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Acute Side Effects of Radiation Therapy pp 191–206Cite as

Hematological Side Effects

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Abstract

Profound hematologic toxicity, prominently leukopenia, frequently develops following radiation therapy that includes a large volume of bone marrow in the radiation field [1–8]. The percentage of patients with radiation-induced leukopenia has been reported in up to 50% and 90% of patients treated with pelvic field irradiation alone and with concurrent chemotherapy, respectively [1, 6]. These values are lower for thrombocytopenia (1% and 30% of patients treated with pelvic field irradiation alone and with concurrent chemotherapy, respectively) and anemia (30% and 50% of patients treated with pelvic field irradiation alone and with concurrent chemotherapy, respectively) [1, 10].

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References

  1. Peters WA, Liu P, Barrett RJ, Stock RJ, Monk BJ, Berek JS et al (2000) Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 18(8):1606–1613

    Article  CAS  PubMed  Google Scholar 

  2. Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL et al (1999) Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 340(15):1154–1161

    Article  CAS  PubMed  Google Scholar 

  3. Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset J, Gonzalez DG et al (1997) Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol 15(5):2040–2049

    Article  CAS  PubMed  Google Scholar 

  4. Pearcey R, Brundage M, Drouin P, Jeffrey J, Johnston D, Lukka H et al (2002) Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol 20(4):966–972

    Article  CAS  PubMed  Google Scholar 

  5. Small W Jr, Winter K, Levenback C, Iyer R, Hymes SR, Jhingran A et al (2011) Extended-field irradiation and intracavitary brachytherapy combined with cisplatin and amifostine for cervical cancer with positive para-aortic or high common iliac lymph nodes: results of arm II of Radiation Therapy Oncology Group (RTOG) 0116. Int J Gynecol Cancer 21(7):1266–1275

    PubMed  Google Scholar 

  6. Wan J, Liu K, Li K, Li G, Zhang Z (2015) Can dosimetric parameters predict acute hematologic toxicity in rectal cancer patients treated with intensity-modulated pelvic radiotherapy? Radiat Oncol 10(1):152

    Article  Google Scholar 

  7. Jefferies S, Rajan B, Ashley S, Traish D, Brada M (1998) Haematological toxicity of cranio-spinal irradiation. Radiother Oncol 48(1):23–27

    Article  CAS  PubMed  Google Scholar 

  8. Farah R, Ultmann J, Griem M, Golomb H, Kalokhe U, Desser R et al (1988) Extended mantle radiation therapy for pathologic stage I and II Hodgkin’s disease. J Clin Oncol 6(6):1047–1052

    Article  CAS  PubMed  Google Scholar 

  9. Cox JD, Stetz J, Pajak TF (1995) Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys 31(5):1341–1346

    Article  CAS  PubMed  Google Scholar 

  10. Harrison L, Shasha D, Shiaova L, White C, Ramdeen B, Portenoy R (eds) (2001) Prevalence of anemia in cancer patients undergoing radiation therapy. Semin Oncol 28(2 Suppl 8):54–59

    Google Scholar 

  11. Fliedner T, Graessle D, Paulsen C, Reimers K (2002) Structure and function of bone marrow hemopoiesis: mechanisms of response to ionizing radiation exposure. Cancer Biother Radiopharm 17(4):405–426

    Article  CAS  PubMed  Google Scholar 

  12. Ellis R (1961) The distribution of active bone marrow in the adult. Phys Med Biol 5(3):255–258

    Article  CAS  PubMed  Google Scholar 

  13. Fliedner TM (1998) The role of blood stem cells in hematopoietic cell renewal. Stem Cells 16(6):361–374

    Article  CAS  PubMed  Google Scholar 

  14. Nothdurft W, Kreja L (1998) Hemopoietic progenitor cells in the blood as indicators of the functional status of the bone marrow after total-body and partial-body irradiation: experiences from studies in dogs. Stem Cells 16(S2):97–111

    Article  PubMed  Google Scholar 

  15. Rozgaj R, Kašuba V, Šentija K, Prlić I (1999) Radiation-induced chromosomal aberrations and haematological alterations in hospital workers. Occup Med 49(6):353–360

    Article  CAS  Google Scholar 

  16. Haas R, Bohne F, Fliedner T (1971) Cytokinetic analysis of slowly proliferating bone marrow cells during recovery from radiation injury. Cell Prolif 4(1):31–45

    Article  CAS  Google Scholar 

  17. Sykes MP, Chu FC, Wilkerson WG (1960) Local bone-marrow changes secondary to therapeutic irradiation 1. Radiology 75(6):919–924

