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Klin Padiatr 2001; 213(S1): A88-A102
DOI: 10.1055/s-2001-17505
ORIGINALARBEIT

Georg Thieme Verlag Stuttgart · New York

Hämatopoetische Wachstumsfaktoren in der Infektionsprävention bei Kindern mit hämatologisch-onkologischen Erkrankungen

Hematopoietic growth factors in the prevention of infections complications in children with hematologic-oncologic diseasesT.  Lehrnbecher
  • Pädiatrische Hämatologie und Onkologie, Universität Frankfurt
  • Für den Arbeitskreis „Infektionen bei Neutropenie” der Deutschen Gesellschaft für Pädiatrische Infektiologie e. V. und der Gesellschaft für Pädiatrische Onkologie und Hämatologie
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Publication History

Publication Date:
27 September 2001 (online)

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Zusammenfassung.

Mit dem Einsatz von gentechnologisch hergestellten hämatopoetischen Wachstumsfaktoren wie G-CSF (granulocyte colony stimulating factor) oder GM-CSF (granulocyte-macrophage colony stimulating factor) versprach man sich einen großen Fortschritt in der Supportivtherapie krebskranker Patienten. Beide Wachstumsfaktoren stimulieren Proliferation und Reifung der myeloischen Vorläuferzellen und verringern so Ausmaß und Dauer der Neutropenie. Allerdings können durch hämatopoetische Wachstumsfaktoren infektiöse Komplikationen nicht verhindert werden. Basierend auf den Ergebnissen zahlreicher Studien wurden in den letzten Jahren Leitlinien für den rationalen Einsatz der teuren Wachstumsfaktoren erstellt [2] [3] [78] [92]. Um das Risiko schwerer infektiöser Komplikationen zu verringern, wird der Einsatz von G-CSF oder GM-CSF bei einer Untergruppe von Patienten kurz nach Gabe der zytotoxischen Therapie oder nach Knochenmark- oder Stammzelltransplantation empfohlen. So profitieren Kinder mit sehr intensiver Chemotherapie, wie z. B. Hochrisikopatienten mit ALL oder NHL und Patienten mit metastasiertem Neuroblastom von der Gabe der Wachstumsfaktoren, während dies für Patienten mit soliden Tumoren, wie z. B. für Patienten mit Rhabdomyosarkom oder Ewing-Sarkom, noch unklar ist. Die Mobilisierung peripherer Stammzellen stellt ein neues und viel versprechendes Einsatzgebiet der hämatopoetischen Wachstumsfaktoren dar. Allerdings müssen zukünftige Studien noch zahlreiche offene Fragen klären. So fehlen Daten, welche Untergruppen von Patienten wirklich von der Gabe der Wachstumsfaktoren profitieren, das heißt, bei welchen Patienten G-CSF oder GM-CSF die Inzidenz von Infektionen oder die Dauer von intravenösen Antibiotikagaben verringert, die Krankenhauszeit verkürzt oder zu einer Verbesserung der Überlebensrate führt. Zudem müssen weitere Studien für die einzelnen Patientengruppen die optimale Dosis und die geeignete Dauer der Wachstumsfaktorgabe herausfinden. Dabei muss für jede Indikationsstellung der teuren Wachstumsfaktoren der klinische und der ökonomische Nutzen mit der Einsparung der Gesamttherapiekosten kritisch gegeneinander abgewogen werden.

The hematopoietic colony-stimulating factors have been introduced into clinical practice as additional supportive measures that can reduce, but not eliminate infectious complications associated with therapy-induced neutropenia. Over the past decade, we have begun to appreciate the subtler aspects of the proper use of G-CSF and GM-CSF, identifying appropriate indications and contraindications. In the course of evaluating the multitude of studies, a set of formal recommendations have been propagated for the judicious use of these expensive growth factors [2] [3] [78] [92]. To prevent serious infection, the use of G- or GM-CSF is recommended in a subset of pediatric cancer patients shortly after receiving chemotherapy or a marrow transplant. Children with intensive chemotherapy (e.g., children with high risk ALL, NHL or metastatic neuroblastoma) seem to benefit from hematopoietic growth factors whereas it is not clear that this applies to children undergoing therapy for solid tumors such as rhabdomyosarkoma or Ewing's sarcoma. An exciting development is the use of G-CSF and GM-CSF to mobilize peripheral-blood progenitor cells. Future studies in pediatric cancer patients are clearly warranted to address several issues. Prospective clinical trials are still needed to define specific treatment groups who can benefit from growth factor support. In this regard, efforts must be directed at better defining the endpoints and in particular, assigning value to reduction in treatment of possible infectious complications, such as days in hospital, antibiotic usage and costs. In addition, randomized studies are required to evaluate the proper dosage and duration of therapy, which most likely will vary between groups, depending upon underlying malignancy and therapy given. In addition, combinations of different growth factors have to be tested, particularly if ex vivo expansion and the storage of hematopoietic stem cells are to be utilized in a wider spectrum of patients.

