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• W2007985065 abstract "The approach to the treatment of a patient with a decreased number of circulating neutrophils has been based primarily on the experience in cancer patients (Pizzo, 1993). Over the past three decades, the supportive care paradigm has evolved into a highly sophisticated process that requires constant attention and a readiness to respond to rapid changes, many of which have been induced by previous interventions. The principles are readily applicable to other patients with neutropenia (e.g. congenital), but it may not be necessary to intervene in this group, especially if there are no other defects in host defence. In contrast, therapy-induced alterations of the immune system other than neutropenia, such as alterations in skin/mucosal barriers and defects in cell-mediated and humoral immunity, increase the predisposition to infection in cancer patients (Lehrnbecher et al, 1997). The clinical significance of these alterations is not clear and is the focus of ongoing studies. Early studies in cancer patients demonstrated the increased likelihood that a serious bacterial infection would occur during absolute neutropenia, which is defined as an absolute neutrophil count (ANC) of less than 0·5 × 109/l (Bodey et al, 1966; Schimpff et al, 1971, 1972). Not only the depth but also the duration of neutropenia contributes to the risk for infection; for example, it was observed that the likelihood of developing a bacterial infection approached 100% when patients remained neutropenic for 3 or more weeks without antibiotic therapy (Bodey et al, 1966; Schimpff et al, 1971, 1972). It was recognized that the presence of fever (greater than 38·5°C) correlated with serious infection in the neutropenic host. In response to the poor outcome observed in the majority of these patients, early empirical antibiotic therapy has evolved and virtually eliminated mortality, which is now < 3% (De Pauw et al, 1994; Freifeld et al, 1995; Chanock & Pizzo, 1996). The success of this approach has been based on clinical intervention before the results of the diagnostic evaluation are available. Despite early antibiotic therapy, fever in the neutropenic host is the most important determinant for modification of therapy as well as one of the most common reasons for hospitalization (Pizzo, 1981, 1993). One of the most notable and clinically useful by-products of recombinant DNA technology is the availability of haematopoietic growth factors which can directly stimulate myelopoiesis. The commercial availability of granulocyte colony-stimulating factor (G-CSF) and granulocyte–monocyte colony-stimulating factor (GM-CSF) has significantly altered supportive care in the neutropenic cancer patient (Welte et al, 1985; Wong et al, 1985; Souza et al, 1986) (Table I). Both G-CSF and GM-CSF expand circulating pools of neutrophils by stimulating proliferation and maturation of myeloid progenitor cells (Strife et al, 1987; Gasson, 1991; Welte et al, 1996a). GM-CSF also accelerates production of monocytes and eosinophils in bone marrow, although the clinical implications of this are not readily appreciated (Chen et al, 1988a, b). During the investigation of the biology of G-CSF and GM-CSF, important similarities and critical differences have been uncovered, few of which influence clinical indications for use. In this regard, the two agents are more similar and thus can be used interchangeably in many, but not all, clinical situations. The observation that both G-CSF and GM-CSF mobilize haematopoietic stem cells in the peripheral blood has had profound implications for harvesting stem cells for transplantation and stem cell rescue. In addition, both myeloid colony factors G-CSF and GM-CSF can enhance phagocytic function in neutrophils ex vivo (Spiekermann et al, 1997). GM-CSF also augments monocyte function in a similar manner to neutrophils (Fabian et al, 1991; Gadish et al, 1991). In ex vivo studies, G-CSF and GM-CSF enhance superoxide generation, phagocytosis, and fungicidal activity against Candida albicans and Aspergillus fumigatus (Roilides et al, 1991, 1992; Cohen et al, 1997). Also GM-CSF has been reported to enhance uptake and destruction of bacterial and parasitic pathogens (Fleischmann et al, 1986; Villalta & Kierszenbaum, 1986), augment