    Article  CAS  PubMed  Google Scholar 

  18. Roeske JC, Lujan A, Reba RC, Penney BC, Yamada SD, Mundt AJ (2005) Incorporation of SPECT bone marrow imaging into intensity modulated whole-pelvic radiation therapy treatment planning for gynecologic malignancies. Radiother Oncol 77(1):11–17

    Article  PubMed  Google Scholar 

  19. Sykes MP, Chu FC, Savel H, Bonadonna G, Mathis H (1964) The effects of varying dosages of irradiation upon sternal-marrow regeneration 1. Radiology 83(6):1084–1088

    Article  CAS  PubMed  Google Scholar 

  20. Hanks GE (1964) In vivo migration of colony-forming units from shielded bone marrow in the irradiated mouse. Nature 203:1393–1395

    Article  CAS  PubMed  Google Scholar 

  21. Croizat H, Frindel E, Tubiana M (1980) The effect of partial body irradiation on haemopoietic stem cell migration. Cell Prolif 13(3):319–325

    Article  CAS  Google Scholar 

  22. Croizat H, Frindel E, Tubiana M (1970) Proliferative activity of the stem cells in the bone-marrow of mice after single and multiple irradiations (total-or partial-body exposure). Int J Radiat Biol Relat Stud Phys Chem Med 18(4):347–358

    Article  CAS  PubMed  Google Scholar 

  23. Mauch P, Constine L, Greenberger J, Knospe W, Sullivan J, Liesveld JL et al (1995) Hematopoietic stem cell compartment: acute and late effects of radiation therapy and chemotherapy. Int J Radiat Oncol Biol Phys 31(5):1319–1339

    Article  CAS  PubMed  Google Scholar 

  24. Parmentier C, Morardet N, Tubiana M (1983) Late effects on human bone marrow after extended field radiotherapy. Int J Radiat Oncol Biol Phys 9(9):1303–1311

    Article  CAS  PubMed  Google Scholar 

  25. Tubiana M, Carde P, Frindel E (1993) Ways of minimising hematopoietic damage induced by radiation and cytostatic drugs—the possible role of inhibitors. Radiother Oncol 29(1):1–17

    Article  CAS  PubMed  Google Scholar 

  26. Salzman JR, Kaplan HS (1971) Effect of prior splenectomy on hematologic tolerance during total lymphoid radiotherapy of patients with Hodgkin’s disease. Cancer 27(2):471–478

    Article  CAS  PubMed  Google Scholar 

  27. Plowman P (1983) The effects of conventionally fractionated, extended portal radiotherapy on the human peripheral blood count. Int J Radiat Oncol Biol Phys 9(6):829–839

    Article  CAS  PubMed  Google Scholar 

  28. Scarantino CW, Rubin P, Constine LS (1984) The paradoxes in patterns and mechanism of bone marrow regeneration after irradiation: 1. Different volumes and doses. Radiother Oncol 2(3):215–225

    Article  CAS  PubMed  Google Scholar 

  29. Rubin P, Landman S, Mayer E, Keller B, Ciccio S (1973) Bone marrow regeneration and extension after extended field irradiation in Hodgkin’s disease. Cancer 32(3):699–711

    Article  CAS  PubMed  Google Scholar 

  30. Zachariah B (1992) Case report: role of granulocyte colony stimulating factor in radiotherapy. Am J Med Sci 304(4):252–253

    Article  CAS  PubMed  Google Scholar 

  31. Mac Manus M, Lamborn K, Khan W, Varghese A, Graef L, Knox S (1997) Radiotherapy-associated neutropenia and thrombocytopenia: analysis of risk factors and development of a predictive model. Blood 89(7):2303–2310

    CAS  PubMed  Google Scholar 

  32. Lujan AE, Mundt AJ, Yamada SD, Rotmensch J, Roeske JC (2003) Intensity-modulated radiotherapy as a means of reducing dose to bone marrow in gynecologic patients receiving whole pelvic radiotherapy. Int J Radiat Oncol Biol Phys 57(2):516–521

    Article  PubMed  Google Scholar 

  33. Hui B, Zhang Y, Shi F, Wang J, Wang T, Wang J et al (2014) Association between bone marrow dosimetric parameters and acute hematologic toxicity in cervical cancer patients undergoing concurrent chemoradiotherapy: comparison of three-dimensional conformal radiotherapy and intensity-modulated radiation therapy. Int J Gynecol Cancer 24(9):1648–1652

    Article  PubMed  PubMed Central  Google Scholar 

  34. Albuquerque K, Giangreco D, Morrison C, Siddiqui M, Sinacore J, Potkul R et al (2011) Radiation-related predictors of hematologic toxicity after concurrent chemoradiation for cervical cancer and implications for bone marrow–sparing pelvic IMRT. Int J Radiat Oncol Biol Phys 79(4):1043–1047