Schlüsselwörter

Hämatopoetische Wachstumsfaktoren - G-CSF - GM-CSF - Infektionsprävention - Kinder - Malignom

Key words

Hematopoietic growth factors - G-CSF - GM-CSF - prevention of infection - children - malignancy

Literatur

  • 001 Abrahamsen  T G, Lange  B J, Packer  R J, Venzon  D J, Allen  J C, Craig  C E, Patronas  N J, Katz  D A, Goldwein  J W, DeLaney  T F, Reaman  G H, Perilongo  G, Philips  P C, Oldfield  E H, Poplack  D G, Horowitz  M E. A phase I and II trial of dose-intensified cyclophosphamide and GM-CSF in pediatric malignant brain tumors.  J Pediatr Hematol Oncol. 1995;;  17 134-139
    Google Scholar
  • 002 American Society of Clinical Oncology .American Society of Clinical Oncology recommendations for the use of hematopoietic colony-stimulating factors: evidence-based clinical practice guidelines. J Clin Oncol 1994; 12: 2471-2508
    Google Scholar
  • 003 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: 1957-1960
    Google Scholar
  • 004 Balis  F M, Holcenberg  J S, Poplack  D G. General principles of chemotherapy. In: Pizzo PA, Poplack DG (eds). Principles and Practice of Pediatric Oncology. JB Lippincott Company, Philadelphia; 1993;: 197-245
    Google Scholar
  • 005 Benedetti Panici  P, Pierelli  L, Scambia  G, Foddai  M L, Salerno  M G, Menichella  G, Vittori  M, Maneschi  F, Caracussi  U, Serafini  R, Leone  G, Mancuso  S. High-dose carboplatin, etoposide and melphalan (CEM) with peripheral blood progenitor cell support as late intensification for high-risk cancer: non-haematological, haematological toxicities and role of growth factor administration.  Br J Cancer. 1997;;  75 1205-1212
    Google Scholar
  • 006 Bennett  C L, Stinson  T J, Laver  J H, Bishop  M R, Godwin  J E, Tallman  M S. Cost analyses of adjunct colony stimulating factors for acute leukemia: can they improve clinical decision making.  Leuk Lymphoma. 2000;;  37 65-70
    Google Scholar
  • 007 Bensinger  W, Appelbaum  F, Rowley  S, Storb  R, Sanders  J, Lilleby  K, Gooley  T, Demirer  T, Schiffman  K, Weaver  C. Factors that influence collection and engraftment of autologous peripheral-blood stem cells.  J Clin Oncol. 1995;;  13 2547-2555
    Google Scholar
  • 008 Boulad  F, Gillio  A, Small  T N, Bonilla  M A, Philips  P, Ruggiero  M, Emanuel  D, Ghavimi  F, Kernan  N A. Correction of neutropenia with rHuG-CSF after loss of response to rHuGM- CSF following autologous bone marrow transplant.  Bone Marrow Transplant. 1994;;  13 661-663
    Google Scholar
  • 009 Bunn  P A Jr, Crowley  J, Kelly  K, Hazuka  M B, Beasley  K, Upchurch  C, Livingston  R, Weiss  G R, Hicks  W J, Gandara  D R. 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. 1995;;  13 1632-1641
    Google Scholar
  • 010 Buonadonna  A, Frustaci  S, Galligioni  E, Gigante  M, Monfardini  S. Comparison between G-CSF and GM-CSF for prophylaxis of severe leukopenia after intensive chemotherapy [abstract].  Proc Am Soc Clin Oncol. 1994;;  13 462
    Google Scholar
  • 011 Burdach  S E, Muschenich  M, Josephs  W, Frisch  J, Schulz  G, Jürgens  H, Göbel  U. Granulocyte-macrophage-colony stimulating factor for prevention of neutropenia and infections in children and adolescents with solid tumors. Results of a prospective randomized study.  Cancer. 1995;;  76 510-516
    Google Scholar
  • 012 Cairo  M, Shen  W, Miser  J, Krailo  M, Blazar  B, Reaman  G. A randomized trial of two doses of G-CSF (5.0 vs 10.0 mcg/kg/d) following ifosfamide, carboplatin, and etoposide (ICE) chemotherapy in children with recurrent solid tumors (RST): significant clinical activity but no improvement in hematopoietic recovery (HR) with increased dose of G-CSF [abstract].  Proc Am Soc Clin Oncol. 1995;;  14 255
    Google Scholar
  • 013 Calderwood  S, Doyle  J J, Hitzler  J K, Saunders  E F, Freedman  M H. Administration of recombinant human granulocyte-macrophage stimulating factor after autologous bone marrow transplantation in children with acute myelogenous leukemia: a note of caution.  Bone Marrow Transplant. 1996;;  18 87-91
    Google Scholar
  • 014 Calderwood  S, Romeyer  F, Blanchette  V, Chan  H, Doyle  J, Greenberg  M, Lorenzana  A, Malkin  D, Saunders  F, Weitzman  S. Concurrent rhGM-CSF does not offset myelosuppression from intensive chemotherapy: randomized placebo-controlled study in childhood acute lymphoblastic leukemia.  Am J Hematol. 1994;;  47 27-32
