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Agnes, Marshalla, Pudjo Hagung Widjajanto, and Wahyu Damayanti. "Kejadian Demam Neutropeni pada Leukemia Limfoblastik Akut Anak di RSUP Dr. Sardjito, Yogyakarta." Sari Pediatri 20, no. 6 (2019): 360. http://dx.doi.org/10.14238/sp20.6.2019.360-5.
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Latar belakang. Leukemia limfoblastik akut (LLA) merupakan keganasan yang sering ditemukan pada anak dan remaja. Demam neutropeni (DN) merupakan kedaruratan medik pada LLA yang sering menyebabkan kematian.Tujuan. Mengetahui angka kejadian dan kematian DN pada LLA anak selama terapi fase induksi.Metode. Penelitian deskriptif dengan disain potong lintang. Subjek adalah pasien LLA anak pada kurun Januari 2013 hingga Desember 2015, usia 1 bulan hingga 18 tahun dan tengah menjalani terapi fase induksi. Neutropeni ditegakkan dengan jumlah neutrofil absolut <1.500/mmk. Pengambilan sampel dilakukan secara consecutive sampling.Hasil. Terdapat 246 kasus LLA baru pada kurun waktu penelitian, 115 (46,7%) mengalami DN selama fase induksi. Kematian terjadi pada 15/115 (13%) kasus, 9/15 (60%) berhubungan dengan DN (sepsis, syok sepsis), sisanya karena sebab lainnya (sindrom lisis tumor, herniasi dan infiltrasi mening). Analisis pada kasus yang rekam mediknya selama fase induksi lengkap (59/115 atau 51,3%) menunjukkan 50/59 (84%) subjek mengalami satu kali kejadian DN, sisanya 9/59 (16%) mengalaminya 2-3 kali. Median terjadinya DN kali pertama setelah diagnosis adalah 8 hari (0-62 hari). Median durasi DN 7 hari (3-23).Kesimpulan. Kejadian demam neutropeni selama fase induksi masih tinggi dan merupakan penyebab kematian yang paling utama.
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Quirion, Eva. "Filgrastim and Pegfilgrastim Use in Patients With Neutropeni." Clinical Journal of Oncology Nursing 13, no. 3 (2009): 324–28. http://dx.doi.org/10.1188/09.cjon.324-328.
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Lahlimi, Fatima Ezzahra, Khawla Khalil, Soumia Lahiaouni, and Illias Tazi. "Neutropenic Enterocolitis Disclosing an Underlying Cyclic Neutropenia." Case Reports in Pediatrics 2020 (December 1, 2020): 1–3. http://dx.doi.org/10.1155/2020/8858764.
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Neutropenic enterocolitis is a syndrome characterized by fever and abdominal pain in a neutropenic patient. It is often reported in children treated for leukemia and rarely reported in patients with other diseases. Herein, we report the case of a 9-year-old patient with a medical history of recurrent fever and mouth ulcers since the age of 4, who presented with neutropenic enterocolitis complicated with intestinal perforation which all leaded to disclose cyclic neutropenia. The patient was successfully treated by aggressive supportive care combined with surgical intervention. Neutropenic enterocolitis with possible complications should be considered and promptly managed in every neutropenic patient and may reveal a rare cause of neutropenia as cyclic neutropenia.
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Pichereau, Solen, Anne Le Louarn, Thierry Lecomte, Hélène Blasco, Chantal Le Guellec, and Hélène Bourgoin. "Cost-Effectiveness of UGT1A1*28 Genotyping in Preventing Severe Neutropenia Following FOLFIRI Therapy in Colorectal Cancer." Journal of Pharmacy & Pharmaceutical Sciences 13, no. 4 (2011): 615. http://dx.doi.org/10.18433/j3wk5s.
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PURPOSE: Functional polymorphisms of the UGT1A1 gene, particularly the UGT1A1*28 variant, are associated with the severity of the bone marrow suppression in patients with metastatic colorectal cancer receiving irinotecan. This study assesses the cost-effectiveness of screening for UGT1A1*28 polymorphism associated with primary prophylactic Granulocytes Colony Stimulating Factor in patients homozygous for the *28 allele. The effectiveness was estimated based on the number of neutropenia avoided. METHODS: We modelled a theoretical population treated with combined 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) for metastatic colorectal cancer. A decision tree simulated the health outcomes, measured by the prevalence of neutropenic events for two strategies, with or without UGT1A1 genotype screening. The model incorporated direct hospital costs and was validated with a sensitivity analysis. We calculated the cost-effectiveness ratio: CE=∆C / ∆E = "genotyping" cost – "no genotyping" cost / number of febrile neutropenia avoided. RESULTS: In the "genotyping strategy", the cost to avoid one febrile neutropenia event per 1000 patients treated was € 942.8 to € 1090.1. The sensitivity analysis showed a better CE ratio of € 733.4 to € 726.6 per febrile neutropenic event avoided.CONCLUSIONS: UGT1A1 genotype screening before irinotecan treatment is a cost-efficient strategy for the hospital. Systematic genotyping prior to chemotherapy, and administration of CSF in patients homozygotes for the *28 allele allow to avoid 91 febrile neutropenias at an acceptable cost.
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Sugahara, Hiroyuki, Masao Mizuki, Sayoko Matsumae, Yoshiko Nabetani, Motoko Kikuchi, and Yuzuru Kanakura. "Footwear Exchange Has No Influence on the Incidence of Febrile Neutropenia in Patients Undergoing Chemotherapy for Hematologic Malignancies." Infection Control & Hospital Epidemiology 25, no. 1 (2004): 51–54. http://dx.doi.org/10.1086/502292.
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AbstractObjective:To determine whether footwear exchange affects the incidence of febrile neutropenia among patients undergoing chemotherapy for hematologic malignancies.Design:Open trial with historical comparison.Setting:The 12-bed high-efficiency particulate air-fil-tered hematology unit at Osaka University Hospital, Suita, Japan.Patients:Those with hematologic malignancies who underwent chemotherapy from January 1997 through January 2003. Footwear exchange was discontinued in January 2000.Methods:The surveillance system was based on the National Nosocomial Infections Surveillance System of the Centers for Disease Control and Prevention. Rates of febrile neutropenia were calculated for neutropenic patient-days (ie, days with neutropenia < 500/μL).Results:From January 1997 through December 1999 and from February 2000 through January 2003, 58 and 54 patients endured 237 and 184 neutropenic periods following chemotherapy, and their total neutropenic days were 3,123 and 2,503, respectively. They showed episodes of febrile neutropenia 89 and 68 times, respectively. Infection rates were 28.5 and 27.2 per 1,000 neutropenic patient-days (P = .83), respectively.Conclusion:The incidence of febrile neutropenia was not affected by footwear exchange. In hematology units, changing shoes does not appear to affect the rate of infections during neutropenic periods.
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Palmblad, Jan, and Helen A. Papadaki. "Chronic idiopathic neutropenias and severe congenital neutropenia." Current Opinion in Hematology 15, no. 1 (2008): 8–14. http://dx.doi.org/10.1097/moh.0b013e3282f172d3.
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Strojnik, Ksenija, Ksenija Mahkovic-Hergouth, Barbara Jezersek Novakovic, and Bostjan Seruga. "Outcome of severe infections in afebrile neutropenic cancer patients." Radiology and Oncology 50, no. 4 (2016): 442–48. http://dx.doi.org/10.1515/raon-2016-0011.
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Abstract Background In some neutropenic cancer patients fever may be absent despite microbiologically and/or clinically confirmed infection. We hypothesized that afebrile neutropenic cancer patients with severe infections have worse outcome as compared to cancer patients with febrile neutropenia. Patients and methods We retrospectively analyzed all adult cancer patients with chemotherapy-induced neutropenia and severe infection, who were admitted to the Intensive Care Unit at our cancer center between 2000 and 2011. The outcome of interest was 30-day in-hospital mortality rate. Association between the febrile status and in-hospital mortality rate was evaluated by the Fisher’s exact test. Results We identified 69 episodes of severe neutropenic infections in 65 cancer patients. Among these, 9 (13%) episodes were afebrile. Patients with afebrile neutropenic infection presented with hypotension, severe fatigue with inappetence, shaking chills, altered mental state or cough and all of them eventually deteriorated to severe sepsis or septic shock. Overall 30-day in-hospital mortality rate was 55.1%. Patients with afebrile neutropenic infection had a trend for a higher 30-day in-hospital mortality rate as compared to patients with febrile neutropenic infection (78% vs. 52%, p = 0.17). Conclusions Afebrile cancer patients with chemotherapy-induced neutropenia and severe infections might have worse outcome as compared to cancer patients with febrile neutropenia. Patients should be informed that severe neutropenic infection without fever can occasionally occur during cancer treatment with chemotherapy.
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Hapsari, M. M., Helmia Farida, Monique Keuter, et al. "Penurunan Penggunaan Antibiotik pada Pasien Anak dengan Demam." Sari Pediatri 8, no. 1 (2016): 16. http://dx.doi.org/10.14238/sp8.1.2006.16-24.
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Latar belakang. Resistensi antibiotik saat ini menjadi problem dunia yang mencemaskan.Penggunaan antibotik secara berlebihan dan tidak rasional merupakan kontributor utamaterjadinya resistensi antibiotik. Upaya mengubah pola peresepan antibiotik menjadi lebihrasional merupakan hal yang tidak mudah.Tujuan. Memperbaiki kuantitas dan kualitas penggunaan antibiotik pada pasien yangdirawat dengan demam, serta mengevaluasi dampak terhadap morbiditas dan mortalitas.Metoda. Penelitian prospektif intervensi di bangsal anak RS Dr Kariadi, Juli 2003 -Desember 2004, dibagi menjadi 4 periode yaitu periode awal, penyusunan pedoman,pelatihan, dan umpan balik. Pada periode awal dilakukan pengambilan data dasar. Padaperiode penyusunan pedoman dilakukan konsensus untuk menyusun pedoman penggunaanantibiotik pada anak dengan demam. Periode pelatihan adalah sosialisasi dan pelatihankepada dokter. Pada periode pascapelatihan dilakukan umpan balik terhadap pesertapelatihan. Subyek penelitian adalah semua pasien usia >1 bulan yang dirawat dengandemam> 38ºC (rektal) dalam 24 jam pertama perawatan, kecuali yang diketahui menderitaHIV/AIDS atau neutropeni karena kemoterapi. Data penggunaan antibiotik diambil daricatatan medik, diamati selama 6 hari pertama perawatan. Data morbiditas dan mortalitasdiamati sampai pasien keluar dari rumah sakit. Uji statistik menggunakan X 2 dan Anova.Hasil. Terdapat penurunan kuantitas penggunaan antibiotik dan peningkatan kualitaspenggunaan antibiotik secara bermakna (p=0.000 dan p=0,000). Penurunan kuantitasantibiotiok terutama disebabkan pengurangan penggunaan antibiotik yang tidakdiperlukan. Tidak terdapat perbedaan lama rawat dan lama demam (p=0.96 dan p=0.32)dan tidak terdapat perbedaan kematian selama periode pengamatan.Kesimpulan. Dengan pedoman yang baik, penggunaan jumlah antibiotik dapatditurunkan tanpa meningkatkan risiko morbiditas dan mortalitas.
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Drognitz, Kathrin, Michael Lubbert, Gerald Illerhaus, Frank Gartner, and Hartmut Bertz. "Therapeutic Granulocyte Transfusions in Neutropenic Patients with Invasive Pulmonary Aspergillosis,." Blood 118, no. 21 (2011): 3372. http://dx.doi.org/10.1182/blood.v118.21.3372.3372.
