Therapy-induced Neutropenia Research Articles

Correlation of therapy-induced neutropenia with survival in patients with metastatic pancreatic cancer treated with GSK-3 inhibitor elraglusib (9-ING-41) in combination with gemcitabine/nab-paclitaxel in the 1801 phase 2 study.

e16311 Background: Previously, elraglusib (9-ING-41), an inhibitor of Glycogen Synthase Kinase-3 (GSK-3), was shown to potentiate the anticancer effects of chemotherapeutic drugs in preclinical models of cancer. The combination of elraglusib and gemcitabine/nab-paclitaxel (GnP) is currently being investigated in a randomized, open-label 1801 phase 2 study as a first-line therapy for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Chemotherapy-induced neutropenia is a common dose-limiting toxicity resulting in dose reductions and/or treatment interruptions. Present evidence shows that therapy-induced neutropenia (TIN) grade 3-4 correlates with survival and is a potential marker for improved clinical outcome in elraglusib/GnP-treated patients. Methods: We correlated overall survival (OS) and time-to-treatment discontinuation (TTD) with TIN grade 3-4 in 72 (GnP arm) and 155 (elraglusib/GnP arm) mPDAC patients previously untreated for advanced disease (1801 Part 3 Arm B study; NCT03678883). TTD was defined as the date of first dose to the date of treatment discontinuation or death. The Kaplan-Meier log-rank test was used for statistical analysis. A p-value < 0.05 was considered statistically significant. Results: The rate of grade 3-4 TIN was 22% (16/72 patients) and 47% (72/155 patients) in the GnP and elraglusib/GnP groups, respectively. Based on 28% of all recorded death events in elraglusib/GnP group and 36% in GnP group, we found that grade 3-4 TIN was significantly associated with improved OS in patients treated with elraglusib/GnP (median OS: 14.4 vs 5.9 months; P < 0.05) but not in patients treated with GnP (median OS: 7.6 vs 7.2 months). In the elraglusib/GnP group, patients with grade 3-4 TIN stayed on treatment significantly longer (median TTD: 7.9 months; P < 0.05) as compared to the patients who did not develop TIN grade 3-4 (median TTD: 1.7 months). Conclusions: Our preliminary results identified grade 3-4 TIN as a potential marker of improved clinical outcome for elraglusib/GnP therapy in previously untreated patients with mPDAC. Recruitment for the 1801 Part 3 Arm B phase 2 trial has been completed. Another interim analysis of OS and its correlation to grade 3-4 TIN will be available by April 2024 and will be included in the final presentation. Clinical trial information: NCT03678883 .

Microbial and host factors contribute to bloodstream infection in a pediatric acute lymphocytic leukemia mouse model

BackgroundHematological malignancies are the most common cancers in the pediatric population, and T-cell acute lymphocytic leukemia (T-ALL) is the most common hematological malignancy in children. Bloodstream infection (BSI) is a commonly occurring complication in leukemia due to underlying conditions and therapy-induced neutropenia. Several studies identified the gut microbiome as a major source of BSI due to bacterial translocation. This study aimed to investigate changes in the intestinal and fecal microbiome, and their roles in the pathophysiology of BSI in a pediatric T-ALL mouse model using high-throughput shotgun metagenomics sequencing, and metabolomics. ResultsOur results show that BSI in ALL is characterized by an increase of a mucin degrading bacterium (Akkermansia muciniphila) and a decrease of butyrate producer Clostridia spp., along with a decrease in short-chain fatty acid (SCFA) concentrations and differential expression of tight junction proteins in the small intestine. Functional analysis of the small intestinal microbiome indicated a reduced capability of SCFA synthesis, while SCFA supplementation ameliorated the development of BSI in ALL. ConclusionsOur data indicates that changes in the microbiome, and the resulting changes in levels of SCFAs contribute significantly to the pathogenesis of bloodstream infection in ALL. Our study provides tailored preventive or therapeutic approaches to reduce BSI-associated mortality in ALL.