    Google Scholar
  • 015 Cavallaro  A M, Lilleby  K, Majolino  I, Storb  R, Appelbaum  F R, Rowley  S D, Bensinger  W I. Three to six year follow-up of normal donors who received recombinant human granulocyte colony-stimulating factor.  Bone Marrow Transplant. 2000;;  25 85-89
    Google Scholar
  • 016 Chen  B D, Clark  C R, Chou  T H. Granulocyte/macrophage colony-stimulating factor stimulates monocyte and tissue macrophage proliferation and enhances their responsiveness to macrophage colony-stimulating factor.  Blood. 1988;;  71 997-1002
    Google Scholar
  • 017 Chen  B D, Mueller  M, Chou  T H. Role of granulocyte/macrophage colony-stimulating factor in the regulation of murine alveolar macrophage proliferation and differentiation.  J Immunol. 1988;;  141 139-144
    Google Scholar
  • 018 Chen  S H, Liang  D C, Liu  H C. High-dose cytarabine-containing chemotherapy with or without granulocyte colony-stimulating factor for children with acute leukemia.  Am J Hematol. 1998;;  58 20-23
    Google Scholar
  • 019 Clark  R E, Shlebak  A A, Creagh  M D. Delayed commencement of granulocyte colony-stimulating factor following autologous bone marrow transplantation accelerates neutrophil recovery and is cost-effective.  Leuk Lymphoma. 1994;;  16 141-146
    Google Scholar
  • 020 Clarke  V, Dunstan  F D, Webb  D K. Granulocyte colony-stimulating factor ameliorates toxicity of intensification chemotherapy for acute lymphoblastic leukemia.  Med Pediatr Oncol. 1999;;  32 331-335
    Google Scholar
  • 021 Cohen  D M, Bhalla  S C, Anaissie  E J, Hester  J P, Savary  C A, Rex  J H. Effects of in vitro and in vivo cytokine treatment, leukapheresis and irradiation on the function of human neutrophils.  Clin Lab Haematol. 1997;;  19 39-47
    Google Scholar
  • 022 Cortelazzo  S, Viero  P, Bellavita  P, Rossi  A, Buelli  M, Borleri  G M, Marziali  S, Bassan  R, Comotti  B, Rambaldi  A. Granulocyte colony-stimulating factor following peripheral-blood progenitor-cell transplant in non-Hodgkin's lymphoma.  J Clin Oncol. 1995;;  13 935-941
    Google Scholar
  • 023 Crawford  J, Ozer  H, Stoller  R, Johnson  D, Lyman  G, Tabbara  I, Kris  M, Grous  J, Picozzi  V, Rausch  G, Smith  R, Gradishar  W, Yahanda  A, Vincent  M, Stewart  M, Glaspy  J. 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;;  325 164-170
    Google Scholar
  • 024 Deb  G, Donfrancesco  A, Sio  L D, Cozza  R, Castellano  A, Paole  F, Helson  L. Shortened time to recovery from chemotherapy induced neutropenia in pediatric patients with high dose combined cytokines.  Anticancer Res. 1998;;  18 489-492
    Google Scholar
  • 025 Demeocq  F, Kanold  J, Chassagne  J, Bezou  M J, Lutz  P, deLumley  L, Philip  I, Vannier  J P, Margueritte  G, Lamagnere  J P, Baranzelli  M C, Lenat  A, Carla  H, Malpuech  G. Successful blood stem cell collection and transplant in children weighing less than 25 kg.  Bone Marrow Transplant. 1994;;  13 43-50
    Google Scholar
  • 026 Diaz  M A, Alegre  A, Villa  M, Benito  A, Bernardo  M R, Lopez-Botet  M, Madero  L. Allogeneic peripheral blood progenitor cell (PBPC) transplantation in children with haematological malignancies.  Br J Haematol. 1997;;  96 161-164
    Google Scholar
  • 027 Diaz  M A, Villa  M, Alegre  A, Lamana  M L, de la Vega  A, Granda  A, Madero  L. Collection and transplantation of peripheral blood progenitor cells mobilized by G-CSF alone in children with malignancies.  Br J Haematol. 1996;;  94 148-154
    Google Scholar
  • 028 Dibenedetto  S P, Ragusa  R, Ippolito  A M, Lo Nigro  L, Di Cataldo  A, D'Amico  S, Miraglia  V. 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 93-96
    Google Scholar
  • 029 Dimitrov  N, Stoller  R, Hamm  J. A NSABP pilot study evaluating GM-CSF and G-CSF used with high-dose chemotherapy [abstract].  Proc Am Soc Clin Oncol. 1993;;  12 138
    Google Scholar
  • 030 Dini  G, Floris  R, Pession  A, Manfredini  L, Dallorso  S, Lanino  E, Garaventa  A, Miano  M, Kotitsa  Z, Rondelli  R. Phase II study of recombinant human granulocyte colony-stimulating factor in children undergoing bone marrow transplantation.  Bone Marrow Transplant. 1996;;  18 Suppl 2 121-128
    Google Scholar