    Article  PubMed  Google Scholar 

  35. Brixey CJ, Roeske JC, Lujan AE, Yamada SD, Rotmensch J, Mundt AJ (2002) Impact of intensity-modulated radiotherapy on acute hematologic toxicity in women with gynecologic malignancies. Int J Radiat Oncol Biol Phys 54(5):1388–1396

    Article  PubMed  Google Scholar 

  36. Liang Y, Bydder M, Yashar CM, Rose BS, Cornell M, Hoh CK et al (2013) Prospective study of functional bone marrow-sparing intensity modulated radiation therapy with concurrent chemotherapy for pelvic malignancies. Int J Radiat Oncol Biol Phys 85(2):406–414

    Article  PubMed  Google Scholar 

  37. Berg BCV, Malghem J, Lecouvet FE, Maldague B (1998) Magnetic resonance imaging of the normal bone marrow. Skeletal Radiol 27(9):471–483

    Article  Google Scholar 

  38. Basu S, Houseni M, Bural G, Chamroonat W, Udupa J, Mishra S et al (2007) Magnetic resonance imaging based bone marrow segmentation for quantitative calculation of pure red marrow metabolism using 2-Deoxy-2-[F-18] fluoro-D-glucose-positron emission tomography: a novel application with significant implications for combined structure–function approach. Mol Imaging Biol 9(6):361–365

    Article  PubMed  Google Scholar 

  39. Uckun FM, Souza L, Waddick KG, Wick M, Song CW (1990) In vivo radioprotective effects of recombinant human granulocyte colony-stimulating factor in lethally irradiated mice. Blood 75(3):638–645

    CAS  PubMed  Google Scholar 

  40. Waddick K, Song C, Souza L, Uckun F (1991) Comparative analysis of the in vivo radioprotective effects of recombinant granulocyte colony-stimulating factor (G-CSF), recombinant granulocyte-macrophage CSF, and their combination. Blood 77(11):2364–2371

    CAS  PubMed  Google Scholar 

  41. Zucali J, Moreb J, Gibbons W, Alderman J, Suresh A, Zhang Y et al (1994) Radioprotection of hematopoietic stem cells by interleukin-1. Exp Hematol 22(2):130–135

    CAS  PubMed  Google Scholar 

  42. Neta R, Douches S, Oppenheim J (1986) Interleukin 1 is a radioprotector. J Immunol 136(7):2483–2485

    CAS  PubMed  Google Scholar 

  43. Slørdal L, Muench MO, Warren DJ, Moore MA (1989) Radioprotection by murine and human tumor-necrosis factor: dose-dependent effects on hematopoiesis in the mouse. Eur J Haematol 43(5):428–434

    Article  PubMed  Google Scholar 

  44. Du N, Feng K, Luo C, Li L, Bai C, Pei X (2003) Radioprotective effect of FLT3 ligand expression regulated by Egr-1 regulated element on radiation injury of SCID mice. Exp Hematol 31(3):191–196

    Article  CAS  PubMed  Google Scholar 

  45. Hudak S, Leach M, Xu Y, Menon S, Rennick D (1998) Radioprotective effects of flk2/flt3 ligand. Exp Hematol 26(6):515–522

    CAS  PubMed  Google Scholar 

  46. Streeter PR, Dudley LZ, Fleming WH (2003) Activation of the G-CSF and Flt-3 receptors protects hematopoietic stem cells from lethal irradiation. Exp Hematol 31(11):1119–1125

    Article  CAS  PubMed  Google Scholar 

  47. Hofer M, Pospíšil M, Holá J, Vacek A, Štreitová D, Znojil V (2008) Inhibition of cyclooxygenase 2 in mice increases production of G-CSF and induces radioprotection. Radiat Res 170(5):566–571

    Article  CAS  PubMed  Google Scholar 

  48. Fukunaga R, Ishizaka-Ikeda E, Pan C, Seto Y, Nagata S (1991) Functional domains of the granulocyte colony-stimulating factor receptor. EMBO J 10(10):2855–2865

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Souza LM, Boone TC, Gabrilove J, Lai PH, Zsebo KM, Murdock DC et al (1986) Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science 232(4746):61–65

    Article  CAS  PubMed  Google Scholar 

  50. Nagata S, Tsuchiya M, Asano S, Kaziro Y, Yamazaki T, Yamamoto O et al (1986) Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature 319(6092):415–418

    Article  CAS  PubMed  Google Scholar 

  51. Babaeipour V, Khanchezar S, Mofid MR, Abbas MPH (2015) Efficient process development of recombinant human granulocyte colony-stimulating factor (rh-GCSF) production in Escherichia coli. Iran Biomed J 19(2):102–110

