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Haemopoietic Growth Factors in Paediatric Oncology

A Review of the Literature

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Abstract

Recombinant haemopoietic growth factors (HGFs) are an attractive adjunct to reduce morbidity from chemotherapy regimens and their use has become widespread in paediatric oncology. Although patients receiving HGFs often have faster haematological recovery after intensive chemotherapy, this does not always translate into meaningful clinical benefits. This article reviews the clinical effectiveness of HGFs in a variety of different contexts.

Most published studies have used granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) as prophylaxis to ameliorate the subsequent neutropenia following intensive chemotherapy. These 2 agents have also been used to mobilise peripheral blood stem cells for autologous transplantation. HGFs specific for anaemia and thrombocytopenia are currently in paediatric clinical trials and it is hoped that the proper context and administration strategy can be found to make their use clinically effective.

This article also reviews data on toxicity, specifically focusing on differences between various formulations of growth factors. HGFs are expensive, and cost-benefit analyses reviewed in this article give an important perspective on the financial aspects of paediatric cancer care. Because HGFs do not benefit every child receiving chemotherapy and overuse increases costs and may result in unnecessary adverse effects, evidence-based guidelines for their rational use in paediatric oncology are proposed.

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References

  1. Marsoni S, Ungerleider RS, Hurson SB, et al. Tolerance to antineoplastic agents in children and adults. Cancer Treat Rep 1985; 69(11): 1263–69

    PubMed  CAS  Google Scholar 

  2. Pinkel D, Hernandez K, Borella L, et al. Drug dosage and remission duration in childhood lymphocytic leukemia. Cancer 1971; 27(2): 247–56

    PubMed  CAS  Google Scholar 

  3. Gaynon PS, Steinherz PG, Bleyer WA, et al. Association of delivered drug dose and outcome for children with acute lymphoblastic leukemia and unfavorable presenting features. Med Pediatr Oncol 1991; 19(4): 221–7

    PubMed  CAS  Google Scholar 

  4. Bacci G, Picci P, Avella M, et al. The importance of dose-intensity in neoadjuvant chemotherapy of osteosarcoma: a retrospective analysis of high-dose methotrexate, cisplatinum and adriamycin used preoperatively. J Chemother 1990; 2(2): 127–35

    PubMed  CAS  Google Scholar 

  5. Cheung NV, Heller G. Chemotherapy dose intensity correlates strongly with response, median survival and median progression-free survival in metastatic neuroblastoma. J Clin Oncol 1991; 9(6): 1050–8

    PubMed  CAS  Google Scholar 

  6. Smith MA, Ungerleider RS, Horowitz ME, et al. Influence of doxorubicin dose intensity on response and outcome for patients with osteogenic sarcoma and Ewing’s sarcoma. J Natl Cancer Inst 1991; 83(20): 1460–70

    PubMed  CAS  Google Scholar 

  7. Bodey GP, Buckley M, Sathe YS, et al. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med 1966; 64(2): 328–40

    PubMed  CAS  Google Scholar 

  8. Pizzo PA, Rubin M, Freifeld A, et al. The child with cancer and infection (I). Empiric therapy for fever and neutropenia and preventive strategies. J Pediatr 1991; 119(5): 679–94

    PubMed  CAS  Google Scholar 

  9. Hann I, Viscoli C, Paesmans M, et al. A comparison of outcome from febrile neutropenic episodes in children compared with adults: results from four EORTC studies. International Antimicrobial Therapy Cooperative Group (IATCG) of the European Organization for Research and Treatment of Cancer (EORTC). Br J Haematol 1997; 99(3): 580–8

    PubMed  CAS  Google Scholar 

  10. Pui CH, Boyett JM, Hughes WT, et al. Human granulocyte colony-stimulating factor after induction chemotherapy in children with acute lymphoblastic leukemia. N Engl J Med 1997; 336(25): 1781–7

    PubMed  CAS  Google Scholar 

  11. Lucas KG, Brown AE, Armstrong D, et al. The identification of febrile, neutropenic children with neoplastic disease at low risk for bacteremia and complications of sepsis. Cancer 1996; 77(4): 791–8

    PubMed  CAS  Google Scholar 

  12. Lord BI, Bronchud MH, Owens S, et al. The kinetics of human granulopoiesis following treatment with granulocyte colony-stimulating factor in vivo. Proc Natl Acad Sci USA 1989; 86(23): 9499–503

    PubMed  CAS  Google Scholar 

  13. Lord BI, Gurney H, Chang J, et al. Haemopoietic cell kinetics in humans treated with rGM-CSF. Int J Cancer 1992; 50(1): 26–31

    PubMed  CAS  Google Scholar 

  14. Spiekermann K, Roesler J, Emmendoerffer A, et al. Functional features of neutrophils induced by G-CSF and GM-CSF treatment: differential effects and clinical implications. Leukemia 1997; 11(4): 466–78

    PubMed  CAS  Google Scholar 

  15. Schaison G, Eden OB, Henze G, et al. Recommendations on the use of colony-stimulating factors in children: conclusions of a European panel. Eur J Pediatr 1998; 157(12): 955–66

    PubMed  CAS  Google Scholar 

  16. American Society of Clinical Oncology. Recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. J Clin Oncol 1994; 12(11): 2471–508

