Hämatopoetische Wachstumsfaktoren in der Prophylaxe und Therapie infektiöser Komplikationen bei Kindern mit Neutropenie

Zusammenfassung.

Der Einsatz von gentechnologisch hergestellten hämatopoetischen Wachstumsfaktoren wie G-CSF (granulocyte colony stimulating factor) oder GM-CSF (granulocyte-macrophage colony stimulating factor) versprach einen großen Fortschritt in der Supportivtherapie von Patienten mit angeborener oder erworbener Neutropenie. Basierend auf den Ergebnissen zahlreicher Studien wurden in den letzten Jahren Leitlinien für den rationalen Einsatz der teuren Wachstumsfaktoren erstellt [3] [4] [152] [174]. Um das Risiko schwerer infektiöser Komplikationen bei krebskranken Patienten 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 von der Gabe der Wachstumsfaktoren, während dies für Patienten mit soliden Tumoren noch unklar ist. Die Mobilisierung peripherer Stammzellen zur autologen oder allogenen Transplantation stellt ein neues und viel versprechendes Einsatzgebiet der hämatopoetischen Wachstumsfaktoren dar. Während Studien zum Einsatz der hämatopoetischen Wachstumsfaktoren bei Kindern mit myelodysplastischem Syndrom weitgehend fehlen, sollen Kinder mit schwerer aplastischer Anämie frühzeitig G-CSF erhalten. Ebenfalls ist die Gabe von G-CSF bei Kindern mit schwerer chronischer Neutropenie indiziert, wobei die Kinder jedoch engmaschig auf zytologtische Auffälligkeiten untersucht werden müssen. Bisher konnte keine größere Studie einen klinischen Nutzen der hämatopoetischen Wachstumsfaktoren bei Früh- und Neugeborenen zeigen, so dass hier der routinemäßige Einsatz der Wachstumsfaktoren nicht empfohlen wird. Zukünftige Studien müssen 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.

Hematopoietic colony-stimulating factors have been introduced into clinical practice as additional supportive measures to reduce infectious complications associated with congenital or acquired 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 corpus of studies, a set of formal recommendations have been propagated for the judicious use of these expensive growth factors [3] [4] [152] [174]. To prevent serious infection, the use of G-CSF or GM-CSF is recommended in a subset of pediatric cancer patients shortly after having received chemotherapy or a form of a marrow transplant. Children with highly intensive chemotherapy (e.g., children with high risk ALL or NHL) seem to benefit from hematopoietic growth factors whereas this is still unclear for children undergoing therapy for solid tumors. An exciting development is the use of G-CSF and GM-CSF to mobilize peripheral-blood progenitor cells for autologous or allogeneic transplantation. In pediatric patients with hematological diseases, there are only few data on the use of hematopoietic growth factors in children with myelodysplastic syndrome. Experts recommend the early administration of G-CSF in children with very severe aplastic anemia. The use of G-CSF is also recommended in children with severe chronic neutropenia, but these patients have to be monitored regularly for cytogenetic abnormalities. No larger study has shown a clinical benefit of hematopoietic growth factor in preterm or term infants. Future studies in pediatric 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 of patients. 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 - Kinder - Infektion - Neutropenie

Key words

Hematopoietic growth factor - G-CSF - GM-CSF - children - infectious complication - neutropenia

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
• 002 Adachi  N, Tsuchiya  H, Nunoi  H, Higuchi  S, Akaboshi  I, Chikazawa  S. rhG-CSF for Shwachman's syndrome [letter].  Lancet. 1990;;  336 1136
• 003 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
• 004 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
• 005 Anaissie  E J, Vartivarian  S, Bodey  G P, Legrand  C, Kantarjian  H, Abi-Said  D, Karl  C, Vadhan-Raj  S. Randomized comparison between antibiotics alone and antibiotics plus granulocyte macrophage colony-stimulating factor (Escherichia coli-derived) in cancer patients with fever and neutropenia.  Am J Med. 1996;;  100 17-23
• 006 Bacigalupo  A, Bruno  B, Saracco  P, Di Bona  E, Locasciulli  A, Locatelli  F, Gabbas  A, Dufour  C, Arcese  W, Testi  G, Broccia  G, Carotenuto  M, Coser  P, Barbui  T, Leoni  P, Ferster  A. Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO/EBMT study on 100 patients. European Group for Blood and Marrow Transplantation (EBMT) Working Party on Severe Aplastic Anemia and the Gruppo Italiano Trapianti di Midolio Osseo (GITMO).  Blood. 2000;;  95 1931-1934