    PubMed  PubMed Central  Google Scholar 

  52. Sharifi TM, Habashi A, Rajabi MH (2013) Human granulocyte colony-stimulating factor (hG-CSF) expression in plastids of Lactuca sativa. Iran Biomed J 17(3):158–164

    Google Scholar 

  53. Schmidberger H, Hess CF, Hoffmann W, Reuss-Borst MA, Bamberg M (1993) Granulocyte colony-stimulating factor treatment of leucopenia during fractionated radiotherapy. Eur J Cancer 29(14):1927–1931

    Article  Google Scholar 

  54. Gava A, Bertossi L, Ferrarese F, Coghetto F, Marazzato G, Andrulli A et al (1998) Use of filgrastim, granulocyte colony stimulating factor (G-CSF), in radiotherapy to reduce drop-outs because of radiogenic leukopenia. Radiol Med 95(3):232–236

    CAS  PubMed  Google Scholar 

  55. Zhang H (1993) Stimulation of low dose radiation on hematopoietic system. Zhonghua Yi Xue Za Zhi 73(2):99–100, 27–28

    CAS  PubMed  Google Scholar 

  56. Fushiki M, Ono K, Sasai K, Shibamoto Y, Tsutsui K, Nishidai T et al (1990) Effect of recombinant human granulocyte colony-stimulating factor on granulocytopenia in mice induced by irradiation. Int J Radiat Oncol Biol Phys 18(2):353–357

    Article  CAS  PubMed  Google Scholar 

  57. Schuening FG, Storb R, Goehle S, Graham TC, Appelbaum FR, Hackman R et al (1989) Effect of recombinant human granulocyte colony-stimulating factor on hematopoiesis of normal dogs and on hematopoietic recovery after otherwise lethal total body irradiation. Blood 74(4):1308–1313

    CAS  PubMed  Google Scholar 

  58. Marks LB, Friedman HS, Kurtzberg J, Oakes WJ, Hockenberger BM (1992) Reversal of radiation-induced neutropenia by granulocyte colony-stimulating factor. Med Pediatr Oncol 20(3):240–242

    Article  CAS  PubMed  Google Scholar 

  59. MacVittie T, Monroy R, Patchen M, Souza L (1990) Therapeutic use of recombinant human G-CSF (rhG-CSF) in a canine model of sublethal and lethal whole-body irradiation. Int J Radiat Biol 57(4):723–736

    Article  CAS  PubMed  Google Scholar 

  60. Knox SJ, Fowler S, Marquez C, Hoppe RT (1994) Effect of filgrastim (G-CSF) in Hodgkin’s disease patients treated with radiation therapy. Int J Radiat Oncol Biol Phys 28(2):445–450

    Article  CAS  PubMed  Google Scholar 

  61. Fyles AW, Manchul L, Levin W, Robertson JM, Sturgeon J, Tsuji D (1998) Effect of filgrastim (G-CSF) during chemotherapy and abdomino-pelvic radiation therapy in patients with ovarian carcinoma. Int J Radiat Oncol Biol Phys 41(4):843–847

    Article  CAS  PubMed  Google Scholar 

  62. Kolotas C, Zamboglou N, Schnabel T, Bojar H, Wintzer A, Vogt H-G et al (1996) Effect of recombinant human granulocyte colony stimulating factor (R-metHuG-CSF) as an adjunct to large-field radiotherapy: a phase I study. Int J Radiat Oncol Biol Phys 35(1):137–142

    Article  CAS  PubMed  Google Scholar 

  63. Root RK, Dale DC (1999) Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor: comparisons and potential for use in the treatment of infections in nonneutropenic patients. J Infect Dis 179(Suppl 2):S342–S352

    Article  CAS  PubMed  Google Scholar 

  64. Price T, Chatta G, Dale D (1996) Effect of recombinant granulocyte colony-stimulating factor on neutrophil kinetics in normal young and elderly humans. Blood 88(1):335–340

    CAS  PubMed  Google Scholar 

  65. Lord B, Bronchud M, Owens S, Chang J, Howell A, Souza L et al (1989) The kinetics of human granulopoiesis following treatment with granulocyte colony-stimulating factor in vivo. Proc Natl Acad Sci 86(23):9499–9503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Bunn PA, Crowley J, Kelly K, Hazuka MB, Beasley K, Upchurch C et al (1995) Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol 13(7):1632–1641

    Article  PubMed  Google Scholar 

  67. American Society of Clinical Oncology (1994) American Society of Clinical Oncology. Recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. J Clin Oncol 12(11):2471–2508

