Incidence Of Febrile Episodes Research Articles

At-home Management of Adult Patients Following Consolidation Chemotherapy for Acute Myeloid Leukemia

Background: Consolidation chemotherapy for adult patients with acute myeloid leukemia (AML) who have achieved a complete response after induction treatment is associated with prolonged, severe neutropenia and a high incidence of infections. In our center, patients were historically followed up during the neutropenic period at the day care unit, usually every 2 or 3 days, where they had routine laboratory tests, blood transfusions, central venous catheter management and medical checkups. Since this strategy was associated with a high incidence of febrile episodes that lead to hospital readmissions with some patients dying due to infectious complications, we designed a specific program for patients with AML receiving consolidation therapy including a specialized at-home management. Patients and Methods: Since March 2011, all consecutive patients with AML without significant co-morbidities or active febrile complications who received consolidation chemotherapy and lived within 60 minutes of the hospital were included in the at-home program (AHP). During the neutropenic period, a specialized nurse took care of every patient daily, either visiting the patient at home or by phone. A record of the vital signs, routine laboratory tests, central venous catheter management and administration of intravenous medication was kept regularly by the nurse. Antibiotic prophylaxis consisted of oral levofloxacin (500 mg daily), oral posaconazole (200 mg, three times per day) and intravenous ceftriaxone during the neutropenic ( Results: Up until February 2014, 29 out of 31 (94%) patients were included in the AHP, with a total of 60 episodes. Only 2 patients were excluded from the program, one because of lack of informed consent and the other due to an active febrile complication. The control group consisted of 40 out of 42 (98%) patients (56 episodes in total), who received consolidation treatment following the standard outpatient from May 2004 to March 2011. Median duration of severe neutropenia was of 11 (4-34) days in the AHP group compared with 18 (2-55) days in the control group (p Conclusion: At-home management after administration of consolidation therapy in adult patients diagnosed with AML is feasible in most patients. It is associated to a lower incidence of febrile complications and readmissions, contributing to increase safety for patients and optimizing hospital resources. Disclosures No relevant conflicts of interest to declare.

Effect of taurine on febrile episodes in acute lymphoblastic leukemia.

The purpose of our study was to evaluate the effect of oral taurine on the incidence of febrile episodes during chemotherapy in young adults with acute lymphoblastic leukemia. Forty young adults with acute lymphoblastic leukemia, at the beginning of maintenance course of their chemotherapy, were eligible for this study. The study population was randomized in a double blind manner to receive either taurine or placebo (2 gram per day orally). Life quality and side effects including febrile episodes were assessed using questionnaire. Data were analyzed using Pearson's Chi square test. Of total forty participants, 43.8% were female and 56.3 % were male. The mean age was 19.16±1.95 years (ranges: 16-23 years). The results indicated that the levels of white blood cells are significantly (P<0.05) increased in taurine treated group. There was no elevation in blasts count. A total of 70 febrile episodes were observed during study, febrile episodes were significantly (P<0.05) lower in taurine patients in comparison to the control ones. The overall incidence of febrile episodes and infectious complications in acute lymphoblastic leukemia patients receiving taurine was lower than placebo group. Taurine's ability to increase leukocyte count may result in lower febrile episodes.

Lipid-Based Nutrient Supplements Do Not Affect the Risk of Malaria or Respiratory Morbidity in 6- to 18-Month-Old Malawian Children in a Randomized Controlled Trial

Background:There is evidence to support the use of lipid-based nutrient supplements (LNSs) to promote child growth and development in low-income countries, but there is also a concern regarding the safety of using iron-fortified products in malaria-endemic areas. Objective:The objective of this study was to test the hypothesis that 6- to 18-mo-old rural Malawian children receiving iron-containing (6 mg/d) LNSs would not have excess morbidity compared with infants receiving no supplementation. Methods:A randomized controlled trial allocated 840 children to receive daily supplementation with 54 g/d LNS with milk protein base (milk-LNS), 54 g/d LNS with soy protein base (soy-LNS), 71 g/d corn-soy blend (CSB), or no supplementation from 6 to 18 mo of age. Morbidity was compared using a non-inferiority margin set at 20% excess morbidity in supplemented groups compared with the nonsupplemented group. Results:Baseline characteristics were similar across groups. The proportion of days with febrile illness between 6 and 18 mo was 4.9%, and there were no differences between the groups: 4.9% (95% CI: 4.3, 5.5%), 4.5% (95% CI: 3.9, 5.1%), 4.7% (95% CI: 4.1, 5.3%), and 5.5% (95% CI: 4.7–6.3%) in the milk-LNS, soy-LNS, CSB, and control groups, respectively. The proportion of days with respiratory problems and diarrhea between 6 and 18 mo also did not differ between groups. Compared with controls, the incident rate ratio (95% CI) for clinical malaria was 0.80 (0.59, 1.09), 0.77 (0.56, 1.06), and 0.79 (0.58, 1.08) in milk-LNS, soy-LNS, and CSB, respectively, with 95% CIs confirming non-inferiority. The incidence of febrile episodes, diarrhea, respiratory problems or admission to hospital, prevalence of malaria parasitemia throughout the follow-up, and mean change in hemoglobin concentration from baseline were also similar between the groups. Conclusions:Daily supplementation with 54 g of milk-based or soy protein–based LNS or 71 g of CSB did not result in increases in malaria or respiratory morbidity in children in a malaria-endemic setting. However, we could not conclude whether LNSs did or did not increase diarrheal morbidity. This trial was registered at clinicaltrials.gov as NCT00524446.