• 007 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
• 008 Barak  Y, Leibovitz  E, Mogilner  B, Juster-Reicher  A, Amitay  M, Ballin  A, Koren  A, Goebel  M. The in vivo effect of recombinant human granulocyte-colony stimulating factor in neutropenic neonates with sepsis.  Eur J Pediatr. 1997;;  156 643-646
• 009 Bearman  S I, Appelbaum  F R, Back  A, Petersen  F B, Buckner  C D, Sullivan  K M, Schoch  H G, Fisher  L D, Thomas  E D. Regimen-related toxicity and early posttransplant survival in patients undergoing marrow transplantation for lymphoma.  J Clin Oncol. 1989;;  7 1288-1294
• 010 Bedu  A, Rohrlich  P, Farnoux  C, Duval  M, Fenneteau  O, Boissinot  C, Pinquier  D, Cartron  J, Vilmer  E, Aujard  Y. Neonatal alloimmune neutropenias. Importance of treatment with granulocyte colony-stimulating factor (G-CSF). Report of 2 new cases.  Arch Pediatr. 1999;;  6 1297-1301
• 011 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
• 012 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
• 013 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
• 014 Bernini  J C, Wooley  R, Buchanan  G R. Low-dose recombinant human granulocyte colony stimulating factor therapy in children with symptomatic chronic idiopathic neutropenia.  J Pediatr. 1996;;  129 551-558
• 015 Bodey  G P, Anaissie  E, Gutterman  J, Vadhan-Raj  S. Role of granulocyte macrophage colony stimulating factor as adjuvant therapy for fungal infection in patients with cancer.  Clin Infect Dis. 1993;;  17 705-707
• 016 Bodey  G P, Buckley  M, Sathe  Y S, Freireich  E J. Quantitative relationships between circulating leukocytes and infections in patients with acute leukemia.  Ann Intern Med. 1966;;  64 328-340
• 017 Bonilla  M A, Dale  D, Zeidler  C, Last  L, Reiter  A, Ruggeiro  M, Davis  M, Koci  B, Hammond  W, Gillio  A, Welte  K. Long-term safety of treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) in patients with severe congenital neutropenias.  Br J Haematol. 1994;;  88 723-730
• 018 Bonilla  M A, Gillio  A P, Ruggeiro  M, Kernan  N A, Brochstein  J A, Abboud  M, Fumagalli  L, Vincent  M, Gabrilove  J L, Welte  K, Souza  L M, O'Reilly  R J. Effects of recombinant human granulocyte colony-stimulating factor on neutropenia in patients with congenital agranulocytosis.  N Engl J Med. 1989;;  320 1574-1580
• 019 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
• 020 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
• 021 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
• 022 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
• 023 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
• 024 Cairo  M S, Agosti  J, Ellis  R, Laver  J J, Puppala  B, deLemos  R, Givner  L, Nesin  M, Wheeler  J G, Seth  T, van de Ven  C, Fanaroff  A. A randomized, double-blind, placebo-controlled trial of prophylactic recombinant human granulocyte-macrophage colony-stimulating factor to reduce nosocomial infections in very low birth weight neonates.  J Pediatr. 1999;;  134 64-70
• 025 Cairo  M S, Christensen  R, Sender  L S, Ellis  R, Rosenthal  J, van de Ven  C, Worcester  C, Agosti  J M. Results of a phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor in very low birthweight neonates: significant induction of circulatory neutrophils, monocytes, platelets, and bone marrow neutrophils.  Blood. 1995;;  86 2509-2515
• 026 Cairo  M S, Plunkett  J M, Mauss  D, van de Ven  C. Seven-day administration of recombinant human granulocyte colony-stimulating factor to newborn rats: modulation of neonatal neutrophilia, myelopoiesis, and group B Streptococcus sepsis.  Blood. 1990;;  76 1788-1794
• 027 Cairo  M S, van de Ven  C, Toy  C, Mauss  D, Sender  L. Recombinant human granulocyte macrophage colony-stimulating factor primes neonatal granulocytes for enhanced oxidative metabolism and chemotaxis.  Pediatr Res. 1989;;  26 395-399
• 028 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
• 029 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
• 030 Calhoun  D A, Lunoe  M, Du  Y, Hutson  A D, Veerman  M, Christensen  R D. Granulocyte colony stimulating factor serum and urine concentrations in neutropenic neonates before and after intravenous administration of recombinant granulocyte colony-stimulating factor.  Pediatrics. 2000;;  105 392-397