    Article  Google Scholar 

  68. Sheikh H, Colaco R, Lorigan P, Blackhall F, Califano R, Ashcroft L et al (2011) Use of G-CSF during concurrent chemotherapy and thoracic radiotherapy in patients with limited-stage small-cell lung cancer safety data from a phase II trial. Lung Cancer 74(1):75–79

    PubMed  Google Scholar 

  69. Pospíšil M, Hofer M, Netíková J, Holá J, Znojil V, Vácha J et al (1999) Pretreatment with granulocyte colony-stimulating factor reduces myelopoiesis in irradiated mice. Radiat Res 151(3):363–367

    Article  PubMed  Google Scholar 

  70. Pape H, Orth K, Heese A, Heyll A, Kobbe G, Schmitt G et al (2006) G-CSF during large field radiotherapy reduces bone marrow recovery capacity. Eur J Med Res 11(8):322–328

    CAS  PubMed  Google Scholar 

  71. Crawford J, Caserta C, Roila F, ESMO Guidelines Working Group (2009) Hematopoietic growth factors: ESMO recommendations for the applications. Ann Oncol 20(Suppl 4):iv162–iv165

    Google Scholar 

  72. Son Y, Bae MJ, Lee CG, Jo WS, Kim SD, Yang K et al (2014) Treatment with granulocyte colony-stimulating factor aggravates thrombocytopenia in irradiated mice. Mol Cell Toxicol 10(3):311–317

    Article  CAS  Google Scholar 

  73. Vanz AL, Renard G, Palma MS, Chies JM, Dalmora SL, Basso LA et al (2008) Human granulocyte colony stimulating factor (hG-CSF): cloning, overexpression, purification and characterization. Microb Cell Fact 7(1):13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Molineux G (2003) Pegfilgrastim: using pegylation technology to improve neutropenia support in cancer patients. Anticancer Drugs 14(4):259–264

    Article  CAS  PubMed  Google Scholar 

  75. FP W, Wang J, Wang H, Li N, Guo Y, Cheng YJ et al (2015) Clinical observation of the therapeutic effects of pegylated recombinant human granulocyte colony-stimulating factor in patients with concurrent chemoradiotherapy-induced grade IV neutropenia. Exp Ther Med 9(3):761–765

    Google Scholar 

  76. Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L et al (2006) 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 24(19):3187–3205

    Article  CAS  PubMed  Google Scholar 

  77. Cohen AM, Zsebo KM, Inoue H, Hines D, Boone TC, Chazin VR et al (1987) In vivo stimulation of granulopoiesis by recombinant human granulocyte colony-stimulating factor. Proc Natl Acad Sci 84(8):2484–2488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Adamietz I, Rosskopf B, Dapper F, Von Lieven H, Boettcher H (1996) Comparison of two strategies for the treatment of radiogenic leukopenia using granulocyte colony stimulating factor. Int J Radiat Oncol Biol Phys 35(1):61–67

    Article  CAS  PubMed  Google Scholar 

  79. Demetri GD, Griffin JD (1991) Granulocyte colony-stimulating factor and its receptor. Blood 78(11):2791–2808

    CAS  PubMed  Google Scholar 

  80. Spiel AO, Bartko J, Schwameis M, Firbas C, Siller-Matula J, Schuetz M et al (2011) Increased platelet aggregation and in vivo platelet activation after granulocyte colony-stimulating factor administration. A randomised controlled trial. Thromb Haemost 105(4):655–662

    Article  CAS  PubMed  Google Scholar 

  81. Akizuki S, Mizorogi F, Inoue T, Sudo K, Ohnishi A (2000) Pharmacokinetics and adverse events following 5-day repeated administration of lenograstim, a recombinant human granulocyte colony-stimulating factor, in healthy subjects. Bone Marrow Transplant 26(9):939–946

    Article  CAS  PubMed  Google Scholar 

  82. Takamatsu Y, Jimi S, Sato T, Hara S, Suzumiya J, Tamura K (2007) Thrombocytopenia in association with splenomegaly during granulocyte–colony-stimulating factor treatment in mice is not caused by hypersplenism and is resolved spontaneously. Transfusion 47(1):41–49

    Article  CAS  PubMed  Google Scholar 

  83. Di Carlo E, Forni G, Lollini P, Colombo MP, Modesti A, Musiani P (2001) The intriguing role of polymorphonuclear neutrophils in antitumor reactions. Blood 97(2):339–345

    Article  PubMed  Google Scholar 

  84. Kim JS, Son Y, Bae MJ, Lee M, Lee CG, Jo WS et al (2015) Administration of granulocyte colony-stimulating factor with radiotherapy promotes tumor growth by stimulating vascularization in tumor-bearing mice. Oncol Rep 34(1):147–154

