Neutropenia In Adult Patients Research Articles

Challenges in prevention, early detection, and management of febrile neutropenia in adult patients with solid tumors

SummaryFebrile neutropenia (FN) is a common oncologic emergency where quick patient assessment and prompt initiation of antimicrobial treatment is crucial. Guidelines provide detailed recommendations on prevention and treatment; however, their real-world implementation can prove to be difficult. Score systems for outcome risk are effective in identifying low-risk patients with FN. After initiation of therapy, regular re-evaluation of antimicrobial treatment is necessary, and further diagnostic studies should be tailored to each patient. Use of granulocyte colony-stimulating factor (G-CSF) prophylactically in chemotherapy regimens with intermediate FN risk as well as therapeutically in patients with manifest FN is variable in clinical practice and needs to be better defined. Future steps of reducing risk of FN involve investigating underlying genetic factors. Regarding early detection of FN, patient education is paramount. This short review gives an overview of current guidelines and highlights key challenges in management of FN.

Clinical factors predictive of recurrent febrile neutropenia in adult patients with acute leukemia

Febrile neutropenia (FN) is considered an oncologic emergency in acute leukemia. There were 250 FN events in 124 hospitalized patients with hematologic malignancy. These data imply that two FN events may occur per patient, yet data on the prevalence, risk factors, and outcomes of recurrent FN in adult patients with leukemia are limited. A retrospective cohort study was conducted that enrolled adult patients diagnosed with acute leukemia who developed FN. The eligible patients were categorized as with or without recurrent FN. A stepwise, multivariate logistic regression analysis was performed to identify predictors of recurrent FN. A total of 203 patients met the study criteria; of these, 46 (22.66%) had recurrent FN, and this group had a median of three recurrent FN emergencies. After adjusted, three independent factors remained in the final model including ALL, FN at admission, and treatment with idarubicin (3 days) and cytarabine (7 days). The three factors were positively associated with recurrent FN with adjusted odds ratios of 6.253, 4.068, and 10.757, respectively. No significant differences were found between the two groups in terms of other sources of infection, other pathogens, ICU stay, hospital stay, and mortality. ALL and FN at admission and treatment with idarubicin (3 days) and cytarabine (7 days) were associated with recurrent FN in acute leukemia patients with FN. Clinical outcomes for patients with or without recurrent FN were mostly comparable; however, due to its small sample size, further studies are required to confirm the results of this study.

Prophylactic Use of Filgrastim on Days 7, 11 and 14 in Patients Receiving R-CHOP for Non-Hodgkin's Lymphoma