    Google Scholar 

  17. American Society of Clinical Oncology. Update of recommendations for the use of hematopoietic colony-stimulating factors: evidence-based clinical practice guidelines. J Clin Oncol 1996; 14(6): 1957–60

    Google Scholar 

  18. Boogaerts M, Cavalli F, Cortes-Funes H, et al. Granulocyte growth factors: achieving a consensus. Ann Oncol 1995; 6(3): 237–44

    PubMed  CAS  Google Scholar 

  19. Beveridge RA, Miller JA, Kales AN, et al. Randomized trial comparing the tolerability of sargramostim yeast-derived RhuGM-CSF and filgrastim bacteria-derived RhuG-CSF in cancer patients receiving myelosuppressive chemotherapy. Support Care Cancer 1997; 5(4): 289–98

    PubMed  CAS  Google Scholar 

  20. Lydaki E, Bolonaki E, Stiakaki E, et al. Efficacy of recombinant human granulocyte colony-stimulating factor and recombinant human granulocyte-macrophage colony-stimulating factor in neutropenic children with malignancies. Pediatr Hematol Oncol 1995; 12(6): 551–8

    PubMed  CAS  Google Scholar 

  21. Mayordomo JI, Rivera F, Diaz-Puente MT, et al. Improving treatment of chemotherapy-induced neutropenic fever by administration of colony-stimulating factors. J Natl Cancer Inst 1995; 87(11): 803–8

    PubMed  CAS  Google Scholar 

  22. Crawford J, Ozer H, Stoller R, et al. Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med 1991; 325(3): 164–70

    PubMed  CAS  Google Scholar 

  23. Trillet-Lenoir V, Green J, Manegold C, et al. Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur J Cancer 1993; 29A(3): 319–24

    PubMed  CAS  Google Scholar 

  24. Chevallier B, Chollet P, Merrouche Y, et al. Lenograstim prevents morbidity from intensive induction chemotherapy in the treatment of inflammatory breast cancer. J Clin Oncol 1995; 13(7): 1564–71

    PubMed  CAS  Google Scholar 

  25. Michon JM, Hartmann O, Bouffet E, et al. An open-label, multicentre, randomised phase 2 study of recombinant human granulocyte colony-stimulating factor filgrastim as an adjunct to combination chemotherapy in paediatric patients with metastatic neuroblastoma. Eur J Cancer 1998; 34(7): 1063–9

    PubMed  CAS  Google Scholar 

  26. Furman WL, Fairclough DL, Huhn RD, et al. Therapeutic effects and pharmacokinetics of recombinant human granulocyte-macrophage colony-stimulating factor in childhood cancer patients receiving myelosuppressive chemotherapy. J Clin Oncol 1991; 9(6): 1022–8

    PubMed  CAS  Google Scholar 

  27. Burdach SE, Muschenich M, Josephs W, et al. Granulocytemacrophage-colony stimulating factor for prevention of neutropenia and infections in children and adolescents with solid tumors. Results of a prospective randomized study. Cancer 1995; 76(3): 510–6

    PubMed  CAS  Google Scholar 

  28. Wexler LH, Weaver-McClure L, Steinberg SM, et al. Randomized trial of recombinant human granulocyte-macrophage colony-stimulating factor in pediatric patients receiving intensive myelosuppressive chemotherapy. J Clin Oncol 1996; 14(3): 901–10

    PubMed  CAS  Google Scholar 

  29. Marina NM, Shema SJ, Bowman LC, et al. Failure of granulocyte-macrophage colony-stimulating factor to reduce febrile neutropenia in children with recurrent solid tumors treated with ifosfamide, carboplatin and etoposide chemotherapy. Med Pediatr Oncol 1994; 23(4): 328–34

    PubMed  CAS  Google Scholar 

  30. Womer RB, Daller RT, Fenton JG, et al. Granulocyte colony stimulating factor permits dose intensification by interval compression in the treatment of Ewing’s sarcomas and soft tissue sarcomas in children. Eur J Cancer 2000; 36(1): 87–94

    PubMed  CAS  Google Scholar 

  31. Seibel NL, Blaney SM, O’Brien M, et al. Phase I trial of docetaxel with filgrastim support in pediatric patients with refractory solid tumors: a collaborative Pediatric Oncology Branch, National Cancer Institute and Children’s Cancer Group trial. Clin Cancer Res 1999; 5(4): 733–7

    PubMed  CAS  Google Scholar 

  32. Nitschke R, Parkhurst J, Sullivan J, et al. Topotecan in pediatric patients with recurrent and progressive solid tumors: a Pediatric Oncology Group phase II study. J Pediatr Hematol Oncol 1998; 20(4): 315–8

    PubMed  CAS  Google Scholar 

  33. Dorr RT. Clinical properties of yeast-derived versus Escherichia coli-derived granulocyte-macrophage colony-stimulating factor. Clin Ther 1993; 15(1): 19–29

    PubMed  CAS  Google Scholar 

  34. Lieschke GJ, Cebon J, Morstyn G. Characterization of the clinical effects after the first dose of bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor. Blood 1989; 74(8): 2634–43