  • 031 Dunlop  D J, Fitzsimons  E J, McMurray  A, Morrison  M, Kyle  E, Alcorn  M J, Steward  W P. Filgrastim fails to improve haemopoietic reconstitution following myeloablative chemotherapy and peripheral blood stem cell rescue.  Br J Cancer. 1994;;  70 943-945
    Google Scholar
  • 032 Eyrich  M, Handgretinger  R, Schumm  M, Bader  P, Klingebiel  T, Niethammer  D, Schlegel  P G. A prospective analysis of the pattern of immunoreconstitution after haploidentical CD34+ peripheral stem cell transplantation in children [abstract].  Blood. 1998;;  92 (Suppl 1) 686a
    Google Scholar
  • 033 Fernandez  M C, Krailo  M D, Gerbing  R R, Matthay  K K. A phase I dose escalation of combination chemotherapy with granulocyte-macrophage-colony stimulating factor in patients with neuroblastoma.  Cancer. 2000;;  88 2838-2844
    Google Scholar
  • 034 Gabrilove  J L, Jakubowski  A, Scher  H, Sternberg  C, Wong  G, Grous  J, Yagoda  A, Fain  K, Moore  M AS, Clarkson  B, Oettgen  H F, Alton  K, Welte  K, Souza  L. Effect of granulocyte colony-stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional-cell carcinoma of the urothelium.  N Engl J Med. 1988;;  318 1414-1422
    Google Scholar
  • 035 Gasson  J C. Molecular physiology of granulocyte-macrophage colony-stimulating factor.  Blood. 1991;;  77 1131-1145
    Google Scholar
  • 036 Gordon  B, Spadinger  A, Hodges  E, Ruby  E, Stanley  R, Coccia  P. Effect of granulocyte-macrophage colony-stimulating factor on oral mucositis after hematopoietic stem-cell transplantation.  J Clin Oncol. 1994;;  12 1917-1922
    Google Scholar
  • 037 Griffin  J, Young  D, Hermann  F, Wiper  D, Wagner  K, Sabbath  K. Effects of recombinant human GM-CSF on proliferation of clonogenic cells in acute myeloblastic leukemia.  Blood. 1986;;  67 1448-1453
    Google Scholar
  • 038 Handgretinger  R, Schumm  M, Lang  P, Greil  J, Reiter  A, Bader  P, Niethammer  D, Klingebiel  T. Transplantation of megadoses of purified haploidentical stem cells.  Ann NY Acad Sci. 1999;;  872 351-361
    Google Scholar
  • 039 Hartmann  O, Le Corroller  A G, Blaise  D, Michon  J, Philip  I, Norol  F, Janvier  M, Pico  J L, Baranzelli  M C, Rubie  H, Coze  C, Pinna  A, Meresse  V, Benhamou  E. Peripheral blood stem cell and bone marrow transplantation for solid tumors and lymphomas: hematologic recovery and costs. A randomized, controlled trial.  Ann Intern Med. 1997;;  126 600-607
    Google Scholar
  • 040 Housholder  S E, Rackoff  W R, Goldman  J, Breitfeld  P P. A case-control retrospective study of the efficacy of granulocyte-colony-stimulating factor in children with neuroblastoma.  Am J Pediatr Hematol Oncol. 1994;;  16 132-137
    Google Scholar
  • 041 Jones  C A, Shaw  P J, Stevens  M M. Use of granulocyte colony stimulating factor to reduce the toxicity of super-VAC chemotherapy in advanced solid tumours in childhood.  Med Pediatr Oncol. 1995;;  25 84-89
    Google Scholar
  • 042 Jones  S, Schottstaedt  M, Duncan  L. A randomized prospective trial to evaluate the effects of rHuGM-CSF versus placebo in a high-dose chemotherapy program for stage II and stage III breast cancer [abstract].  Proc Am Soc Clin Oncol. 1995;;  14 106
    Google Scholar
  • 043 Kalmanti  M, Lydaki  E, Dimitriou  H, Kalmantis  T, Vlachonicolis  I, Kambourakis  A, Zioga  I, Bolonaki  I. Effect of granulocyte colony-stimulating factor on chemotherapy-induced neutropenia in children with cancer.  Pediatr Hematol Oncol. 1994;;  11 147-155
    Google Scholar
  • 044 Kanold  J, Berger  M, Halle  P, Rapatel  C, Schoepfer  C, de Lumley  L, Vannier  J P, Lutz  P, Plantaz  D, Stephan  J L, Malpuech  G, Demeocq  F. Kinetics of hematopoietic progenitor cell release induced by G-CSF-alone in children with solid tumors and leukemias.  Bone Marrow Transplant. 1998;;  21 59-63
    Google Scholar
  • 045 Kanold  J, Halle  P, Rapatel  C, Berger  M, Gembara  P, deLumley  L, Vannier  J P, Lutz  P, Plantaz  D, Malpuech  G, Demeocq  F. Safe and efficient peripheral blood stem cell collection in the smallest of children.  Ther Apher. 1998;;  2 49-57
    Google Scholar
  • 046 Kanold  J, Rapatel  C, Berger  M, Chassagne  J, Lutz  P, de Lumley  L, Plantaz  D, Vannier  J P, Malpuech  G, Demeocq  F. Use of G-CSF alone to mobilize peripheral blood stem cells for collection from children.  Br J Haematol. 1994;;  88 633-635
    Google Scholar