Rapid DNA visual detection of polymicrobial bloodstream infection using filter paper

Bloodstream infection (BSI) is a major complication in patients with cancers due to therapy-induced neutropenia and underlying conditions, which increases hospitalization time and mortality rate. Targeted and timely antimicrobial management is crucial to save the patients’ lives and reduce the social and economic burdens. Blood culture is a routine clinical diagnostic method of BSI with a long turnaround time, and generally identifies monomicrobial BSI. Thus, polymicrobial BSI often goes undetected although it occurs more frequently in these patients and results in more severe outcomes compared to monomicrobial BSI. In this work, we apply glutaric anhydride, N-hydroxysuccinimide and N,N′-dicyclohexylcarbodiimide to fabricate a functional surface on cellulose filter paper. Targeting three pathogens (Escherichia coli, Saccharomyces cerevisiae, and human cytomegalovirus) commonly occurring in BSI in neutropenic patients, we demonstrate rapid and accurate triplex pathogen DNA detection using the functionalized paper. All three pathogen DNA was identified in 1–5 min with a detection limit of 0.1–0.5 ng/µL. The developed test tool has the potential to provide rapid polymicrobial BSI diagnosis in support of timely, accurate antimicrobial treatment, and could be integrated into an automatic sample-to-result portable equipment.

NUDT15 genetic variants are related to thiopurine-induced neutropenia in Thai children with acute lymphoblastic leukemia.

Aim: 6-Mercaptopurine (6MP) is key to the treatment of acute lymphoblastic leukemia (ALL) as part of maintenance therapy. NUDT15 was identified as a novel thiopurine regulator conferring 6MP sensitivity. The aim of this study was to evaluate the influence of NUDT15 variants on 6MP-induced neutropenia in Thai children with ALL.Materials& methodology: Genotyping of NUDT15 (c.415C>T; rs116855232) and c.36_37insGGAGTC; rs554405994) was performed by Sanger sequencing in 100 patients with ALL. Patients were classified into wild-type (group 1), heterozygous variant (group 2) and homozygous variant (group 3). Clinical and laboratory features during the first 6 months of maintenance therapy were investigated. Therapy-induced neutropenia was observed in 31 patients during the weeks 1-8 (early myelotoxicity), while therapy-induced neutropenia was observed in 47 patients during the weeks 9-24 (late myelotoxicity).Results: There were 85 wild-type patients, 14 heterozygous variant patients and one homozygous variant patient. NUDT15 variants were associated with neutropenia as compared with wild-type (odds ratio: 17.862; 95% CI: 4.198-75.992, padj=9.5×10-5). Multivariate analysis showed that the low-risk group was associated with neutropenia (p=0.014) in the first 8weeks of 6MP therapy. Group 2 and group 3 patients had significantly lower absolute neutrophil counts compared with group 1. The adjusted dose during the first 6months of maintenance therapy with NUDT15 genotype group 1, 2 and 3 were 50, 36.6 and 12.5mg/m2/day, respectively.Conclusion: Taken together, our results indicate NUDT15 variants may cause neutropenia, and the 6MP dosage should be considered in patients according to the NUDT15 variants to inform personalized 6MP therapy.

69P - Irinotecan and cisplatin therapy-induced neutropenia as a prognostic factor in patients with extensive-disease small cell lung cancer