    PubMed  CAS  Google Scholar 

  35. McCowage GB, White L, Carpenter P, et al. Granulocyte-macrophage colony-stimulating factor in association with high-dose chemotherapy (VETOPEC) for childhood solid tumors: a report from the Australia and New Zealand Children’s Cancer Study Group. Med Pediatr Oncol 1997; 29(2): 108–14

    PubMed  CAS  Google Scholar 

  36. Dibenedetto SP, Ragusa R, Ippolito AM, et al. Assessment of the value of treatment with granulocyte colony-stimulating factor in children with acute lymphoblastic leukemia: a randomized clinical trial. Eur J Haematol 1995; 55(2): 93–6

    PubMed  CAS  Google Scholar 

  37. Laver J, Amylon M, Desai S, et al. Randomized trial of r-metHu granulocyte colony-stimulating factor in an intensive treatment for T-cell leukemia and advanced-stage lymphoblastic lymphoma of childhood: a Pediatric Oncology Group pilot study. J Clin Oncol 1998; 16(2): 522–6

    PubMed  CAS  Google Scholar 

  38. Weite K, Reiter A, Mempel K, et al. A randomized phase-III study of the efficacy of granulocyte colony-stimulating factor in children with high-risk acute lymphoblastic leukemia. Berlin-Frankfurt-Munster Study Group. Blood 1996; 87(8): 3143–50

    Google Scholar 

  39. Clarke V, Dunstan FD, Webb DK. Granulocyte colony-stimulating factor ameliorates toxicity of intensification chemotherapy for acute lymphoblastic leukemia. Med Pediatr Oncol 1999; 32(5): 331–5

    PubMed  CAS  Google Scholar 

  40. Saarinen-Pihkala UM, Lanning M, Perkkio M, et al. Granulocyte-macrophage colony-stimulating factor support in therapy of high-risk acute lymphoblastic leukemia in children. Med Pediatr Oncol 2000; 34(5): 319–27

    PubMed  CAS  Google Scholar 

  41. Michel G, Landman-Parker J, Auclerc MF, et al. Use of recombinant human granulocyte colony-stimulating factor to increase chemotherapy dose-intensity: a randomized trial in very high-risk childhood acute lymphoblastic leukemia. J Clin Oncol 2000; 18(7): 1517–24

    PubMed  CAS  Google Scholar 

  42. Schiffer CA. Hematopoietic growth factors as adjuncts to the treatment of acute myeloid leukemia. Blood 1996; 88(10): 3675–85

    PubMed  CAS  Google Scholar 

  43. Dillman RO, Davis RB, Green MR, et al. A comparative study of two different doses of cytarabine for acute myeloid leukemia: a phase III trial of Cancer and Leukemia Group B. Blood 1991; 78(10): 2520–6

    PubMed  CAS  Google Scholar 

  44. Rowe JM, Andersen JW, Mazza JJ, et al. A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients >55 to 70 years of age with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490). Blood 1995; 86(2): 457–62

    PubMed  CAS  Google Scholar 

  45. Stone RM, Berg DT, George SL, et al. Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia. Cancer and Leukemia Group B. N Engl J Med 1995; 332(25): 1671–7

    PubMed  CAS  Google Scholar 

  46. Heil G, Hoelzer D, Sanz MA, et al. Arandomized, double-blind, placebo-controlled, phase III study of filgrastim in remission induction and consolidation therapy for adults with de novo acute myeloid leukemia. The International Acute Myeloid Leukemia Study Group. Blood 1997; 90(12): 4710–8

    PubMed  CAS  Google Scholar 

  47. Dombret H, Chastang C, Fenaux P, et al. A controlled study of recombinant human granulocyte colony-stimulating factor in elderly patients after treatment for acute myelogenous leukemia. AML Cooperative Study Group. N Engl J Med 1995; 332(25): 1678–83

    PubMed  CAS  Google Scholar 

  48. Motoji T, Watanabe M, Uzumaki H, et al. Granulocyte colony-stimulating factor G-CSF receptors on acute myeloblastic leukaemia cells and their relationship with the proliferative response to G-CSF in clonogenic assay. Br J Haematol 1991; 77(1): 54–9

    PubMed  CAS  Google Scholar 

  49. Tsuchiya H, Adachi N, Asou N, et al. Responses to granulocyte colony-stimulating factor G-CSF and granulocyte-macrophage CSF in Phi-positive acute lymphoblastic leukemia with myeloid surface markers [letter]. Blood 1991; 77(2): 411–3

    PubMed  CAS  Google Scholar 

  50. Ohno R, Hiraoka A, Tanimoto M, et al. No increase of leukemia relapse in newly diagnosed patients with acute myeloid leukemia who received granulocyte colony-stimulating factor for life-threatening infection during remission induction and consolidation therapy. Japan Adult Leukemia Study Group [letter]. Blood 1993; 81(2): 561–2

    PubMed  CAS  Google Scholar 

  51. Rahiala J, Perkkio M, Riikonen P. Prospective and randomized comparison of early versus delayed prophylactic administration of granulocyte colony-stimulating factor filgrastim in children with cancer. Med Pediatr Oncol 1999; 32(5): 326–30