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Abstract Abstract 3372 Background: Granulocyte transfusions (GTX) are used as an additional therapeutic option in patients with severe neutropenia following chemotherapy constituting an increased risk for life-threatening bacterial and fungal infections. We hypothesized that interventional GTX would provide a clinical benefit for neutropenic patients with invasive pulmonary aspergillosis (IPA). Methods: We reviewed the clinical outcome of 44 patients with severe neutropenia (46 cases) and underlying hematological malignancies suffering from IPA unresponsive to standard antifungal therapy. They received a total of 181 human recombinant granulocyte colony-stimulating factor (rh G-CSF) stimulated GTX at Freiburg University medical center from 1996 – 2009. Neutropenias were caused by conventional chemotherapy (n=38), conditioning chemotherapy for allogeneic (n=4) and autologous (n=2) hematopoietic cell transplantation (HCT), aplastic anemia (n=1) and by intense immunosuppressive (n=1). Donors were exclusively relatives and acquaintances of the recipients. IPA was diagnosed by clinic, computed tomography (CT) scan, serological or microbiological measures. Response of GTX was evaluated by repeated CT, decreasing C-reactive protein (CRP) levels, hematopoietic regeneration and clearance of serum galactomannan antigen. Results: A median of 3 GTX (range 1–25) containing a median total of 59.4×109 (range 3–170) white blood cells per GTX were administered. All but five (3%) transfusions were well tolerated. Median duration of neutropenia proceeding GTX was 15.5 d (range 4–70). Resolution of infection or clinical improvement was achieved in 29 (63%) patients with IPA and haematopoietic recovery has been assumed within 10 days after the last GTX in 34 patients (74%). Thirty-three (72%) patients were alive one month after the first GTX. Overall, progressive malignant disease was the main cause of death. Patients not responding to GTX died without on septic complications despite appropriate antibacterial and antifungal treatment. Nine out of 26 neutropenic patients receiving GTX after conventional chemotherapy underwent allogeneic HCT later on after control of IPA. Conclusions: Rh G-CSF stimulated GTX are a safe and effective therapeutic tool for patients with hematological malignancies suffering from profound neutropenia and antifungal-therapy resistant IPA. GTX may serve as a bridging therapy in severe neutropenic patients with IPA scheduled for allo-HCT. Disclosures: Bertz: GILEAD: Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees.
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Shahriari, Mahdi, Mohammad Azadbakht, Maryam Roohparvar, Babak Daneshfard, and Majid Nimrouzi. "Effect of chamomile on chemotherapy-induced neutropenia: a pilot open-label controlled trial." Pakistan Journal of Medical and Health Sciences 15, no. 7 (2021): 1966–68. http://dx.doi.org/10.53350/pjmhs211571966.
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Neutropenia is a common complication of chemotherapy in leukemic patients. An herbal formulation of chamomile was hypothesized to be effective on neutropenia. A group of healthy volunteers and two groups of patients received chamomile oral drop to be compared with a control group of neutropenic patients. Results showed an increase of white blood cells and resolution of neutropenia in all groups except for the control group. In conclusion, chamomile could be used as an effective complementary medicine for increasing the immunity of neutropenic patients (in addition to healthy individuals). Keywords: Chamomile; Leukemia; Chemotherapy; Neutropenia; Integrative Medicine; Persian Medicine
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Shahriari, Mahdi, Mohammad Azadbakht, Maryam Roohparvar, Babak Daneshfard, and Majid Nimrouzi. "Effect of chamomile on chemotherapy-induced neutropenia: a pilot open-label controlled trial." Pakistan Journal of Medical and Health Sciences 15, no. 6 (2021): 2016–18. http://dx.doi.org/10.53350/pjmhs211562016.
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Neutropenia is a common complication of chemotherapy in leukemic patients. An herbal formulation of chamomile was hypothesized to be effective on neutropenia. A group of healthy volunteers and two groups of patients received chamomile oral drop to be compared with a control group of neutropenic patients. Results showed an increase of white blood cells and resolution of neutropenia in all groups except for the control group. In conclusion, chamomile could be used as an effective complementary medicine for increasing the immunity of neutropenic patients (in addition to healthy individuals). Keywords: Chamomile; Leukemia; Chemotherapy; Neutropenia; Integrative Medicine; Persian Medicine
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Donowitz, Gerald R., Dennis G. Maki, Christopher J. Crnich, Peter G. Pappas, and Kenneth V. I. Rolston. "Infections in the Neutropenic Patient— New Views of an Old Problem." Hematology 2001, no. 1 (2001): 113–39. http://dx.doi.org/10.1182/asheducation-2001.1.113.
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Abstract Infection in the neutropenic patient has remained a major clinical challenge for over three decades. While diagnostic and therapeutic interventions have improved greatly during this period, increases in the number of patients with neutropenia, changes in the etiologic agents involved, and growing antibiotic resistance have continued to be problematic. The evolving etiology of infections in this patient population is reviewed by Dr. Donowitz. Presently accepted antibiotic regimens and practices are discussed, along with ongoing controversies. In Section II, Drs. Maki and Crnich discuss line-related infection, which is a major infectious source in the neutropenic. Defining true line-related bloodstream infection remains a challenge despite the fact that various methods to do so exist. Means of prevention of line related infection, diagnosis, and therapy are reviewed. Fungal infection continues to perplex the infectious disease clinician and hematologist/oncologist. Diagnosis is difficult, and many fungal infections will lead to increased mortality even with rapid diagnosis and therapy. In Section III, Dr. Pappas reviews the major fungal etiologies of infection in the neutropenic patient and the new anti-fungals that are available to treat them. Finally, Dr. Rolston reviews the possibility of outpatient management of neutropenic fever. Recognizing that neutropenics represent a heterogeneous group of patients, identification of who can be treated as an outpatient and with what antibiotics are discussed.
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Chow, E. J., and K. D. Bishop. "Painless neutropenic enterocolitis in a patient undergoing chemotherapy." Current Oncology 23, no. 5 (2016): 514. http://dx.doi.org/10.3747/co.23.3119.
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Case Description A 60-year-old man developed painless neutropenic enterocolitis after induction chemotherapy for newly diagnosed acute myelogenous leukemia. The patient had recurrent fever while neutropenic, without experiencing abdominal pain or tenderness on physical examination. His diagnosis was delayed by the fact that he had no localizing symptoms.Discussion Neutropenic enterocolitis is a common complication, generally occurring in patients who are severely neutropenic; the condition presents with fever and abdominal pain. No cases of painless neutropenic enterocolitis have yet been reported. Review of the literature shows that patients can develop this condition in the absence of fever and, sometimes, neutropenia. Furthermore, few comprehensive studies or reviews have investigated the utility of computed tomography imaging in identifying a source for abdominal pain in neutropenic patients with fever.Summary Many potential causes of febrile neutropenia should be considered in chemotherapy patients.
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Da Silva, Thamires Branco, Guilherme Rossi Assis de Mendonça, Maiara Marx Luz Fiusa, et al. "Sepsis in Patients with Febrile Neutropenia: A Clinical and Autopsy-Based Study." Blood 126, no. 23 (2015): 4622. http://dx.doi.org/10.1182/blood.v126.23.4622.4622.
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Abstract Introduction: Sepsis in febrile neutropenia (FN) is a life threatening condition, and a health problem of increasing proportions. Although multiple organ dysfunction syndrome (MODS) frequently precedes death in patients with sepsis, the ultimate mechanisms responsible for organ dysfunction and tissue damage in sepsis are yet to be determined. Currently, tissue damage is attributed to an exacerbated response of the immune and hemostatic systems, mediated by endothelial cells, platelets and neutrophils. Of note, recent evidence demonstrated that neutrophils, platelets and fibrin participate in this response by mediating neutrophil extracellular traps (NET) formation, and promoting the hemostatic containment of infectious foci. In animal models, down-regulation of NET formation, coagulation and platelet activation are usually associated with deficiencies in pathogen clearance. Unfortunately, activation of hemostasis and NET formation could potentially contribute to tissue damage by a process called "immunethrombosis". Although the increase of sepsis severity in patients with severe neutropenia is well described, the mechanisms of sepsis-associated tissue damage in the context of severe neutropenia/thrombocytopenia are yet to be determined. Methods: In order to investigate the mechanisms of tissue damage in the context of severe neutropenia/thrombocytopenia, we compiled clinical data from two different prospective sepsis cohorts (A, neutropenic; n=129; and B, non-neutropenic; n=30) followed at our Institution. In addition, we reviewed histopathological data from 16 autopsies of individuals with hematological malignancies and septic shock from our institution (cohort C; n=16). H&E-stained slides from liver, kidneys and lungs were systematically analyzed by one investigator, and reviewed by 2 experienced pathologists, all of them blind to the presence or absence of neutropenia and thrombocytopenia. In each organ, we characterized (as present or absent) three main organic lesions: thrombi in microvessels, microorganism colonies, and inflammatory infiltrate (mononuclear and polymorphonuclear). Inflammation was graded as weak or intense, and only considered when there was no neoplastic infiltration. Results: Median ages of patients from cohorts A and B were respectively 46.0 years (13-78), and 59.4 years (22-85); P<0.0001. In cohort A, neutrophil counts were < 100/mcl in 55.8% of patients and between 100-500/mcl in 42.6%. Platelet counts were also lower in cohort A (30,126 vs 213,933/mcl; P<0.0001). Median SOFA scores (at admission) were 4 (0-15) and 5 (0-17); P=0.3 in neutropenic and non-neutropenic patients respectively, and sepsis-related mortality was 22.5% and 10.3% in the same groups (P=0.19). Among patients with a higher SOFA score, mortality was higher in neutropenic patients (100% vs 33.3%; p=0.04). The frequencies of clinically-evident infection foci were 60% in cohort A and 100% in cohort B (P=0.0001). In contrast, positive blood cultures were present in 38% of neutropenic, but in only 3.3% of non-neutropenic patients (P<0.0001). The autopsy-based study included 10 patients with lymphoma and 6 with acute leukemia. The cause of death was septic shock in all of them, and three patients presented severe neutropenia (<500/mcl). The main histological findings are shown in table 1. The only neutropenic patient with microthrombi presented AML-M3 and leukostasis. Using H&E staining, no bacterial colonies were found in any slide. Conclusions: as expected, septic patients with severe neutropenia presented a worse outcome compared to non-neutropenic patients in our cohort. In addition, the lower frequency of clinically-defined infectious foci, coupled with a strikingly higher frequency of positive blood cultures, suggest that severe neutropenia and thrombocytopenia could impair pathogen containment and clearance. Severe neutropenia/thrombocytopenia was compatible with inflammatory infiltrates and microvascular thrombosis in lungs, although the latter was only observed in a patient with leukostasis and promyelocityc acute leukemia. Table 1. Histological findings in autopsies of neutropenic and non-neutropenic patients Microthrombi Inflammation (weak/intense) Lungs Kidney Liver Lungs Kidney Liver Neutropenic 33% 33% 0% 50%/50% 0%/0% 0%/0% Non-neutropenic 56.25% 25% 6.25% 70%/20% 34%/9% 67%/0% Disclosures No relevant conflicts of interest to declare.
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Raufi, Ali Mehmood, Shada Attraplsi, and Yehuda Z. Lebowicz. "Better utilization of neutropenic precautions and adherence to guidelines to improve cost effectiveness and patient convenience." Journal of Clinical Oncology 34, no. 7_suppl (2016): 227. http://dx.doi.org/10.1200/jco.2016.34.7_suppl.227.
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227 Background: Cancer patient are generally immunocompromised and are at increased risk of infections once absolute neutrophils count is less than 500. The aim of the study to evaluate the inpatient utilization of a standardized neutropenic precautions in cancer patients admitted with febrile neutropenia. Methods: From Jan 2010 to May 2015, established cancer patients were included in this retrospective study who were admitted in Cabel Huntington hospital, Huntington, WV with a diagnosis of febrile neutropenia and were placed on Neutropenic precautions (NP). We analyzed if NP were discontinued once patient is stable and no longer neutropenic during hospital stay. Results: A total of 159 cancer patients with admitting diagnosis of febrile neutropenia were identified. 107 out of 159 (67%) patients had solid malignancies while 33% had hematologic malignancies. Median age was 61 (Range of 20-88 years). 69 patients were male while 90 patients were female. Median duration of Neutropenic precautions (NP) was 4 (Mean 5.69 and range: 1-35). NP were appropriately discontinued in 30% of patients during hospital stay however approximately 70% of patients continued to be on NP even after neutropenia resolved (48 vs 111 patients). Median duration of unnecessary NP was 3 with a mean of 3.87 and range of 1-18 days. Conclusions: Better utilization of Neutropenic precautions and adherence to guidelines will improve overall cost effectiveness as well as patient convenience by avoiding unnecessary restriction.