BackgroundChemotherapy-induced neutropenia (CIN) is a dose-limiting toxicity of many chemotherapy agents. Recently, CIN has been associated with longer survival time in various types of cancer, suggesting a role as a prognostic factor. However, no large-scale study has yet investigated the utility of CIN as a prognostic factor in small cell lung cancer. We therefore conducted this multicenter retrospective observational study to investigate the utility of CIN as a prognostic factor for overall survival (OS) in patients with extensive-disease small-cell lung cancer (ED-SCLC) treated with chemotherapy. MethodsClinical data, including data on CIN onset during chemotherapy, were collected from electronic medical records of patients with ED-SCLC who received standard-dose irinotecan and cisplatin (IP regimen) as primary therapy at 14 participating institutions across Japan between January 1, 2012 and December 31, 2016. Landmark analysis, with the association between OS and neutropenia as the primary endpoint was performed with 102 patients who completed all four cycles of the IP regimen and whose OS was ≥112 days. Univariate analysis using the log-rank test and multivariate analysis using the Cox proportional hazards model with factors previously identified as possible prognostic factors as covariates were also performed to examine the association between CIN and OS. ResultsAnalysis of median OS by grade among patients who developed CIN revealed significantly longer survival in the group with grade 4 CIN (633 days, 95% confidence interval [CI]: 379–757) than in the group with grade 0 to 3 CIN (444 days, 95% CI: 360–505) (P = 0.0279). Multivariate analysis suggested that lactate dehydrogenase (LDH) of ≥ 230 IU/L (hazard ratio [HR]: 2.937; 95% CI: 1.739–4.958, P < 0.001) and grade 0 to 3 CIN (HR: 2.096; 95% CI: 1.151–3.818, P = 0.0156) are independent poor prognostic factors for ED-SCLC. ConclusionsOnset of grade 4 CIN was associated with longer OS in patients with ED-SCLC. Our results also show that both LDH and CIN may be prognostic factors in patients treated using the IP regimen. Clinical trial identificationThis study was approved by the Institutional Review Board of our institution (approval no: T29-8-30-2-3). Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Preclinical evaluation of a biobetter candidate: Pharmacokinetics and pharmacodynamics of GX-G3 in healthy and neutropenia-induced rats.

Neutropenia is a condition of an abnormally low number of neutrophils which render patients more susceptible to infections, especially to bacterial infections, as the condition may become life threatening and deadly without prompt medical attention. Various factors such as, anticancer drugs, radiotherapy, infectious diseases, congenital defects, or vitamin B12/B9 deficiency can trigger neutropenia. GX-G3, a human hybrid (hy) Fc-fused granulocyte colony stimulating factor (G-CSF), was developed as next-generation G-CSF for the treatment of cancer therapy-induced neutropenia. In this study, with the aim of investigating this promising potential next-generation G-CSF, comparative pharmacokinetic and pharmacodynamic studies were conducted in healthy and neutropenia-induced rats. It was found that t1/2 of GX-G3 is longer than same mass injection of filgrastim and pegfilgrastim and AUEClast (area under theeffect-time curve from time zero to the last measurable ANC level) of absolute neutrophil count showed a significant increase after GX-G3 injection compared with filgrastim and pegfilgrastim in healthy rats. Besides, in duration of neutropenia after the same mass injection GX-G3 showed about 3.3 days of reduction effect compared with that of filgrastim, and 1.3 days of reduction effect compared with that of pegfilgrastim in neutropenia-induced rats. These results demonstrate that the half-life of GX-G3 is longer than pegfilgrastim and GX-G3 is more effective than filgrastim and pegfilgrastim in neutropenia-induced rats.

Implementation of a Nursing Based Order Set: Improved Antibiotic Administration Times for Pediatric ED Patients with Therapy-Induced Neutropenia and Fever