    PubMed  CAS  Google Scholar 

  52. Meropol NJ, Miller LL, Korn EL, et al. Severe myelosuppression resulting from concurrent administration of granulocyte colony-stimulating factor and cytotoxic chemotherapy. J Natl Cancer Inst 1992; 84(15): 1201–3

    PubMed  CAS  Google Scholar 

  53. Morstyn G, Lieschke GJ, Sheridan W, et al. Clinical experience with recombinant human granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor. Semin Hematol 1989; 26 (2 Suppl. 2): 9–13

    PubMed  CAS  Google Scholar 

  54. Mitchell PL, Morland B, Stevens MC, et al. Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients. J Clin Oncol 1997; 15(3): 1163–70

    PubMed  CAS  Google Scholar 

  55. Riikonen P, Rahiala J, Salonvaara M, et al. Prophylactic administration of granulocyte colony-stimulating factor (filgrastim) after conventional chemotherapy in children with cancer. Stem Cells 1995; 13: 289–94

    PubMed  CAS  Google Scholar 

  56. Soda H, Oka M, Fukuda M, et al. Optimal schedule for administering granulocyte colony-stimulating factor in chemotherapy-induced neutropenia in non-small-cell lung cancer. Cancer Chemother Pharmacol 1996; 38(1): 9–12

    PubMed  CAS  Google Scholar 

  57. Gerhartz HH, Stern AC, Wolf-Hornung B, et al. Intervention treatment of established neutropenia with human recombinant granulocyte-macrophage colony-stimulating factor rhGM-CSF in patients undergoing cancer chemotherapy. Leuk Res 1993; 17(2): 175–85

    PubMed  CAS  Google Scholar 

  58. Nemunaitis J, Rabinowe SN, Singer JW, et al. Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer. N Engl J Med 1991; 324(25): 1773–78

    PubMed  CAS  Google Scholar 

  59. Greenberg P, Advani R, Keating A, et al. GM-CSF accelerates neutrophil recovery after autologous hematopoietic stem cell transplantation. Bone Marrow Transplant 1996; 18(6): 1057–64

    PubMed  CAS  Google Scholar 

  60. Gisselbrecht C, Prentice HG, Bacigalupo A, et al. Placebo-controlled phase III trial of lenograstim in bone-marrow transplantation [published erratum appears in Lancet 1994; 343 (8900): 804]. Lancet 1994; 343(8899): 696–700

    PubMed  CAS  Google Scholar 

  61. Gulati SC, Bennett CL. Granulocyte-macrophage colony-stimulating factor GM-CSF as adjunct therapy in relapsed Hodgkin disease. Ann Intern Med 1992; 116(3): 177–82

    PubMed  CAS  Google Scholar 

  62. Gorin NC, Coiffier B, Hayat M, et al. Recombinant human granulocyte-macrophage colony-stimulating factor after high-dose chemotherapy and autologous bone marrow transplantation with unpurged and purged marrow in non-Hodgkin’s lymphoma: a double-blind placebo-controlled trial. Blood 1992; 80(5): 1149–57

    PubMed  CAS  Google Scholar 

  63. Link H, Boogaerts MA, Carella AM, et al. A controlled trial of recombinant human granulocyte-macrophage colony-stimulating factor after total body irradiation, high-dose chemotherapy and autologous bone marrow transplantation for acute lymphoblastic leukemia or malignant lymphoma. Blood 1992; 80(9): 2188–95

    PubMed  CAS  Google Scholar 

  64. Khwaja A, Linch DC, Goldstone AH, et al. Recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for malignant lymphoma: a British National Lymphoma Investigation double-blind, placebo-controlled trial. Br J Haematol 1992; 82(2): 317–23

    PubMed  CAS  Google Scholar 

  65. Stahel RA, Jost LM, Cerny T, et al. Randomized study of recombinant human granulocyte colony-stimulating factor after high-dose chemotherapy and autologous bone marrow transplantation for high-risk lymphoid malignancies. J Clin Oncol 1994; 12(9): 1931–8

    PubMed  CAS  Google Scholar 

  66. Schmitz N, Dreger P, Zander AR, et al. Results of a randomised, controlled, multicentre study of recombinant human granulocyte colony-stimulating factor filgrastim in patients with Hodgkin’s disease and non-Hodgkin’s lymphoma undergoing autologous bone marrow transplantation. Bone Marrow Transplant 1995; 15(2): 261–6

    PubMed  CAS  Google Scholar 

  67. Madero L, Muonz A, Diaz DH, et al. G-CSF after autologous bone marrow transplantation for malignant diseases in children. Spanish Working Party for Bone Marrow Transplantation in Children. Bone Marrow Transplant 1995; 15(3): 349–51

    PubMed  CAS  Google Scholar 

  68. Vey N, Molnar S, Faucher C, et al. Delayed administration of granulocyte colony-stimulating factor after autologous bone marrow transplantation: effect on granulocyte recovery. Bone Marrow Transplant 1994; 14(5): 779–82

    PubMed  CAS  Google Scholar 

  69. Hagglund H, Ringden O, Oman S, et al. A prospective randomized trial of filgrastim r-metHuG-CSF given at different times after unrelated bone marrow transplantation. Bone Marrow Transplant 1999; 24(8): 831–36