• 031 Carr  R, Modi  N. Haemopoietic colony stimulating factors for preterm neonates.  Arch Dis Child Fetal Neonatal Ed. 1997;;  76 F128-133
• 032 Carr  R, Modi  N, Dore  C J, El-Rifai  R, Lindo  D. A randomized, controlled trial of prophylactic granulocyte-macrophage colony-stimulating factor in human newborns less than 32 weeks gestation.  Pediatrics. 1999;;  103 796-802
• 033 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
• 034 Chanock  S J, Pizzo  P A. Fever in the neutropenic host.  Infect Dis Clin North Am. 1996;;  10 777-796
• 035 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
• 036 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
• 037 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
• 038 Christensen  R D, Calhoun  D A, Rimsza  L M. A practical approach to evaluating and treating neutropenia in the neonatal intensive care unit.  Clin Perinatol. 2000;;  27 577-601
• 039 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
• 040 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
• 041 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
• 042 Cortelazo  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
• 043 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
• 044 Dale  D C, Bonilla  M A, Davis  M W, Nakanishi  A M, Hammond  W P, Kurtzberg  J, Wang  W, Jakubowski  A, Winton  E, Lalezari  P, Robinson  W, Glaspy  J A, Emerson  S, Gabrilove  J, Vincent  M, Boxer  L A. A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia.  Blood. 1993;;  81 2496-2502
• 045 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
• 046 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
• 047 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
• 048 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
• 049 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
• 050 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
• 051 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
• 052 Donadieu  J, Boutard  P, Tchernia  G, Oster  G, Gordon-Smith  E C, Philippe  N, Le Gall  E, Nivelon  J L, Dopfer  P, Babin-Boilletot  A, Coulombel  L, Pocidalo  M A, Yver  A, Griscelli  C. A phase II study of recombinant human granulocyte-colony stimulating factor (rHuG-CSF, lenograstim) in the treatment of agranulocytosis in children.  Nouv Rev Fr Hematol. 1994;;  36 441-448
• 053 Dong  F, Brynes  R K, Tidow  N, Welte  K, Lowenberg  B, Touw  I P. 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;;  333 487-493
• 054 Drossou-Agakidou  V, Kanakoudi-Tsakalidou  F, Sarafidis  K, Taparkou  A, Tzimouli  V, Tsandali  H, Kremenopoulos  G. Administration of recombinant human granulocyte-colony stimulating factor to septic neonates induces neutrophilia and enhances the neutrophil respiratory burst and beta2 integrin expression. Results of a randomized controlled trial.  Eur J Pediatr. 1998;;  157 583-588
• 055 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
• 056 Economopoulos  T, Mellou  S, Papageorgiou  E, Pappa  V, Kokkinou  V, Stathopoulou  E, Pappa  M, Raptis  S. Treatment of anemia in low risk myelodysplastic syndromes with granulocyte macrophage colony-stimulating factor plus recombinant human erythropoietin.  Leukemia. 1999;;  13 1009-1012
• 057 Estey  E H, Kurzrock  R, Talpaz  M, McCredie  K B, O'Brien  S, Kantarjian  H M, Keating  M J, Deisseroth  A B, Gutterman  J U. Effects of low doses of recombinant human granulocyte macrophage colony stimulating factor (GM-CSF) in patients with myelodysplastic syndromes.  BrJ Haematol. 1991;;  77 291-295
• 058 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
• 059 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
• 060 Fink  F M, Maurer-Dengg  K, Fritsch  G, Mann  G, Zoubek  A, Falk  M, Gadner  H. Recombinant human granulocyte-macrophage colony-stimulating factor in septic neutropenic pediatric cancer patients: detection of circulating hematopoietic precursor cells correlates with rapid granulocyte recovery.  Med Pediatr Oncol. 1995;;  25 365-371
• 061 Flynn  T N, Kelsey  S M, Hazel  D L, Guest  J F. Cost effectiveness of amphotericin B plus G-CSF compared with amphotericin B monotherapy. Treatment of presumed deep-seated fungal infection in neutropenic patients in the UK.  Pharmacoeconomics. 1999;;  16 543-550