antibody-dependent cellular cytotoxicity (Baldwin et al, 1988, 1989), and increase release of pro-inflammatory cytokines. One group has reported synergistic microbicidal activity between antibiotics and neutrophils treated with G-CSF (Kropec et al, 1995). Both G-CSF and GM-CSF have undergone commercial development and are now widely available for use in the form of recombinant proteins. However, the judicious use of these costly agents is not as well defined and is the source of ongoing controversy. Evidence-based clinical practice guidelines have been established in the USA (American Society of Clinical Oncology, 1994, 1996; Ozer et al, 2000) and in Europe (Boogaerts et al, 1995), but these guidelines extensively appraise the appropriate use of haematopoietic growth factors in adults. Less consideration has been given to paediatric patients (Schaison et al, 1998). The focus of this review is to examine the existing data on clinical trials of haematopoietic growth factors in paediatric patients and discuss their judicious use in clinical settings. Growth factors as primary prophylaxis. The use of the haematopoietic growth factors G-CSF and GM-CSF has been evaluated in multiple trials in paediatric cancer patients, but the burden of evidence has been accumulated in studies with G-CSF (Tables II and III). Neither growth factor can eliminate neutropenic episodes, but it has been demonstrated that both G-CSF and GM-CSF significantly shorten the duration of neutropenia and frequently lessen the degree(i.e. depth) of neutropenia (Saarinen et al, 1992; Housholder et al, 1994; Kalmanti et al, 1994; Marina et al, 1994; Burdach et al, 1995; Jones et al, 1995; Riikonen et al, 1995; Welte et al, 1996b; Wexler et al, 1996; McCowage et al, 1997; van Pelt et al, 1997; Pui et al, 1997; Chen et al, 1998; Laver et al, 1998; Michon et al, 1998; Clarke et al, 1999; Michel et al, 2000; Saarinen-Pihkala et al, 2000). However, the clinical implications of shortening neutropenia have not necessarily translated into a demonstrable reduction of risk for infection. For the most part, the significant findings have been an indirect measurement of infection, such as days of fever, hospital days and duration of antibiotic therapy. The effects of G-CSF given in a dosage of 5 µg/kg/d or 10 µg/kg/d shortly after completion of a cycle of chemotherapy but before the onset of neutropenia (‘primary prophylaxis’) were examined in two prospective randomized studies in a total of 198 children (aged 0–17 years) with acute lymphoblastic leukaemia (ALL) (Welte et al, 1996b; Pui et al, 1997). G-CSF reduced the incidence of febrile, neutropenic episodes from 40% to 17% (P = 0·007) (Welte et al, 1996b), and the incidence of documented infections from 15% to 8% (P = 0·04) (Welte et al, 1996b) and from 36% to 16% (P = 0·009) respectively (Pui et al, 1997). In addition, the total duration of antibiotic use during chemotherapy was significantly reduced from 32 to 18 d per patient (P = 0·02) (Welte et al, 1996b) and the comparable median hospitalization time was shortened from 10 to 6 d (P = 0·011) (Pui et al, 1997). These results were also observed in smaller randomized trials in children with ALL, comparing either interior intraindividual chemotherapy courses with and without the use of G-CSF (Riikonen et al, 1995; Clarke et al, 1999). Conversely, other studies did not observe a significant clinical benefit of G-CSF or GM-CSF in paediatric patients with ALL (Calderwood et al, 1994; Dibenedetto et al, 1995; Saarinen-Pihkala et al, 2000). It was suggested that growth factors may be unnecessary in children with neutropenia of short duration in contrast to children with expected episodes of long and deep neutropenia (Dibenedetto et al, 1995). This is supported by a randomized trial in which G-CSF was administered to 55 children with T-cell leukaemia and to 33 children with advanced-stage lymphoblastic lymphoma (Laver et al, 1998). In the induction phase, G-CSF at a dosage of 10 µg/kg/d did not significantly shorten the median duration of neutropenia of 4·5 d, whereas, in the continuation-therapy phase, the duration of neutropenia was shortened by G-CSF from 11 to 6 d (P = 0·017) (Laver et al, 1998). Accordingly, in a randomized study in children with ALL and high-risk non-Hodgkin's lymphoma (NHL) receiving intensive