    PubMed  CAS  Google Scholar 

  70. Saarinen UM, Hovi L, Juvonen E, et al. Granulocyte-colony-stimulating factor after allogeneic and autologous bone marrow transplantation in children. Med Pediatr Oncol 1996; 26(6): 380–6

    PubMed  CAS  Google Scholar 

  71. Nemunaitis J, Singer JW, Buckner CD, et al. Use of recombinant human granulocyte-macrophage colony-stimulating factor in graft failure after bone marrow transplantation. Blood 1990; 76(1): 245–53

    PubMed  CAS  Google Scholar 

  72. Giralt S, Escudier S, Kantarjian H, et al. Preliminary results of treatment with filgrastim for relapse of leukemia and myelodysplasia after allogeneic bone marrow transplantation. N Engl J Med 1993; 329(11): 757–61

    PubMed  CAS  Google Scholar 

  73. Locatelli F, Pession A, Zecca M, et al. Use of recombinant human granulocyte colony-stimulating factor in children given allogeneic bone marrow transplantation for acute or chronic leukemia. Bone Marrow Transplant 1996; 17(1): 31–7

    PubMed  CAS  Google Scholar 

  74. Klumpp TR, Mangan KF, Goldberg SL, et al. Granulocyte colony-stimulating factor accelerates neutrophil engraftment following peripheral-blood stem-cell transplantation: a prospective, randomized trial. J Clin Oncol 1995; 13(6): 1323–7

    PubMed  CAS  Google Scholar 

  75. Kawano Y, Takaue Y, Mimaya J, et al. Marginal benefit/disadvantage of granulocyte colony-stimulating factor therapy after autologous blood stem cell transplantation in children: results of a prospective randomized trial. The Japanese Cooperative Study Group of PBSCT. Blood 1998; 92(11): 4040–6

    PubMed  CAS  Google Scholar 

  76. Suzue T, Takaue Y, Watanabe A, et al. Effects of rhG-CSF filgrastim on the recovery of hematopoiesis after high-dose chemotherapy and autologous peripheral blood stem cell transplantation in children: a report from the Children’s Cancer and Leukemia Study Group of Japan. Exp Hematol 1994; 22(12): 1197–202

    PubMed  CAS  Google Scholar 

  77. Ciernik IF, Schanz U, Gmur J. Delaying treatment with granulocyte colony-stimulating factor after allogeneic bone marrow transplantation for hematological malignancies: a prospective randomized trial. Bone Marrow Transplant 1999; 24(2): 147–51

    PubMed  CAS  Google Scholar 

  78. Kessinger A, Armitage JO. The evolving role of autologous peripheral stem cell transplantation following high-dose therapy for malignancies [editorial]. Blood 1991; 77(2): 211–3

    PubMed  CAS  Google Scholar 

  79. Socinski MA, Cannistra SA, Elias A, et al. Granulocyte-macrophage colony stimulating factor expands the circulating haemopoietic progenitor cell compartment in man. Lancet 1988; I(8596): 1194–8

    Google Scholar 

  80. Beyer J, Schwella N, Zingsem J, et al. Hematopoietic rescue after high-dose chemotherapy using autologous peripheral-blood progenitor cells or bone marrow: a randomized comparison. J Clin Oncol 1995; 13(6): 1328–35

    PubMed  CAS  Google Scholar 

  81. Schmitz N, Linch DC, Dreger P, et al. Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients [published erratum appears in Lancet 1996; 347 (9005): 914]. Lancet 1996; 347(8998): 353–7

    PubMed  CAS  Google Scholar 

  82. Peters WP, Rosner G, Ross M, et al. Comparative effects of granulocyte-macrophage colony-stimulating factor GM-CSF and granulocyte colony-stimulating factor G-CSF on priming peripheral blood progenitor cells for use with autologous bone marrow after high-dose chemotherapy. Blood 1993; 81(7): 1709–19

    PubMed  CAS  Google Scholar 

  83. Kawano Y, Takaue Y, Watanabe T, et al. Efficacy of the mobilization of peripheral blood stem cells by granulocyte colony-stimulating factor in pediatric donors. Cancer Res 1999; 59(14): 3321–4

    PubMed  CAS  Google Scholar 

  84. Miniero R, Busca A, Bonetti F, et al. Allogeneic transplantation of peripheral blood progenitor cells in children: experience of two pediatric centers. Bone Marrow Transplant 1998; 22(Suppl. 5): S33–6

    PubMed  Google Scholar 

  85. Kawano Y, Takaue Y, Watanabe T, et al. Peripheral blood stem cell mobilization with granulocyte colony-stimulating factor and a harvesting procedure in pediatric donors. Bone Marrow Transplant 1998; 21Suppl. 3: S32–4

    PubMed  Google Scholar 

  86. Neupogen (filgrastim) package insert. Thousand Oaks (CA): Amgen Inc., Jun 2000

  87. Estey EH. Use of colony-stimulating factors in the treatment of acute myeloid leukemia [editorial; comment]. Blood 1994; 83(8): 2015–9

    PubMed  CAS  Google Scholar 

  88. Hoglund M. Glycosylated and non-glycosylated recombinant human granulocyte colony-stimulating factor rhG-CSF: what is the difference? Med Oncol 1998; 15(4): 229–33