Introduction Chemotherapy-induced febrile neutropenia (FN) is a side effect of cytotoxic chemotherapy and a major risk factor for infection as well as a dose-limiting toxicity. One method of reducing the incidence of febrile neutropenia is through the use of granulocyte stimulating factor (G-CSF). Patients with Non-Hodgkin's Lymphoma (NHL) receiving R- CHOP chemotherapy are thought to have a 10-20% risk of FN (Aapro et al 2010). Elderly patients (aged 65 and over) have an elevated risk of FN. The Newcastle upon Tyne Hospitals (NuTH) local guidelines recommend a novel regime prescribing one dose of filgrastim on days 7, 11 and 14 of treatment regime as primary prophylaxis. Several randomised studies and retrospective reviews of practice have examined the question of G-CSF prophylaxis in older patients. There is little doubt that the use of G-CSF as primary prophylaxis in this group reduces the incidence of FN, however the data are conflicting with respect to impact on overall survival (Osby et al 2003. Doorduijn et al 2003) Aims To audit prophylactic G-CSF prescribing against trust guidelines for patients over 65 with NHL receiving R-CHOP chemotherapy. We also assessed the frequency of hospital admissions for FN in patients over 65 receiving curative R-CHOP for NHL. Methods Patients with NHL over 65 who received R-CHOP at NuTH between 01/06/2017 - 31/01/2018 were identified using our electronic chemotherapy prescribing system. Electronic medical records were used to extract patient, chemotherapy, and hospital admission details. A data collection tool was used to record; patient age, cycle number, details about neutropenic sepsis related admissions and neutrophil counts between 1- 4 days prior to a cycle commencing. Results 30 patients with an average age of 73, cumulatively received 138 cycles of R-CHOP during the defined time period. 91.3% (126/138) of G-CSF prescriptions co-prescribed with chemotherapy were in accordance with trust policy. G-CSF on day 7, 11 and 14 corresponded with 8 hospital neutropenic admissions and 0 non-neutropenic. Comparatively 8.7% (12/138) of G-CSF prescriptions were for ≥5 days and corresponded with 5 hospital admissions with FN and 1 non-neutropenic. However, patients who received 5 or more days G-CSF had multiple risk factors for FN or had a previous episode of FN. The average length of admission due to FN was 6 days which has an associated financial implication. 17 chemotherapy prescriptions were dose reduced, of which 82.4% (14/17) were co-prescribed with the day 7, 11 and 14 regime. There were no deaths as a result of neutropenic sepsis in this cohort of 30 patients. Conclusion The NuTH G-CSF regime resulted in FN admission at a rate of 6.35% (8/126). This is lower than the expected rate of 10-20 % in the absence of G-CSF prophylaxis. These data support the use of the modified regimen of filgrastim on days 7, 11 and 14. References Aapro, M.S. et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. European Journal of Cancer, Volume 47, Issue 1, 8 - 32 Doorduijn JK, an der Holt B, Imhoff GW, Hem KG, Kramer MHH, Oers MHJ, et al. CHOP compared to CHOP plus granulocyte colony‐stimulating factor in elderly patients with aggressive Non‐Hodgkin's Lymphoma. Journal of Clinical Oncology 2003;21(16):3041‐50. Ösby K, Hagberg H, Kvaloy S, Teerenhovi L, Anderson H, Cavallin‐Stahl E, et al. CHOP is superior to CNOP in elderly patients with aggressive lymphoma while outcome is unaffected by filgrastim treatment: results of a Nordic Lymphoma Group randomized trial. Blood 2003;101(10):3840‐8. Disclosures Gabriel: Abbvie: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Kite: Honoraria. OffLabel Disclosure: Filgrastim - granulocyte colony stimulating factor

Primary Prophylaxis of Chemotherapy-Induced Febrile Neutropenia in Adult Patients with Lymphoproliferative Disorders - Clinical Experience in University Hospital of Split

Primary Prophylaxis of Chemotherapy-Induced Febrile Neutropenia in Adult Patients with Lymphoproliferative Disorders - Clinical Experience in University Hospital of Split

Critical appraisal of clinical practice guidelines for adult cancer patients with febrile neutropenia.

To critically appraise published international clinical practice guidelines (CPGs) for management of febrile neutropenia in adult patients with cancer and to determine opportunities for improved development and reporting. A literature search identified CPGs for adult cancer patients with febrile neutropenia. Four independent assessors evaluated each included CPG according to the Appraisal of Guidelines for Research and Evaluation II instrument. Standardized scores were calculated for each guideline and polled collectively. Reliability of assessment was determined using a two-way random model intraclass correlation coefficients. Eight CPGs were independently evaluated by four assessors. Collectively, the highest scoring domain was editorial independence (83.3), followed by clarity of presentation (55.4), scope and purpose (53.4), stakeholder involvement (53.1), rigour of development (52.7) and applicability (47.8). Overall assessments ranged from 28.6 to 96.4 of 100 possible points. Three (37.5%) guidelines were recommended for use without alterations, two (25%) guidelines were recommended with alterations, and three (37.5%) guidelines were not recommended for implementation into practice. Reliability varied between guidelines with intraclass correlation coefficients ranging from 0.41 to 0.82. Clinical practice guidelines for febrile neutropenia in adult patients with cancer were moderately rated with a 37.5% of guidelines being recommended for use in practice. Guideline developers should focus on improving CPG applicability and rigour in the development and reporting processes. Critical appraisal of guidelines should become a standard practice prior to implementation into clinical settings.