PurposeFor patients with chemotherapy-induced neutropenia and fever, delays in antibiotic administration are associated with poor outcomes, such as ICU admission and need for further interventions. The objective of this quality improvement project was to significantly reduce the time from initiation of triage to antibiotic administration for pediatric patients arriving to the emergency department with therapy-induced neutropenia and fever. MethodsAn interdisciplinary team set an evidence-based goal for time to antibiotics (TTA) at 60-min. A six-month retrospective chart review of Emergency Department (ED) patients revealed a 128 min TTA mean when measured from the initiation of triage to antibiotic administration, which also reflected 0% of patients receiving antibiotics within the goal of 60 min. Members of the interdisciplinary team evaluated delays in patient care workflow and identified three primary interventions to decrease the TTA. These three evidenced-based interventions were implemented and evaluated using the Plan-Do-Check-Act (PDCA) quality improvement methodology. ResultsBy the end of the implementation period mean TTA improved to 53 min and patients received antibiotics within 60 min (83% of the time). ConclusionThe interventions focused on both provider and nursing workflow, however the implementation of an evidence-based practice nursing order set made the greatest impact on timeliness of antibiotic delivery time.

Metagenomic analysis of bloodstream infections in patients with acute leukemia and therapy-induced neutropenia.

Leukemic patients are often immunocompromised due to underlying conditions, comorbidities and the effects of chemotherapy, and thus at risk for developing systemic infections. Bloodstream infection (BSI) is a severe complication in neutropenic patients, and is associated with increased mortality. BSI is routinely diagnosed with blood culture, which only detects culturable pathogens. We analyzed 27 blood samples from 9 patients with acute leukemia and suspected BSI at different time points of their antimicrobial treatment using shotgun metagenomics sequencing in order to detect unculturable and non-bacterial pathogens. Our findings confirm the presence of bacterial, fungal and viral pathogens alongside antimicrobial resistance genes. Decreased white blood cell (WBC) counts were associated with the presence of microbial DNA, and was inversely proportional to the number of sequencing reads. This study could indicate the use of high-throughput sequencing for personalized antimicrobial treatments in BSIs.

Bacterial Landscape of Bloodstream Infections in Neutropenic Patients via High Throughput Sequencing.

BackgroundBloodstream infection (BSI) is a common and potentially life-threatening complication in patients with hematological malignancies and therapy-induced neutropenia. Administration of broad spectrum antibiotics has substantially decreased the mortality rate in febrile neutropenia, but bacterial infection is documented in only one-third or fewer of the cases. BSI is typically diagnosed by blood culture; however, this method can detect only culturable pathogens.MethodsIn the present study, a total of 130 blood samples from hematological patients receiving dose-intensive antitumoural treatment were subjected to 16S rRNA PCR and 62 of them were cultured. PCR positive samples were processed to high throughput sequencing by amplifying the V1-V3 regions of the 16S rRNA gene to obtain a full spectrum of bacteria present in BSI.ResultsFive phyla and 30 genera were identified with sequencing compared to 2 phyla and 4 genera with culture. The largest proportion of bacteria detected by sequencing belonged to Proteobacteria (55.2%), Firmicutes (33.4%) and Actinobacteria (8.6%), while Fusobacteria (0.4%) and Bacteroidetes (0.1%) were also detected. Ninety-eight percent of the bacteria identified by sequencing were opportunistic human pathogens and 65% belonged to the normal human microbiota.ConclusionsThe present study indicates that BSIs in neutropenic hosts contain a much broader diversity of bacteria, likely with host origin, than previously realized. The elevated ratio of Proteobacteria in BSI corroborates the results found in other systemic inflammatory diseases, such as inflammatory bowel disease or mucosal infections. This knowledge may become of value for tailoring antimicrobial drug administration.

Traditional Japanese oral mucositis medicine hangeshashinto to upregulate antimicrobial peptides in human salivary gland cells.