Impact Of Systemic Antibiotic Prophylaxis In Hematopoietic Stem Cell Transplantation Recipients. A Meta-Analysis Of Randomized Controlled Trials

Objectives Fever during neutropenia occurs in &gt; 90% and 80% of allogeneic and autologous hematopoietic stem cell transplantation (HSCT) recipients, respectively. Current guidelines recommend the prophylaxis with fluoroquinolones (FQs) in HSCT patients. Although there is evidence that antibiotic prophylaxis improve clinical outcome in patients with chemotherapy-induced neutropenia, prophylactic antibiotic therapy has not been thoroughly evaluated in HSCT recipients. Therefore, we performed a meta-analysis to evaluate the impact of systemic antibiotic prophylaxis in HSCT recipients on mortality, incidence of infection and related adverse events. Data sources We identified reports that were not restricted to those in English and not restricted to published trials through PubMed, the Cochrane Library, and references of identified studies. Review Methods We included prospective, randomized studies on systemic antibiotic prophylaxis in HSCT recipients. The outcome measures included the all-cause mortality, infection-related mortality, febrile episodes, incidence of clinically or microbiologically documented infection, bacteremia, or related adverse events. The summarized odds ratios (ORs) were calculated using the Mantel–Haenszel method and the DerSimonian–Laird method. Results Seventeen trials with 1453 patients (842 autologous and 407 allogeneic HSCT recipients) were included. The percentage of autologous and allogeneic HSCT recipients was not specified in 2 trials. Systemic antibiotic prophylaxis was compared with placebo or no prophylaxis in 10 trials and with non-absorbable antibiotic in 2 trials, respectively. Systemic antibiotics other than FQs were evaluated in five out of these 12 trials. Four trials evaluated the effect of addition of antibiotics for gram positive bacteria to FQs. Remaining 1 trial compared the two different systemic antibiotic regimens, FQs versus trimethoprim sulfamethoxazole. As a result, systemic antibiotic prophylaxis reduced the incidence of febrile episodes (OR 0.16; 95 percent confidence interval [CI], 0.09-0.30), clinically or microbiologically documented infection (OR 0.41; 95% CI 0.30-0.57) and bacteremia (OR 0.37; 95% CI 0.26-0.53) without the significant effect on all-cause mortality or infection-related mortality (OR 0.89; 95% CI 0.48-1.66, OR 1.37; 95% CI 0.50-3.76, respectively). Impact of prophylaxis with FQs on mortality was inconclusive because of small number of clinical trials evaluated. Adverse events increased in patients with systemic antibiotic prophylaxis compared to controls (OR 3.32; 95% CI 1.45-7.63). In meta-regression, percentage of allogeneic HSCT recipients was not associated with each outcome measure. With regard to the comparison between different prophylactic regimens, addition of antibiotics for gram positive bacteria to FQs decreased the incidence of bacteremia (OR 0.44; 0.24-0.80) without significant effects on all-cause mortality, infection related death and febrile episodes. There was not significant, but consistent decrease in clinically or microbiologically documented infection (OR 0.55; 95% CI 0.30-1.01). There was significant increase of adverse events in patients receiving addition of antibiotics for gram positive bacteria to FQs (OR 6.65; 95% CI 2.15-20.54). Conclusions Systemic antibiotic prophylaxis successfully reduced the incidence of infection in HSCT recipients. However, there was no significant impact on mortality. Impact of prophylaxis with FQs on mortality in HSCT recipients was inconclusive because of small number of trials evaluated. Disclosures: No relevant conflicts of interest to declare.

Effect of provision of daily zinc and iron with several micronutrients on growth and morbidity among young children in Pakistan: a cluster-randomised trial