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Yokoyama, Yasuhisa, Masahiko Gosho, Takahiro Suzuki, et al. "Analysis of the Prevalence and Risk Factors of Adult Neutropenia in a Large Cohort in Japan." Blood 128, no. 22 (2016): 4738. http://dx.doi.org/10.1182/blood.v128.22.4738.4738.
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Abstract Background: The prevalence of neutropenia is estimated to be 0.5% to 25% based on the definition of neutrophil count less than 1,500 /μL. The high variety mostly depends on the race. Most of the estimation have been based on the values obtained from one measurement of neutrophil count. The prevalence of "chronic" neutropenia is largely unknown, particularly in adults, with only a few small epidemiological studies of adult chronic neutropenia being found. Here we analyzed the medical-check data from over 30,000 Japanese adults, and report the prevalence and characteristics of neutropenia in Japanese adults referring to chronic cases. Methods: Data of medical-checks including neutrophil count from 2010 to 2014 were collected. The entire cohort included 33,255 adults. Neutropenia was defined as neutrophil count less than 1,500 /μL. Anemia was defined as hemoglobin level less than 13 g/dL in men and 12 g/dL in women, and thrombocytopenia as platelet count less than 100,000 /μL. Data of past histories and comorbidities were based on the self-report by the participants. When simple neutropenia (not necessarily chronic) was analyzed, the minimum neutrophil count was used for those who received more than one medical-checks, and other data at the time of the minimum neutrophil count were adopted. For the statistical analysis for comparison of subjects with and without neutropenia, Student's t-test or Wilcoxon's rank sum test were used for continuous variables, and chi-square test was used for categorical variables. Univariate and multivariate regression analyses were performed for testing the effect of the candidate factors on the neutrophil count. For the analysis of the risk factors of neutropenia, multivariate logistic regression analysis was used. For the analysis of chronic neutropenia, only those who received at least 2 medical-checks with measurement of neutrophil count were included. Those who showed neutropenia at least twice were defined as having chronic neutropenia. Results: After exclusion of the cases with past histories of hematological malignancies, 33,201 cases were included. Among them, 1,391 (4.18%) cases had neutropenia. Frequencies of collagen diseases, hypothyroidism, and under-treatment hyperthyroidism were higher in the neutropenic group than the non-neutropenic group. When the subjects with these diseases were excluded, 1,348 (4.12%) out of 32,695 cases had neutropenia. Among them, frequencies of anemia and thrombocytopenia in the neutropenic group were higher than in the non-neutropenic group (18.7% vs 6.2%, and 0.7% and 0.1%, respectively, p < 0.001). In order to analyze isolated neutropenic cases, the subjects with anemia and/or thrombocytopenia were further excluded from the cohort. As the result, 28,615 cases were analyzed. Among them, 1,083 (3.78%) cases were diagnosed to have neutropenia, in which 1,025 (94.6%) cases had mild neutropenia (1,000 - 1,499 /μL) and 58 (5.4%) had moderate neutropenia (500 - 999 /μL). There were no cases of severe neutropenia (< 500 /μL). The neutropenic group showed older age (52.2 vs 50.2 years old), female predominance (64.2% vs 37.1%), lower bone mass index (BMI) (21.5 vs 23.4), lower smoking habit (23.3% vs 46.5%), lower drinking habit (30.8% vs 38.3%) (p < 0.001 for all). Diabetes mellitus (3.0% vs 4.9%, p = 0.005), hypertension (10.6% vs 15.7%, p < 0.001), and hyperuricemia (1.7% vs 3.3%, p = 0.003) were less frequent, and pollen allergy (6.3% vs 4.2%, p < 0.001) and viral hepatitis (1.1% vs 0.3%, p < 0.001) were more frequent in the neutropenic group. In multivariate regression analysis, female, drinking habit, pollen allergy, and viral hepatitis were associated with decrease in neutrophil count, whereas higher BMI and smoking habit with increase in neutrophil count. Risk factors of neutropenia were female with adjusted odds ratio (OR) 2.18 (p < 0.001), drinking habit (OR 1.31, p < 0.001), pollen allergy (OR 1.32, p = 0.034), and viral hepatitis (OR 3.98, p < 0.001). Higher BMI and smoking habit were negative factors of neutropenia (OR 0.40 and 0.52, respectively, p < 0.001).Among the 18,279 subjects who received at least 2 medical checks with measurement of neutrophil count, the number of chronic neutropenia was 294 (1.61%). Conclusion: The prevalence of isolated neutropenia in Japanese cohort was 3.78%, and chronic neutropenia was seen in 1.61%. Risk factors of neutropenia were female, drinking habit, pollen allergy, and viral hepatitis. Disclosures No relevant conflicts of interest to declare.
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Vakkalanka, Bhanu, and Brian K. Link. "Neutropenia and Neutropenic Complications in ABVD Chemotherapy for Hodgkin Lymphoma." Advances in Hematology 2011 (2011): 1–7. http://dx.doi.org/10.1155/2011/656013.
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A combination of Adriamycin (a.k.a. Doxorubicin), Bleomycin, Vinblastine, and Dacarbazine (ABVD) is the most commonly used chemotherapy regime for Hodgkin lymphoma. This highly effective treatment is associated with a significant risk of neutropenia. Various strategies are adopted to counter this commonly encountered problem, including dose modification, use of colony stimulating factors, and prophylactic or therapeutic use of antibiotics. Data to support these approaches is somewhat controversial, and in keeping with the paucity of definitive evidence, there is a wide disparity in the management of neutropenia in patients receiving ABVD chemotherapy. This paper summarizes the evidence for managing ABVD-related neutropenia during the treatment of Hodgkin lymphoma.
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Callejas, Angel, Kari Nadeau, Kokil Bakshi, et al. "Identification of Specific Chemokines and Apoptosis Molecules in Pediatric Idiopathic Neutropenia." Blood 108, no. 11 (2006): 3851. http://dx.doi.org/10.1182/blood.v108.11.3851.3851.
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Abstract In order to explore possible mechanisms for idiopathic neutropenia, molecular and functional analyses on neutrophils and plasma of pediatric neutropenic patients were performed. 22 subjects, 8 acute and 14 chronic neutropenia, aged 5 months to 12 years, were recruited through Lucile Salter Packard Children’s Hospital hematology clinics with an IRB-approved consent. Patients with known neutrophil elastase mutations were excluded. We first examined whether the neutrophils of neutropenia patients had increased expression of molecules associated with cell death. QT-PCR was performed and transcript levels in neutrophils of neutropenia subjects were compared against those of normal subjects. In addition, to assess if a factor(s) in the plasma of neutropenia patients induced neutrophil cell death, neutrophil survival assays were done by incubating neutrophils isolated from normal healthy controls with 200 ul of undiluted plasma from chronic neutropenic subjects. Neutrophil death was then analyzed via Annexin V-PI staining. Finally, to identify specific plasma proteins, which may have a potential role in neutrophil-mediated cell death, 2D gels were run on neutropenic and control plasma. Results: Due to limited sample size, assays were not run on all subjects. Acute and chronic neutropenic patients (n=10) experienced an increase in FAS, an apoptotic marker and protein known to be associated with neutrophil cell death. There were no significant differences in fold expression between acute and chronic patients. Neutrophil survival assays (n=9) revealed a median of 6.5 and mean 6.8 fold (range 2–24 fold) higher level of plasma-mediated cell death with neutropenic plasma. Preliminary studies of 2D gels on plasma revealed differential expression of inflammatory proteins in neutropenia patients compared to normal healthy controls. Further investigation on these proteins is ongoing. In summary, rapid cell death can be induced in normal neutrophils through neutropenia plasma incubation. Further identification of these apoptosis-associated plasma proteins is in process. In addition, the increase in certain apoptosis-associated chemokines and cytokines could lead to further target identification for diagnostic and/or treatment purposes of neutropenia. Table 1 Patient Number Trascripts Expressed in Neutrophils (Fold Over Trancripts from Neutrophil of Normal, Healthy Control *= acute neutropenic patient TNF-α R1 FAS 1 2 13 2* 1.5 12.5 3 2 10 4 1 14 5* 2 12 6 2 13.5 7* 1 11 8* 2 10.5 9 2 7 10 1.5 10
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Lonial, Sagar, Rachid Baz, Arlene S. Swern, Donna Weber, and Meletios A. Dimopoulos. "Neutropenia Is a Predictable and Early Event in Affected Patients with Relapsed/Refractory Multiple Myeloma Treated with Lenalidomide in Combination with Dexamethasone." Blood 114, no. 22 (2009): 2879. http://dx.doi.org/10.1182/blood.v114.22.2879.2879.
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Abstract Abstract 2879 Poster Board II-855 Background: Lenalidomide (len) is an immunomodulatory compound with established clinical efficacy and safety in patients with multiple myeloma (MM). Two pivotal phase III trials in patients with relapsed/refractory MM evaluating lenalidomide + dexamethasone (len + dex) vs placebo + dex (MM-009 and MM-010) demonstrated that len + dex is well tolerated with significant improvements in response and overall survival in comparison to placebo + dex (Weber et al, NEJM 2007; Dimopoulos et al, NEJM 2007). Despite a favorable safety profile, neutropenia is one of the most common hematologic adverse events in patients receiving len + dex. Patients who experience neutropenia may require dose adjustments or discontinuation of len + dex therapy. The aim of this study was to understand the incidence, onset, and duration of neutropenia in patients with relapsed/refractory MM receiving long-term administration of len + dex. Methods: Pooled data for patients treated with len + dex from the two phase III studies (MM-009/010) with a median follow-up of 48 months in all patients surviving as of the data cutoff of July 2008, were analyzed for all neutropenia reported as adverse events (neutropenic AE), including all related terms. The change in incidence and severity of neutropenic AE over time was determined by capturing the highest grade of event reported for each patient within each month. Both the severity (grades 1-4) and duration (days) of neutropenic AE were also determined for patients within each month. To evaluate the change in the rate of neutropenic AE for all patients by month, monthly rates were modeled using Poisson regression with a factor for month and the log of the total number of patients included as an offset parameter. Results: Of 353 patients treated with len + dex, 164 (46%) experienced a neutropenic AE of any grade at some point during the course of the study. A grade 3 or 4 event occurred in 137 (39%) patients. Of the patients who experienced neutropenic AE of any grade, 97 (59%) received G-CSF at some point in the study compared to 8 (4%) of the patients without neutropenic AE. Sixty percent of patients who experienced a neutropenic AE, experienced more than 1 event. Overall, neutropenic AE occurred early, with 52% and 76% of patients experiencing their most severe event within 6 and 12 months of therapy, respectively (Figure). Only 24% of patients who experienced neutropenia experienced their highest grade of event after 12 months of therapy. The median duration of neutropenic AE overall was 10 (25th percentile 8; 75th percentile 29) days. The majority of severe neutropenic AE were grade 3, with very few patients experiencing a grade 4 event. Of the 353 patients treated with len + dex, only 11 (3.1%) patients had febrile neutropenia (12 events). Seven of the patients had their first febrile neutropenia within the first 6 months and 4 patients after 12 months. Twelve patients (3.3%) had their study drug discontinued due to a neutropenic event. Overall, the incidence, severity, and the duration of any neutropenic events did not significantly change over time. Conclusions: Overall, the first neutropenic AE in patients receiving len + dex occurs early, with more than 50% of patients experiencing their highest grade of event within 6 months of initiation of therapy and only 3.1% of patients treated with len + dex developed febrile neutropenia. These data support the predictable safety profile of len + dex, thereby supporting the long-term use of len + dex in patients with relapsed/refractory MM, and demonstrating the predictable safety profile of this combination therapy. Disclosures: Lonial: Gloucester: Research Funding; Novartis: Consultancy; BMS: Consultancy; Millenium: Consultancy, Research Funding; Celgene: Consultancy. Baz:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Swern:Celgene: Employment. Weber:Celgene: Honoraria, Research Funding. Dimopoulos:Celgene: Honoraria.