Rates of neutropenia in adults with influenza A or B: a retrospective analysis of hospitalised patients in South East Queensland during 2015.

Neutropenia in adult patients is often attributed to intercurrent viral infections; however, there are limited data describing the frequency or natural history of this phenomenon. We examined all patients presenting to three large hospitals in the Metro South region of South East Queensland with laboratory-confirmed influenza A or B throughout the 2015 influenza season (January-October). Four hundred and thirty-six patients were studied and 15.3% of this cohort were neutropenic (absolute neutrophil count <2.0 × 109 /L) with no identifiable cause other than the influenza. Importantly, the majority of cases were mild, with absolute neutrophil count remaining >1.0 × 109 /L. The incidence of neutropenia was significantly higher in association with influenza B than influenza A (18.3% vs 10.3%). We conclude that mild, transient neutropenia is common among patients with influenza infection and advise that it should not cause alarm or invite specific investigation unless severe or prolonged.

Review on lipegfilgrastim.

Dear editor Having read the original Hoggatt et al article1 and the corrigendum published online on August 27, 2015,2 we do not consider the description of lipegfilgrastim to be entirely accurate, and we would therefore like to clarify what lipegfilgrastim actually is. The description of lipegfilgrastim used in the original article was a “long-acting biosimilar filgrastim”.1 This description was subsequently amended in the corrigendum to “lipegfilgrastim has an active substance that is similar to filgrastim, with similar pharmacokinetics, receptor binding affinity, safety and efficacy as pegfilgrastim”.2 It is true that lipegfilgrastim is not a long-acting biosimilar of filgrastim. It is not approved under the biosimilar classification by the European Medicines Agency, and has its own distinct Anatomical Therapeutic Chemical (ATC) code (ATC code L03AA14, lipegfilgrastim; ATC code L03AA02, filgrastim; ATC code L03AA13, pegfilgrastim).3 Further, we believe lipegfilgrastim would be more accurately described as “glycopegylated, long-acting form of recombinant human filgrastim”. Furthermore, the original article does not give the correct indications for either filgrastim or lipegfilgrastim (eg, pages 2,648 and 2,649).1 In August 2013, the European Medicines Agency (EMA) approved lipegfilgrastim to be used for reducing the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).4 Lipegfilgrastim is currently marketed throughout Europe with this indication.

Neutropenia in Congenital and Adult Babesiosis.

Anemia and thrombocytopenia are expected hematologic abnormalities in patients with acute babesiosis, whereas neutropenia (defined as an absolute neutrophil count of ≤1,800 neutrophils/μL for adults and <1,200 neutrophils/μL for infants) is not usually considered a feature of this infection. We studied the frequency with which neutropenia occurs in congenital and adult cases of babesiosis. The frequency of neutropenia in cases of congenital babesiosis was determined based on a literature review and on the findings in an unreported case. The frequency of neutropenia in adult patients was assessed based on a review of the medical records of 51 patients who were diagnosed with babesiosis between 2010 and 2013 at two medical centers in the Northeastern United States. Four (80%; 95% confidence interval [CI], 36%-98%) of five infants with congenital babesiosis whose neutrophil count was reported were neutropenic. Among 51 adult cases with babesiosis, 11 (22%; 95% CI, 12%-35%) were neutropenic on clinical presentation, and seven others developed neutropenia over the next 1 to 21 days. Thus, a total of 18 (35%; 95% CI, 24%-49%) of the adult patients with babesiosis had neutropenia. Neutropenia appears to be a common finding in infants with congenital babesiosis and is also observed not infrequently in adults with this infection.