517 Background: The cause of chemotherapy-induced oral mucositis (COM) is thought to be direct injury and indirect stomatotoxic effects that result from the release of inflammatory mediators, loss of protective salivary constituents, and therapy-induced neutropenia. We previously found that gargling with hangeshashinto (HST), a traditional Japanese medicine, was effective for treatment of COM. Focusing on the pain and inflammation of COM, we reported at ASCO-GI 2013 and DDW 2013 that HST exhibited ameliorating effects in a hamster model of COM and multi-targeted effects on prostaglandin E2 (PGE2) production, followed by identification of active ingredients by PGE2 culture systems and LC-MS/MS. Our aim in this study was to address whether HST affects protective oral constituents. Methods: Human oral keratinocytes (HOK) and human salivary gland (HSG) cells were used for cell culture assays. Expression levels of mRNAs for antimicrobial peptides, extracellular matrixes, keratinocyte growth factor, amylase, COX-1/COX-2, and cNOS/iNOS in cells with or without HST (10–300 μg/mL) treatment were measured by RT-PCR. Results: HST increased gene expressions of some antimicrobial peptides (defensin β1, adrenomedullin, cathelicidin antimicrobial peptide), and amylase 1A in HSG cells. Further, HST dramatically inhibited COX-2 and iNOS mRNAs in IL-1β treated HOK cells, while it exerted no or little effect on expressions of any protective oral constituents in non-treated HOK cells. A random test to identify the ingredients that increase defensin β1 revealed that isoquinoline alkaloids like berberine were active. Conclusions: HST is expected to maintain oral homeostasis through two paths: increased production of antimicrobial peptides and decreased oral damage induced by excessive prostanoids and nitric oxide. HST thus functions as a multitarget agent, indicating that it may be beneficial in COM treatment.

Administration Of E-Selectin Antagonist GMI-1271 Improves Survival After High-Dose Chemotherapy By Alleviating Mucositis and Accelerating Neutrophil Recovery

Cytotoxic chemotherapies used to treat acute leukemia and high-grade lymphoma target rapidly-dividing cells including the malignant cells but also normal HSC needed to replenish the blood and immune system, as well as mucosal cells lining the respiratory and gastrointestinal tracts. Consequences include therapy-induced mucositis (providing a portal of entry for bacteria) and neutropenia leading to increased morbidity and potentially life-threatening infections. In acute myeloid leukemia and high-grade lymphoma patients, treatment-related mortality can reach 20% (Elmaagacli, BMT, 2007).We now report a novel therapy (therapeutic blockade of E-selectin) that may enhance survival after repeated rounds of high-dose chemotherapy. In mice we find the mechanism contributing to this enhanced survival to be a combination of accelerated neutrophil recovery and a dramatic reduction in therapy-related weight loss and intestinal mucositis when E-selectin is therapeutically blocked or genetically-deleted.Our studies were performed using two treatment regimens (chemotherapy or radiation). For chemotherapy, cohorts of mice received repeated rounds of the anti-metabolite, 5-fluorouracil (5-FU) at a dose of 150mg/kg every 10 days without prophylactic antibiotic support. Using this regime, 80% of E-selectin gene-deleted mice (E-/-) survived >6 weeks. In sharp contrast all wild-type mice died (p<0.05). To determine whether febrile neutropenia was potentially involved, blood was collected for analysis on the 10th day following each round of treatment, just prior to the administration of the next round of 5-FU. After 4 rounds of chemotherapy E-/- mice had recovered acceptable neutrophil counts (n=10). In contrast, only 5 of 10 wild-type mice had recovered from therapy-induced neutropenia. Most of those that could not subsequently died.Deletion of the E-selectin gene also prevented therapy-induced weight loss (from 16% average weight loss in wild-type mice, to only 2% in E-/- mice after 2 rounds 5-FU, p<0.05) which was completely unanticipated. To investigate this further, cohorts of mice were administered 5-FU as described above for histological scoring of intestinal mucositis. To our surprise, we found that deletion of the E-selectin gene almost completely alleviated chemotherapy-induced mucositis. In sharp contrast, intestines of wild-type mice showed extensive ulceration and villous loss with inflammatory infiltrates occurring at the same time as neutropenia – very likely contributing to their death. Moreover we found E-selectin was up-regulated 10-fold in the intestines following chemotherapy or radiation damage, which we hypothesis is critical for recruitment of inflammatory cells to the mucosa. Indeed by immunohistology and flow cytometry, migration of F4/80+ macrophages to 5-FU damaged intestines was increased 7-10-fold in wild-type mice but completely absent in E-/- mice. Similar results were also observed following 8.0 Gy total body irradiation.Therapy-induced mucositis is greatly exacerbated by a wave of secondary inflammation following initial direct damage. We found administration of the selective E-selectin antagonist GMI-1271 (20 mg/kg bi-daily) for 5 days following each round of chemotherapy enhanced neutrophil recovery and similarly protected mice from weight loss and mucositis following chemotherapy. Importantly the administration of GMI-1271 effectively blocked secondary migration of inflammatory F4/80+ Ly-6C+ macrophages to intestines of mice following chemotherapy or irradiation.In conclusion, our results suggest that inflammatory macrophages play a major role in chemotherapy-induced mucositis and are recruited to damaged intestine following E-selectin up-regulation. Importantly there is no current highly-effective treatment to prevent mucositis. Therapeutic blockade of E-selectin by administration of GMI-1271 at the same time as chemotherapy represents a potential effective and novel therapy to block recruitment of inflammatory macrophages to damaged mucosa whilst also enhancing neutrophil recovery, thus protecting patients from two chemotherapy-induced side-effects. Therapeutic blockade of E-selectin should provide an opportunity for improved completion rates of toxic chemotherapy or radiotherapy regimes and reduce therapy-related morbidity and mortality. Disclosures:Magnani:GlycoMimetics, Inc.: Employment, Equity Ownership.