• 062 Freedman  M H, Bonilla  M A, Fier  C, Bolyard  A A, Scarlata  D, Boxer  L A, Brown  S, Cham  B, Kannourakis  G, Kinsey  S E, Mori  P G, Cottle  T, Welte  K, Dale  D C. Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy.  Blood. 2000;;  96 429-436
• 063 Freifeld  A, Hathorn  J, Pizzo  P. Infectious complications in the pediatric cancer patient. In: Pizzo P, Poplack D (eds). Principles and Practice of Pediatric Oncology. Lippincott Co., Philadelphia; 1993;: 987-1020
• 064 Führer  M, Rampf  U, Burdach  S, Dörffel  W, Ebell  W, Friedrich  W, Haas  R, Klingebiel  T, Niemeyer  C, Ritter  J, Sörensen  J, Stollmann-Gibbels  B, Walther  J U, Zeidler  C, Bender-Götze  C. Immunosuppressive therapy (IST) and bone marrow transplantation (BMT) for aplastic anemia (AA) in children: results ofthe study SAA [abstract].  Blood. 1998;;  92 (suppl) 156a
• 065 Furukawa  T, Takahashi  M, Moriyama  Y, Koike  T, Kurokawa  I, Shibata  A. Successful treatment of chronic idiopathic neutropenia using recombinant granulocyte colony-stimulating factor.  Ann Hematol. 1991;;  62 22-24
• 066 Gabarre  J, Lepage  E, Thyss  A, Tubiana  R, Bastion  Y, Schlaifer  D, Sebban  C, Ribrag  V, Fereres  M, Raphael  M. Chemotherapy combined with zidovudine and GM-CSF in human immunodeficiency virus-related non-Hodgkin's lymphoma.  Ann Oncol. 1995;;  6 1025-1032
• 067 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 ofthe urothelium.  N Engl J Med. 1988;;  318 1414-1422
• 068 Gasson  J C. Molecular physiology of granulocyte-macrophage colony-stimulating factor.  Blood. 1991;;  77 1131-1145
• 069 Germeshausen  M, Tidow  N, Pilz  C, Tschan  C, Zeidler  C, Welte  K. G-CSF receptor mutations in patients with severe congenital neutropenia: frequency and implications in leukemic development [abstract].  Blood. 1999;;  94 45a
• 070 Gessler  P, Neu  S, Nebe  T, Speer  C P. Granulocyte colony-stimulating factor receptor expression on neutrophils of term and preterm neonates with and without signs of infection.  Eur J Pediatr. 1999;;  158 497-500
• 071 Gillan  E R, Christensen  R D, Suen  Y, Ellis  R, van de Ven  C, Cairo  M S. A randomized, placebo controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia.  Blood. 1994;;  84 1427-1433
• 072 Gilmore  M M, Stroncek  D F, Korones  D N. Treatment of alloimmune neonatal neutropenia with granulocyte colony-stimulating factor.  J Pediatr. 1994;;  125 948-951
• 073 Gluckman  E, Rokicka-Milewska  R, Gordon-Smith  E C, Hann  I, Nikiforakis  E, Tavakoli  F, Cohen Scali  S, Bacigalupo  A. Results of randomized study of glycosylated rHuG-CSF lenograstim in severe aplastic anemia [abstract].  Blood. 1998;;  92 (suppl) 376a
• 074 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
• 075 Greenberg  P, Taylor  K, Larson  R, Koeffler  P, Negrin  R, Saba  H, Ganser  A, Jakubowski  A, Gabrilove  J, Mufti  G, Cruz  J, Hammond  W, Broudy  V, Langley  G R, Keating  A, Vardiman  J, Lamborn  K, Brown  S. Phase III randomized multicenter trial of G-CSF vs. observation for myelodysplastic syndromes (MDS) [abstract].  Blood. 1993;;  82 (suppl) 196
• 076 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
• 077 Hammond  W PT, Price  T H, Souza  L M, Dale  D C. Treatment of cyclic neutropenia with granulocyte colony-stimulating factor.  N Engl J Med. 1989;;  320 1306-1311
• 078 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 N Y Acad Sci. 1999;;  872 351-361
• 079 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
• 080 Hellstrom-Lindberg  E, Ahlgren  T, Beguin  Y, Carlsson  M, Carneskog  J, Dahl  I M, Dybedal  I, Grimfors  G, Kanter-Lewensohn  L, Linder  O, Luthman  M, Lofvenberg  E, Nilsson-Ehle  H, Samuelsson  J, Tangen  J M, Winqvist  I, Oberg  G, Osterborg  A, Ost  A. Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients.  Blood. 1998;;  92 68-75
• 081 Hill  H R. Host defenses in the neonate: prospects for enhancement.  Semin Perinatol. 1985;;  9 2-11
• 082 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
• 083 Hughes  W T, Armstrong  D, Bodey  G P, Brown  A E, Edwards  J E, Feld  R, Pizzo  P A, Rolston  K VI, Shenep  J L, Young  L S. 1997 guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever.  Clin Infect Dis. 1997;;  25 551-573
• 084 Ishiguro  A, Nakahata  T, Shimbo  T, Amano  Y, Yasui  K, Koike  K, Komiyama  A. Improvement of neutropenia and neutrophil dysfunction by granulocyte colony-stimulating factor in a patient with glycogen storage disease type Ib.  Eur J Pediatr. 1993;;  152 18-20