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Inoue, Susumu, Isra’a Khan, Rao Mushtaq, Dawn Carson, Elna Saah, and Nkechi Onwuzurike. "Postinduction Supportive Care of Pediatric Acute Myelocytic Leukemia: Should Patients be Kept in the Hospital?" Leukemia Research and Treatment 2014 (September 29, 2014): 1–4. http://dx.doi.org/10.1155/2014/592379.
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Children with AML become profoundly neutropenic while they undergo remission induction chemotherapy. It is unknown whether these children should be kept in the hospital while they are severely neutropenic to prevent life-threatening complications associated with neutropenia and reduce fatality. We at our institution routinely discharge patients after completing remission induction chemotherapy in the presence of profound neutropenia, unless it is clinically contraindicated. We reviewed all AML patients who were consecutively treated at our hospital from 1989 to 2011. Thirteen patients were electively discharged after completion of induction I chemotherapy. Of the 13, 4 died due to relapse or complications of stem cell transplants (not due to neutropenia related complications). Another eight are long term survivors. In this very small series, discharge from the hospital even though patients were severely neutropenic did not adversely affect the survival.
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Steinberg, James P., Chad Robichaux, Sheri Chernetsky Tejedor, Mary Dent Reyes, and Jesse T. Jacob. "Distribution of Pathogens in Central Line–Associated Bloodstream Infections among Patients with and without Neutropenia following Chemotherapy Evidence for a Proposed Modification to the Current Surveillance Definition." Infection Control & Hospital Epidemiology 34, no. 2 (2013): 171–75. http://dx.doi.org/10.1086/669082.
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Objective.Many bloodstream infections (BSIs) occurring in patients with febrile neutropenia following cytotoxic chemotherapy are due to translocation of intestinal microbiota. However, these infections meet the National Healthcare Safety Network (NHSN) definition of central line-associated BSIs (CLABSIs). We sought to determine the differences in the microbiology of NHSN-defined CLABSIs in patients with and without neutropenia and, using these data, to propose a modification of the CLABSI definition.Design.Retrospective review.Setting.Two large university hospitals over 18 months.Methods.All hospital-acquired BSIs occurring in patients with central venous catheters in place were classified using the NHSN CLABSI definition. Patients with postchemotherapy neutropenia (500 neutrophils/mm3or lower) at the time of blood culture were considered neutropenic. Pathogens overrepresented in the neutropenic group were identified to inform development of a modified CLABSI definition.Results.Organisms that were more commonly observed in the neutropenic group compared with the nonneutropenic group includedEscherichia coli(22.7% vs 2.5%;P< .001) but not other Enterobacteriaceae,Enterococcus faecium(18.2% vs 6.1%;P= .002), and streptococci (18.2% vs 0%;P< .001). Application of a modified CLABSI definition (removing BSI with enterococci, streptococci, orE. coli) excluded 33 of 66 neutropenic CLABSIs and decreased the CLABSI rate in one study hospital with large transplant and oncology populations from 2.12 to 1.79 cases per 1,000 line-days.Conclusions.Common gastrointestinal organisms were more common in the neutropenia group, suggesting that many BSIs meeting the NHSN criteria for CLABSI in the setting of neutropenia may represent translocation of gut organisms. These findings support modification of the NHSN CLABSI definition.
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Wright, DG, AI Meierovics, and JM Foxley. "Assessing the delivery of neutrophils to tissues in neutropenia." Blood 67, no. 4 (1986): 1023–30. http://dx.doi.org/10.1182/blood.v67.4.1023.1023.
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Abstract Studies of neutrophil kinetics in neutropenic individuals, as well as clinical observations of variability in the occurrence of infection among patients with neutropenia, have suggested that blood neutrophil counts may not uniformly reflect the effective delivery of neutrophils to extravascular tissues where the cells perform their principal host defense functions. To evaluate this possibility we developed a sensitive, reproducible method of measuring the extravascular delivery of neutrophils to a normal mucosal site of neutrophil turnover. This method is based upon the quantification of neutrophils recoverable from saline mouth wash specimens. Twenty-five mL specimens, obtained in a controlled manner from neutropenic patients and normal subjects, were centrifuged and the sediments resuspended in 1.0 mL Hank's buffer with 2 micrograms acridine orange, incubated at 37 degrees C for 15 minutes, and then examined in a hemocytometer chamber by fluorescence microscopy. Neutrophils could be clearly distinguished by their characteristic fluorescence and were counted. With this method as few as 1,500 neutrophils were detected reliably in mouth wash specimens. Mucosal neutrophil counts varied less than 10% with repeated sampling of individual subjects over 5-day periods and were consistently greater than 1.3 X 10(5)/specimen in non-neutropenic individuals. Although profound neutropenia was generally reflected by lower than normal oral mucosal neutrophil counts, these counts were significantly higher in individuals with chronic severe neutropenia (blood neutrophils less than 300/mm3) than in patients with acute neutropenia of comparable severity that had developed following chemotherapy. Also, in individuals recovering from profound neutropenia, neutrophils usually reappeared earlier in mouth wash specimens than in blood, and oral mucosal neutrophil counts attained recovery levels more rapidly than did blood counts. This phenomenon was particularly evident in an individual with cyclic neutropenia. Moreover, mucosal neutrophils could occasionally be detected in profoundly neutropenic patients when neutrophils were not present in blood samples. These findings indicate that mucosal neutrophil counts in individuals with neutropenia provide information about the delivery of neutrophils to tissues that may not be apparent from blood neutrophil counts alone.
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Wright, DG, AI Meierovics, and JM Foxley. "Assessing the delivery of neutrophils to tissues in neutropenia." Blood 67, no. 4 (1986): 1023–30. http://dx.doi.org/10.1182/blood.v67.4.1023.bloodjournal6741023.
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Studies of neutrophil kinetics in neutropenic individuals, as well as clinical observations of variability in the occurrence of infection among patients with neutropenia, have suggested that blood neutrophil counts may not uniformly reflect the effective delivery of neutrophils to extravascular tissues where the cells perform their principal host defense functions. To evaluate this possibility we developed a sensitive, reproducible method of measuring the extravascular delivery of neutrophils to a normal mucosal site of neutrophil turnover. This method is based upon the quantification of neutrophils recoverable from saline mouth wash specimens. Twenty-five mL specimens, obtained in a controlled manner from neutropenic patients and normal subjects, were centrifuged and the sediments resuspended in 1.0 mL Hank's buffer with 2 micrograms acridine orange, incubated at 37 degrees C for 15 minutes, and then examined in a hemocytometer chamber by fluorescence microscopy. Neutrophils could be clearly distinguished by their characteristic fluorescence and were counted. With this method as few as 1,500 neutrophils were detected reliably in mouth wash specimens. Mucosal neutrophil counts varied less than 10% with repeated sampling of individual subjects over 5-day periods and were consistently greater than 1.3 X 10(5)/specimen in non-neutropenic individuals. Although profound neutropenia was generally reflected by lower than normal oral mucosal neutrophil counts, these counts were significantly higher in individuals with chronic severe neutropenia (blood neutrophils less than 300/mm3) than in patients with acute neutropenia of comparable severity that had developed following chemotherapy. Also, in individuals recovering from profound neutropenia, neutrophils usually reappeared earlier in mouth wash specimens than in blood, and oral mucosal neutrophil counts attained recovery levels more rapidly than did blood counts. This phenomenon was particularly evident in an individual with cyclic neutropenia. Moreover, mucosal neutrophils could occasionally be detected in profoundly neutropenic patients when neutrophils were not present in blood samples. These findings indicate that mucosal neutrophil counts in individuals with neutropenia provide information about the delivery of neutrophils to tissues that may not be apparent from blood neutrophil counts alone.
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Degerli, Vermi, Fulya Yilmaz Duran, Mustafa Kucuk, and Ibrahim Atasoy. "A rare cause of neutropenic enterocolitis: Propylthiouracil-induced agranulocytosis." Hong Kong Journal of Emergency Medicine 25, no. 5 (2018): 286–89. http://dx.doi.org/10.1177/1024907918755175.
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Introduction: Neutropenic enterocolitis is a life-threatening gastrointestinal complication of neutropenia that is rarely seen in adults. Neutropenic enterocolitis is more common in oncology patients, especially in those with leukemia. Antithyroid drugs are widely used to treat hyperthyroidism, but they can rarely cause agranulocytosis. Although the pathophysiology is not well understood, high clinical suspicion and immediate and appropriate treatment responses are essential to reduce the mortality rate of neutropenic enterocolitis. Case presentation: We present a case of a 57-year-old male patient who developed neutropenic enterocolitis as a result of agranulocytosis caused by the use of propylthiouracil. He had history of hyperthyroidism and was on propylthiouracil. He presented to the emergency department with abdominal pain but eventually died due to rapid deterioration of sepsis and multiple organ failure despite medical and surgical treatment. Discussion: Thioamides can cause agranulocytosis which can result in serious complication including neutropenic enterocolitis. Complete blood count must be monitored in patients receiving thioamides, and these patients should be educated on symptoms of agranulocytosis. Conclusion: Since patients with neutropenic enterocolitis are often evaluated first by emergency physicians, emergency physicians must be vigilant for neutropenic enterocolitis in patients with neutropenia and abdominal pain.
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Carlisle, Penelope S., Rasim Gucalp, and Peter H. Wiernik. "Nosocomial Infections in Neutropenic Cancer Patients." Infection Control & Hospital Epidemiology 14, no. 6 (1993): 320–24. http://dx.doi.org/10.1086/646750.
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AbstractObjective:Identification of overall and site-specific rates of nosocomial infection in neutropenic patients with cancer and associated pathogens.Design:Cumulative continuous prospective surveillance over a 42-month period. Criteria and definitions of infection in neutropenic patients (absolute neutrophil counts < 1,000/mm3) were developed, and surveillance was carried out by a certified infection control nurse and a senior oncology research fellow.Setting:A cancer research center with two designated oncology nursing units.Patients:Neutropenic patients with hematological and solid malignancies undergoing high-dose chemotherapy with and without autologous bone marrow transplantation. All patients admitted to both of the units during the study period were surveyed. Those who developed neutropenia are included in this report.Results:A total of 444 nosocomial infections were identified in 920 neutropenic patients during 9,582 days of neutropenia for an overall rate of 48.3 per 100 neutropenic patients, or 46.3 per 1,000 days at risk. The rate of bloodstream infection per 100 neutropenic patients was 13.5 (gram-positive, 9.2; gram-negative, 4.8; and Candida 1.2). Other site-specific rates were: urinary tract, 5.7; respiratory tract, 5.5; thrush, 6.6; skin, 3.4; and gastrointestinal tract, 3.4. Among 392 pathogens identified, there were 137 (35%) gram-positive cocci, 105 (27%) gram-negative rods, 70 (18%) Candida, 37 (9%) gram-positive rods, 22 (6%) viruses, and 15 (4%) Aspergillus.Conclusions:The rate of both overall and site-specific nosocomial infections in neutropenic patients is high. Neutropenia is a significant intrinsic risk factor that should be addressed in surveillance programs. Infection control and infectious diseases practitioners may need to modify techniques for surveillance, control, and management of infection in this population.
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Nyatsanza, Ignatius, Irum Khan, Jennifer Windhorst, et al. "Timely antibiotic administration in febrile neutropenia." Journal of Clinical Oncology 35, no. 8_suppl (2017): 204. http://dx.doi.org/10.1200/jco.2017.35.8_suppl.204.