  • 047 Kawano  Y, Takaue  Y, Mimaya  J, Horikoshi  Y, Watanabe  T, Abe  T, Shimizu  Y, Matsushita  T, Kikuta  A, Watanabe  A, Iwai  A, Ito  E, Endo  M, Kodani  N, Ohta  S, Gushi  K, Azuma  H, Etoh  T, Okamoto  Y, Amano  K, Hattori  H, Eguchi  H, Kuroda  Y. 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 4040-4046
    Google Scholar
  • 048 Klumpp  T R, Mangan  K F, Goldberg  S L, Pearlman  E S, Macdonald  J S. Granulocyte colony-stimulating factor accelerates neutrophil engraftment following peripheral-blood stem-cell transplantation: a prospective, randomized trial.  J Clin Oncol. 1995;;  13 1323-1327
    Google Scholar
  • 049 Knox  S J, Fowler  S, Marquez  C, Hoppe  R T. Effect of filgrastim (G-CSF) in Hodgkin's disease patients treated with radiation therapy.  Int J Radiat Oncol Biol Phys. 1994;;  28 445-450
    Google Scholar
  • 050 Kolotas  C, Zamboglou  N, Schnabel  T, Bojar  H, Wintzer  A, Vogt  H G, Schmitt  G. 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. 1996;;  35 137-142
    Google Scholar
  • 051 Kubota  M, Akiyama  Y, Mikawa  H, Tsutsui  T. Comparative effect of 100 versus 250 micrograms/m2/day of G-CSF in pediatric patients with neutropenia induced by chemotherapy.  Pediatr Hematol Oncol. 1995;;  12 393-397
    Google Scholar
  • 052 Laver  J, Amylon  M, Desai  S, Link  M, Schwenn  M, Mahmoud  H, Shuster  J. 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;;  16 522-526
    Google Scholar
  • 053 Lee  S M, Radford  J A, Dobson  L, Huq  T, Ryder  W D, Pettengell  R, Morgenstern  G R, Scarffe  J H, Crowther  D. Recombinant human granulocyte colony-stimulating factor (filgrastim) following high-dose chemotherapy and peripheral blood progenitor cell rescue in high-grade non-Hodgkin's lymphoma: clinical benefits at no extra cost.  Br J Cancer. 1998;;  77 1294-1299
    Google Scholar
  • 054 Lee  V, Li  C K, Shing  M M, Chik  K W, Li  K, Tsang  K S, Zhao  D C, Lai  D H, Wong  A, Yuen  P M. Single vs twice daily G-CSF dose for peripheral blood stem cells harvest in normal donors and children with non-malignant diseases.  Bone Marrow Transplant. 2000;;  25 931-935
    Google Scholar
  • 055 Legros  M, Fleury  J, Bay  J O, Choufi  B, Basile  M, Condat  P, Glenat  C, Communal  Y, Tavernier  F, Bons  J M, Chollet  P, Plagne  R, Chassagne  J. RhGM-CSF vs placebo following rhGM-CSF-mobilized PBPC transplantation: a phase III double-blind randomized trial.  Bone Marrow Transplant. 1997;;  19 209-213
    Google Scholar
  • 056 Lehrnbecher  T, Chanock  S J. Myeloid growth factors in supportive care of cancer and marrow transplant therapies. In: Holland S (Hrsg). Cytokine therapeutics in infectious diseases. Lippincott-Raven (im Druck):
    Google Scholar
  • 057 Lehrnbecher  T, Foster  C, Vazquez  N, Mackall  C L, Chanock  S J. Therapy-induced alterations in host defense in children receiving chemotherapy.  J Ped Hematol Oncol. 1997;;  19 399-417
    Google Scholar
  • 058 Levine  J E, Wiley  J, Kletzel  M, Yanik  G, Hutchinson  R J, Koehler  M, Neudorf  S. Cytokine-mobilized allogeneic peripheral blood stem cell transplants in children result in rapid engraftment and a high incidence of chronic GVHD.  Bone Marrow Transplant. 2000;;  25 13-18
    Google Scholar
  • 059 Linch  D C, Milligan  D W, Winfield  D A, Kelsey  S M, Johnson  S A, Littlewood  T J, Smith  G M, Hutchinson  R M, Goldstone  A H, Fielding  A K, Vaughan Hudson  G. G-CSF after peripheral blood stem cell transplantation in lymphoma patients significantly accelerated neutrophil recovery and shortened time in hospital: results of a randomized BNLI trial.  Br J Haematol. 1997;;  99 933-938
    Google Scholar
  • 060 Locatelli  F, Pession  A, Zecca  M, Bonetti  F, Prete  L, Carra  A M, Prete  A, Montagna  D, Comoli  P, Taibi  R M, Paolucci  G. 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 31-37
    Google Scholar
  • 061 Lowenberg  B, Touw  I P. Hematopoietic growth factors and their receptors in acute leukemia.  Blood. 1993;;  81 281-292
    Google Scholar
  • 062 Lydaki  E, Bolonaki  E, Stiakaki  E, Dimitriou  H, Kalmantis  T, Kalmanti  M. 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;;  12 551-558
    Google Scholar
  • 063 Mac Manus  M P, McCormick  D, Trimble  A, Abram  W P. Value of granulocyte colony stimulating factor in radiotherapy induced neutropenia: clinical and laboratory studies.  Eur J Cancer. 1995;;  3 302-307