• 085 Jakubowski  A A, Souza  L, Kelly  F, Fain  K, Budman  D, Clarkson  B, Bonilla  M A, Moore  M A, Gabrilove  J. Effects of human granulocyte colony-stimulating factor in a patient with idiopathic neutropenia.  N Engl J Med. 1989;;  320 38-42
• 086 Jayabose  S, Tugal  O, Sandoval  C, Li  K. Recombinant human granulocyte colony stimulating factor in cyclic neutropenia: use of a new 3-day-a-week regimen.  Am J Pediatr Hematol Oncol. 1994;;  16 338-340
• 087 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
• 088 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
• 089 Juul  S E, Calhoun  D A, Christensen  R D. Idiopathic neutropenia in very low birthweight infants.  Acta Paediatr. 1998;;  87 963-968
• 090 Kaito  K, Kobayashi  M, Katayama  T, Masuoka  H, Shimada  T, Nishiwaki  K, Sekita  T, Otsubo  H, Ogasawara  Y, Hosoya  T. Long-term administration of G-CSF for aplastic anaemia is closely related to the early evolution of monosomy 7 MDS in adults.  Br J Haematol. 1998;;  103 297-303
• 091 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
• 092 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
• 093 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
• 094 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
• 095 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
• 096 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
• 097 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
• 098 Kocherlakota  P, La Gamma  E F. Human granulocyte colony-stimulating factor may improve outcome attributable to neonatal sepsis complicated by neutropenia.  Pediatrics. 1997;;  100 E6
• 099 Kocherlakota  P, La Gamma  E F. Preliminary report: rhG-CSF may reduce the incidence of neonatal sepsis in prolonged preeclampsia-associated neutropenia.  Pediatrics. 1998;;  102 1107-1111
• 100 Kojima  S, Fukuda  M, Miyajima  Y, Matsuyama  T, Horibe  K. Treatment of aplastic anemia in children with recombinant human granulocyte colony-stimulating factor.  Blood. 1991;;  77 937-941
• 101 Kojima  S, Hibi  S, Kosaka  Y, Yamamoto  M, Tsuchida  M, Mugishima  H, Sugita  K, Yabe  H, Ohara  A, Tsukimoto  I. Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia.  Blood. 2000;;  96 2049-2054
• 102 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
• 103 Kostmann  R. Infantile genetic agranulocytosis.  Acta Pediatr Scand. 1956;;  45 1-78
• 104 Koyanagi  Y, O'Brien  W A, Zhao  J Q, Golde  D W, Gasson  J C, Chen  I S. Cytokines alter production of HIV-1 from primary mononuclear phagocytes.  Science. 1988;;  241 1673-1675
• 105 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
• 106 Kümmerle-Deschner  J, Scheel-Walter  H G, Speer  C P. G-CSF therapy in a neonate with alloimmune neutropenia.  Z Geburtshilfe Neonatol. 1997;;  201 273-276
• 107 La Gamma  E F, Alpan  O, Kocherlakota  P. Effect of granulocyte colony-stimulating factor on preeclampsia-associated neonatal neutropenia.  J Pediatr. 1995;;  126 457-459
• 108 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
• 109 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
• 110 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
• 111 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
• 112 Lehrnbecher  T, Chanock  S J. Myeloid growth factors in supportive care of cancer and marrow transplant therapies. In: Holland S (ed). Cytokine therapeutics in infectious diseases. Lippincott-Raven (im Druck)
• 113 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
• 114 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
• 115 Liang  D C, Chen  S H, Lean  S F. Role of granulocyte colony-stimulating factor as adjunct therapy for septicemia in children with acute leukemia.  Am J Hematol. 1995;;  48 76-81
• 116 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
• 117 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
• 118 Locatelli  F, Zecca  M, Pession  A, Maserati  E, De Stefano  P, Severi  F. Myelodysplastic syndromes: the pediatric point of view.  Haematologica. 1995;;  80 268-279
• 119 Lowenberg  B, Touw  I P. Hematopoietic growth factors and their receptors in acute leukemia.  Blood. 1993;;  81 281-292
• 120 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
• 121 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
• 122 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