    PubMed  CAS  Google Scholar 

  89. Honkoop AH, Hoekman K, Wagstaff J, et al. Continuous infusion or subcutaneous injection of granulocyte-macrophage colony-stimulating factor: increased efficacy and reduced toxicity when given subcutaneously. Br J Cancer 1996; 74(7): 1132–6

    PubMed  CAS  Google Scholar 

  90. Abrahamsen TG, Lange BJ, Packer RJ, et al. A phase I and II trial of dose-intensified cyclophosphamide and GM-CSF in pediatric malignant brain tumors. J Pediatr Hematol Oncol 1995; 17(2): 134–9

    PubMed  CAS  Google Scholar 

  91. Nash RA, Burstein SA, Storb R, et al. Thrombocytopenia in dogs induced by granulocyte-macrophage colony-stimulating factor: increased destruction of circulating platelets. Blood 1995; 86(5): 1765–75

    PubMed  CAS  Google Scholar 

  92. Furman WL, Luo X, Marina N, et al. Comparison of cytokines in children with recurrent solid tumors treated with intensive chemotherapy. J Pediatr Hematol Oncol 1998; 20(1): 62–8

    PubMed  CAS  Google Scholar 

  93. Parsons SK, Mayer DK, Alexander SW, et al. Growth factor practice patterns among pediatric oncologists: results of a 1998 Pediatric Oncology Group Survey. Economic Evaluation Working Group, the Pediatric Oncology Group. J Pediatr Hematol Oncol 2000; 223: 227–41

    Google Scholar 

  94. Sakamaki S, Matsunaga T, Hirayama Y, et al. Haematological study of healthy volunteers 5 years after G-CSF [letter]. Lancet 1995; 346(8987): 1432–3

    PubMed  CAS  Google Scholar 

  95. Rosen RB, Kang SJ. Congenital agranulocytosis terminating in acute myelomonocytic leukemia. J Pediatr 1979; 94(3): 406–8

    PubMed  CAS  Google Scholar 

  96. Gilman PA, Jackson DP, Guild HG. Congenital agranulocytosis: prolonged survival and terminal acute leukemia. Blood 1970; 36(5): 576–85

    PubMed  CAS  Google Scholar 

  97. Dong F, Brynes RK, Tidow N, et al. Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia. N Engl J Med 1995; 333(8): 487–93

    PubMed  CAS  Google Scholar 

  98. Freedman MH. Safety of long-term administration of granulocyte colony-stimulating factor for severe chronic neutropenia. Curr Opin Hematol 1997; 4(3): 217–24

    PubMed  CAS  Google Scholar 

  99. Ohara A, Kojima S, Hamajima N, et al. Myelodysplastic syndrome and acute myelogenous leukemia as a late clonal complication in children with acquired aplastic anemia. Blood 1997; 90(3): 1009–13

    PubMed  CAS  Google Scholar 

  100. Santana VM, Bowman LC, Furman WL, et al. Trial of chemotherapy plus recombinant human granulocyte colony stimulating factor in children with advanced neuroblastoma. Med Pediatr Oncol 1990; 18: 395–6

    Google Scholar 

  101. Bolwell B, Goormastic M, Dannley R, et al. G-CSF post-autologous progenitor cell transplantation: a randomized study of 5, 10 and 16 micrograms/kg/day. Bone Marrow Transplant 1997; 19(3): 215–9

    PubMed  CAS  Google Scholar 

  102. Bokemeyer C, Scmoll H, Illiger H, et al. 5 compared to 10 micro-grams/kilogram/day of GM-CSF following dose-intensified chemotherapy with cisplatin, etoposide and ifosfamide PEI in patients with advanced testicular cancer [abstract]. Proc Am Soc Clin Oncol 1993; 12: 245

    Google Scholar 

  103. Rosenfeld CS, Sulecki M, Evans C, et al. Comparison of intravenous versus subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor in patients with primary myelodysplasia. Exp Hematol 1991; 19(4): 273–7

    PubMed  CAS  Google Scholar 

  104. Cebon J, Lieschke GJ, Bury RW, et al. The dissociation of GM-CSF efficacy from toxicity according to route of administration: a pharmacodynamic study. Br J Haematol 1992; 80(2): 144–50

    PubMed  CAS  Google Scholar 

  105. Brandt SJ, Peters WP, Atwater SK, et al. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on hematopoietic reconstitution after high-dose chemotherapy and autologous bone marrow transplantation. N Engl J Med 1988; 318(14): 869–76

    PubMed  CAS  Google Scholar 

  106. Schwenn M, Laver J. Effective use of G-CSF with an early stop role in intensive POG protocols for B-cell leukemia/lymphoma. Proc Am Soc Clin Oncol 1994; 13: 453

    Google Scholar 

  107. Lyman GH, Balducci L. A cost analysis of hematopoietic colony-stimulating factors. Oncology (Huntingt) 1995; 9(11 Suppl.): 85–91

    CAS  Google Scholar 

  108. Bennett CL, Stinson TJ, Lane D, et al. Cost analysis of filgrastim for the prevention of neutropenia in pediatric T-cell leukemia and advanced lymphoblastic lymphoma: a case for prospective economic analysis in cooperative group trials. Med Pediatr Oncol 2000; 34(2): 92–6