Epidemiology of febrile neutropenia in adult patients with acute leukemia and lymphoma: Cohort study of public and private hospital of Santiago, Chile

Febrile neutropenia (FN) is a common complication of patients undergoing chemotherapy (QMT). Clinical presentation is varied, from mild fever to severe sepsis with invasive bacterial infection (IBI) or invasive fungal infection (IFI), with great impact on prognosis and patient mortality. Prospective cohort study of FN episodes in adult patients with acute leukemia (AL) or lymphoma (L), diagnosed and treated at the Hospital Clínico Universidad Católica and Hospital Dr. Sótero del Río in Santiago from April 2010 to January 2012. 130 patients were included with 105 episodes of NF, with an incidence of 0.65 per 100 days of observation, higher in AL than L (1.31 vs 0.25, p = 0.001). Etiology or clinical focus was documented in 67 (63.8%) episodes, with IBI in 33 (31.4%) and IFI in 21 (20%) cases. Mortality related to infection occurred in 4 (6.2%) patients. This study reports that the FN incidence and frequency of IBI and IFI during episodes are higher in AL vs. L. It is necessary to evaluate the impact of interventions to reduce its incidence, including the benefit and risk of using antibacterial and antifungal prophylaxis in high-risk subgroups.

Efficacy of Lipegfilgrastim (Lipeg) and Pegfilgrastim (Peg) in Breast Cancer Patients Receiving Chemotherapy (Ctx) Stratified By Status, Age, and Disease Stageby Status, Age, and Disease Stage

ABSTRACT Aim: Lipegfilgrastim is a once-per-cycle, glycoPEGylated recombinant human granulocyte colony-stimulating factor approved by the European Medicines Agency to reduce the duration of severe neutropenia (DSN) and incidence of febrile neutropenia in adult patients receiving CTx. Methods: Breast cancer patients scheduled for CTx (doxorubicin 60 mg/m2+docetaxel 75 mg/m2 on Day 1 for up to 4 cycles) were randomized to 6-mg subcutaneous injections of Lipeg (n = 101) or Peg (n = 101) on Day 2 of each cycle. Post-hoc analyses compared efficacy outcomes during CTx cycle 1 within treatment groups stratified by Eastern Cooperative Oncology Group (ECOG) status, age (≤50 and >50 years of age [y]), and disease stage at baseline. Results: The DSN within treatment groups was comparable regardless of ECOG status (0.7 vs 0.7 days [d] for Lipeg and 0.8 vs 0.9 d for Peg, status 0 vs 1, respectively) or age (0.6 vs 0.7 d for Lipeg and 0.8 vs 0.9 d for Peg, ages ≤50 y vs >50 y, respectively), but shorter in stage IV Lipeg-treated patients (0.7, 0.7, 0.4 d for Lipeg and 0.7, 0.9, 0.9 d for Peg, stages II, III, IV, respectively). The incidence of severe neutropenia (SN) was comparable regardless of ECOG status (45.5% vs 42.0% for Lipeg and 50.0% vs 52.1% for Peg, status 0 vs 1, respectively), higher in patients >50 y within both treatments (40.7% vs 47.5% for Lipeg and 47.7% vs 54.0% for Peg, ≤50 y vs >50 y, respectively), and lower within both treatment groups in stage IV patients (44.7%, 45.7%, 30.0% for Lipeg and 51.4%, 52.3%, 46.7% for Peg, stages II, III, IV, respectively). Time to ANC recovery was similar regardless of ECOG status (5.9 vs 5.8 d for Lipeg and 7.1 vs 7.7 d for Peg, status 0 vs 1, respectively), shorter in Lipeg patients ≤50 y (5.5 vs 6.4 d for Lipeg and 7.5 vs 7.3 d for Peg, ≤50 y vs >50 y, respectively), and similar regardless of disease stage (5.6, 6.0, 6.0 d for Lipeg and 7.0, 7.6, 7.7 d for Peg, stages II, III, IV, respectively). Conclusions: Within treatment groups, ECOG status did not affect DSN, incidence of SN, or time to ANC recovery. Age did not influence DSN or time to ANC recovery; however, more patients >50 y had SN vs those ≤50 y. DSN was shorter and SN was lower in stage IV patients. Disclosure: P. Bias: TEVA employee and receives stock options; U. Muller: TEVA employee and receives stock options; A. Buchner: TEVA employee and receives stock options. All other authors have declared no conflicts of interest.