chemotherapy, G-CSF significantly reduced the proportion of patients requiring antibiotic treatment (54% versus 25%, P < 0·05) and shortened hospitalization (10 versus 6 d, P < 0·05) (Kalmanti et al, 1994), whereas this was not seen in 123 children with NHL stratified to low-, medium- and high-risk groups (12 patients with low risk NHL, 93 with medium risk NHL and 18 with high risk NHL) (Rubino et al, 1998). In a retrospective study in 17 children with acute lymphoblastic or myelogenous leukaemia (AML), G-CSF significantly reduced the use of antibiotics (17 versus 8 d, P = 0·0006) and hospitalization (37 versus 17 d, P = 0·0001) (Chen et al, 1998). While two patients of the control group died of sepsis and pneumonia, none of the G-CSF treated patients died. There was concern about using haematopoietic growth factors in patients with AML as most of myeloid leukaemia cells express receptors for the growth factors and growth factors have the ability to induce proliferation of leukaemic blasts in vitro (Griffin et al, 1986; Souza et al, 1986; Motoji et al, 1991; Lowenberg & Touw, 1993). However, clinical studies in adult patients have not shown any harmful effects of growth factor administration when given after completion of chemotherapy. According to the recommendations for the use of haematopoietic colony-stimulating factors by the American Society of Clinical Oncology (ASCO), primary administration of growth factors can be used after completion of induction chemotherapy in adults (Ozer et al, 2000). Analyses of the results from ongoing, prospective trials evaluating G-CSF prophylaxis in paediatric patients are necessary before firm conclusions can be drawn regarding the value of growth factor use after induction chemotherapy for paediatric patients with AML. Compared with patients with ALL, AML and high-risk patients with NHL, the potential benefit of growth factors in children with a solid tumour is less clear. In a randomized phase II study of G-CSF as an adjunct to combination chemotherapy in 59 paediatric patients with metastatic neuroblastoma, a significant reduction of duration of neutropenia was observed in chemotherapy courses 2, 3 and 4 (7 versus 1 d, 7 versus 2 d and 4 versus 0 d; P = 0·002, 0·008 and 0.001 respectively) (Michon et al, 1998). However, no significant reduction was seen in clinical endpoints, such as the incidence of febrile neutropenic episodes, documented infections or the duration of hospitalization. Similar results were reported for both G-CSF (Jones et al, 1995) and GM-CSF (Saarinen et al, 1992; Marina et al, 1994; Wexler et al, 1996; McCowage et al, 1997; van Pelt et al, 1997) in children with Ewing's sarcoma, osteosarcoma or rhabdomyosarcoma. Prospective randomized studies are clearly indicated to determine the benefit of the prophylactic use of growth factors for these patients. In conclusion, the routine primary prophylactic administration of growth factors cannot be recommended at present (American Society of Clinical Oncology, 1994, 1996; Schaison et al, 1998; Ozer et al, 2000). The use of G-CSF or GM-CSF should be reserved for patients with an expected incidence of febrile neutropenia > 40%, such as forchildren following dose-intensive therapy for some advanced stage tumours [e.g. high-risk ALL, AML, NHL (B-cell) or neuroblastoma] (American Society of Clinical Oncology, 1994, 1996; Schaison et al, 1998; Ozer et al, 2000). Otherwise, use of G-CSF and GM-CSF should be guided by specific protocols designed to investigate these questions. Growth factors to increase dose intensity of cytotoxic therapy. A number of retrospective analyses have correlated the success of chemotherapy with the dose intensity of treatment. Only a few trials in paediatric patients report on the use of growth factors in order to escalate doses of cytotoxic agents or to compress the interval between chemotherapy courses (Jones et al, 1995; Seibel et al, 1999; Michel et al, 2000; Saarinen-Pihkala et al, 2000). As cytotoxic therapy may damage early bone progenitors with subsequent thrombocytopenia (e.g. carboplatin, thiotepa) or has dose-limiting extramedullar toxicities, such as mucositis, neuropathy or cardiomyopathy, escalating the intensity of cytotoxic therapy with growth factor support may be limited (Rusthoven et al, 1991; Moore & Pazdur, 1992; O'Dwyer