    CAS  PubMed  Google Scholar 

  85. Natori T, Sata M, Washida M, Hirata Y, Nagai R, Makuuchi M (2002) G-CSF stimulates angiogenesis and promotes tumor growth: potential contribution of bone marrow-derived endothelial progenitor cells. Biochem Biophys Res Commun 297(4):1058–1061

    Article  CAS  PubMed  Google Scholar 

  86. Garcia-Barros M, Paris F, Cordon-Cardo C, Lyden D, Rafii S, Haimovitz-Friedman A et al (2003) Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science 300(5622):1155–1159

    Article  CAS  PubMed  Google Scholar 

  87. Vokes EE, Haraf DJ, Mick R, McEvilly J-M, Weichselbaum RR (1994) Intensified concomitant chemoradiotherapy with and without filgrastim for poor-prognosis head and neck cancer. J Clin Oncol 12(11):2351–2359

    Article  CAS  PubMed  Google Scholar 

  88. Staar S, Rudat V, Stuetzer H, Dietz A, Volling P, Schroeder M et al (2001) Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy—results of a multicentric randomized German trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 50(5):1161–1171

    Article  CAS  PubMed  Google Scholar 

  89. Ohigashi T, Tachibana M, Tazaki H, Nakamura K (1992) Bladder cancer cells express functional receptors for granulocyte-colony stimulating factor. J Urol 147(1):283–286

    CAS  PubMed  Google Scholar 

  90. Berdel WE, Danhauser-Riedl S, Steinhauser G, Winton EF (1989) Various human hematopoietic growth factors (interleukin-3, GM-CSF, G-CSF) stimulate clonal growth of nonhematopoietic tumor cells [see comments]. Blood 73(1):80–83

    CAS  PubMed  Google Scholar 

  91. Mac Manus M, McCormick D, Trimble A, Abram W (1995) Value of granulocyte colony stimulating factor in radiotherapy induced neutropenia: clinical and laboratory studies. Eur J Cancer 31(3):302–307

    Article  Google Scholar 

  92. Farese AM, Williams DE, Seiler FR, Macvittie TJ (1993) Combination protocols of cytokine therapy with interleukin-3 and granulocyte-macrophage colony-stimulating factor in a primate model of radiation-induced marrow aplasia. Blood 82(10):3012–3018

    CAS  PubMed  Google Scholar 

  93. Williams D, Dunn J, Park L, Frieden E, Seiler F, Farese A et al (1992) A GM-CSF/IL-3 fusion protein promotes neutrophil and platelet recovery in sublethally irradiated rhesus monkeys. Biotechnol Ther 4(1–2):17–29

    Google Scholar 

  94. Vadhan-Raj S (1994) PIXY321 (GM-CSF/IL-3 fusion protein): biology and early clinical development. Stem Cells 12(3):253–261

    Article  CAS  PubMed  Google Scholar 

  95. Van der Meeren A, Mouthon M-A, Vandamme M, Squiban C, Aigueperse J (2004) Combinations of cytokines promote survival of mice and limit acute radiation damage in concert with amelioration of vascular damage. Radiat Res 161(5):549–559

    Article  PubMed  Google Scholar 

  96. MacVittie TJ, Farese AM, Herodin F, Grab LB, Baum CM, McKearn JP (1996) Combination therapy for radiation-induced bone marrow aplasia in nonhuman primates using synthokine SC-55494 and recombinant human granulocyte colony-stimulating factor. Blood 87(10):4129–4135

    CAS  PubMed  Google Scholar 

  97. Farese AM, Hunt P, Grab LB, MacVittie TJ (1996) Combined administration of recombinant human megakaryocyte growth and development factor and granulocyte colony-stimulating factor enhances multilineage hematopoietic reconstitution in nonhuman primates after radiation-induced marrow aplasia. J Clin Investig 97(9):2145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Hérodin F, Bourin P, Mayol J-F, Lataillade J-J, Drouet M (2003) Short-term injection of antiapoptotic cytokine combinations soon after lethal γ-irradiation promotes survival. Blood 101(7):2609–2616

    Article  PubMed  CAS  Google Scholar 

  99. Schiffer CA, Anderson KC, Bennett CL, Bernstein S, Elting LS, Goldsmith M et al (2001) Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 19(5):1519–1538

    Article  CAS  PubMed  Google Scholar 

  100. Vadhan-Raj S, Murray LJ, Bueso-Ramos C, Patel S, Reddy SP, Hoots WK et al (1997) Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer. Ann Intern Med 126(9):673–681

    Article  CAS  PubMed  Google Scholar 

  101. Kuter DJ (2009) Thrombopoietin and thrombopoietin mimetics in the treatment of thrombocytopenia. Annu Rev Med 60:193–206