A Phase IV Clinical Trial of Patients with Solid Tumors Receiving Lenograstim as Primary Prophylaxis for Chemotherapy-Induced Neutropenia, in a Docetaxel-Based Regimen

Docetaxel-based chemotherapy regimens have substantially improved survival and recurrence rates for cancer patients. Safety profile of docetaxel regimens includes toxicities, particularly a high risk of neutropenia and febrile neutropenia. Granotax was a prospective, open label, multicentre, national phase IV study that evaluated the incidence and severity of neutropenia in adult patients with solid tumors being treated with a docetaxel-based regimen while receiving the GCSF lenograstim. Among the 394 enrolled patients the incidence of grade 3-4 neutropenia was 16.2% and of febrile neutropenia was 1.5%, far lower than the reported 85–100% and 30–40% incidence without G-CSFs. A total of 68 patients (17.3%) were reported to have experienced at least one grade 3-4 adverse event during the study. Two (0.5%) patients and 32 (8.1%) patients had dose delayed due to febrile neutropenia and neutropenia, respectively. Four (1.0%) patients and 32 (8.1%) patients had a dose changed due to febrile neutropenia and neutropenia, respectively. The low incidence of adverse effects and chemotherapy dose changes, delays, and withdrawals supports the use of lenograstim as effective primary prophylaxis in South African patients being treated with a docetaxel-based regimen. Furthermore, lenograstim may increase the patient’s exposure to chemotherapy allowing patients to receive optimal dosing and duration of treatment, benefitting survival.

Risk factors for multidrug-resistant bacteremia in hospitalized cancer patients with febrile neutropenia: A cohort study

We conducted a prospective cohort study in a single tertiary hospital with the aim of assessing predictors of multidrug-resistant bacteremia in 307 cases of febrile neutropenia in adult patients with cancer. On multivariate analysis using stepwise logistic regression, age (P = .009), duration of neutropenia (P = .022), and presence of an indwelling central venous catheter (P = .022) were associated with bloodstream infection by multidrug-resistant bacteria.

Abstract P1-15-10: Chemotherapy-Induced Neutropenia in Breast Cancer Patients Receiving Sequential Anthracycline and Taxane Chemotherapy: An institutional experience

Abstract Background: Sequential regimen of anthracyclines and taxanes are commonly used in patients with early stage breast cancer (BC) and curative treatment intent. Due to the associated myelotoxicity, internationally accepted guidelines recommend granulocyte-colony stimulating factors (G-CSF) as primary or secondary prophylaxis, dependent on chemotherapy (CT) and patient-associated risk of febrile neutropenia. As part of a quality control initiative at our center, we have analyzed rates of grade 1 or 2 (&amp;lt;2.0 to &amp;gt;1.0 × 109/L) and 3 or 4 (&amp;lt;1.0 to &amp;lt;0.5 × 109/L) neutropenia, febrile neutropenia (&amp;lt;0.5 × 109/L and single oral temperature ≥38.3°C/100.4°F), CT dose reductions, anti-infective use, and hospitalizations in cycles with pegfilgrastim prophylaxis. Methods: Patients (pts) with BC stages I to III received four three-weekly (q21) cycles of adjuvant or neoadjuvant EC (Epirubicin 90 mg/m2 + Cyclophosphamide 600 mg/m2 q21) followed by four cycles of D (Docetaxel 100 mg/m2 q21) plus primary or secondary pegfilgrastim prophylaxis. Chart records were collected and analyzed retrospectively for patients treated between 2009 and 2012 at our institution for incidence of neutropenia and for the presence of neutropenia-associated risk factors. Only cycles with pegfilgrastim prophylaxis were considered for this analysis. Results: 100 consecutive patients were identified who had overall received 200 EC cycles followed by 251 D cycles under G-CSF prophylaxis with pegfilgrastim. Pts age mean: 51,57 (SD:11,23), BMI mean: 25,8 (SD:5,03) were well controlled in both sequences. Overall, neutropenia was significantly higher for EC (p = 0.001), however higher grade neutropenia (Grade3 and 4) were comparable (p = 0.200). No statistically significant correlations were found between neutropenia and age or body mass index. Conclusions: Sequential use of EC followed by D in combination with prophylactic pegfilgrastim results in lower den expected FN rate [1]. In contrast to most published trials EC leads to significantly more neutropenias than D. However, the use of pegfilgrastim reduces both EC and D associated neutropenias grade 3 and 4 to a similar extent.