et al, 1992; Schiller et al, 1994). For example, in a phase I study in 29 children with recurrent neuroblastoma or primitive neuroectodermal tumour (PNET) (aged 0–21 years), a further increase of dose intensity of ifosfamide and etoposide was limited by gastrointestinal toxicity and required supportive measures other than GM-CSF (Fernandez et al, 2000). Although one preliminary observation suggested that mucositis associated with combined modality cytotoxic treatment might be reduced by growth factor use (Gabrilove et al, 1988), other authors have not seen a statistical benefit (Gordon et al, 1994; Welte et al, 1996b; Michel et al, 2000). In addition, G-CSF and GM-CSF do not positively influence therapy-induced alterations of the host defence other than neutropenia. For example, children receiving chemotherapy for cancer often have defects in cell-mediated immunity (Hersh et al, 1971; Esber et al, 1976; Magrath & Simon, 1976), and occasionally such defects result in devastating clinical consequences (Simone et al, 1975; Craft et al, 1977). In a paediatric study using high-dose cyclophosphamide and G-CSF for brain tumours, cycles of therapy were administered approximately every 14 d. Fifty-six per cent of patients in this study developed opportunistic infections, such as Pneumocystis carinii pneumonia, severe adenoviral pneumonia and herpes zoster (Mackall et al, 1994). This study provides evidence that compression of the chemotherapy cycle length with G-CSF can be administered, but at the expense of clinically significant immunosuppression. It was suggested that compression of cycle length from 21 to approximately 14 d abrogated the time needed for regeneration of T-cell populations. Only one single study, evaluating the effect of G-CSF in 59 paediatric patients with metastatic neuroblastoma, observed that less treatment delays in the G-CSF group were associated with a trend in better event-free survival in the G-CSF than in the control group (2·4 versus 1·3 years, P = 0·072) (Michon et al, 1998). However, these results have not been confirmed in other trials. The financial savings of G-CSF or GM-CSF because of less antibiotic usage and shorter hospital stay did not offset the high cost of the growth factors and, except in two studies (Riikonen et al, 1994; Mitchell et al, 1997; Saarinen-Pihkala et al, 2000), no decrease in overall cost of treatment was reported (Pui et al, 1997; Laver et al, 1998; Rubino et al, 1998; Bennett et al, 2000). In conclusion, there is no justification for the use of growth factors to increase chemotherapy dose-intensity or schedule or both outside a clinical trial in which the question of the role of growth factors in this clinical setting is addressed (Ozer et al, 2000). Growth factors as secondary prophylaxis. No prospective, randomized, placebo-controlled study has evaluated whether G-CSF or GM-CSF can prevent new episodes of neutropenic fever in children or adults with a prior episode in an earlier cycle of chemotherapy (‘secondary prophylaxis’). There are preliminary data from a randomized trial of G-CSF in adults treated for small cell lung cancer (Crawford et al, 1991). In this study, the treatment of patients who had fever with neutropenia in cycle 1 was unblinded, and all these patients received open-label G-CSF in subsequent cycles of identical chemotherapy. The patients who were assigned to placebo during cycle 1 but received G-CSF during cycle 2 had a shorter duration of grade IV neutropenia (median 2·5 d in cycle 2 versus 6 d in cycle 1) and also had a lower incidence of febrile neutropenia (23% versus 100%). In contrast, the neutrophil profile of those patients continuing to receive placebo during cycle 2 was very similar to the profile during cycle 1, as well as the low incidence of 5% of febrile neutropenia. These data suggest that administration of growth factors as secondary prophylaxis could reduce the risk of recurrence of febrile neutropenia in further chemotherapy cycles. According to an European panel of haematologists and oncologists, secondary prophylaxis is recommended for children who have experienced at least one previous episode of prolonged (> 7 d) or severe neutropenia with proven bacterial or fungal infection which led to modification of their chemotherapy regimen, or two previous episodes of prolonged