Powders containing iron and other micronutrients are recommended as a strategy to prevent nutritional anaemia and other micronutrient deficiencies in children. We assessed the effects of provision of two micronutrient powder formulations, with or without zinc, to children in Pakistan. We did a cluster randomised trial in urban and rural sites in Sindh, Pakistan. A baseline survey identified 256 clusters, which were randomly assigned (within urban and rural strata, by computer-generated random numbers) to one of three groups: non-supplemented control (group A), micronutrient powder without zinc (group B), or micronutrient powder with 10 mg zinc (group C). Children in the clusters aged 6 months were eligible for inclusion in the study. Powders were to be given daily between 6 and 18 months of age; follow-up was to age 2 years. Micronutrient powder sachets for groups B and C were identical except for colour; investigators and field and supervisory staff were masked to composition of the micronutrient powders until trial completion. Parents knew whether their child was receiving supplementation, but did not know whether the powder contained zinc. Primary outcomes were growth, episodes of diarrhoea, acute lower respiratory tract infection, fever, and incidence of admission to hospital. This trial is registered with ClinicalTrials.gov, number NCT00705445. The trial was done between Nov 1, 2008, and Dec 31, 2011. 947 children were enrolled in group A clusters, 910 in group B clusters, and 889 in group C clusters. Micronutrient powder administration was associated with lower risk of iron-deficiency anaemia at 18 months compared with the control group (odds ratio [OR] for micronutrient powder without zinc=0·20, 95% CI 0·11-0·36; OR for micronutrient powder with zinc=0·25, 95% CI 0·14-0·44). Compared with the control group, children in the group receiving micronutrient powder without zinc gained an extra 0·31 cm (95% CI 0·03-0·59) between 6 and 18 months of age and children receiving micronutrient powder with zinc an extra 0·56 cm (0·29-0·84). We recorded strong evidence of an increased proportion of days with diarrhoea (p=0·001) and increased incidence of bloody diarrhoea (p=0·003) between 6 and 18 months in the two micronutrient powder groups, and reported chest indrawing (p=0·03). Incidence of febrile episodes or admission to hospital for diarrhoea, respiratory problems, or febrile episodes did not differ between the three groups. Use of micronutrient powders reduces iron-deficiency anaemia in young children. However, the excess burden of diarrhoea and respiratory morbidities associated with micronutrient powder use and the very small effect on growth recorded suggest that a careful assessment of risks and benefits must be done in populations with malnourished children and high diarrhoea burdens. Bill & Melinda Gates Foundation.

The role of prophylactic antimicrobials during autologous stem cell transplantation: a single-center experience

The aim of this study was to investigate the efficacy of antibiotic prophylaxis in patients undergoing autologous stem cell transplantation (ASCT) for multiple myeloma and non-Hodgkin lymphoma. Among 232 ASCT cases performed at the Asan Medical Center, 114 cases underwent treatment with ciprofloxacin, fluconazole, and acyclovir (between January 2001 and August 2005), while 118 cases were performed without antimicrobial prophylaxis (between February 2004 and June 2008). The two-rate χ2 test was applied to accommodate the differences in neutropenia duration. The incidence of febrile episodes was 9.8 cases per 100 person-days in the prophylactic group, while it was 16.2 cases in the no-prophylactic group (p<0.001). The rate of unexplained fever was 8.0 cases per 100 person-days in the prophylactic group, while it was 13.8 cases in the no-prophylactic group (p<0.001). The rate of clinically and microbiologically documented infection was 1.7 cases per 100 person-days in the prophylactic group, while it was 2.3 cases in the no-prophylactic group (p=0.404). There were fewer cases of methicillin-susceptible Staphylococcus aureus infection and a greater number of quinolone-resistant Escherichia coli in the prophylactic group compared with the no-prophylactic group (p=0.056 and p=0.040, respectively). The prophylactic antimicrobials reduced the incidence rate of febrile episodes, especially unexplained fever, despite there being no difference in the incidence of documented infection. Resistant microbe infection occurred more frequently in the prophylactic group.

Comparable Outcomes with or without Routine Granulocyte Growth Factor Support Following Autologous Peripheral Blood Stem Cell Transplantation (PBSCT): A Single Center Experience.

Abstract 1178Poster Board I-200 Background:High-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) has been shown to be of value in selected patients with malignant lymphoma and multiple myeloma (MM). Both granulocyte macrophage colony stimulating factor (GMCSF) and granulocyte colony stimulating factor (GCSF) are widely used following stem cell transplantation to support accelerated myeloid recovery and potentially shorten hospital stay. In the recent years, PBSCT is increasingly done in an ambulatory care setting and it is not clear if routine growth factor use has any potential benefit. We undertook this study to compare engraftment kinetics, incidence of febrile episodes, hospitalization duration and other outcomes among transplants done with or without growth factor support Patients and Methods:We included adult patients undergoing PBSCT for myeloma and lymphoma between May 2007 and June 2009 in an ambulatory care setting. Prior to April 2008 (Group-1) all patients received GMCSF 500 mcg/ day starting on day 6 routinely. Since April 2008, there was a shift in clinical practice and routine use of GMCSF was discontinued due to lack of clear evidence regarding benefit. Patients transplanted between April 2008 and June 2009 did not routinely receive GMCSF (Group-2). Typical conditioning regimen for lymphoma was BEAM (BCNU, Etoposide, Cytosine Arabinose, Melphalan) and for multiple myeloma was melphalan 200mg/m2. Patients' demographics details, indication for PBSCT, duration of neutropenic fever, hospital stay, and neutrophil and platelet engraftment were collected from electronic medical records. Neutrophil engraftment is defined as the first day of 2 consecutive days when ANC was > 0.5 × 109/L and platelet engraftment is defined as first of 7 consecutive days on which patient's unsupported platelet count was greater than 20× 109/L. Results:A total of 309 were included in this study, 126 (40%) patients in group-1 (69 with MM, 57 with lymphoma) and 183 (60%) in group-2 (100 with MM, 83 with lymphoma). In group-1, 73 (58%) and in group-2 130 (71%) were male patients. Median age was 59 (29-74) years in group 1 and 58 (24-76) years in group-2. Patients in group 1 received a median of 3.65 (1.1-8.7) versus 4.37 (1.1-9.54) CD34+ x106/kg in group 2 (P =0.005). Median time to neutrophil engraftment was 12 (95% CI 12, 12) for group-1 and 14 (95% CI; 13-14) for group-2 (Kaplan Meier analysis; log rank P < 0.0001). Median estimated time to platelet engraftment was 14 days (95% CI; 13, 15) for group 1 and 13 days (95% CI; 13-13) for group 2 (Kaplan Meier analysis; log rank P 0.007). In group-1 98 (78%) patients developed febrile episodes compared to 117(64%) in group-2 (P = 0.009). Median duration of fever was 2 days (range, 1-8) in group-1 compared to 1 day (range, 1-8) in group-2 (P = 0.0003). The median (range) duration of hospital stay was 7 (1-40) days for group-1 compared to 8 (2-56) days for group-2 (P=NS). There was no significant difference in mortality between these two groups. Conclusion:Routine use of granulocyte growth factors is associated with a shorter time to neutrophil engraftment, but associated with a delay in platelet engraftment. The longer time to neutrophil engraftment without growth factor use does not translate into any increase in frequency of febrile episodes. On the contrary, higher number of febrile days is seen with use of growth factors, likely explained on the basis of drug fever. No difference in the frequency of engraftment syndrome or treatment related mortality was seen. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Incidence of Febrile Episodes During Stem Cells Mobilization After High Dose Cyclophosphamide Chemotherapy and G-CSF (filgrastim or lenograstim) Administration in Multiple Myeloma Patients: Preliminary Final Results.