• 123 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
• 124 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
• 125 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-S10
• 126 Maher  D, Lieschke  G, Green  M, Bishop  J, Stuart-Harris  R, Wolf  M, Sheridan  W P, Kefford  R F, Cebon  J, Olver  I, McKendrick  J, Toner  G, Bradstock  K, Lieschke  M, Cruickshank  S, Tomita  D K, Hoffman  E W, Fox  R M, Morstyn  G. Filgastrim in patients with chemotherapy-induced febrile neutropenia. A double-blind, placebo controlled trial.  Ann Intern Med. 1994;;  121 492-501
• 127 Makhlouf  R A, Doron  M W, Bose  C L, Price  W A, Stiles  A D. Administration of granulocyte colony-stimulating factor to neutropenic low birth weight infants of mothers with preeclampsia.  J Pediatr. 1995;;  126 454-456
• 128 Marcolongo  R, Zambello  R, Trentin  L, Cassatella  M, Gasparotto  G, Agostini  C. Childhood onset cyclic neutropenia: G-CSF therapy restores neutrophil count but does not influence superoxide anion and cytokine release by neutrophils.  Br J Haematol. 1995;;  89 277-281
• 129 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 if osfamide, carboplatin, and etoposide chemotherapy.  Med Pediatr Oncol. 1994;;  23 328-334
• 130 Mayordomo  J I, Rivera  F, Diaz-Puente  M T, Lianes  P, Colomer  R, Lopez-Brea  M, Lopez  E, Paz Ares  L, Hitt  R, Garcia-Ribas  I. Improving treatment of chemotherapy-induced neutropenic fever by administration of colony-stimulating factors.  J Natl Cancer Inst. 1995;;  87 803-808
• 131 McCawley  L J, Korchak  H M, Douglas  S D, Campbell  D E, Thornton  P S, Stanley  C A, Baker  L, Kilpatrick  L. In vitro and in vivo effects of granulocyte colony-stimulating factor on neutrophils in glycogen storage disease type IB: granulocyte colony-stimulating factor therapy corrects the neutropenia and the defects in respiratory burst activity and Ca2+ mobilization.  Pediatr Res. 1994;;  35 84-90
• 132 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
• 133 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
• 134 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
• 135 Miles  S A, Mitsuyasu  R T, Moreno  J, Baldwin  G, Alton  N K, Souza  L, Glaspy  J A. Combined therapy with recombinant granulocyte colony-stimulating factor and erythropoietin decreases hematologic toxicity from zidovudine.  Blood. 1991;;  77 2109-2117
• 136 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
• 137 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 oftwo pediatric centers.  Bone Marrow Transplant. 1998;;  22 Suppl 5 S33-S36
• 138 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
• 139 Mitchell  P LR, Morland  B, Stevens  M CG, Dick  G, Easlea  D, Meyer  L C, Pinkerton  C R. Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients.  J Clin Oncol. 1997;;  15 1163-1170
• 140 Mori  P G, Pasino  M, Dufour  C, Boeri  E, Molinari  A C. Recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) and rhG-CSF in the treatment of a child with severe chronic neutropenia [letter].  Blood. 1994;;  84 3244-3245
• 141 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
• 142 Mueller  B U, Jacobsen  F, Butler  K M, Husson  R N, Lewis  L L, Pizzo  P A. Combination treatment with azidothymidine and granulocyte colony-stimulating factor in children with human immunodeficiency virus infection.  J Pediatr. 1992;;  121 797-802
• 143 Negrin  R S, Haeuber  D H, Nagler  A, Kobayashi  Y, Sklar  J, Donlon  T, Vincent  M, Greenberg  P L. Maintenance treatment of patients with myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor.  Blood. 1990;;  76 36-43
• 144 Negrin  R S, Stein  R, Doherty  K, Cornwell  J, Vardiman  J, Krantz  S, Greenberg  P L. 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 4076-4081
• 145 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
• 146 Newell  M, Goldstein  D, Milliken  S, Lewis  C, Hoy  J, Thomson  B, Cooper  D. Phase I/II trial of filgrastim (r-metHuG-CSF), CEOP chemotherapy and antiretroviral therapy in HIV-related non-Hodgkin's lymphoma.  Ann Oncol. 1996;;  7 1029-1036
• 147 Notarangelo  L D, Duse  M, Ugazio  A G. Immunodeficiency with hyper-IgM (HIM).  Immunodeficiency Rev. 1992;;  3 101-122
• 148 Notarangelo  L D, Duse  M, Ugazio  A G. Immunodeficiency with hyper-IgM (HIM).  Immunodefic Rev. 1992;;  3 101-121