    Google Scholar
  • 064 Mackall  C, Fleisher  T, Brown  M, Andrich  M, Chen  C, Feuerstein  I, Horowitz  M, Magrath  I, Shad  A, Steinberg  S, Wexler  L, Gress  R. Age, thymopoiesis, and CD 4+ T-lymphocyte regeneration after intensive chemotherapy.  N Engl J Med. 1995;;  332 143-149
    Google Scholar
  • 065 Madero  L, Diaz  M A, Ortega  J J, Olive  T, Martinez  A, Badell  I, Munoz  A, Gomez  P. Recombinant human granulocyte-macrophage colony-stimulating factor accelerates engraftment kinetics after allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia.  Haematologica. 1999;;  84 133-137
    Google Scholar
  • 066 Madero  L, Muonz  A, Diaz de Heredia  A, Martinez  A, Badell  I, Esquembre  C, Ramirez  M, Otheo  E, Olive  A, Sastre  A, Pardo  N, Castell  V. 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;;  15 349-351
    Google Scholar
  • 067 Madero  L, Villa  M, Benito  A, Gonzalez  M, Diaz  M A. Peripheral blood progenitor cells for autologous transplant in children.  Bone Marrow Transplant. 1998;;  21 Suppl 2 S8-10
    Google Scholar
  • 068 Marina  N M, Shema  S J, Bowman  L C, Rodman  J, Douglass  E C, Furman  W L, Pappo  A, Santana  V M, Hudson  M, Meyer  W H, Pratt  C B. 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;;  23 328-334
    Google Scholar
  • 069 McCowage  G B, White  L, Carpenter  P, Lockwood  L, Toogood  I, Tiedemann  K, Shaw  P J. 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;;  29 108-114
    Google Scholar
  • 070 Michel  G, Landman-Parker  J, Auclerc  M F, Mathey  C, Leblanc  T, Legall  E, Bordigoni  P, Lamagnere  J P, Demeocq  F, Perel  Y, Auvrignon  A, Berthou  C, Bauduer  F, Pautard  B, Schneider  P, Schaison  G, Leverger  G, Baruchel  A. 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 1517-1524
    Google Scholar
  • 071 Michon  J M, Hartmann  O, Bouffet  E, Meresse  V, Coze  C, Rubie  H, Bordigoni  P, Cattiaux  E, Ward  N, Bernard  J L, Lemerle  J, Zucker  J M, Philip  T. 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 1063-1069
    Google Scholar
  • 072 Miller  L L, Smith  M A, Nagler  C H. The role of hematopoietic growth factors in supportive care. In: Pizzo PA, Poplack DG (eds). Principles and Practice of Pediatric Oncology. Lippincott-Raven Publishers, Philadelphia; 1997;: 1115-1165
    Google Scholar
  • 073 Miniero  R, Busca  A, Bonetti  F, Giorgiani  G, Zecca  M, Berger  M, Incarbone  E, Vassallo  E, Perotti  C, Locatelli  F. Allogeneic transplantation of peripheral blood progenitor cells in children: experience of two pediatric centers.  Bone Marrow Transplant. 1998;;  22 Suppl 5 S33-36
    Google Scholar
  • 074 Miniero  R, Busca  A, Roncarolo  M G, Saitta  M, Iavarone  A, Timeus  F, Biondi  A, Amoroso  A, Perugini  L, Ciuti  E. HLA-haploidentical umbilical cord blood stem cell transplantation in a child with advanced leukemia: clinical outcome and analysis of hematopoietic recovery.  Bone Marrow Transplant. 1995;;  16 229-240
    Google Scholar
  • 075 Motoji  T, Watanabe  M, Uzumaki  H, Kusaka  M, Fukamachi  H, Shimosaka  A, Oshimi  K, Mizoguchi  H. 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 54-59
    Google Scholar
  • 076 Nemunaitis  J, Singer  J W, Buckner  C D, Durnam  D, Epstein  C, Hill  R, Storb  R, Thomas  E D, Appelbaum  F R. Use of recombinant human granulocyte-macrophage colony-stimulating factor in graft failure after bone marrow transplantation.  Blood. 1990;;  76 245-253
    Google Scholar
  • 077 Ottmann  O G, Hoelzer  D, Gracien  E, Ganser  A, Kelly  K, Reutzel  R, Lipp  T, Busch  F W, Schwonzen  M, Heil  G, Wandt  H, Koch  P, Kolbe  K, Heyll  A, Bentz  M, Peters  S, Diedrich  H, Dethling  J, Meyer  P, Nowrousian  M R, Löffler  B, Weiss  A, Kneba  M, Föller  A, Graf  M, Hecht  T. Concomitant granulocyte colony-stimulating factor and induction chemoradiotherapy in adult acute lymphoblastic leukemia: a randomized phase III trial.  Blood. 1995;;  86 444-450
    Google Scholar
  • 078 Ozer  H, Armitage  J O, Bennett  C L, Crawford  J, Demetri  G D, Pizzo  P A, Schiffer  C A, Smith  T J, Somlo  G, Wade  J C, Winn  R J, Wozniak  A J, Somerfield  M R. 2000 update of recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines.  J Clin Oncol. 2000;;  18 3558-3585