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204 Background: The University of Illinois currently lacks a standard process to ensure timely antibiotic administration for patients with febrile neutropenia. The Infectious disease society of America (IDSA) guidelines recommend administration of antibiotics within two hours. Given the variability in patient encounters, we sought to implement an early identification and interventional strategy in the ambulatory setting for febrile neutropenic patients. A retrospective chart review over 10 weeks demonstrated that of 40 patients diagnosed with neutropenia 15 % (N = 6) had febrile neutropenia. Of these 6 patients, 50% (N = 3) received antibiotics within the IDSA time frame. We aimed to increase the percentage of febrile neutropenic patients receiving antibiotics within 2 hours from 50% to 100% in 8 weeks. Methods: A focus group at our quarterly morbidity mortality and improvement conference brainstormed a list of causes of delay in antibiotic initiation based on an index case discussion. A task force generated a pareto chart after affinity sorting the prior list, and created actual and ideal process maps, from identification of neutropenic patients to patient disposition. A standard operative protocol (SOP) was developed involving the creation and implementation of an electronic provider generated neutropenia check list triggering specific actions per IDSA recommendations, and a standardized order set including STAT cultures, and STAT antibiotics. Results: The febrile neutropenia SOP will be piloted over an 8 week period starting in early November in four ambulatory settings. The primary outcome data is the time from event to antibiotic administration. Process data will include time from event to antibiotic order, time from antibiotic order to administration and compliance with high risk neutropenic check list. We plan to assess our interventions every 3-4 weeks, and pilot at least 2 PDSA cycles within the next 8 weeks. Conclusions: Although febrile neutropenia is a recognized medical emergency with clear guidelines on treatment, not all patients may receive antibiotics within the appropriate time frame. It is therefore imperative for institutions to be aware of their level of IDSA compliance and implement appropriate quality improvements as required.
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Morgan, Jessica E. "Fifteen minute consultation: Fever in children being treated for cancer." Archives of disease in childhood - Education & practice edition 104, no. 3 (2018): 124–28. http://dx.doi.org/10.1136/archdischild-2017-314718.
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Fever is a common symptom in children receiving treatment for cancer. Clinicians and families are most concerned about febrile neutropenia, though non-neutropenic fever often causes more challenging treatment dilemmas. This article provides a structured approach to the initial assessment, examination, investigation and risk assessment of children with fever during treatment for childhood cancer. Non-neutropenic fever in children with cancer is not well researched. There are no systematic reviews of its management and no National Institute for Health and Care Excellence (NICE) (or other international) guidance about what to do. Features to consider when managing non-neutropenic fever are discussed. Febrile neutropenia, meanwhile, is an oncological emergency and requires management using standard sepsis principles including administration of broad-spectrum antibiotics. Relevant NICE guidance provides a clear structure for treatment. Ongoing management depends on the response to initial treatment.
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Lee, Pauline, Randall W. Knoebel, Jennifer Pisano, and Natasha N. Pettit. "Moxifloxacin versus levofloxacin for antibacterial prophylaxis in acute leukemia patients." Journal of Oncology Pharmacy Practice 25, no. 3 (2018): 758–61. http://dx.doi.org/10.1177/1078155217752074.
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Objective The primary endpoint of this study was to determine the incidence of febrile neutropenia among patients receiving either moxifloxacin or levofloxacin for antibacterial prophylaxis. Secondary endpoints were number of documented infections and in-hospital mortality in patients who develop febrile neutropenia. Methods A single-center retrospective cohort analysis at a large tertiary care academic medical center was conducted. This study included adult acute leukemia patients (age ≥18 years old) who received inpatient antibacterial prophylaxis (moxifloxacin or levofloxacin) from 1 July 2012 to 1 October 2014. Patients were excluded from the study if they were treated with antimicrobial therapy in the preceding five days or admitted to the hospital with neutropenic fever. Fisher’s exact test was used for categorical data and Mann–Whitney test for continuous data. Logistic regression analysis was used to determine risk factors for febrile neutropenia. Results Eighty-five patients were included in the final analysis with 40 patients who received moxifloxacin and 45 patients who received levofloxacin. Baseline characteristics were similar between the two groups. Twenty-two patients experienced febrile neutropenia requiring intravenous antibiotics in the moxifloxacin group and 30 patients in the levofloxacin group (P = 0.190). Age and duration of neutropenia appeared to predict for febrile neutropenia; however, after multivariate analysis, longer duration of neutropenia was shown to be the best predictor for febrile neutropenia with an odds ratio of 4.69 (95% CI, 1.697–12.968). Both groups had similar rates of documented infections and in-hospital morality. Conclusion Moxifloxacin and levofloxacin showed similar rates of febrile neutropenia when used for neutropenic antibacterial prophylaxis in acute leukemia patients.
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Ball, Somedeb, Timothy J. Brown, Avash Das, Rohan Khera, Sahil Khanna, and Arjun Gupta. "Effect of Neutropenic Diet on Infection Rates in Cancer Patients With Neutropenia." American Journal of Clinical Oncology 42, no. 3 (2019): 270–74. http://dx.doi.org/10.1097/coc.0000000000000514.
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Lehmkuhl, Michelle, Leo Chen, and Winson Y. Cheung. "Population-based patterns of granulocyte colony stimulating factor (GCSF) use in breast cancer (BrCa) patients receiving myelosuppressive chemotherapy." Journal of Clinical Oncology 31, no. 15_suppl (2013): 9625. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.9625.
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9625 Background: Prophylaxis with GCSF can reduce hospitalization due to neutropenic fever, but early studies show that use of GCSF is frequently suboptimal. Our aims were to 1) characterize patterns of GCSF use in a population-based cohort of BrCa patients, 2) determine the rate of neutropenia and neutropenic fever in those who received and did not receive GCSF, and 3) identify patient and physician factors associated with appropriate GCSF prophylaxis. Methods: Patients diagnosed with BrCa from January to December 2008, seen at any 1 of 5 regional cancer centers in British Columbia, Canada and treated with chemotherapy protocols that posed >20% risk of neutropenic fever were reviewed. Using regression models that adjusted for confounders, the relationship between GCSF use and 1) various patient and physician characteristics and 2) treatment outcomes, such as neutropenic fever, were analyzed. Results: A total of 525 women were included: median age was 51 years (IQR 45 to 59 years), 38% reported smoking, 50% used alcohol regularly, 62% were ECOG 0, and 26% had private health insurance. In the entire cohort, 203 (38%) patients were given GCSF. Among those treated with GCSF, 80 (39%) and 123 (61%) individuals received GCSF as primary and secondary prophylaxis, respectively. Overall, neutropenia was noted in 292 (56%) cases while neutropenic fever was experienced by 117 (22%) patients. When compared to those who did not use GCSF, patients who used GCSF experienced a lower rate of neutropenia (15 vs 49%, p<0.01) and a decreased incidence of neutropenic fever (7 vs 13%, p<0.01). In regression models, patients lacking extended medical coverage (35 vs 49%, p=0.02), poor performance status (31 vs 53%, p=0.03), and those who were evaluated at non-teaching institutions (24 vs 68% p<0.01) were less likely to receive GCSF. Patients seen at non-teaching institutions were also given primary GCSF prophylaxis less frequently (15 vs 57%, p<0.01) than those at teaching centers. Conclusions: GCSF prophylaxis was associated improved neutropenia-related outcomes. However, use of GCSF was low in this population-based cohort of BrCa patients, especially in specific marginalized subgroups.
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Ozer, H., B. Mirtsching, M. Rader, B. Ding, D. Truscinski, and L. Dreiling. "Final results of a large, community-based, prospective study evaluating the impact of first and subsequent cycle pegfilgrastim on neutropenic events in patients receiving myelosuppressive chemotherapy." Journal of Clinical Oncology 24, no. 18_suppl (2006): 8569. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.8569.
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8569 Background: Neutropenia is the major dose-limiting complication of myelosuppressive chemotherapy (CT). The Awareness of Neutropenia in CT (ANC) Study Group has prospectively documented cycle 1 febrile neutropenia (FN) in 8% of patients (pts) receiving CT with or without growth factor support in community practice. Our study was conducted to assess the impact of first and subsequent cycle pegfilgrastim use on neutropenic events in pts receiving CT in community practice. Interim data were previously reported (Ozer ASCO 2005). Methods: Pts ≥18 years with cancers other than leukemia or MDS were eligible, including pts with major comorbidities. Key exclusion criteria of this open-label study were weekly CT or concurrent radiotherapy (RT). Pts were to receive pegfilgrastim 6 mg ∼24 hours after CT (min 4 cycles planned). Primary endpoints were neutropenic hospitalization and CT dose delays and reductions; additionally, FN (absolute neutrophil count <1×109/L with temperature ≥38.2oC) was measured. Results: 319 centers enrolled 2,249 pts (2,500 planned); 2,112 patients who received CT and pegfilgrastim after proper consent were included in final analyses. Most pts were women (75%). Major tumor types included: breast (46%), lung (16%), and ovarian (8%) cancers, and lymphoma (18%). 36% of pts were ≥65 years (mean age [SD]: 59 [12.8]), 55% had stage 3/4 or extensive disease, 23% received prior CT, 17% received prior RT, and 27% had a significant comorbidity. Neutropenic complications occurred infrequently (table). FN was experienced by 3.6% (95% CL: 2.8, 4.5) of pts in cycle 1 and in 6.3% (5.3, 7.5) in all cycles. Serious adverse events were consistent with toxicities observed in pts receiving CT. Conclusions: Pts treated in community practice receiving pegfilgrastim in every cycle of myelosuppressive CT experienced a low incidence of neutropenic complications and alterations in CT dose and schedule due to neutropenia. [Table: see text] [Table: see text]
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Ventham, Nicholas, Vamsi Velchuru, Earl Scout, and John Studley. "Unusual cause of acute abdomen – omental infarction occurring in a child with cyclical neutropenia." Annals of The Royal College of Surgeons of England 92, no. 2 (2010): e32-e34. http://dx.doi.org/10.1308/147870810x476773.
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Omental infarction is a rare cause of acute abdomen in childhood. We describe a case of omental infarction mimicking acute appendicitis occurring in a child with cyclical neutropenia. Neutropenic enterocolitis, a serious cause of the acute abdomen, has been linked with cyclical neutropenia. In neutropenic patients, omental infarction when diagnosed pre-operatively can be managed conservatively with the focus on improving the neutrophil count. If after imaging the diagnosis is in doubt, there should be a low threshold for laparoscopy. The low incidence of omental infarction will continue to mean that it is a diagnosis made at operation for suspected appendicitis. In these cases, the infarcted tissue may be removed by the laparoscopic or open technique.
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Silva, Edward, Melanie Higgins, Barbara Hammer, and Paul Stephenson. "Clozapine re-challenge and initiation following neutropenia: a review and case series of 14 patients in a high-secure forensic hospital." Therapeutic Advances in Psychopharmacology 11 (January 2021): 204512532110150. http://dx.doi.org/10.1177/20451253211015070.
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Objective: Clozapine remains the most effective intervention for treatment resistant schizophrenia; however, its use is prohibited following neutropenias. We review neutrophil biology as applied to clozapine and describe the strategies to initiate clozapine following neutropenia used in a case series of 14 consecutive patients rechallenged in a United Kingdom (UK) high-secure psychiatric hospital. We examine outcomes including the use of seclusion and transfer. Methods: A case series of 14 male patients with treatment resistant schizophrenia treated with clozapine despite previous episodes of neutropenia between 2006 and 2015 is presented. Data were collected during 2015 and 2019. Using this routinely collected clinical data, we describe the patient characteristics, causes of neutropenia, the strategies used for rechallenging with clozapine and clinical outcomes. Results: Previous neutropenias were the result of benign ethnic neutropenia, clozapine, other medications and autoimmune-related. Our risk mitigation strategies included: granulocyte-colony stimulating factor (G-CSF), lithium and watch-and-wait. There were no serious adverse events; at follow up half of the patient’s had improved sufficiently to transfer them to conditions of lesser security. There were dramatic reductions in the use of seclusion. Conclusion: Even in this extreme group, clozapine can be safely and effectively re/initiated following neutropenias, resulting in marked benefits for patients. This requires careful planning based on an understanding of neutrophil biology and the aetiology of the specific episode of neutropenia.