and severe neutropenia with or without infection (Schaison et al, 1998). Growth factors and radiation therapy. There are only few data regarding the use of haematopoietic growth factors in neutropenia induced by radiation therapy. A prospective randomized study evaluated the effects of the simultaneous administration of G-CSF and induction therapy in 67 patients with adult ALL (Ottmann et al, 1995). Induction therapy consisted of cyclophosphamide, cytarabine, mercaptopurine, intrathecal methotrexate and cranial irradiation with 24 Gy given in 12 d (Ottmann et al, 1995). The use of G-CSF (5 µg/kg/d) increased the relative dose intensity by preventing prolonged interruptions of chemotherapy and, hence, decreasing the duration of therapy (44 versus 39 d, P = 0·008). However, a median follow-up of 20 months did not show a prolonged disease-free survival. Similar results were reported by other authors (Sakata et al, 1993; Schmidberger et al, 1993; MacManus et al, 1995; Kolotas et al, 1996). On the other hand, a randomized phase III study in adults with limited-stage small-cell lung cancer showed that the administration of GM-CSF (250 µg/m2 twice daily) to patients receiving chemoradiotherapy increased both frequency and duration of life-threatening thrombocytopenia (P < 0·001). This may be the cumulative effect of administered GM-CSF and thoracic radiotherapy which is known to enhance toxicity of concurrent chemotherapy (Bunn, Jr, et al, 1995). In conclusion, growth factors should be avoided in children receiving concomitant chemotherapy and radiation therapy (Schaison et al, 1998; Ozer et al, 2000). In contrast, several small studies evaluating the effect of haematopoietic growth factors in adult patients undergoing large-field irradiation without concomitant chemotherapy have demonstrated that, in this setting, growth factors may help to ameliorate the effect of radiation on neutropenia (Knox et al, 1994; MacManus et al, 1995; Kolotas et al, 1996). Accordingly, the prophylactic administration of G-CSF to patients with Hodgkin's disease receiving large-field subdiaphragmatic irradiation or to patients receiving craniospinal irradiation for a variety of central nervous system neoplasms and abbreviated episodes of neutropenia was well tolerated and did not have negative effects on platelet counts (Knox et al, 1994; MacManus et al, 1995; Kolotas et al, 1996). Conflicting results have been reported as to whether the administration of haematopoietic growth factors has a positive effect on radiotherapy-induced oral/oropharyngeal mucositis (Mascarin et al, 1999; Schneider et al, 1999; Makkonen et al, 2000). In conclusion, in the absence of chemotherapy, the use of growth factors may be considered in patients receiving radiation therapy involving large fields, if prolonged delays secondary to neutropenia are expected (Ozer et al, 2000). Growth factors in special circumstances. Although there are no conclusive clinical data, experts recommend the primary or secondary use of growth factors in special circumstances. In particular, patients with relapse or secondary malignancy who received extensive prior chemotherapy or radiotherapy might benefit from the administration of growth factors as haematopoietic progenitor cells are impaired (Welte et al, 1996a). G-CSF or GM-CSF may be warranted in patients at higher risk for infectious complications. Such risk factors might include poor performance status, more advanced cancer or open wounds, but this is not intended as an all-inclusive list (Ozer et al, 2000). Whether the clinical benefit of growth factor therapy justifies its use in individual circumstances is ultimately a matter of clinical judgement. Clearly, additional studies are required to determine the proper use of growth factors in these subsets of patients. Dose and schedule of growth factors. In adult cancer patients, the recommended growth factor doses are 5 µg/kg/d of G-CSF or 250 µg/m2/d of GM-CSF (Ozer et al, 2000). In children, the optimal dosages of growth factors remain uncertain. In the setting of peripheral blood stem cell (PBSC) mobilization, one study compared mobilization with G-CSF at 10 µg/kg/d versus G-CSF at 20 µg/kg/d in children with solid tumours or leukaemia (Halle et al, 2000). The authors found that mobilization with G-CSF at 20 µg/kg/d reduced the