Abstract 4560 IntroductionThe G-CSF, primary regulator of granulopoiesis, has shown its efficacy in reducing duration of neutropenia after chemotherapy or myelosuppressive therapy. In these situations G-CSF, accelerating the granulocytous reconstitution, may enable a significant reduction of the incidence, duration and severity of infection. Commercially formulations of rHu-G-CSF include lenograstim, a glycosylated form, and filgrastim, a non-glycosylated form. Glycosylation of the molecule contribute to pharmacokynetis advantages and to higher affinity to specific receptor. Additionally, lenograstim exposed neutrophils maintain unchanged all their functions in vitro, while filgrastim exposed neutrophils present functional defects due to higher adhesivity, cytoscheletric alterations and a more immature phenotype. AimOn these bases, we hypotized that lenograstim may prevent febrile episodes (FE) and reduce their lasting in patients with chemotherapy derived neutropenia more efficiently than filgrastim. Primary endpoint is the incidence of FE (ClinicalTrials.gov ID: NCT00932217). Patients and methodsstarting from April 2005, 180 multiple myeloma patients achieving high dose cyclophosphamide for stem cells mobilization were enrolled in 11 Italian Centers. Treatment plan consisted in: high dose cyclophosphamide (3 or 4 g/sqm) on day 1, G-CSF (random 1:1 on the base of a generated random list: filgrastim or lenograstim) 30 MU/day from day +4 to +9, 60 MU/day from day +10 to the achievement of an optimal CD34+ cell count for staminoapheresis. FE, significant if equal or higher than 38 °C for at least 2 different determinations, were recorded till day +30. Results176 of 180 patients received scheduled treatment and are eligible for final analyses. All 176 patients underwent post-chemo grade 4 neutropenia and G-CSF was administered starting from day +4. FE were recorded in 26 pts, 16 in the filgrastim arm (89 total patients) and 10 in the lenograstim arm (87 total patients). The global fever incidence was 14.77%, 17.98% with filgrastim and 11.49% with lenograstim. However, to demonstrate functional block of filgrastim exposed neutrophils, FE have been related to neutrophil absolute count. Related to the neutropenia grade, 8 FE are recorded with filgrastim (8.99%) and 1 FE with lenograstim (1.15%) with absolute neutrophil count >500/μL (grade 3) (chi square test with Yates' correction: p=0.0436); this difference is still evident when neutrophils are >1000/μL (grade 2), with 7 episodes with filgrastim (7.87%) versus 1 (1.15%) with lenograstim. ConclusionsLenograstim is associated with a reduced global incidence of FE in multiple myeloma patients undergoing to high dose cyclophosphamide and stem cells mobilization when compared to filgrastim. Additionally, excluding the time frame when neutrophils are not yet recovered (neutrophils <500/μL; grade 4 neutropenia) and G-CSF effects may not be demonstrated, filgrastim treated patients present, when compared to lenograstim treated patients, an higher FE incidence at neutrophil absolute count recovery (both with grade 3 and grade 2 neutropenia), confirming the functional block of filgrastim exposed neutrophils described in vitro. On the contrary, lenograstim allows to recovery normally functional neutrophils as demonstrated by the very low incidence of FE (1.15% with neutrophils >500/μL) in treated patients. Disclosures:No relevant conflicts of interest to declare.