Management of the patient with neutropenic sepsis

British Journal of Hospital MedicineVol. 73, No. sup7 What You Need To Know AboutManagement of the patient with neutropenic sepsisSarah J Welsh, Sandra J StraussSarah J WelshSearch for more papers by this author, Sandra J StraussSearch for more papers by this authorSarah J Welsh; Sandra J StraussPublished Online:16 Aug 2013https://doi.org/10.12968/hmed.2012.73.sup7.C101AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Aapro MS, Bohlius J, Cameron DA et al. (2011) 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 47: 8–32 Crossref, Medline, Google ScholarAzoulay E, Darmon M, Delclaux C et al. (2002) Deterioration of previous acute lung injury during neutropenia recovery. Crit Care Med 30: 781–6 Crossref, Medline, Google ScholarClark OA, Lyman GH, Castro AA et al. (2005) Colony-stimulating factors for chemotherapy-induced febrile neutropenia: a meta-analysis of randomized controlled trials. J Clin Oncol 23: 4198–214 Crossref, Medline, Google ScholarDellinger RP, Levy MM, Carlet JM et al. (2008) Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 36: 296–327 Crossref, Medline, Google ScholarHaji-Michael P, Dodgson K, Kaczmarski E, Mutton K (2010) Guidelines for the management of sepsis (including neutropenic sepsis). www.christie.nhs.uk/neutropenic/ (accessed 25 May 2012) Google ScholarNational Chemotherapy Advisory Group (2009) Chemotherapy services in England: ensuring quality and safety. National Chemotherapy Advisory Group, London Google ScholarNational Confidential Enquiry into Patient Outcome and Death (2008) For Better, for Worse? National Confidential Enquiry into Patient Outcome and Death, London Google Scholar FiguresReferencesRelatedDetailsCited byBloodstream InfectionsMicrobiology Spectrum, Vol. 4, No. 4Bloodstream Infections15 April 2016The clinical use of granulocyte-colony stimulating factor18 March 2014 | British Journal of Hospital Medicine, Vol. 75, No. Sup2 1 July 2012Volume 73Issue sup7ISSN (print): 1750-8460ISSN (online): 1759-7390 Metrics History Published online 16 August 2013 Published in print 1 July 2012 Information© MA Healthcare LimitedPDF download

2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours

Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact the success of treatment, particularly when treatment intent is either curative or to prolong survival. In Europe, prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim (including approved biosimilars), lenograstim or pegfilgrastim is available to reduce the risk of chemotherapy-induced neutropenia. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. The need for generally applicable, European-focused guidelines led to the formation of a European Guidelines Working Party by the European Organisation for Research and Treatment of Cancer (EORTC) and the publication in 2006 of guidelines for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. A new systematic literature review has been undertaken to ensure that recommendations are current and provide guidance on clinical practice in Europe. We recommend that patient-related adverse risk factors, such as elderly age (⩾65 years) and neutrophil count be evaluated in the overall assessment of FN risk before administering each cycle of chemotherapy. It is important that after a previous episode of FN, patients receive prophylactic administration of G-CSF in subsequent cycles. We provide an expanded list of common chemotherapy regimens considered to have a high (⩾20%) or intermediate (10–20%) risk of FN. Prophylactic G-CSF continues to be recommended in patients receiving a chemotherapy regimen with high risk of FN. When using a chemotherapy regimen associated with FN in 10–20% of patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Clinical evidence shows that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications where indicated. Filgrastim biosimilars are also approved for use in Europe. While other forms of G-CSF, including biosimilars, are administered by a course of daily injections, pegfilgrastim allows once-per-cycle administration. Choice of formulation remains a matter for individual clinical judgement. Evidence from multiple low level studies derived from audit data and clinical practice suggests that some patients receive suboptimal daily G-CSFs; the use of pegfilgrastim may avoid this problem.

