Skip Navigation

U.S. Department of Health & Human Services
Navigation to Home, Contact Us, Site Map, About REMM
Radiation Event Medical Management (REMM)
REMM Banner
Search REMM Web Site
What Kind of Emergency? Initial Event Activities Patient Management Algorithms Management Modifiers Tools & Guidelines

REMM Home Contact Us Site Map About REMM
 

You are here: Home > Exposure: Diagnose/Manage Acute Radiation Syndrome > Hematopoietic Countermeasures


Hematopoietic Countermeasures



Growth Factors/Cytokines for White Blood Cells 1 2

Print as PDF View/Print as PDF (PDF - 53 KB)

CytokineAdult DosePregnant Women
G-CSF
or filgrastim
(Neupogen)
  • Subcutaneous administration
  • 5 ug/kg/day via single daily injection
  • Continued until absolute neutrophil count > 1.0 x 109 cells/L
Class C (Same as adults)
Pegylated G-CSF
or pegfilgrastim
(Neulasta)
  • 1 subcutaneous dose, 6 mg


Class C (Same as adults)
GM-CSF
or sargramostim
(Leukine)
  • Subcutaneous administration
  • 250 ug/m2/day
  • Continued until absolute neutrophil count > 1.0 x 109 cells/L
Class C (Same as adults)
G-CSF = granulocyte colony-stimulating factor; GM-CSF = granulocyte-macrophage colony-stimulating factor.

General comments:
  • Prescribers are strongly urged to consult detailed information for each drug in the hyperlinks.
  • Although the 3 drugs listed in the table above are FDA approved for the treatment of chemotherapy induced neutropenia, none is approved for radiation induced neutropenia.
    • No prospective randomized trials have proven the either the efficacy or long term safety of hematopoietic growth factors in humans exposed to radiation.
    • However, efficacy after radiation exposure has been observed with incidents involving small numbers of patients, as tracked by REAC/TS, and in smaller clinical studies.
    • Evidence from animal studies indicates that outcomes may be improved if growth factors are administered as soon as possible after radiation exposure, and prior to the onset of neutropenia.
  • In a mass casualty radiation event, procurement and use of these drugs from the Strategic National Stockpile would require a formal Emergency Use Authorization. Off label use by individual clinicians might occur, but FDA still recommends an EUA. Incident managers will probably provide direction on this issue during a mass casualty event.
  • General guidance on when to initiate treatment with growth factors
    • Initiation of treatment should be strongly considered for victims who develop an absolute neutrophil count of < 0.500 x 109 cells/L and are not already receiving growth factor.
    • In mass casualty events, some clinicians may suggest prophylactic use for victims likely to have been exposed to a whole body dose of ≥2 Gy instead of waiting for the onset of neutropenia. (See REMM Exposure algorithm, and Emergency Use Authorization)
  • For pregnant women
    • Experts in biodosimetry must be consulted.
    • Any pregnant patient with exposure to radiation should be evaluated by a health physicist and maternal-fetal specialist for an assessment of risk to the fetus.
    • Class C refers to U.S. Food and Drug Administration Pregnancy Category C, which indicates that studies have shown animal, teratogenic, or embryocidal effects, but there are no adequate controlled studies in women; or no studies are available in animals or pregnant women.
Additional issues/warning suggested by REMM consultants:
  • Safety and efficacy of growth factors in pediatric patients have not been established; however, available safety data for some of the growth factors (e.g., GM-CSF) indicate that this particular growth factor does not produce any greater toxicity in pediatric patients than in adults. Emergency use authorization would be required in a mass casualty event.
  • Daily G-CSF (filgrastim and pegfilgrastim) therapy leads to splenic enlargment in a small majority of patients, and splenic rupture has been documented. Patients should avoid all but minimal left upper quadrant trauma (including abdominal palpation) for at least a week after G-CSF has been discontinued.
  • Allergic reactions involving skin, respiratory, and cardiovascular symptoms have been reported in patients administered filgrastim and pegfilgrastim. Although these have occurred at a relatively low rate (<1 in 4000 patients for filgrastim), in a large scale radiological incident there may be patients who experience this side effect.
  • See practice guidelines for myeloid growth factors from
References:

top of page


Growth Factors/Cytokines for Platelets 4 5

  • Thrombopoietin (Other names: Tpo, c-Mpl ligand, megakaryocyte growth and differentiation factor)
    • Tpo acts primarily to regulate megakaryocytopoiesis and platelet production.
    • Not currently approved for human use, but in an emergency the FDA may be petitioned for an EUA (Emergency Use Authorization).

top of page


References

  1. 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]
  2. Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, Bennett CL, Cantor SB, Crawford J, Cross SJ, Demetri G, Desch CE, Pizzo PA, Schiffer CA, Schwartzberg L, Somerfield MR, Somlo G, Wade JC, Wade JL, Winn RJ, Wozniak AJ, Wolff AC. 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]
  3. Kaushansky KN. Lineage-specific hematopoietic growth factors. N Engl J Med. 2006 May 11;354(19):2034-45. [PubMed Citation]
  4. 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]
  5. Kuter DJ. New thrombopoietic growth factors. Blood. 2007 Feb 8 [PubMed Citation]
  6. 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]
  7. Sung L, Nathan PC, Alibhai SM, Tomlinson GA, Beyene J. Meta-analysis: effect of prophylactic hematopoietic colony-stimulating factors on mortality and outcomes of infection. Ann Intern Med. 2007 Sep 18;147(6):400-11. [PubMed Citation]

US Department of Health & Human Services     
U.S. Department of Health & Human Services Office of the Assistant Secretary for Preparedness and Response National Library of Medicine