• 149 Ohara  A, Kojima  S, Hamajima  N, Tsuchida  M, Imashuku  S, Ohta  S, Sasaki  H, Okamura  J, Sugita  K, Kigasawa  H, Kiriyama  Y, Akatsuka  J, Tsukimoto  I. Myelodysplastic syndrome and acute myelogenous leukemia as a late clonal complication in children with acquired aplastic anemia.  Blood. 1997;;  90 1009-1013
• 150 Ohls  R K, Christensen  R D, Schibler  K. A randomized, double-blind, placebo-controlled trial of granulocyte colony stimulating factor administration to treat neonatal neutropenia [abstract].  Pediatr Res. 1999;;  45 272A
• 151 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
• 152 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
• 153 Petros  W P. Pharmacokinetics and administration of colony-stimulating factors.  Pharmacotherapy. 1992;;  12 32S-38S
• 154 Pizzo  P A. Management of fever in patients with cancer and treatment-induced neutropenia.  N Engl J Med. 1993;;  328 1323-1332
• 155 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
• 156 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
• 157 Ravaud  A, Chevreau  C, Cany  L, Houyau  P, Dohollou  N, Roche  H, Soubeyran  P, Bonichon  F, Mihura  J, Eghbali  H, Tabah  I, Bui  B N. Granulocyte-macrophage colony-stimulating factor in patients with neutropenic fever is potent after low-risk but not after high-risk neutropenic chemotherapy regimens: results of a randomized phase III trial.  J Clin Oncol. 1998;;  16 2930-2936
• 158 Reisner  Y, Bachar-Lustig  E, Li  H W, 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 intolerance induction for organ transplantation.  Ann NY Acad Sci. 1999;;  872 336-348
• 159 Repiso  T, Garcia-Patos  V, Martin  N, Creus  M, Bastida  P, Castells  A. Disseminated fusariosis.  Pediatr Dermatol. 1996;;  13 118-121
• 160 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
• 161 Riikonen  P, Saarinen  U M, Mäkipernaa  A, Hovi  L, Komulainen  A, Pikhala  J, Jalanko  H. Recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of febrile neutropenia: a double blind placebo-controlled study in children.  Pediatr Infect Dis J. 1994;;  13 197-202
• 162 Robert-Koch-Institut, Kommission für Krankenhaushygiene und Infektionsprävention .Kategorisierung für Richtlinien für Krankenhaushygiene und Infektionsprävention am Robert-Koch-Institut. In:. Urban & Fischer Verlag, München Jena; 2000:
• 163 Rodwell  R L, Gray  P H, Taylor  K M, Minchinton  R. Granulocyte colony stimulating factor treatment for alloimmune neonatal neutropenia.  Arch Dis Child Fetal Neonatal Ed. 1996;;  75 F57-F58
• 164 Rodwell  R L, Taylor  K M, Tudehope  D I, Gray  P H. Hematologic scoring system in early diagnosis of sepsis in neutropenic newborns.  Pediatr Infect Dis J. 1993;;  12 372-376
• 165 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
• 166 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
• 167 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
• 168 Rosenthal  J, Healey  T, Ellis  R, Gillan  E, Cairo  M S. A two-year follow-up of neonates with presumed sepsis treated with recombinant human granulocyte colony-stimulating factor during the first week of life.  J Pediatr. 1996;;  128 135-137
• 169 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
• 170 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
• 171 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
• 172 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
• 173 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
• 174 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
• 175 Schibler  K R, Osborne  K A, Leung  L Y, Le  T V, Baker  S I, Thompson  D D. A randomized, placebo controlled trial of granulocyte colony-stimulating factor administration to newborn infants with neutropenia and clinical signs of early-onset sepsis.  Pediatrics. 1998;;  102 6-13
• 176 Schimpff  S, Satterlee  W, Young  V, Serpick  A. Empiric therapy with carbenicillin and gentamicin for febrile, patients with cancer and granulocytopenia.  N Engl J Med. 1971;;  284 1061-1065
• 177 Schimpff  S C, Young  V M, Greene  W H, Vermeulen  G D, Moody  M R, Wiernik  P H. Origin of infection in acute nonlymphocytic leukemia: Significance of hospital acquisition of potential pathogens.  Ann Intern Med. 1972;;  77 707-714
• 178 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
• 179 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
• 180 Schoepfer  C, Carla  H, Bezou  M J, Cambon  M, Girault  D, Demeocq  F, Malpuech  G. Malassezia furfur septicemia after bone marrow graft.  Arch Pediatr. 1995;;  2 245-248