Blood stream infections during chemotherapy-induced neutropenia in adult patients with acute myeloid leukemia: treatment cycle matters

The purpose of this study was to assess the frequency of blood stream infections (BSIs) during neutropenia in different cycles of intensive chemotherapy treatment in acute myeloid leukemia (AML). The register data of 327 consecutive patients aged 16-66years having de novo AML between September 1992 and December 2001 were prospectively gathered in five Finnish tertiary care leukemia centers. The patients had not received fluoroquinolone prophylaxis. Reported BSI rates were compared during neutropenia in four chemotherapy treatment cycles (C). There were 956 treatment episodes, with 456 (47.7%) positive blood cultures. BSI was monomicrobial in 327 episodes (71.7%) and polymicrobial in 129 (28.3%). The overall incidence rate (per 1,000 hospital days) for BSI was 13.2, varying from 6.8 in CI after idarubicin, conventional-dose cytarabine, and thioguanine to 15.6 in CII, 15.8 in CIII, and 17.6 in CIV. The distribution of monomicrobial gram-positive BSIs was as follows: CI, 71.7%; CII, 62.8%; CIII, 53.3%; CIV, 36.6%; and CI-IV together, 43.2%. The most common finding in the four different cycles was coagulase-negative staphylococci (38.3 to 30.6%). Viridans group streptococci were most commonly observed (in 20.4% of positive blood cultures) during CII after high-dose cytarabine and idarubicin treatments. The distribution of monomicrobial gram-negative BSIs was as follows: CI, 21.7%; CII, 36.3%; CIII, 45.7%; CIV, 46.9%; and CI-IV together, 37.9%. A great variation of incidence and types of microorganisms between AML chemotherapy cycles was found. It would be more reasonable to analyze chemotherapy cycle-based BSI results rather than the overall results.

EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours

Chemotherapy-induced neutropenia is not only a major risk factor for infection-related morbidity and mortality, but is also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact on the success of treatment, particularly when treatment intent is either curative or to prolong survival. The incidence of severe or FN can be reduced by prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim, lenograstim or pegfilgrastim. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. While several academic groups have produced evidence-based clinical practice guidelines in an effort to standardise and optimise the management of FN, there remains a need for generally applicable, European-focused guidelines. To this end, we undertook a systematic literature review and formulated recommendations for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. We recommend that patient-related adverse risk factors such as elderly age (⩾65 years), be evaluated in the overall assessment of FN risk prior to administering each cycle of chemotherapy. In addition, when using a chemotherapy regimen associated with FN in >20% patients, prophylactic G-CSF is recommended. When using a chemotherapy regimen associated with FN in 10–20% patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Finally, studies have shown that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications, where indicated.