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Okhmat, V. A., G. A. Klyasova, E. N. Parovichnikova, et al. "Infectious complications in patients with acute leukemia according to the duration of neutropenia." Oncohematology 13, no. 3 (2018): 55–62. http://dx.doi.org/10.17650/1818-8346-2018-13-3-55-62.
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Introduction. Patients with hematological malignancies undergoing chemotherapy (CT) have high incidence of infections which profile is affected by various factors including neutropenia.Objective was to evaluate incidence and type of infections in patients with de novo acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) according to neutropenia duration.Materials and methods. Prospective study (2013–2015) included 110 patients (66 AML, 44 ALL) that received 480 CT cycles throughout 6 month.Results. Neutropenia with median duration of 15 (2–55) days was in 288 (60 %) of CT cycles. Infections occurred in 242 (50 %) of CT cycles and predominated in neutropenic compared to non-neutropenic patients (80 % vs 6 %, p <0.0001). Infections prevailed in patients with AML compared to ALL patients (93 % vs 18 %, p <0.0001) as in patients with neutropenia (96 % vs 45 %, p <0.0001) and without neutropenia (27 % vs 4 %, p = 0.02). Prolongation of neutropenia from 1–7 days to ≥22 days was associated with increase of infections rate from 52 to 96 % (p <0.0001). Incidence of infections in AML patients was high (92–100 %) regardless of neutropenia duration, whereas in ALL patients it increased from 25–33 to 91 % if neutropenia lengthened from 2 weeks to ≥22 days. During neutropenia the probability of fever of unknown origin was 33.9 %, clinically documented infection – 31.3 %, bacteremia – 17.2 %. They predominated in the first 2 weeks of neutropenia. Probability of invasive aspergillosis (IA) increased after 28 days of neutropenia and reached 66 % on the 55th day. First case of IA in patients with ALL was on 28th day of neutropenia whilst in AML patients – 4 (44 %) of 9 occurred more early (6–16 days of neutropenia). Nine (6 %) of 110 patients died, 4 (4 %) of them due to infection.Conclusions. Neutropenia was a predictor of infectious complications in patients with AML and ALL. Correlation between duration of neutropenia and incidence of infections was in patients with ALL, whereas in AML patients the rate of infections was high regardless of neutropenia duration. In patients with neutropenia for 2 weeks the most common types of infection were fever of unknown origin, clinically documented infection and bacteremia whilst IA predominated if neutropenia duration was ≥28 days.
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Maahs, Lucas, Amy Tang, Zaid Al Saheli, Brigid Jacob, Rishika Polasani, and Clara Hwang. "Pegfilgrastim on-body injector: Post-market performance analysis." Journal of Clinical Oncology 38, no. 15_suppl (2020): e19226-e19226. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e19226.
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e19226 Background: Granulocyte colony-stimulating factors (G-CSF) are widely used in medical oncology for the prevention of neutropenia and its complications. On-body injectors (OBI) have an advantage over the traditional injection (TI) method of not requiring a second visit to the oncology clinic the day after chemotherapy, but these devices are subject to failure. The objective of this study was to assess the efficacy of OBIs in the real world. Methods: Adult women with breast cancer diagnosed between June 2015 and June 2016 treated with cytotoxic chemotherapy and a G-CSF were retrospectively identified from the medical records of Henry Ford Hospital (Detroit, MI, USA). The primary outcome was the incidence of severe neutropenia (SN), defined as an absolute neutrophil count (ANC) ≤500. Secondary outcomes included incidence of neutropenia (ANC ≤1500), neutropenic fever, and mortality. A secondary analysis of the data was performed to identify predictors of SN. Results: A total of 837 cycles of chemotherapy were analyzed. The OBI was used in 395 cycles and the TI in 442. The OBI group had patients that were older, had higher ANC, were more often black, had worse performance status, and were more often smokers. The incidences of SN, neutropenic fever and neutropenia were not different between groups (Table). Mortality was not different between groups when adjusted for confounding variables (OR 1.8, 95% CI 0.9-3.6, p=0.09). Patients with a lower baseline ANC and white ethnicity were at a higher risk for SN. TAC (docetaxel, doxorubicin and cyclophosphamide combined) carried the highest risk for SN among the chemotherapy regimens used. Conclusions: There was no difference in the efficacy of the OBI and TI methods for preventing SN, neutropenic fever, neutropenia, and death. Independent predictors of SN included the chemotherapy regimen used, baseline ANC and ethnicity. [Table: see text]
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Solis, Krystian, and Walter Dehority. "Antibiotic-Induced Neutropenia During Treatment of Hematogenous Osteoarticular Infections in Otherwise Healthy Children." Journal of Pediatric Pharmacology and Therapeutics 24, no. 5 (2019): 431–37. http://dx.doi.org/10.5863/1551-6776-24.5.431.
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OBJECTIVES We studied the frequency and characteristics of antibiotic-induced neutropenia in otherwise healthy children receiving antibiotic therapy for hematogenous osteoarticular infections (OAIs). METHODS We retrospectively enrolled otherwise healthy children between 1 month and 18 years of age discharged with an OAI from our institution over an 11-year period. An absolute neutrophil count (ANC) ≤1500 cells/μL was defined as neutropenia. We recorded demographic and clinical information, as well as the value and timing of each ANC in relation to changes in antibiotic therapy. A multivariable regression model assessed the contributions of various risk factors. RESULTS A total of 186 children were enrolled (mean age, 7.6 years; 67.2% boys). β-Lactams represented 61.2% of all prescriptions. During treatment, 61 subjects (32.8%) developed neutropenia (median time to onset, 24 days). An ANC &lt; 500 cells/μL occurred in 7 subjects (3.8%). Neutropenic subjects (mean age, 6.0 years) were significantly younger than those without neutropenia (mean age, 8.5 years) (OR = 0.86; 95% CI: 0.79–0.93; p &lt; 0.001) and received significantly longer courses of total (89.3 vs. 55.8 days) and parenteral (24.6 vs. 19.9 days) antibiotic therapy (OR = 1.01; 95% CI: 1.01–1.02; p = 0.004 and OR = 1.02; 95% CI: 1.01–1.04; p = 0.041, respectively). Recurrent neutropenia occurred in 23.0% of all neutropenic subjects and was significantly more common in those with a longer mean duration of parenteral therapy (OR = 1.05; 95% CI: 1.02–1.09; p = 0.004.). No complications from neutropenia occurred. CONCLUSIONS Neutropenia was common in our cohort of children receiving prolonged antibiotic therapy for OAIs. Younger age and longer courses of therapy were associated with an increased risk of neutropenia.
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Girmenia, Corrado, Alessandra Micozzi, Giuseppe Gentile, et al. "Clinically Driven Diagnostic Antifungal Approach in Neutropenic Patients: A Prospective Feasibility Study." Journal of Clinical Oncology 28, no. 4 (2010): 667–74. http://dx.doi.org/10.1200/jco.2009.21.8032.
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Purpose Preemptive strategies in neutropenic patients based on serum galactomannan (GM) –guided triggering of diagnostic work-up may be time-consuming and expensive when applied to the entire population. We have assessed the feasibility of a clinically driven diagnostic strategy without GM screening. Patients and Methods Patients with neutropenic fever underwent a baseline diagnostic work-up (BDWU; three blood cultures and other examinations as indicated). An intensive diagnostic work-up (IDWU; GM for 3 days, chest computed tomography and other examinations as indicated) was reserved for patients with 4 days of persisting or relapsing fever or with other clinical findings possibly related to an invasive fungal diseaser (IFD). Antifungal therapy was administered to patients diagnosed with IFD and empirically (negative IDWU) only to those with persisting neutropenic fever and worsening clinical conditions. Results Of 220 neutropenia episodes, fever occurred in 159 cases and recurred in 28 cases. Overall, 49 IFDs were diagnosed (two by BDWU and 47 by IDWU) during 48 episodes (21.8%). Diagnostic-driven therapy was administered to 48 patients with IFDs; one patient with zygomycosis died without treatment. Only one patient received empirical therapy. IDWU was required in 40% of neutropenia episodes, and only 1.4 mean blood samples per neutropenia episode were tested for GM. Our strategy allowed a 43% reduction in antifungal treatments compared with a standard empirical approach. At 3-month follow-up, 63% of patients with IFD survived, and no undetected IFDs were found. Conclusion A clinically driven diagnostic approach in selected neutropenia episodes offered effective antifungal control and reduced the exposure to unnecessary antifungal treatment.
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Lyman, Gary H., Eva Culakova, Marek S. Poniewierski, Jeffrey Crawford, David C. Dale, and Nicole M. Kuderer. "Personalizing Cancer Supportive Care: Predicting Neutropenic Complications in Patients Receiving Intermediate Risk Cancer Chemotherapy." Blood 118, no. 21 (2011): 1022. http://dx.doi.org/10.1182/blood.v118.21.1022.1022.
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Abstract Abstract 1022 Background: Neutropenic complications represent important dose-limiting toxicities of cancer chemotherapy. We recently developed and validated a risk model for neutropenic complications in patients with solid tumors or lymphoma receiving cancer chemotherapy (Lyman et al. Cancer 2011). While practice guidelines recommend primary colony-stimulating factor (CSF) prophylaxis for patients at >20% risk of febrile neutropenia (FN), many patients receive chemotherapy regimens associated with an intermediate risk (10–20%) of FN. For these patients, the decision to give or withhold primary CSF prophylaxis is based on clinical judgment. We report here the ability of the risk model to identify patients with individual characteristics placing them at high risk for neutropenic complications among patients receiving intermediate risk chemotherapy regimens. Methods: A prospective cohort study was conducted of consenting patients initiating a new chemotherapy regimen at 115 randomly selected US oncology practices between 2002–2006. The risk of cycle 1 severe or febrile neutropenia was estimated [95% CI] utilizing logistic regression analysis adjusting for key clinical factors including: planned chemotherapy, prior chemotherapy, age, abnormal hepatic or renal function, low pretreatment white blood count, and immunosuppressive medications. The cumulative incidence of severe neutropenia and FN across 4 cycles was estimated by the product limit method of Kaplan and Meier. Results: Among 3,760 patients with cancers of breast, lung, ovary, colon, or lymphoma, 2,270 received an intermediate risk chemotherapy regimen based on NCCN guidelines. Overall, in the subpopulation receiving intermediate risk regimens, severe or febrile neutropenia occurred in cycle 1 in 21.4% while FN over 4 cycles was observed in 11%, and primary CSF prophylaxis was utilized in 16.4%. The performance of the risk model was good in this subgroup with a c-statistic of 0.82 [0.80–0.84]. Among the half of patients classified as high risk based on the model despite receiving an intermediate risk chemotherapy regimen, cycle 1 severe or febrile neutropenia occurred in 38% [35%–41%] compared to 5% [4%–6%] of patients classified as low risk based on the model receiving such regimens. Model sensitivity and specificity were 89% and 61%, respectively. The cumulative risk of FN over 4 cycles of chemotherapy was 20% in predicted high risk group versus 5% in the low risk group (Figure). The majority of severe or febrile neutropenia events (67%) and FN events (55%) were observed in cycle 1. One-half of high risk patients who did not receive primary CSF prophylaxis in cycle 1 received CSF during subsequent cycles following a neutropenic event. Conclusions: Our model for predicting neutropenic complications can identify patients at high individual risk for severe neutropenia in cycle 1 or FN in the first 4 cycles of chemotherapy when receiving intermediate risk chemotherapy. This analysis emphasizes the potential value of determining an individual patient's risk of chemotherapy complications based on a validated risk model. Disclosures: Lyman: Amgen: Research Funding. Crawford:Amgen: Consultancy, Honoraria, Research Funding. Dale:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kuderer:Amgen: Research Funding.