Effect of a structurally modified human granulocyte colony stimulating factor, G-CSFa, on leukopenia in mice and monkeys

BackgroundGranulocyte colony stimulating factor (G-CSF) regulates survival, proliferation, and differentiation of neutrophilic granulocyte precursors, Recombinant G-CSF has been used for the treatment of congenital and therapy-induced neutropenia and stem cell mobilization. Due to its intrinsic instability, recombinant G-CSF needs to be excessively and/or frequently administered to patients in order to maintain a plasma concentration high enough to achieve therapeutic effects. Therefore, there is a need for the development of G-CSF derivatives that are more stable and active in vivo.MethodsUsing site-direct mutagenesis and recombinant DNA technology, a structurally modified derivative of human G-CSF termed G-CSFa was obtained. G-CSFa contains alanine 17 (instead of cysteine 17 as in wild-type G-CSF) as well as four additional amino acids including methionine, arginine, glycine, and serine at the amino-terminus. Purified recombinant G-CSFa was tested for its in vitro activity using cell-based assays and in vivo activity using both murine and primate animal models.ResultsIn vitro studies demonstrated that G-CSFa, expressed in and purified from E. coli, induced a much higher proliferation rate than that of wild-type G-CSF at the same concentrations. In vivo studies showed that G-CSFa significantly increased the number of peripheral blood leukocytes in cesium-137 irradiated mice or monkeys with neutropenia after administration of clyclophosphamide. In addition, G-CSFa increased neutrophil counts to a higher level in monkeys with a concomitant slower declining rate than that of G-CSF, indicating a longer half-life of G-CSFa. Bone marrow smear analysis also confirmed that G-CSFa was more potent than G-CSF in the induction of granulopoiesis in bone marrows of myelo-suppressed monkeys.ConclusionG-CSFa, a structurally modified form of G-CSF, is more potent in stimulating proliferation and differentiation of myeloid cells of the granulocytic lineage than the wild-type counterpart both in vitro and in vivo. G-CSFa can be explored for the development of a new generation of recombinant therapeutic drug for leukopenia.