    Article  CAS  PubMed  Google Scholar 

  102. Kuter DJ (2008) New drugs for familiar therapeutic targets: thrombopoietin receptor agonists and immune thrombocytopenic purpura. Eur J Haematol 80(Suppl 69):9–18

    Article  CAS  Google Scholar 

  103. Parameswaran R, Lunning M, Mantha S, Devlin S, Hamilton A, Schwartz G et al (2014) Romiplostim for management of chemotherapy-induced thrombocytopenia. Support Care Cancer 22(5):1217–1222

    Article  CAS  PubMed  Google Scholar 

  104. Lambert MP, Xiao L, Nguyen Y, Kowalska MA, Poncz M (2011) The role of platelet factor 4 in radiation-induced thrombocytopenia. Int J Radiat Oncol Biol Phys 80(5):1533–1540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Teramura M, Kobayashi S, Yoshinaga K, Iwabe K, Mizoguchi H (1996) Effect of interleukin 11 on normal and pathological thrombopoiesis. Cancer Chemother Pharmacol 38(1):S99–S102

    Article  CAS  PubMed  Google Scholar 

  106. Gordon M, McCaskill-Stevens W, Battiato L, Loewy J, Loesch D, Breeden E et al (1996) A phase I trial of recombinant human interleukin-11 (neumega rhIL-11 growth factor) in women with breast cancer receiving chemotherapy. Blood 87(9):3615–3624

    CAS  PubMed  Google Scholar 

  107. Isaacs C, Robert NJ, Bailey FA, Schuster MW, Overmoyer B, Graham M et al (1997) Randomized placebo-controlled study of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin. J Clin Oncol 15(11):3368–3377

    Article  CAS  PubMed  Google Scholar 

  108. Tepler I, Elias L, Hussein M, Rosen G, Chang A, Moore J et al (1996) A randomized placebo-controlled trial of recombinant human interleukin-11 in cancer patients with severe thrombocytopenia due to chemotherapy. Blood 87(9):3607–3614

    CAS  PubMed  Google Scholar 

  109. Harrison LB, Shasha D, White C, Ramdeen B (2000) Radiotherapy-associated anemia: the scope of the problem. Oncologist 5(Suppl 2):1–7

    Article  Google Scholar 

  110. Dunst J (2004) Low hemoglobin levels: influence on tumor biology and radiotherapy treatment outcome. Eur J Cancer 2(Suppl 2):3–10

    Article  CAS  Google Scholar 

  111. Grogan M, Thomas GM, Melamed I, Wong FL, Pearcey RG, Joseph PK et al (1999) The importance of hemoglobin levels during radiotherapy for carcinoma of the cervix. Cancer 86(8):1528–1536

    Article  CAS  PubMed  Google Scholar 

  112. Hofheinz R-D, Raab B, Mai S, Wenz F, Willeke F, Emig M et al (2004) Impact of chemoradiotherapy-induced anemia on survival in uniformly staged patients with locally advanced squamous cell carcinoma of the esophagus. Oncol Res Treat 27(5):462–466

    Article  Google Scholar 

  113. Lambin P, Ramaekers BL, van Mastrigt GA, Van den Ende P, de Jong J, De Ruysscher DK et al (2009) Erythropoietin as an adjuvant treatment with (chemo) radiation therapy for head and neck cancer. Cochrane Libr. doi:10.1002/14651858.CD006158.pub2

    Google Scholar 

  114. Shenouda G, Zhang Q, Ang KK, Machtay M, Parliament MB, Hershock D et al (2015) Long-term results of radiation therapy oncology group 9903: a randomized phase 3 trial to assess the effect of erythropoietin on local-regional control in anemic patients treated with radiation therapy for squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 91(5):907–915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Machtay M, Pajak TF, Suntharalingam M, Shenouda G, Hershock D, Stripp DC et al (2007) Radiotherapy with or without erythropoietin for anemic patients with head and neck cancer: a randomized trial of the Radiation Therapy Oncology Group (RTOG 99-03). Int J Radiat Oncol Biol Phys 69(4):1008–1017

    Article  CAS  PubMed  Google Scholar 

  116. Henke M, Laszig R, Rübe C, Schäfer U, Haase K-D, Schilcher B et al (2003) Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet 362(9392):1255–1260

    Article  CAS  PubMed  Google Scholar 

  117. Overgaard J (2013) SP-033: randomized study of darbepoetin alfa as modifier of radiotherapy in patients SCCHN. Final outcome of the dahanca 10 trial. Radiother Oncol 106:S13

    Article  Google Scholar 

  118. Harrison LB, Chadha M, Hill RJ, Hu K, Shasha D (2002) Impact of tumor hypoxia and anemia on radiation therapy outcomes. Oncologist 7(6):492–508