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Jurkonis, Mantas, Indrė Tamulienė, Rimantė Čerkauskienė, Arijanda Neverauskienė, Rytis Žilevičius, and Gražina Kleinotienė. "FEBRILINĖS NEUTROPENIJOS GYDYMO STANDARTAI PEDIATRIJOJE." Medicinos teorija ir praktika 21, no. 2.1 (2015): 131–36. http://dx.doi.org/10.15591/mtp.2015.019.
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Managing cancer patients with fever and neutropenia must be considered as a medical emergency since any delay in initiating appropriate empirical antibacterial therapy may result in high rates of mortality and morbidity. Emerging antibacterial resistance in bacterial pathogens infecting febrile neutropenic patients complicates management, and choosing the type of empirical antimicrobial therapy has become a challenge. To further complicate the decision process, not all neutropenic patients are in the same category of susceptibility to develop severe infection. This review gives a brief overview of current antimicrobial regiment strategy in febrile neutropenic cancer patients.
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Michniacki, Thomas F., Kelly J. Walkovich, Julie Sturza, et al. "Neutropenia Is an Under-Recognized Finding in Pediatric Primary Immunodeficiency Diseases: An Analysis of the United States Immunodeficiency Network Registry." Blood 132, Supplement 1 (2018): 3685. http://dx.doi.org/10.1182/blood-2018-99-113199.
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Abstract Background: Neutropenia is recognized as a defining or common element in a limited number of primary immunodeficiency diseases (PIDDs) (Dotta L et al. Immunol Let 2014; Cham B et al. Semin Hematol 2002); but, the overall prevalence of neutropenia within the more than 300 known PIDDs is not well described. Many of the PIDDs rely on a high index of clinical suspicion for diagnosis which may not be readily apparent to hematologists evaluating a neutropenic patient, underscoring the importance of understanding the rate of neutropenia in PIDDs and impact on clinical outcomes. The goal of this study was to evaluate the frequency and characteristics of neutropenia in a large registry of patients with primary immunodeficiency (PID). Methods: The United States Immunodeficiency Network (USIDNET) is a research consortium that maintains a national registry for the collection of data on patients with PIDDs. The USIDNET was queried for data regarding patients aged 21 years or less. Data utilized included reported PID diagnosis, gene mutation, gender, race, status of patient (living or deceased), year of birth, age at death, age of disease diagnosis, and results of reported complete blood counts (CBCs). PID diagnoses were grouped according to the 2017 International Union of Immunological Societies (IUIS) Phenotypic Classification for Primary Immunodeficiencies (Bousfiha A et al. J Clin Immunol 2018). Mild, moderate, and severe neutropenia were defined as absolute neutrophil counts of 1000-1499 cells/μL, 500-999 cells/μL, and < 500 cells/μL, respectively. Data are presented with descriptive statistics. The frequency of neutropenia was compared between genders and by race using chi-square test analysis. Results: An initial data request resulted in information on 1577 patients; 384 patients were eliminated from analysis given insufficient recorded registry data due to a lack of a documented absolute neutrophil count. An additional 48 patients were excluded given that complete blood cell counts were only reported following hematopoietic stem cell transplantation. Data was thus available for 1145 pediatric patients with PIDDs. A total of 2058 neutrophil values were analyzed with 62.7% (719) patients having only a single neutrophil value available for review. Overall, 15.8% of PIDD pediatric patients in the USIDNET registry had neutropenia, ranging from 12.01% (combined immunodeficiencies with associated or syndromic features) to 66.67% (defects in intrinsic and innate immunity) in IUIS categories (Table 1) and in USIDNET categories from 2.94% (autoimmune lymphoproliferative syndrome) to 75.00% (susceptibility to mycobacterial infections) (Table 2). Of PID patients with neutropenia, 20.4% had severe neutropenia, 33.1% had moderate neutropenia, and 46.4% had mild neutropenia. Neutropenia was most likely to be severe in patients with predisposition to severe viral infections as well as those with a defect in intrinsic and innate immunity (Tables 1-2). There was no statistically significant difference in neutropenia between genders (p = 0.64). However, females were more likely to have severe neutropenia than males (28% versus 16%; p=0.03). Additionally, 28% of African-American patients had recorded neutropenia while only 17% of Caucasians and 2% of Asian/Pacific Islanders were neutropenic (p=0.005). There was no statistically significant difference in severity of neutropenia and death nor in the rate of bacterial and fungal infections detected between neutropenic and non-neutropenic patients with 93% of patients in the dataset living at the time of data collection. Conclusions: The frequency of neutropenia within pediatric patients diagnosed with PIDD is higher and more ubiquitous than previously suspected. Hematologists should consider a PIDD in the assessment of neutropenia, particularly if other concerning signs or symptoms are present. Although this evaluation did not detect a difference in morbidity or mortality, the data set was constrained by a limited number of CBCs per patient and the rarity of the PIDDs. The impact of neutropenia on PIDD outcomes requires further study, ideally through a prospective longitudinal study. Acknowledgments: The U.S. Immunodeficiency Network (USIDNET), a program of the Immune Deficiency Foundation (IDF), is supported by a cooperative agreement, U24AI86837, from the National Institute of Allergy and Infectious Diseases (NIAID). Disclosures Dale: Athelas, Inc.: Equity Ownership; Amgen: Consultancy, Research Funding; Sanofi-Aventi: Consultancy, Honoraria; Cellerant: Other: Scientific Advisory Board; Hospira: Consultancy; Prolong: Consultancy; Beheringer-Ingelheim: Consultancy; Coherus: Consultancy.
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LaVie, Katherine W., Scott W. Anderson, Hollis R. O'Neal, Todd W. Rice, Tatiana C. Saavedra, and Catherine S. O'Neal. "Neutropenia Associated with Long-Term Ceftaroline Use." Antimicrobial Agents and Chemotherapy 60, no. 1 (2015): 264–69. http://dx.doi.org/10.1128/aac.01471-15.
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ABSTRACTCeftaroline is a fifth-generation cephalosporin with potent antimicrobial activity against Gram-positive and Gram-negative pathogens. Neutropenia is a rare serious adverse event for the class of cephalosporins; however, we observed several cases of severe neutropenia in our outpatient infectious disease practice believed to be associated with ceftaroline use. The aim of this study was to determine the incidence of neutropenia among patients receiving ceftaroline therapy for more than 7 days. We conducted a retrospective cohort analysis of patients admitted to an 800-bed regional medical center between June 2012 and December 2014 who received ceftaroline for more than 7 days to assess the incidence of developing clinically significant neutropenia. Demographic and patient care data points as well as underlying admitting and chronic diagnoses were retrospectively collected from the medical record. Clinically significant neutropenia was defined as an absolute neutrophil count (ANC) less than 1,500 cells/mm3. Analysis was performed to determine the incidence, severity, and outcome of neutropenia following ceftaroline administration. A total of 39 patients were included in the cohort. The median duration of therapy was 27 days. Seven patients (18%) developed neutropenia while on ceftaroline therapy. Four (10%) of the neutropenic patients had an ANC of <500 cells/mm3. The median first neutropenic day was day 17, with the median ANC nadir of 432 cells/mm3on day 24. We determined that extended ceftaroline infusion is associated with the development of neutropenia. We recommend obtaining a complete blood count (CBC) with differential at the onset of therapy and weekly thereafter. Should the ANC fall below 2,500 cells/mm3, then twice-weekly CBCs should be monitored for the duration of ceftaroline therapy, and therapy should be discontinued if the ANC falls to 1,500 cells/mm3or less.
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Rattanathammethee, Thanawat, Pokpong Piriyakhuntorn, Sasinee Hantrakool, et al. "Gut Microbiota Profiles of Treatment-Naïve Adult Acute Myeloid Leukemia Patientswith Neutropenic Fever during Intensive Chemotherapy." Blood 136, Supplement 1 (2020): 38–39. http://dx.doi.org/10.1182/blood-2020-140936.
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Background : The intestinal bacterial flora of febrile neutropenic patients has been found to be significantly diverse and may play a role in clinical decisions regarding antimicrobial de-escalation with predictive complications. However, there are few reports of microbiota alteration of adult acute myeloid leukemia (AML) patients. Methods : Stool samples of each treatment-naïve AML patient were collected the day before the initiation of induction chemotherapy (pretreatment), on the first date of neutropenic fever and first date of bone marrow recovery. Bacterial DNA was extracted from stool samples and bacterial 16s ribosomal RNA genes were sequenced by next-generation sequencing. Relative abundance, overall richness, Shannon's diversity index and Simpson's diversity index were calculated. Results : Ten AML patients (4 men and 6 women) were included with a median age of 39 years (range: 19-49). Twenty-four stool samples were collected and assigned into three groups: (1) pretreatment (n = 10); (2) first date of febrile neutropenia (n=9); and (3) first date of bone marrow recovery (n=5). All of patients developed febrile neutropenia; three patients had detectable infectious organisms and all of these cases had invasive pulmonary aspergillosis with two being co-infected with Pseudomonas pneumonia and Escherichia coli septicemia. Median absolute neutrophil count was 2.85 x 109/L (range: 1.42-7.67 x 109/L), 0.04 x 109/L (range: 0.01-0.43 x 109/L) and 3.65 x 109/L (range: 2.09-5.78 x 109/L) at pretreatment, first date of febrile neutropenia and first date of bone marrow recovery, respectively. At the phylum level, Firmicutes dominated over the period of neutropenic fever, subsequently declining after bone marrow recovery a pattern in contrast to that shown by Bacteroidetes and Proteobacteria. At the genus level, Enterococcus was more abundant in the febrile neutropenia period compared to pretreatment (mean difference of 20.2, [95%CI (5.9, 34.6)]; P &lt;0.01) whileBacteroides and Escherichia notably declined during the same period (mean difference of -11.7, [95%CI (-21.9, -1.4)]; P= 0.027 and -11.6, [95%CI (-22.7, -0.4)]; P = 0.034, respectively). At the operational taxonomic units (OTUs) level, there was a significantly higher level of overall richness in the pretreatment period than in the febrile neutropenic episode (mean OTUs of 203.1 vs. 131.7; P = 0.012). Both of the diversity indexes of Shannon and Simpson showed a significant decrease in the febrile neutropenic period. Conclusions : Adult AML patients with a first episode of febrile neutropenia after initial intensive chemotherapy demonstrated a significant decrease in gut microbiota diversity and the level of diversity remained constant despite recovery of bone marrow. Figure Disclosures No relevant conflicts of interest to declare.
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Lee, M., K. Aldred, E. Lee, and M. Feldman. "Aspirin-induced acute gastric mucosal injury is a neutrophil-dependent process in rats." American Journal of Physiology-Gastrointestinal and Liver Physiology 263, no. 6 (1992): G920—G926. http://dx.doi.org/10.1152/ajpgi.1992.263.6.g920.
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Aspirin, one of the most widely used drugs in the world, consistently produces gastric mucosal injury, but the pathogenic mechanisms are incompletely understood. The present study was designed to determine the role of neutrophils in aspirin-induced acute gastric mucosal injury. Gastric mucosal lesions induced by acidified aspirin (300 mg/kg) were completely prevented in rats that had been rendered profoundly neutropenic by anti-neutrophil serum. Aspirin-induced acute gastric mucosal lesions were also significantly, albeit incompletely, reduced in rats that had been rendered moderately neutropenic by methotrexate. Moreover, in the methotrexate-induced neutropenia model, the neutropenia-associated mucosal protection against aspirin-induced injury could be reversed by leucovorin rescue. Aspirin caused a marked and statistically significant reduction in gastric mucosal 6-ketoprostaglandin F1 alpha synthesis, but no significant changes in gastric mucosal leukotriene synthesis. Thus no gastric mucosal lesions were observed in profoundly neutropenic rats that were treated with aspirin, despite the marked inhibition of prostaglandin synthesis. These findings demonstrate that aspirin-induced acute gastric mucosal injury is a neutrophil-dependent process.