Capillary electrophoretic separation of poly(ethylene glycol)-modified granulocyte-colony stimulating factor

We evaluated the utility of capillary electrophoretic methods for analyzing poly(ethylene glycol) (PEG)-modified granulocyte-colony stimulating factor (G-CSF), a long-acting form of GCSF for the treatment of cancer therapy-induced neutropenia. Low- and high-molecularweight PEG-G-CSF conjugates prepared with aldehyde-activated PEG-5K and PEG-20K were separated by high-performance size-exclusion chromatography (HP-SEC), capillary zone electrophoresis (CZE), and sodium dodecyl sulfate-capillary gel electrophoresis (SDS-CGE). HPSEC showed low resolution for separating mono- and di-PEG-G-CSFs. SDS-CGE had higher resolution, but required a long analysis and had low peak efficiency. CZE could successfully separate both PEG-5K- and PEG-20K-conjugated G-CSFs with a running time of 20 min and high peak efficiency. In conclusion, CZE was better than SDS-CGE for separating PEG-G-CSF conjugates and will be useful for PEGylation studies, such as reaction monitoring for optimization of the PEGylation reaction, and purity and stability tests of PEG-G-CSF.

Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor Promote Malignant Growth of Cells from Head and Neck Squamous Cell Carcinomas In vivo

Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are used to ameliorate cancer therapy-induced neutropenia and mucositis. Yet, first data in head and neck squamous cell carcinoma (HNSCC) indicate an impaired long-term prognosis on G-CSF treatment, and previous studies showed a contribution of both factors to the progression of human epithelial tumors. Therefore, we investigate the role of G-CSF and GM-CSF in progression of tumor cells from human HNSCC. Both factors stimulated proliferation and migration of tumor cell lines established from patient tumors expressing G-CSF and GM-CSF and/or their receptors. Blockade of G-CSF and GM-CSF inhibited tumor cell invasion in a three-dimensional organotypic culture model. The contribution of both factors to tumor malignancy was further confirmed in nude mouse transplants in vivo. Invasive and malignant growth yielding a similar tumor phenotype as the original patient tumor was exclusively observed in G-CSF- and GM-CSF-expressing tumors and was associated with enhanced and persistent angiogenesis and enhanced inflammatory cell recruitment. Although factor-negative tumors grew somewhat faster, they were characterized by lack of invasion, reduced and transient angiogenesis, and large necrotic areas. These data provide evidence for a progression-promoting effect of G-CSF and GM-CSF in human HNSCC and suggest further detailed evaluation of their use in the therapy of these tumors.

Infektionen in der pädiatrischen Hämatologie und Onkologie

Infectious complications are still a major cause of morbidity and mortality in pediatric patients undergoing therapy for malignancy. Therapy-induced neutropenia is the most important risk factor for infectious risk in pediatric patients with cancer, but other factors, such as alterations in skin/mucosal barriers, and defects in cell-mediated or humoral immunity also contribute to the risk for infection. In most centers, about two thirds of bacteremic isolates are gram-positive pathogens, whereas gram-negative organisms are isolated less frequently, but are associated with considerably higher mortality rates. Prolonged neutropenia increases the risk for invasive fungal infection. In most cases, fever is an important and early indication of serious infection, particularly in children with neutropenia. Discrimination between serious and inconsequential infection in febrile children with neutropenia at the time of presentation is difficult, and serum markers have not been proven to reliably indicate infection. Although several groups investigate risk categories based on clinical tests or the genetic background, the current paradigm is to treat all pediatric patients with neutropenia and fever with intravenous broad-spectrum antibiotics. It is hoped that the identification of one or more predictive factors may be useful for tailoring antibiotic prophylaxis and therapy in children with cancer.

Cost considerations in using filgrastim to prevent antineoplastic therapy-induced neutropenia

Cost considerations in using filgrastim to prevent antineoplastic therapy-induced neutropenia

Granulocyte-colony stimulating factor (G-CSF) in the treatment of therapy-induced neutropenia: Three hopeful studies

Granulocyte-colony stimulating factor (G-CSF) in the treatment of therapy-induced neutropenia: Three hopeful studies