    Article  PubMed  Google Scholar 

  119. Glaser CM, Millesi W, Kornek GV, Lang S, Schüll B, Watzinger F et al (2001) Impact of hemoglobin level and use of recombinant erythropoietin on efficacy of preoperative chemoradiation therapy for squamous cell carcinoma of the oral cavity and oropharynx. Int J Radiat Oncol Biol Phys 50(3):705–715

    Article  CAS  PubMed  Google Scholar 

  120. Vijayakumar S, Roach M, Wara W, Chan SK, Ewing C, Rubin S et al (1993) Effect of subcutaneous recombinant human erythropoietin in cancer patients receiving radiotherapy: preliminary results of a randomized, open-labeled, phase II trial. Int J Radiat Oncol Biol Phys 26(4):721–729

    Article  CAS  PubMed  Google Scholar 

  121. Lavey RS, Dempsey WH (1993) Erythropoietin increases hemoglobin in cancer patients during radiation therapy. Int J Radiat Oncol Biol Phys 27(5):1147–1152

    Article  CAS  PubMed  Google Scholar 

  122. Dusenbery KE, McGuire WA, Holt PJ, Carson LF, Fowler JM, Twiggs LB et al (1994) Erythropoietin increases hemoglobin during radiation therapy for cervical cancer. Int J Radiat Oncol Biol Phys 29(5):1079–1084

    Article  CAS  PubMed  Google Scholar 

  123. Pastorino U, Valente M, Cataldo I, Lequaglie C, Ravasi G (1986) Perioperative blood transfusion and prognosis of resected stage Ia lung cancer. Eur J Cancer Clin Oncol 22(11):1375–1378

    Article  CAS  PubMed  Google Scholar 

  124. Moffat L, Sunderland G, Lamont D (1987) Blood transfusion and survival following nephrectomy for carcinoma of kidney. Br J Urol 60(4):316–319

    Article  CAS  PubMed  Google Scholar 

  125. Rosenberg SA, Seipp CA, White DE, Wesley R (1985) Perioperative blood transfusions are associated with increased rates of recurrence and decreased survival in patients with high-grade soft-tissue sarcomas of the extremities. J Clin Oncol 3(5):698–709

    Article  CAS  PubMed  Google Scholar 

  126. Kaneda M, Horimi T, Ninomiya M, Nagae S, Mukai K, Takeda I et al (1987) Adverse affect of blood transfusions on survival of patients with gastric cancer. Transfusion 27(5):375–377

    Article  CAS  PubMed  Google Scholar 

  127. Creasy T, Veitch P, Bell P (1987) A relationship between perioperative blood transfusion and recurrence of carcinoma of the sigmoid colon following potentially curative surgery. Ann R Coll Surg Engl 69(3):100–103

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Arnoux R, Corman J, Peloquin A, Smeesters C, St-Louis G (1988) Adverse effect of blood transfusions on patient survival after resection of rectal cancer. Can J Surg 31(2):121–126

    CAS  PubMed  Google Scholar 

  129. Jones KR, Weissler MC (1990) Blood transfusion and other risk factors for recurrence of cancer of the head and neck. Arch Otolaryngol Head Neck Surg 116(3):304–309

    Article  CAS  PubMed  Google Scholar 

  130. Bush RS (1986) The significance of anemia in clinical radiation therapy. Int J Radiat Oncol Biol Phys 12(11):2047–2050

    Article  CAS  PubMed  Google Scholar 

  131. Arcasoy MO, Jiang X, Haroon ZA (2003) Expression of erythropoietin receptor splice variants in human cancer. Biochem Biophys Res Commun 307(4):999–1007

    Article  CAS  PubMed  Google Scholar 

  132. Westenfelder C, Baranowski RL (2000) Erythropoietin stimulates proliferation of human renal carcinoma cells. Kidney Int 58(2):647–657

    Article  CAS  PubMed  Google Scholar 

  133. Belenkov AI, Shenouda G, Rizhevskaya E, Cournoyer D, Belzile J-P, Souhami L et al (2004) Erythropoietin induces cancer cell resistance to ionizing radiation and to cisplatin. Mol Cancer Ther 3(12):1525–1532

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Oncology, Imam Hossein Educational Hospital, Shahid Beheshti University of Medical Sciences (SBMU), Shahid Madani Street, Tehran, Iran

    Ainaz Sourati & Ahmad Ameri

  2. Department of Radiotherapy and Oncology, Shohadaye Tajrish Educational Hospital Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran

    Mona Malekzadeh

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  1. Ainaz Sourati
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Sourati, A., Ameri, A., Malekzadeh, M. (2017). Hematological Side Effects. In: Acute Side Effects of Radiation Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-55950-6_19

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