The role of prophylactic antimicrobials during autologous stem cell transplantation: A single center experience

7105 Background: The aim of this retrospective study was to investigate the efficacy of antibiotic prophylaxis during autologous peripheral stem cell transplantation (ASCT) in patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). Methods: We searched Asan Medical Center Registry for NHL and MM: Total 114 cases received antimicrobial prophylaxis; while 118 cases did not receive antimicrobial prophylaxis during ASCT. Results: In prophylaxis group, 80 of 114 (70.2%) patients had experienced febrile episodes at median day +6 after transplantation with a statistically significant difference (P&lt;0.001). In no-prophylaxis group, 111 of 118 (94.1%) patients had experienced at median day +5. Documented infection occurred in 14 of 114 (12.3%) patients in prophylaxis group, and 16 of 118 (13.6%) patients in no-prophylaxis group (P=0.846). In these patients, the positive blood culture was seen in 12 (10.5%) of 114 patients in prophylaxis group, and 12 (10.7%) of 118 patients in no-prophylaxis group (P=1.000). Documented viral infection or reactivation was not observed in prophylaxis group, but observed in 4 patients of no-prophylaxis group. Both groups showed no invasive fungal infection or serious adverse event during ASCT. The day of infection resolved was a median day +15 (range, 3–29) in prophylaxis group and day +14 (range, 2–70) in no-prophylaxis group (P=0.945). The duration of antimicrobial treatment was median 10 days both in prophylaxis group and in no-prophylaxis group (P=0.565). Conclusions: In our experience, the antimicrobial prophylaxis seems to decrease the incidence of febrile episodes during ASCT, but seems to have no beneficial effect on reducing infectious complications. The antimicrobial prophylaxis of our study did not show the difference in the detection of causative organism as an infective agent, duration of antimicrobial therapy and hospitalization between two groups. No significant financial relationships to disclose.

Incidence of Febrile Episode During Stem Cell Mobilization (SCM) After High Dose Ciclophosphamide Chemotherapy (HD-CTX) and G-CSF (filgrastim or lenograstim) Administration in Multiple Myeloma (MM) Patients: II Interim Evaluation

Introduction: Clinical use of G-CSF in pts with high grade chemotherapy induced neutropenia does not conduce to a reduction of the incidence of febrile episodes (FE). This paradox may be explained by the acquisition of a defective chemotaxis by neutrophils (PMN) exposed to filgrastim (Fil), due to a higher adhesivity and cytoscheletric alterations. Lenograstim (Leno), a glicosilated form of G-CSF, is able to stimulate PMN production, manteining in vitro all the functional capabilities. On these bases, we hypotized that Leno may prevent FE and reduce their lasting in pts with chemotherapy derived neutropenia.Patients and methods: starting from April 2005, 105 MM pts achieving HD-CTX for SCM were enrolled in 12 Centers. Treatment plan consisted in: HD-CTX (3 or 4 g/sqm) on day 1, G-CSF (random: Fil or Leno) 30 MU/day from day +4 to +9, 60 MU/day from day +10 to the achievement of an optimal CD34+ cell count for staminoapheresis. Random, 1:1, was effectuated on the base of a generated random list. FE, significant if equal or higher than 38 °C for at least 2 different determinations, were recorded till day +30. Primary endpoint is the incidence of FE; secondary endpoints are the duration of FE, efficacy in the CD34+ cell mobilization, time to mobilization.Results: 105 pts were enrolled. All pts underwent post-chemo grade 4 neutropenia and G-CSF was administred starting from day +4. FE were recorded in 23 pts, 14 in the Fil arm (53 total pts) and 9 in the Leno arm (52 total pts). The global fever incidence was 21.9%, 26.4% with Fil and 17.3% with Leno, with a 9.1% difference. Average days with fever are 4.00 with Fil and 3.67 with Leno. Related to the neutropenia grade, 8 FE are recorded with Fil and 1 FE with Leno with absolute PMN count >500/μL (grade 4); 7 episodes with Fil vs 1 with Leno when PMN are >1000/μL (grade 3–4). CD34+ SCM occurs in after an average time of 10.3 day with Fil and 9.8 day with Leno, with an higher absolute count with Leno when compared to Fil: 131.9 CD34+/μL (range 40–640) vs 111.6 (range 40–616) CD34+/μL.Conclusions: Leno is associated with a reduced incidence (17.3% vs 26.3%) of FE in MM patients undergoing to HD-CTX and SCM when compared to Fil. FE are recorded with Fil even in presence of PMN confirming the functional block by Fil on PMN documented in vitro. CD34+ mobilization occurs shorter and with higher efficiency with Leno when compared to Fil. On these evidences, patients' enrollment will continue to 180 to validate these results.

Incidence and Characteristics of Infections Following Cord Blood Stem Cell Transplantation in Children.