    PubMed  CAS  Google Scholar 

  109. Rubino C, Laplanche A, Patte C, et al. Cost-minimization analysis of prophylactic granulocyte colony-stimulating factor after induction chemotherapy in children with non-Hodgkin’s lymphoma. J Natl Cancer Inst 1998; 90(10): 750–5

    PubMed  CAS  Google Scholar 

  110. MacMillan ML, Freedman MH. Recombinant human erythropoietin in children with cancer. J Pediatr Hematol Oncol 1998; 20(3): 187–9

    PubMed  CAS  Google Scholar 

  111. Miller CB, Jones RJ, Piantadosi S, et al. Decreased erythropoietin response in patients with the anemia of cancer. N Engl J Med 1990; 322(24): 1689–92

    PubMed  CAS  Google Scholar 

  112. Henry DH, Abels RI. Recombinant human erythropoietin in the treatment of cancer and chemotherapy-induced anemia: results of double-blind and open-label follow-up studies. Semin Oncol 1994; 21 (2 Suppl. 3): 21–8

    PubMed  CAS  Google Scholar 

  113. Ludwig H, Sundal E, Pecherstorfer M, et al. Recombinant human erythropoietin for the correction of cancer associated anemia with and without concomitant cytotoxic chemotherapy. Cancer 1995; 76(11): 2319–29

    PubMed  CAS  Google Scholar 

  114. Beck MN, Beck D. Recombinant erythropoietin in acute chemotherapy-induced anemia of children with cancer. Med Pediatr Oncol 1995; 25(1): 17–21

    PubMed  CAS  Google Scholar 

  115. Leon P, Jimenez M, Barona P, et al. Recombinant human erythropoietin for the treatment of anemia in children with solid malignant tumors. Med Pediatr Oncol 1998; 30(2): 110–6

    PubMed  CAS  Google Scholar 

  116. Porter JC, Leahey A, Polise K, et al. Recombinant human erythropoietin reduces the need for erythrocyte and platelet transfusions in pediatric patients with sarcoma: a randomized, double-blind, placebo-controlled trial. J Pediatr 1996; 129(5): 656–60

    PubMed  CAS  Google Scholar 

  117. Paganini EP, Eschbach JW, Lazarus JM, et al. Intravenous versus subcutaneous dosing of epoetin alfa in hemodialysis patients. Am J Kidney Dis 1995; 26(2): 331–40

    PubMed  CAS  Google Scholar 

  118. Negrin RS, Stein R, Doherty K, et al. Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy. Blood 1996; 87(10): 4076–81

    PubMed  CAS  Google Scholar 

  119. Bolonaki I, Stiakaki E, Lydaki E, et al. Treatment with recombinant human erythropoietin in children with malignancies. Pediatr Hematol Oncol 1996; 13(2): 111–21

    PubMed  CAS  Google Scholar 

  120. Locatelli F, Zecca M, Pedrazzoli P, et al. Use of recombinant human erythropoietin after bone marrow transplantation in pediatric patients with acute leukemia: effect on erythroid repopulation in autologous versus allogeneic transplants. Bone Marrow Transplant 1994; 13(4): 403–10

    PubMed  CAS  Google Scholar 

  121. Link H, Boogaerts MA, Fauser AA, et al. A controlled trial of recombinant human erythropoietin after bone marrow transplantation. Blood 1994; 84(10): 3327–35

    PubMed  CAS  Google Scholar 

  122. Beguin Y, Oris R, Fillet G. Dynamics of erythropoietic recovery following bone marrow transplantation: role of marrow proliferative capacity and erythropoietin production in autologous versus allogeneic transplants. Bone Marrow Transplant 1993; 11(4): 285–92

    PubMed  CAS  Google Scholar 

  123. Pawlicki M, Jassem J, Bosze P, et al. A multicenter study of recombinant human erythropoietin epoetin alpha in the management of anemia in cancer patients receiving chemotherapy. Anticancer Drugs 1997; 8(10): 949–57

    PubMed  CAS  Google Scholar 

  124. Heddle NM, Klama L, Singer J, et al. The role of the plasma from platelet concentrates in transfusion reactions. N Engl J Med 1994; 331(10): 625–8

    PubMed  CAS  Google Scholar 

  125. Du X, Williams DA. Interleukin-11: review of molecular, cell biology and clinical use. Blood 1997; 89(11): 3897–908

    PubMed  CAS  Google Scholar 

  126. Isaacs C, Robert NJ, Bailey FA, et al. 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 1997; 15(11): 3368–77

    PubMed  CAS  Google Scholar 

  127. Tepler I, Elias L, Smith JW, et al. A randomized placebo-controlled trial of recombinant human interleukin-11 in cancer patients with severe thrombocytopenia due to chemotherapy. Blood 1996; 87(9): 3607–14

    PubMed  CAS  Google Scholar 

  128. Ali-Nazir A, Davenport V, Reaman G, et al. Preliminary results of a phase I/II study following ifosfamide, carboplatin and etoposide ICE chemotherapy in pediatric patients with solid tumors or lymphoma; enhancement of hematologic reconstitution [abstract]. Blood 2000; 86: 686a

