(3):113-22. Epub 2011 Feb 12. [PubMed Citation]
• Schiffer CA, Anderson KC, Bennett CL, Bernstein S, Elting LS, Goldsmith M, Goldstein M, Hume H, McCullough JJ, McIntyre RE, Powell BL, Rainey JM, Rowley SD, Rebulla P, Troner MB, Wagnon AH; American Society of Clinical Oncology. Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol., 2001 Mar 1;19(5):1519-38 [PubMed Citation]

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Use of blood products

See: Use of blood products

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Radiation skin effects

• Dainiak N, Gent RN, et al. Literature Review and Global Consensus on Management of Acute Radiation Syndrome Affecting Nonhematopoietic Organ Systems. Disaster Med Public Health Prep. 2011 Oct;5(3):183-201. [PubMed Citation]
• How to recognize and initially respond to an accidental radiation injury - images of radiation skin effects and injury (poster, PDF - 436 KB) (pamphlet, PDF - 322 KB) (Radiation dermatological injuries, IAEA, WHO)
• Cutaneous radiation injury: Fact sheet for physicians (HHS/CDC 5/10/2006)
• See also:
  • Cutaneous Radiation Subsyndrome
  • Cutaneous Radiation Injury - Introduction (YouTube - 2:43 minutes) (HHS/CDC)

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