Infection is one of the most important causes of morbidity and mortality after hematopoietic stem cell transplantation. We assessed the incidence and characteristics of infections in 163 cord blood stem cell transplantation (CBT) recipients from 13 transplant centers of Korea between October, 1996 and April, 2005. The patients underwent CBT with standardized conditioning, GVHD prophylaxis and supportive care including pre-emptive ganciclovir therapy for cytomegalovirus (CMV) antigenemia. The median time to neutrophil engraftment was 19 days (10–62 days) and to platelet engraftment was 45 days (14–394 days). Within the post-transplant day 0 to day 30, 81.6% of patients (133/163) experienced febrile episodes with 11.7% (19/163) of clinically documented infection (CDI) and 19.6% (32/163) of microbiologically documented infection (MDI). The neutrophil engraftment was delayed in the patients with CDI and MDI rather than without CDI and MDI (day 26.3 vs day 21.5, P=0.03) before day 30. In the time period of day 30 to 100, febrile episodes, CDI and MDI occurred in 54.3% (82/151), 14.6% (42/151) and 13.2% (20/151), respectively. After day 100, 38.5% of patients (45/117) experienced febrile episodes with 17.9% (21/117) of CDI and 7.7% (9/117) of MDI. Although the incidence of febrile episodes before day 30 was significantly higher than after day 30, the incidence of CDI and MDI was comparable. There were no significant differences of infection rate according to the infused cell dose, the degree of HLA disparity, acute GVHD and chronic GVHD. The overall mortality rate after CBT was 40% (65/163). Infection was considered the primary cause of transplant-related mortality and represented 18.4% (106/163) of the causes of death with the median day of 96.5 (1∼1,081 days). The incidence of pre-transplant CMV-seropositivity was 85.5% of the patients (106/123) and CMV antigenemia developed in 52.7% of CMV-seropositive patients compared to 11.8% of CMV-seronegative patients (P=0.002). CMV disease developed in 25.7% of CMV-seropositive patients and 6.7% of CMV-seronegative patients, which showed statistiacally not significant. Pre-transplant conditioning regimens such as antithymocyte globulin did not affect on the incidence of CMV antigenemia or CMV disease. Based on our study, the infection was still the primary cause of mortality after CBT, particularly in patients with delayed neutrophil engraftment. The high prevalence of CMV seropositive patients in Korea was associated with increased incidence of CMV antigenemia, not with CMV disease.

Percutaneous nephrostomy versus indwelling ureteral stents in the management of extrinsic ureteral obstruction in advanced malignancies: Are there differences?

ObjectivesTo compare the complications and morbidities after placement of a percutaneous nephrostomy (PCN) tube or an internal ureteral stent (IUS) in the management of malignant ureteral obstruction in patients with advanced malignancy. MethodsA retrospective analysis was performed on a total of 148 patients (80 women and 68 men, mean age 57.3 years, range 20 to 84) with malignant ureteral obstruction, who underwent PCN tube placement (n = 80) or IUS placement (n = 68) between January 2000 and December 2002. The incidence of fever and acute pyelonephritis was expressed as the number of episodes per 100 person-days. ResultsThe accumulated incidence of fever and acute pyelonephritis was not different in the two groups. The accumulated incidence and the incidence of febrile episodes in the IUS group was 10.3% and 0.0004/100 person-days; the corresponding values for the PCN group were 15.0% and 0.2154/100 person-days. The incidence of acute pyelonephritis in the IUS and PCN groups was 0.0002/100 person-days and 0.0005/100 person-days, respectively. These patients were treated conservatively and recovered uneventfully. The difference in overall stent-related or catheter-related complications between the IUS and PCN groups was not statistically significant. The accumulated incidence of failed diversion due to obstruction was 11% (8 of 68) and 1.3% (1 of 80) in the IUS and PCN groups, respectively (P = 0.012). ConclusionsOur results have demonstrated that morbidities after internal or external diversion were minimal in cases of malignant obstruction. However, patients scheduled to receive an IUS should be more carefully monitored for ongoing obstruction than patients scheduled for PCN tube placement.

Infections urinaires nosocomiales chez l’immunocompétent en milieu médical : qui traiter, quand traiter et comment traiter ?

Guidelines for the treatment of nosocomial urinary tract infections (NUTI) have to take into account: i) the high prevalence of catheter-associated bacteriuria; ii) the lack of important clinical studies; iii) a variable bacterial count (between 10 3 and 10 5 mL –1) considered as significant by authors. NUTI without catheterization are clinically similar to UTI in outpatients, but more frequently due to multi-resistant bacteria. Among catheterized patients, the incidence of dysuria, pain, and urgency is not different between patients who develop bacteriuria and those who do not. However, fever has a high positive diagnostic value. Systematic treatment of NUTI is not recommended despite the morbidity because it reduces neither the incidence of febrile episodes, nor the rate of complications. Moreover, it promotes the selection of resistant bacteria. Exceptions to these recommendations are: treatment of asymptomatic NUTI in patients at high risk of severe complications (neutropenic patients, pregnant women, immunosuppressed patients, patients with diabetes mellitus), as part of a plan to control a cluster of multiresistant infections, before surgery (implantation of a prosthesis, urinary tract procedures), or persistent bacteriuria after catheter removal. All febrile NUTI should be treated given their specific morbidity and mortality. Empirical treatment depends on the local prevalence of resistant bacteria. In febrile NUTI, a 7 to 10 day antibiotic treatment is recommended, combined with the removal or the replacement of the catheter (immediately or after 48h of treatment). A longer treatment is necessary for complicated pyelonephritis or bacteremia, according to bacteria dissemination and urinary tract impairment.