duration of priming but did not reduce the number of leukaphareses, and most experts recommend a dose of 10 µg/kg/d of G-CSF (Ozer et al, 2000). Only a few studies in paediatric cancer patients compared the effect of different schedules and dosages of growth factors and reported conflicting results. For example, it is not clear whether G-CSF given at a dosage of 5 µg/kg/d versus 10 µg/kg/d offers a discernible advantage (Cairo et al, 1995a, 2001; Deb et al, 1998). In contrast, in a study in 29 children with various malignancies comparing GM-CSF dosages of 100 and 250 µg/m2/d, both the duration of neutropenia and median days from the nadir of neutrophil counts to recovery were significantly shorter in the group receiving 250 µg/m2/d (Kubota et al, 1995). However, there were no differences in other clinical endpoints, such as the duration of febrile neutropenia. Both G-CSF and GM-CSF can be administered subcutaneously or intravenously, but it was suggested that the subcutaneous administration may be more effective and less toxic, and is therefore preferred by experts (Rosenfeld et al, 1991; Petros, 1992; Ozer et al, 2000). Because of the short half-life, the time of the intravenous infusion should be at least 60 min (Welte et al, 1996a). Initiation of prophylactic G-CSF or GM-CSF administration should begin 1–5 d after the end of achemotherapy cycle (Schaison et al, 1998). As growth factors mobilize progenitor cells into the peripheral blood, a later start of G-CSF and GM-CSF is preferable after regimens containing doxorubicin or any other drug with a long half-life (Schaison et al, 1998). No difference in duration of neutropenia, the incidence of febrile neutropenic episodes or duration of hospitalization was observed in a randomized study in 18 children with cancer (aged 1–18 years) comparing the initiation of G-CSF on d +1 or on d +5 after chemotherapy (Rahiala et al, 1999). Most experts recommend that the administration of growth factors should be continued until the absolute neutrophil count exceeds between 1 × 109/l and 5 × 109/l (Pui et al, 1997; Michel et al, 2000). Comparison of G-CSF and GM-CSF. Few data can be found comparing efficacy and toxicity profiles of G-CSF and GM-CSF. Most of the clinical trials have been undertaken for G-CSF, and many GM-CSF studies suffer from small patient numbers or suboptimal protocol design (Miller et al, 1997). One study compared the effect of G-CSF and GM-CSF, both given at a dosage of 5 µg/kg/d to 39 children with neutropenia secondary to chemotherapy (Lydaki et al, 1995). No difference between patients receiving G-CSF or GM-CSF was observed regarding the incidence of severe infection and the duration of hospitalization. However, preliminary reports indicate a higher toxicity profile for GM-CSF including fever and injection site reactions, which was suggested to be as a result of the additional effects of GM-CSF on monocytes and macrophages (Dimitrov et al, 1993; Buonadonna et al, 1994). Growth factors in febrile neutropenia. With the early administration of potent antibiotic therapy in febrile neutropenic cancer patients, mortality of infectious complications is low (now < 3%) (Freifeld et al, 1995; Chanock & Pizzo, 1996). Therefore, adjuvant haematopoietic growth factors do not significantly lower acute mortality in febrile neutropenic patients. This was shown in several randomized clinical trials in adult (Mayordomo et al, 1995; Anaissie et al, 1996; Vellenga et al, 1996) and paediatric cancer patients (Riikonen et al, 1994; Mitchell et al, 1997) (Table IV). On the other hand, in a double-blind, randomized study in 112 paediatric cancer patients with a total of 186 episodes of fever and neutropenia, the use of G-CSF (5 µg/kg/d) resulted in a more rapid neutrophil recovery (6 versus 5 d; P = 0·02) and a shorter hospital stay (7 versus 5 d; P = 0·04) (Mitchell et al, 1997). Similar results were reported by Riikonen et al (1994) for GM-CSF in a trial comprising 40 children with various malignant diseases with 58 episodes of febrile neutropenia and in a preliminary, non-comparative study of 18 neutropenic paediatric cancer patients with 30 febrile and/or septic episodes (Fink et al, 1995). Apart from the marginal benefits in quality of life, no study has shown that the use of adjuvant growth factors in cancer patients with