• 181 Schroten  H, Roesler  J, Breidenbach  T, Wendel  U, Elsner  J, Schweitzer  S, Zeidler  C, Burdach  S, Lohmann-Matthes  M L, Wahn  V, Welte  K. Granulocyte and granulocyte-macrophage colony stimulating factors for treatment of neutropenia in glycogen storage disease type Ib.  J Pediatr. 1991;;  119 748-754
• 182 Schuster  M W, Thompson  J A, Larson  R, Coiffier  B, Bennett  J, Dugan  M. Randomized phase II study of recombinant granulocyte macrophage-colony stimulating factor (rGM-CSF) in patients with neutropenia secondary to myelodysplastic syndromes (MDS) [abstract].  Blood. 1995;;  86 338
• 183 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
• 184 Sloand  E, Kumar  P N, Pierce  P F. Chemotherapy for patients with pulmonary Kaposi's sarcoma: benefit of filgrastim (G-CSF) in supporting dose administration.  South Med J. 1993;;  86 1219-1224
• 185 Speer  C P, Johnston  R B Jr. Neutrophil function in newborn infants. In: Polin RA, Fox WW (eds). Fetal and neonatal physiology. WB Saunders, Philadelphia; 1998;: 1954-1960
• 186 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
• 187 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
• 188 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
• 189 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
• 190 Tidow  N, Pilz  C, Teichmann  B, Müller-Brechlin  A, Germeshausen  M, Kasper  B, Rauprich  P, Sykora  K W, Welte  K. Clinical relevance of point mutations in the cytoplasmic domain of the granulocyte colony-stimulating factor receptor gene in patients with severe congenital neutropenia.  Blood. 1997;;  89 2369-2375
• 191 Vadhan-Raj  S, Keating  M, LeMaistre  A, Hittelman  W N, McCredie  K, Trujillo  J M, Broxmeyer  H E, Henney  C, Gutterman  J U. Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes.  N Engl J Med. 1987;;  317 1545-1552
• 192 van der Sande  F M, Hillen  H F. Correction of neutropenia following treatment with granulocyte colony-stimulating factor results in a decreased frequency of infections in Shwachman's syndrome.  Neth J Med. 1996;;  48 92-95
• 193 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
• 194 Vellenga  E, Uyl-de Groot  C A, de Wit  R, Keizer  H J, Lowenberg  B, ten Haaft  M A, de Witte  T J, Verhagen  C A, Stoter  G J, Rutten  F F, Mulder  N H, Smid  W M, de Vries  E G. Randomized placebo-controlled trial of granulocyte-macrophage stimulating factor in patients with chemotherapy-related febrile neutropenia.  J Clin Oncol. 1996;;  14 619-627
• 195 Ventura  A, Dragovich  D, Luxardo  P, Zanazzo  G. Human granulocyte colony-stimulating factor (rHuG-CSF) for treatment of neutropenia in Shwachman syndrome.  Haematologica. 1995;;  80 227-229
• 196 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
• 197 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
• 198 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
• 199 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
• 200 Wang  W C, Cordoba  J, Infante  A J, Conley  M E. Successful treatment of neutropenia in the hyper immunoglobulin M syndrome with granulocyte colony-stimulating factor.  Am J Pediatr Hematol Oncol. 1994;;  16 160-163
• 201 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
• 202 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
• 203 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
• 204 Welte  K, Gabrilove  J, Bronchud  M H, Platzer  E, Morstyn  G. Filgrastim (r-metHuG-CSF): The first 10 years.  Blood. 1996;;  88 1907-1929
• 205 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
• 206 Welte  K, Zeidler  C, Reiter  A, Muller  W, Odenwald  E, Souza  L, Riehm  H. Differential effects of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in children with severe congenital neutropenia.  Blood. 1990;;  75 1056-1063
• 207 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
• 208 Yoshida  Y, Nakahata  T, Shibata  A, Takahashi  M, Moriyama  Y, Kaku  K, Masaoka  T, Kaneko  T, Miwa  S. Effects of long-term treatment with recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndrome.  Leuk Lymphoma. 1995;;  18 457-463
• 209 Zeidler  C, Boxer  L, Dale  D C, Freedman  M H, Kinsey  S, Welte  K. Management of Kostmann syndrome in the G-CSF era.  Br J Haematol. 2000;;  109 490-495
• 210 Zeidler  C, Schwinzer  B, Welte  K. Schwere angeborene Neutropenie: Neue Aspekte der Diagnostik und Therapie.  Klin Pädiatr. 2000;;  212 145-152