The role of irinotecan in the treatment of advanced colorectal cancer

PURPOSE: The purpose of the study was the evaluation of efficacy and the side effects of irinotecan in treatment of advanced colorectal cancer. METHODS: The authors presented their experiences with irinotecan in the treatment of 10 patients suffering from advanced colorectal cancer. The dose of irinotecan was 350 mg/m(2) every 21 days. Seven out of ten patients have taken oral fluoroquinolon to investigate its effect on the incidence of febrile episodes in case of febrile neutropenia. Three out of ten patients did not receive any antibiotic. The authors have examined the efficacy and safety of the treatment. RESULTS: One complete remission was obtained. Authors describe the observed side effects and the administered supportive care against serious complications. DISCUSSION: Serious diarrhoea has not been found in case of these 10 patients. The diarrhoea caused by irinotecan can be stopped by loperamide. The authors give accounts of early and following results.

Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia

AbstractA prospective multicenter trial of 119 children 1 to 18 years of age with newly diagnosed aplastic anemia (AA) was conducted, comparing treatment using antithymocyte globulin (ATG), cyclosporine (CyA), and danazol (DAN) with or without rhG-CSF (400 μg/m2, day on days 1-90). All children with very severe AA received rhG-CSF (VSAA group, n = 50). The other children were randomized to receive ATG, CyA, DAN, and rhG-CSF (G-CSF+ group, n = 35) or ATG, CyA, and DAN without rhG-CSF (G-CSF− group, n = 34). After 6 months, the hematologic response rate was 71%, 55%, and 77% in the VSAA group, G-CSF+ group, and G-CSF− group, respectively. There was no difference in the incidence of febrile episodes and documented infections between the G-CSF+ and G-CSF− groups. Bone marrow transplantation (BMT) was attempted in 22 patients in whom initial immunosuppressive therapy (IST; n = 18) failed or in whom a relapse occurred after an initial response (n = 4). Nineteen of the 22 patients are alive and well after a median follow-up of 18 months (range, 3 to 66 months) since BMT. The probability of survival at 4 years was 83% ± 7% in the VSAA group, 91% ± 5% in the G-CSF+ group, and 93% ± 6% in the G-CSF− group. Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) developed in one patient in each of the three groups; the overall risk for MDS/AML was 3% ± 2% at 4 years. Because the results of IST were encouraging, it is suggested that children with AA receive IST as first-line therapy if there is no human leukocyte antigen-matched sibling donor.

Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia

A prospective multicenter trial of 119 children 1 to 18 years of age with newly diagnosed aplastic anemia (AA) was conducted, comparing treatment using antithymocyte globulin (ATG), cyclosporine (CyA), and danazol (DAN) with or without rhG-CSF (400 μg/m2, day on days 1-90). All children with very severe AA received rhG-CSF (VSAA group, n = 50). The other children were randomized to receive ATG, CyA, DAN, and rhG-CSF (G-CSF+ group, n = 35) or ATG, CyA, and DAN without rhG-CSF (G-CSF− group, n = 34). After 6 months, the hematologic response rate was 71%, 55%, and 77% in the VSAA group, G-CSF+ group, and G-CSF− group, respectively. There was no difference in the incidence of febrile episodes and documented infections between the G-CSF+ and G-CSF− groups. Bone marrow transplantation (BMT) was attempted in 22 patients in whom initial immunosuppressive therapy (IST; n = 18) failed or in whom a relapse occurred after an initial response (n = 4). Nineteen of the 22 patients are alive and well after a median follow-up of 18 months (range, 3 to 66 months) since BMT. The probability of survival at 4 years was 83% ± 7% in the VSAA group, 91% ± 5% in the G-CSF+ group, and 93% ± 6% in the G-CSF− group. Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) developed in one patient in each of the three groups; the overall risk for MDS/AML was 3% ± 2% at 4 years. Because the results of IST were encouraging, it is suggested that children with AA receive IST as first-line therapy if there is no human leukocyte antigen-matched sibling donor.

Economic impact of febrile morbidity and use of permethrin-impregnated bed nets in a malarious area II. Determinants of febrile episodes and the cost of their treatment and malaria prevention.

The objective of this study is to determine the effect of permethrin insecticide-treated bed net (PITN) use on the incidence of febrile episodes and on household malaria expenses in Benin. Over the course of one year, 208 randomly selected PITN user and non-user households were visited weekly to determine expenditures on febrile morbidity and its treatment, and to monitor spending on malaria prevention. Multivariate analyses were performed to distinguish the effects of PITN use from other important determinants of morbidity, such as malaria-related beliefs and practices, income, and other socio-economic variables. Results from the logistic regression analysis show that the use of PITNs decreases the risk of febrile episodes by 34% in children living in the rural zone. Multiple regression analysis reveals that PITN use does not reduce prevention and treatment expenses. These expenses are significantly associated with women's income. This report also discusses other factors associated with febrile morbidity and malaria-related expenditures.