    Google Scholar
  • 079 Petros  W P. Pharmacokinetics and administration of colony-stimulating factors.  Pharmacotherapy. 1992;;  12 32S-38S
    Google Scholar
  • 080 Pui  C H, Boyett  J M, Hughes  W T, Rivera  G K, Hancock  M L, Sandlund  J T, Synold  T, Relling  M V, Ribeiro  R C, Crist  W M, Evans  W E. Human granulocyte colony-stimulating factor after induction chemotherapy in children with acute lymphoblastic leukemia.  N Engl J Med. 1997;;  336 1781-1787
    Google Scholar
  • 081 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;;  32 326-330
    Google Scholar
  • 082 Reisner  Y, Bachar-Lustig  E, Li  HW, Aversa  F, Velardi  A, Martelli  M F. The role of megadose CD34 + progenitor cells in the treatment of leukemia patients without a matched donor and in tolerance induction for organ transplantation.  Ann N Y Acad Sci. 1999;;  872 336-348
    Google Scholar
  • 083 Riikonen  P, Rahiala  J, Salonvaara  M, Perkkio  M. Prophylactic administration of granulocyte colony-stimulating factor (filgrastim) after conventional chemotherapy in children with cancer.  Stem Cells (Dayt). 1995;;  13 289-294
    Google Scholar
  • 084 Roilides  E, Uhlig  K, Venzon  D, Pizzo  P A, Walsh  T J. Neutrophil oxidative burst in response to blastoconidia and pseudohyphae of candida albicans: augmentation by granulocyte colony-stimulating factor and interferon-gamma.  J Infect Dis. 1992;;  166 668-673
    Google Scholar
  • 085 Roilides  E, Walsh  T J, Pizzo  P A, Rubin  M. Granulocyte colony-stimulating factor enhances the phagocytic and bactericidal activity of normal and defective human neutrophils.  J Infect Dis. 1991;;  163 579-583
    Google Scholar
  • 086 Rosenfeld  C S, Sulecki  M, Evans  C, Shadduck  R K. Comparison of intravenous versus subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor in patients with primary myelodysplasia.  Exp Hematol. 1991;;  19 273-277
    Google Scholar
  • 087 Rubino  C, Laplanche  A, Patte  C, Michon  J. Cost-minimization analysis of prophylactic granulocyte colony-stimulating factor after induction chemotherapy in children with non-Hodgkin's lymphoma.  J Natl Cancer Inst. 1998;;  90 750-755
    Google Scholar
  • 088 Saarinen  U M, Hovi  L, Juvonen  E, Riikonen  P, Mottonen  M, Makipernaa  A. Granulocyte-colony-stimulating factor after allogeneic and autologous bone marrow transplantation in children.  Med Pediatr Oncol. 1996;;  26 380-386
    Google Scholar
  • 089 Saarinen  U M, Hovi  L, Riikonen  P, Pihkala  J, Juvonen  E. Recombinant human granulocyte-macrophage colony-stimulating factor in children with chemotherapy-induced neutropenia.  Med Pediatr Oncol. 1992;;  20 489-496
    Google Scholar
  • 090 Saarinen-Pihkala  U M, Lanning  M, Perkkio  M, Makipernaa  A, Salmi  T T, Hovi  L, Vettenranta  K. Granulocyte-macrophage colony-stimulating factor support in therapy of high-risk acute lymphoblastic leukemia in children.  Med Pediatr Oncol. 2000;;  34 319-327
    Google Scholar
  • 091 Sakata  K, Aoki  Y, Muta  N, Therahara  A, Karasawa  K, Onogi  Y, Nakagawa  K, Hasezawa  K, Sasaki  Y, Akanuma  A. Effect of human granulocyte colony-stimulating factor on neutropenia induced by radiotherapy and chemotherapy.  Oncology. 1993;;  50 238-240
    Google Scholar
  • 092 Schaison  G, Eden  O B, Henze  G, Kamps  W A, Locatelli  F, Ninane  J, Ortega  J, Riikonen  P, Wagner  H P. Recommendations on the use of colony-stimulating factors in children: conclusions of a European panel.  Eur J Pediatr. 1998;;  157 955-966
    Google Scholar
  • 093 Schmidberger  H, Hess  C F, Hoffmann  W, Reuss-Borst  M A, Bamberg  M. Granulocyte colony-stimulating factor treatment of leucopenia during fractionated radiotherapy.  Eur J Cancer. 1993;;  14 1927-1931
    Google Scholar
  • 094 Schmitz  N, Linch  D C, Dreger  P, Goldstone  A H, Boogaerts  M A, Ferrant  A, Demuynck  H MS, Link  H, Zander  A, Barge  A, Borkett  K. Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients.  Lancet. 1996;;  347 353-357
    Google Scholar
  • 095 Seibel  N L, Blaney  S M, O'Brien  M, Krailo  M, Hutchinson  R, Mosher  R B, Balis  F M, Reaman  G H. 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;;  5 733-737
    Google Scholar