Surveillance of Nosocomial Sepsis and Pneumonia in Patients with a Bone Marrow or Peripheral Blood Stem Cell Transplant: A Multicenter Project

For surveillance of nosocomial bloodstream infections (BSIs) and pneumonia during neutropenia in adult patients who have undergone bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT), a multicenter study--the Hospital Infection Surveillance System for Patients with Hematologic/Oncologic Malignancies (ONKO-KISS)--was initiated in Germany in 2000. Nosocomial infections were identified in neutropenic patients by means of Centers for Disease Control and Prevention definitions for laboratory-confirmed BSI and modified criteria for pneumonia. During the first 38-month period of the study (i.e., through December 2003), a total of 1899 patients associated with 28,273 neutropenic days were investigated. Of these, 1173 (62%) had undergone allogeneic and 726 (38%) had undergone autologous BMT or PBSCT. The mean duration of neutropenia was 14.9 days (9.6 and 18.1 days after autologous and allogeneic transplantation, respectively). Overall, 395 BSIs and 168 cases of pneumonia were identified. The pooled mean site-specific incidence density per 1000 neutropenic days was 14.0 for BSI (12.4 and 18.9 for the allogeneic and autologous transplantation groups, respectively) and 5.9 for pneumonia (6.1 and 5.6 in the allogeneic and autologous transplantation groups, respectively). After allogeneic transplantation, 22.4 BSIs per 100 patients and 11.0 cases of pneumonia per 100 patients occurred, whereas 18.2 BSIs per 100 patients and 5.4 cases of pneumonia per 100 patients occurred after autologous transplantation. The majority (57%) of pathogens associated with BSI were coagulase-negative staphylococci. The ongoing ONKO-KISS project provides unprecedented reference data about the incidence of pneumonia and sepsis among BMT recipients and PBSCT recipients in Germany. These data will be used for further evaluation of the impact of hygiene measures and therapeutic regimens for these patients.

Comparison of pegfilgrastim vs. lenograstim in the treatment of chemotherapy-induced neutropenia in adult patients with acute myelogenous leukemia (AML)

6669 Background: Two phase III trials in breast cancer patients treated with myelosuppressive chemotherapy showed that a single dose of pegfilgrastim provides neutrophil support comparable with tha...

Comparison of pegfilgrastim vs. lenograstim in the treatment of chemotherapy-induced neutropenia in adult patients with acute myelogenous leukemia (AML)

6669 Background: Two phase III trials in breast cancer patients treated with myelosuppressive chemotherapy showed that a single dose of pegfilgrastim provides neutrophil support comparable with that provided by an average of 11 daily injections of filgrastim. In acute myelogenous leukemia (AML) data are sparse regarding the recovery of neutrophil counts (NC) after therapy with G-CSF in chemotherapy-induced neutropenia. We compared the effects of pegfilgrastim vs. lenograstim by these patients (pts). Methods: Retrospective analysis of unselected pts with AML, 18–75 yrs of age, ECOG ≤ 2, excluding pregnancy received at least one cycle of chemotherapy. On day 1 after chemotherapy treatment either pegfilgrastim 6 mg/once per cycle or lenograstim 5 micg/kg b.w. was administered. Primary objective was the time to recovery (TTR) of NC ≥ 1.0 G/L in each treatment group after injection of G-CSF if NC nadired < 1.0 G/L temporarily. Secondary objectives were the rate of transfusion of packed red blood (PRB) and pooled platelets (PLT). Results: 29 pts, 11 m + 18 f, aged median 61.4 yrs (range: 27–75) received 47 cycles. In 5 pts (3 pts in the pegfilgrastim and 2 pts in the lenograstim group) treatment failed to elevate NC ≥ 1.0 G/L. There was a difference in the TTR of NC between pegfilgrastim 11.1 ± 6.2 days (range: 6–28) and lenograstim 13.3 ± 3.6 days (range: 6–22). Detailed characteristics are summarized in table 1. Conclusions: Both G-CSF showed adequate recovery of NC with a faster increase in those patients where pegfilgrastim was administered. Less frequently blood products were transfused in the pegfilgrastim group. According to the whole-sale pharmacy prices in Germany, G-CSF treatment per cycle for a median of 13 vials of lenograstim was about € 2,321/US $ 2,785 (range: € 1,071–3,928/US $ 1,285–4,714) compared with 1 syringe of pegfilgrastim € 1,762/US $ 2,114. No significant financial relationships to disclose.