febrile neutropenia decreased the incidence of documented infections. A further retrospective analysis suggested that three groups of febrile neutropenic patients benefited most from the use of growth factors: those with acute lymphoblastic leukaemia, those with early onset (< 10 d) of fever after chemotherapy and those without documented septicaemia or focal infection (Mitchell et al, 1997). However, the results are based on small numbers and have to be validated in further clinical trials. Growth factors in neutropenic patients with documented infections. The published literature addressing the use of haematopoietic growth factors in neutropenic children with documented infections is limited to small, uncontrolled studies or case reports. Prospective studies, while clearly indicated, are difficult to perform because of the paucity of patients in one centre with an invasive infection on a similar protocol. A subanalysis of a randomized study, using adjuvant GM-CSF (3 µg/kg/d) in neutropenic febrile adult cancer patients, showed that the administration of the haematopoietic growth factor did not affect response to antibiotic therapy or overall survival of neutropenic patients with documented infections (n = 18) (Anaissie et al, 1996). Similar results were reported in a non-randomized study of adjuvant G-CSF in 34 children with 50 episodes of febrile neutropenia (Liang et al, 1995). An analysis of a randomized, double-blind, placebo-controlled study in 130 neutropenic adult cancer patients with documented infections showed that the administration of G-CSF (12 µg/kg/d) led to a reduction of the median neutrophil count by 1 d (5 versus 4 d; P = 0·01), but not to a reduction of the median number of febrile days or the duration of hospitalization (Maher et al, 1994). Anecdotal reports suggest that growth factors can be useful in neutropenic paediatric or adult patients with life-threatening fungal infections (Bodey et al, 1993; Schoepfer et al, 1995; Repiso et al, 1996; Flynn et al, 1999). For example, together with amphotericin B, G-CSF or GM-CSF has been associated with successful outcome in patients with infections with Candida spp. or Aspergillus spp. who otherwise had a poor prognosis (Bodey et al, 1993). A non-randomized clinical trial in 59 adult cancer patients showed that 62% of patients (n = 29) responded to antifungal treatment with amphotericin B (1 mg/kg/d) plus subcutaneous G-CSF or GM-CSF (3–5 µg/kg/d) compared with 33% of patients (n = 30) who responded to amphotericin B monotherapy (P = 0·027) (Flynn et al, 1999). In addition, G-CSF or GM-CSF reduced the mean duration in hospital (15 versus 9 d) and, therefore, a cost reduction of £3070 per patient could be achieved (Flynn et al, 1999). In conclusion, the routine administration of growth factors is not recommended for febrile neutropenic patients or neutropenic patients with a documented infection (Schaison et al, 1998; Ozer et al, 2000). However, certain febrile neutropenic patients may have prognostic factors that are predictive of clinical deterioration, such as pneumonia, hypotension, multiorgan dysfunction or fungal infection. In these patients, the use of growth factors in addition to antibiotics may be reasonable, even though the benefits of administration under these circumstances have not been definitely demonstrated (Schaison et al, 1998; Ozer et al, 2000). Recipients of autologous or allogeneic progenitor cell transplantation are at especially high risk for infection during the period of recovery following marrow ablation, marked by severe and protracted neutropenia. It was hoped that G-CSF and GM-CSF would reduce the incidence of infection by accelerating recovery of marrow. Growth factors in patients undergoing autologous bone marrow transplantation. Only a few, non-randomized studies have been performed in children undergoing autologous bone marrow transplantation (BMT) (Saarinen et al, 1992, 1996; Gordon et al, 1994; Madero et al, 1995; Calderwood et" @default.
• W2007985065 created "2016-06-24" @default.
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• W2007985065 date "2002-01-01" @default.
• W2007985065 modified "2023-10-17" @default.
• W2007985065 title "HAEMATOPOIETIC GROWTH FACTORS IN CHILDREN WITH NEUTROPENIA" @default.
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