  • 096 Spitzer  G, Adkins  D R, Spencer  V, Dunphy  F R, Petruska  P J, Velasquez  W S, Bowers  C E, Kronmueller  N, Niemeyer  R, McIntyre  W. Randomized study of growth factors post-peripheral-blood-stem-cell transplant: neutrophil recovery is improved with modest clinical benefit.  J Clin Oncol. 1994;;  12 661-670
    Google Scholar
  • 097 Strife  A, Lambek  C, Wisniewski  D, Gulati  S, Gasson  J C, Golde  D W, Welte  K, Gabrilove  J L, Clarkson  B. Activities of four purified growth factors on highly enriched human hematopoietic progenitor cells.  Blood. 1987;;  69 1508-1523
    Google Scholar
  • 098 Suzue  T, Takaue  Y, Watanabe  A, Kawano  Y, Watanabe  T, Abe  T, Kuroda  Y, Matsushita  T, Kikuta  A, Iwai  A. 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 1197-1202
    Google Scholar
  • 099 Tarella  C, Castellino  C, Locatelli  F, Caracciolo  D, Corradini  P, Falda  M, Novarino  A, Tassi  V, Pileri  A. G-CSF administration following peripheral blood progenitor cell (PBPC) autograft in lymphoid malignancies: evidence for clinical benefits and reduction of treatment costs.  Bone Marrow Transplant. 1998;;  21 401-407
    Google Scholar
  • 100 van Pelt  L J, de Craen  A J, Langeveld  N E, Weening  R S. Granulocyte-macrophage colony-stimulating factor (GM-CSF) ameliorates chemotherapy-induced neutropenia in children with solid tumors.  Pediatr Hematol Oncol. 1997;;  14 539-545
    PubMedGoogle Scholar
  • 101 Vey  N, Molnar  S, Faucher  C, Le Corroller  A G, Stoppa  A M, Viens  P, Bouabdallah  R, Camerlo  J, Novakovitch  G, Mannoni  P. Delayed administration of granulocyte colony-stimulating factor after autologous bone marrow transplantation: effect on granulocyte recovery.  Bone Marrow Transplant. 1994;;  14 779-782
    PubMedGoogle Scholar
  • 102 Villa  M, Madero  L, Diaz  M A, Alegre  A, Granda  A, Velasco  M, Vicario  J L. Allogeneic peripheral blood progenitor cell (PBPC) transplantation in children.  Bone Marrow Transplant. 1996;;  18 231-233
    PubMedGoogle Scholar
  • 103 Wagner  J E, Kernan  N A, Steinbuch  M, Broxmeyer  H E, Gluckman  E. Allogeneic sibling umbilical-cord-blood transplantation in children with malignant and non-malignant disease.  Lancet. 1995;;  346 214-219
    CrossrefPubMedGoogle Scholar
  • 104 Wagner  J E, Rosenthal  J, Sweetman  R, Shu  X O, Davies  S M, Ramsay  N K, McGlave  P B, Sender  L, Cairo  M S. Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease.  Blood. 1996;;  88 795-802
    PubMedGoogle Scholar
  • 105 Watanabe  T, Kajiume  T, Abe  T, Kawano  Y, Iwai  A, Iwai  T, Takaue  Y, Kuroda  Y. Allogeneic peripheral blood stem cell transplantation in children with hematologic malignancies from HLA-matched siblings.  Med Pediatr Oncol. 2000;;  34 171-176
    CrossrefPubMedGoogle Scholar
  • 106 Weaver  C H, Hazelton  B, Birch  R, Palmer  P, Allen  C, Schwartzberg  L, West  W. An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloablative chemotherapy.  Blood. 1995;;  86 3961-3969
    PubMedGoogle Scholar
  • 107 Weisdorf  D J, Verfaillie  C M, Davies  S M, Filipovich  A H, Wagner  J E Jr, Miller  J S, Burroughs  J, Ramsay  N K, Kersey  J H, McGlave  P B. Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte-CSF.  Blood. 1995;;  85 3452-3456
    PubMedGoogle Scholar
  • 108 Welte  K, Gabrilove  J, Bronchud  M H, Platzer  E, Morstyn  G. Filgrastim (r-metHuG-CSF): The first 10 years.  Blood. 1996;;  88 1907-1929
    PubMedGoogle Scholar
  • 109 Welte  K, Reiter  A, Mempel  K, Pfetsch  M, Schwab  G, Schrappe  M, Riehm  H. A randomized phase-III study of the efficacy of granulocyte colony-stimulating factor in children with high-risk acute lymphoblastic leukemia. Berlin-Frankfurt-Münster Study Group.  Blood. 1996;;  87 3143-3150
    PubMedGoogle Scholar
  • 110 Wexler  L H, Weaver-McClure  L, Steinberg  S M, Jacobson  J, Jarosinski  P, Avila  N, Pizzo  P A, Horowitz  M E. Randomized trial of recombinant human granulocyte-macrophage colony-stimulating factor in pediatric patients receiving intensive myelosuppressive chemotherapy.  J Clin Oncol. 1996;;  14 901-910
    PubMedGoogle Scholar

PD Dr. med. Thomas Lehrnbecher

Pädiatrische Hämatologie und Onkologie
Klinik für Kinderheilkunde III
Universität Frankfurt

Theodor-Stern-Kai 7

60590 Frankfurt

Phone: 0 69/63 01-49 18

Fax: 0 69/63 01-67 00

Email: thomas_lehrnbecher@yahoo.com

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