    Google Scholar 

  129. Ault K, Mitchell J, Knowles C, et al. Recombinant human interleukin eleven increases plasma volume and decreases urine sodium excretion in normal human subjects [abstract]. Blood 1994; 84: 276a

    Google Scholar 

  130. Hofmann WK, Ottmann OG, Hoelzer D. Memorial lecture. Megakaryocytic growth factors: is there a new approach for management of thrombocytopenia in patients with malignancies? Leukemia 1999; 13Suppl. 1: S14–8

    PubMed  CAS  Google Scholar 

  131. Basser RL, Rasko JE, Clarke K, et al. Thrombopoietic effects of pegylated recombinant human megakaryocyte growth and development factor PEG-rHuMGDF in patients with advanced cancer. Lancet 1996; 348(9037): 1279–81

    PubMed  CAS  Google Scholar 

  132. Basser RL, Rasko JE, Clarke K, et al. Randomized, blinded, placebo-controlled phase I trial of pegylated recombinant human megakaryocyte growth and development factor with filgrastim after dose-intensive chemotherapy in patients with advanced cancer [published erratum appears in Blood 1997; 90 (6): 2513]. Blood 1997; 89(9): 3118–28

    PubMed  CAS  Google Scholar 

  133. Fanucchi M, Glaspy J, Crawford J, et al. Effects of polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor on platelet counts after chemotherapy for lung cancer. N Engl J Med 1997; 336(6): 404–9

    PubMed  CAS  Google Scholar 

  134. Li J, Xia Y, Bertino A, et al. Characterization of an antithrombopoietin antibody that developed in a cancer patient following the injection of PEG-RHUMGDF [abstract]. Blood 1999; 94: 51a

    Google Scholar 

  135. Yang C, Xia Y, Kuter D. The appearance of antithrombopoietin antibody and circulating thrombopoietin-IgG complexes in a patient developing thrombocytopenia after the injection of PEG-rHuMGDF [abstract]. Blood 1999; 94: 681a

    Google Scholar 

  136. Ganser A, Lindemann A, Seipelt G, et al. Effects of recombinant human interleukin-3 in patients with normal hematopoiesis and in patients with bone marrow failure. Blood 1990; 76(4): 666–76

    PubMed  CAS  Google Scholar 

  137. Curtis BM, Williams DE, Broxmeyer HE, et al. Enhanced hematopoietic activity of a human granulocyte/macrophage colony-stimulating factor-interleukin 3 fusion protein. Proc Natl Acad Sci USA 1991; 88(13): 5809–13

    PubMed  CAS  Google Scholar 

  138. Vose JM, Pandite AN, Beveridge RA, et al. Granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein versus granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for non-Hodgkin’s lymphoma: results of a randomized double-blind trial. J Clin Oncol 1997; 15(4): 1617–23

    PubMed  CAS  Google Scholar 

  139. Cairo MS, Krailo MD, Weinthal JA, et al. A Phase I study of granulocyte-macrophage-colony stimulating factor/interleukin-3 fusion protein PIXY321 following ifosfamide, carboplatin and etoposide therapy for children with recurrent or refractory solid tumors: a report of the Children’s Cancer Group. Cancer 1998; 83(7): 1449–60

    PubMed  CAS  Google Scholar 

  140. Bearman SI. Use of stem cell factor to mobilize hematopoietic progenitors. Curr Opin Hematol 1997; 4(3): 157–62

    PubMed  CAS  Google Scholar 

  141. Molineux G, McCrea C, Yan XQ, et al. Flt-3 ligand synergizes with granulocyte colony-stimulating factor to increase neutrophil numbers and to mobilize peripheral blood stem cells with long-term repopulating potential. Blood 1997; 89(11): 3998–4004

    PubMed  CAS  Google Scholar 

  142. Nemunaitis J, Shannon-Dorcy K, Appelbaum FR, et al. Long-term follow-up of patients with invasive fungal disease who received adjunctive therapy with recombinant human macrophage colony-stimulating factor. Blood 1993; 82(5): 1422–7

    PubMed  CAS  Google Scholar 

  143. Jyung RW, Wu L, Pierce GF, et al. Granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor: differential action on incisional wound healing. Surgery 1994; 115(3): 325–34

    PubMed  CAS  Google Scholar 

  144. Hess G, Kreiter F, Kosters W, et al. The effect of granulocyte-macrophage colony-stimulating factor GM-CSF on hepatitis B vaccination in haemodialysis patients. J Viral Hepat 1996; 3(3): 149–53

    PubMed  CAS  Google Scholar 

  145. Spitler LE, Grossbard ML, Ernstoff MS, et al. Adjuvant therapy of stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor. J Clin Oncol 2000; 18(8): 1614–21

    PubMed  CAS  Google Scholar 

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Acknowledgements

The authors wish to thank the American Lebanese Syrian Associated Charities for their support during the preparation of this manuscript. The authors also thank Florence Witte for technical assistance with scientific editing. This work was supported by Support Grant 5P01-CA23009-22.

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Wagner, L.M., Furman, W.L. Haemopoietic Growth Factors in Paediatric Oncology. Paediatr Drugs 3, 195–217 (2001). https://doi.org/10.2165/00128072-200103030-00003

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