Optimal Timing (Preemptive versus Supportive) of Granulocyte Colony-Stimulating Factor Administration following High-Dose Cyclophosphamide

Purpose: The aim of this study is to compare various time schedules of granulocyte colony-stimulating factor (G-CSF) treatment in a clinical model of patients who received high-dose cyclophosphamide (HDCY 45 g/m²) for the treatment of an underlying malignancy in order to investigate the optimal time (preemptive vs. supportive) of G-CSF initiation upon the incidence and duration of cytopenias and related parameters, such as incidence of febrile episodes, antibiotic use, duration and cost of G-CSF administration and overall clinical benefit and cost effectiveness of various schedules used. Patients and Methods: Seventy-two courses were given in a sequential cohort study. G-CSF was administered either 24, 48, 72, 96 h after chemotherapy (preemptive treatment) or upon the onset of leukopenia (WBC ≤1,000/µl) (supportive treatment). Study parameters were compared among the various groups as well as to a control group who received HDCY without G-CSF support. Results: (1) Patients who received G-CSF early (24, 48 h) had a shorter duration of leukopenia (WBC ≤1,000/µl) compared to those who received G-CSF at a later stage (72, 96 h) or as supportive treatment (p < 0.05). However the duration of neutropenia (ANC ≤500/µl) or thrombocytopenia (platelets ≤20,000/µl) was not affected by the different time schedules of treatment. (2) Patients who received G-CSF early (up to 72 h) had less febrile days with neutropenia in comparison to late treatment (>96 h), supportive and control groups (p < 0.05). The cost of antibiotics was also in favor of the early treatment group. The median duration of febrile days of the delayed (>72 h) treatment groups and antibiotic cost was similar to those in patients who did not receive G-CSF at all. (3) When G-CSF was given preemptively a shorter time was required to reach normal WBC (5,000/µl) in comparison to the sup- portive and control group. This was due to a prolonged WBC recovery rather than to an early onset of leukopenia (tail effect). A delayed leukopenia recovery occurs as administration of G-CSF is delayed. (4) As a result the required length of G-CSF treatment to reach normal WBC (5,000/µl) was shorter in the early treatment group and the cost from G-CSF use was less in that group in comparison to the late (>72 h) and supportive groups which indicated an increased cost without clinical benefit over controls. Conclusions: G-CSF administration after HDCY has a similar effect upon the incidence and duration of severe leukopenia and thrombocytopenia. However, severe leukopenia is shorter when G-CSF starts up to 72 h after HDCY. The length of G-CSF administration and its cost is also in favor of early initiation of treatment as well as the number of febrile days and antibiotic use. Delayed (>72 h) or supportive treatment indicate more febrile episodes, antibiotic use and higher cost when compared to the early groups. Late (>72 h) or supportive G-CSF administration in this study indicates no benefit versus no treatment in relation to length of leukopenia, febrile days, antibiotic use and overall treatment cost.

Granulocyte-Colony Stimulating Factor (G-CSF) Administration for Chemotherapy-Induced Neutropenia.

This study was aimed to evaluate the efficacy of G-CSF (Granulocyte colony stimulating factor) administration to 37 patients with neutropenia following intensive combination chemotherapy. The patients were divided into two subgroups including solid tumors given ifosfamide and etoposide combination chemotherapy (IMET subgroup) and acute myeloid leukemia (AML) patients treated with mitoxantrone and cytarabine. Control group consisted of 31 acute myeloid leukemia patients. G-CSF was started on the first day of absolute neutropenia until the absolute neutrophil count was above 1000/mm(3) for two consecutive days. G-CSF was found to be effective for early recovery of neutrophil count. Expected response was achieved within 14 days in 91.5% of the courses with a median of fifth day of G-CSF treatment. In conclusion, this study showed the efficacy of G-CSF in early recovery of neutrophil count without any reduction in the incidence of febrile episodes and documented rates of bacterial and fungal infections in patients with acute myeloid leukemia.

Granulocyte-Macrophage Colony-Stimulating Factor in Newly Diagnosed Adult Patients with Acute Lymphoblastic Leukemia Treated with Conventional Chemotherapy.

Twenty consecutive adult patients with newly diagnosed acute lymphoblastic leukemia (ALL) were treated with conventional therapy consisting of daunorubicin, vincristine, prednisone and L-asparaginase in standard doses. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered at a single subcutaneous daily dose of 5 microgram per kilogram body weight for fourteen days starting on day 7 of chemotherapy. Twenty two adult patients with acute lymphoblastic leukemia and similar risk characteristics who received the same chemotherapeutic regimen without GM-CSF served as a historical control group. The complete remission rate and the rate of early mortality were similar in both groups of patients. Patients treated with GM-CSF showed significantly faster neutrophil recovery above 0.5 × 10(9)/L than the control patients (P < 0.005). The incidence of febrile episodes and the rate of documented infection were similar in the two groups of patients.