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Tek, Ibrahim, Selami Kocak Toprak, Efe Hasdemir, Samed Rahatli, and Aysegül Yesilkaya. "Influence of Febrile Neutropenia Period on Plasma Viscosity at Malignancy." Scientific World Journal 2013 (2013): 1–5. http://dx.doi.org/10.1155/2013/507270.
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Cancer, chemotherapy, and infections all together make changes in blood rheology and may affect the defense mechanisms by changing the thrombocyte function and endothelial cell. We have examined changes of blood rheology on plasma viscosity to put on probable following criteria for starting the treatment of febrile neutropenia immediately. A total of 27 postchemotherapy patients (16 males and 11 females) with febrile neutropenia diagnosed according to international guidelines have been included into the study. The plasma viscosity of the patients whose febrile neutropenia has been successfully treated was also measured to assess the impact of the duration of neutropenia on viscosity. The plasma viscosities of the patients were significantly higher during neutropenic episode than in nonneutropenic state () except for alkaline phosphatase. All study parameters, particularly acute phase reactants, were statistically similar during both states. In the correlation of analysis with study parameters and stages, significant correlation was not observed between plasma viscosity alteration and leukocyte-neutrophil alteration, also other study parameters. We have demonstrated significantly elevated plasma viscosity in our patients during febrile neutropenic episode. Despite normal values of various parameters known to trigger plasma viscosity, particularly fibrinogen, it can be easily argued that the main mechanism may be the endothelial injury during infectious process and immune response mediated microcirculatory blood flow alterations.
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Devi, Yumkham Monica, Amit Sehrawat, Prasan Kumar Panda, and Uttam Kumar Nath. "Febrile neutropenia due to COVID-19 in an immunocompetent patient." BMJ Case Reports 14, no. 4 (2021): e242683. http://dx.doi.org/10.1136/bcr-2021-242683.
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While lymphopenia has been a common finding in COVID-19 infection, particularly in severe cases, febrile neutropenia has been very rarely reported in immunocompetent patients with COVID-19. Herein, we report the case of a 76-year-old hypertensive and diabetic man who was hospitalised with severe COVID-19 infection and developed delayed-onset severe neutropenia with neutropenic fever, which responded to treatment with antibiotics and granulocyte colony-stimulating factor. This case highlights the importance of identifying a rare complication (febrile neutropenia on the fifth week) of COVID-19 infection in hospitalised patients by intensive monitoring and aggressive management for favourable outcomes.
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Kornelsen, Emily, and Winson Y. Cheung. "Use of granulocyte colony stimulating factor (GCSF) in patients receiving highly myelosuppressive chemotherapy for breast cancer." Journal of Clinical Oncology 35, no. 15_suppl (2017): e21677-e21677. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e21677.
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e21677 Background:We hypothesized that GCSF use may be suboptimal in the real world despite prior research that shows prophylaxis with GCSF can reduce neutropenic fevers and hospitalizations. Our aims were to characterize patterns of GCSF use in a population-based cohort of breast cancer patients receiving highly myelosuppressive chemotherapy and to describe outcomes and predictors associated with appropriate GCSF prophylaxis. Methods:Patients diagnosed with breast cancer from 2008 to 2012, seen at any 1 of 5 comprehensive cancer centers in a Canadian province, and treated with chemotherapy that posed > 20% risk of neutropenic fever were reviewed. Associations between GCSF use and 1) patient and physician factors and 2) treatment outcomes, including rate of neutropenic fevers, were analyzed using regression models. Results:We included 805 women: median age was 52 (IQR 44 to 61) years, 40% reported smoking, 52% used alcohol regularly, 64% were ECOG 0, and 24% had private health insurance. In this cohort, 330 (41%) patients were given GCSF. Among those treated with GCSF, 132 (40%) and 198 (60%) individuals received GCSF as primary and secondary prophylaxis, respectively. Overall, neutropenia was noted in 467 (58%) cases while neutropenic fever was experienced by 161 (20%) patients. When compared to those who did not use GCSF, patients who used GCSF experienced a lower rate of neutropenia (14% vs. 61%, p < 0.01) and a decreased incidence of neutropenic fever (8% vs. 23%, p < 0.01). In regression models, patients lacking extended medical coverage (32% vs. 49%, p = 0.02), poor performance status (30% vs. 55%, p = 0.03), and those who were evaluated at non-teaching institutions (25% vs. 69% p < 0.01) were less likely to receive GCSF. Patients seen at non-teaching institutions were also given primary GCSF prophylaxis less frequently (16% vs 59%, p < 0.01) than those at teaching centers. Conclusions:GCSF prophylaxis was associated with improved neutropenia-related outcomes in the real world. Despite evidence-based recommendations, use of GCSF remains suboptimal in this population-based cohort of breast cancer patients receiving highly myelosuppressive chemotherapy.
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Mullen, C. A., and G. R. Buchanan. "Early hospital discharge of children with cancer treated for fever and neutropenia: identification and management of the low-risk patient." Journal of Clinical Oncology 8, no. 12 (1990): 1998–2004. http://dx.doi.org/10.1200/jco.1990.8.12.1998.
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Children with leukemia and solid tumors are often hospitalized for empiric broad-spectrum antibiotic therapy because of fever during periods of chemotherapy-induced neutropenia. Conventional practice dictates that parenteral antibiotics be continued until the patient is afebrile and has recovered from neutropenia, ie, until the absolute neutrophil count (ANC) exceeds 500 cells per cubic millimeter. However, the practice in our center has been to discontinue parenteral antibiotic therapy and discharge many such patients before resolution of neutropenia. Since the feasibility and safety of this approach has not been studied, we reviewed the records of 114 consecutive hospitalizations for fever and neutropenia in 61 patients during a 13-month period. Seventy-seven children (68%) were discharged to their homes while still neutropenic after they had been afebrile for 1 to 2 days on parenteral antibiotics, had negative blood cultures, appeared well, and usually had some evidence of bone marrow recovery. Five patients (4.4%) developed recurrent fever and required rehospitalization within 7 days of discharge. Only three of the 77 patients (3.9%) who were sent home with neutropenia had recurrent fever. Each had a brief and uneventful second hospitalization. Two of the 37 children discharged with an ANC over 500 cells per cubic millimeter required rehospitalization. A declining ANC and advanced malignancy were risk factors in predicting recurrence of fever following discharge. A rising monocyte count was a predictor of imminent recovery from neutropenia. These results suggest that "early" discharge of an afebrile yet still neutropenic patient is safe when the patient is in remission, has no evidence of serious infection, appears clinically stable, and has indications of bone marrow recovery. The conventional approach of routinely continuing the hospitalization until resolution of neutropenia may be unnecessary in such low-risk patients.
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Kukec, Renata Rezonja, Iztok Grabnar, Tomaz Vovk, Ales Mrhar, Viljem Kovac, and Tanja Cufer. "Febrile neutropenia in chemotherapy treated small-cell lung cancer patients." Radiology and Oncology 49, no. 2 (2015): 173–80. http://dx.doi.org/10.2478/raon-2014-0050.
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Abstract Background. Chemotherapy with platinum agent and etoposide for small-cell lung cancer (SCLC) is supposed to be associated with intermediate risk (10-20%) of febrile neutropenia. Primary prophylaxis with granulocyte colonystimulating factors (G-CSFs) is not routinely recommended by the treatment guidelines. However, in clinical practice febrile neutropenia is often observed with standard etoposide/platinum regimen. The aim of this analysis was to evaluate the frequency of neutropenia and febrile neutropenia in advanced SCLC patients in the first cycle of standard chemotherapy. Furthermore, we explored the association between severe neutropenia and etoposide peak plasma levels in the same patients. Methods. The case series based analysis of 17 patients with advanced SCLC treated with standard platinum/etoposide chemotherapy, already included in the pharmacokinetics study with etoposide, was performed. Grade 3/4 neutropenia and febrile neutropenia, observed after the first cycle are reported. The neutrophil counts were determined on day one of the second cycle unless symptoms potentially related to neutropenia occurred. Adverse events were classified according to Common Toxicity Criteria 4.0. Additionally, association between severe neutropenia and etoposide peak plasma concentrations, which were measured in the scope of pharmacokinetic study, was explored. Results. Two out of 17 patients received primary GCS-F prophylaxis. In 15 patient who did not receive primary prophylaxis the rates of both grade 3/4 neutropenia and febrile neutropenia were high (8/15 (53.3%) and 2/15 (13.3%), respectively), already in the first cycle of chemotherapy. One patient died due to febrile neutropenia related pneumonia. Neutropenic events are assumed to be related to increased etoposide plasma concentrations after a standard etoposide and cisplatin dose. While the mean etoposide peak plasma concentration in the first cycle of chemotherapy was 17.6 mg/l, the highest levels of 27.07 and 27.49 mg/l were determined in two patients with febrile neutropenia. Conclusions. Our study indicates that there is a need to reduce the risk of neutropenic events in chemotherapy treated advanced SCLC, starting in the first cycle. Mandatory use of primary G-CSF prophylaxis might be considered. Alternatively, use of improved risk models for identification of patients with increased risk for neutropenia and individualization of primary prophylaxis based on not only clinical characteristics but also on etoposide plasma concentration measurement, could be a new, promising options that deserves further evaluation.
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Flowers, Christopher R., Jerome Seidenfeld, Eric J. Bow, et al. "Antimicrobial Prophylaxis and Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology Clinical Practice Guideline." Journal of Clinical Oncology 31, no. 6 (2013): 794–810. http://dx.doi.org/10.1200/jco.2012.45.8661.
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Purpose To provide guidelines on antimicrobial prophylaxis for adult neutropenic oncology outpatients and on selection and treatment as outpatients of those with fever and neutropenia. Methods A literature search identified relevant studies published in English. Primary outcomes included: development of fever and/or infections in afebrile neutropenic outpatients and recovery without complications and overall mortality in febrile neutropenic outpatients. Secondary outcomes included: in afebrile neutropenic outpatients, infection-related mortality; in outpatients with fever and neutropenia, defervescence without regimen change, time to defervescence, infectious complications, and recurrent fever; and in both groups, hospital admissions, duration, and adverse effects of antimicrobials. An Expert Panel developed guidelines based on extracted data and informal consensus. Results Forty-seven articles from 43 studies met selection criteria. Recommendations Antibacterial and antifungal prophylaxis are only recommended for patients expected to have < 100 neutrophils/μL for > 7 days, unless other factors increase risks for complications or mortality to similar levels. Inpatient treatment is standard to manage febrile neutropenic episodes, although carefully selected patients may be managed as outpatients after systematic assessment beginning with a validated risk index (eg, Multinational Association for Supportive Care in Cancer [MASCC] score or Talcott's rules). Patients with MASCC scores ≥ 21 or in Talcott group 4, and without other risk factors, can be managed safely as outpatients. Febrile neutropenic patients should receive initial doses of empirical antibacterial therapy within an hour of triage and should either be monitored for at least 4 hours to determine suitability for outpatient management or be admitted to the hospital. An oral fluoroquinolone plus amoxicillin/clavulanate (or plus clindamycin if penicillin allergic) is recommended as empiric therapy, unless fluoroquinolone prophylaxis was used before fever developed.
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Richardet, Martin Eduardo, Ruben Dario Kowalyszyn, Mirta Susana Varela, et al. "A randomized, multicenter clinical trial to determine the efficacy and safety of pegfilgrastim (GEMA BIOTECH) compared to pegfilgrastim (Roche) for prevention of chemotherapy induced neutropenia in patients with breast cancer." Journal of Clinical Oncology 37, no. 15_suppl (2019): 3113. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.3113.
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3113 Background: Peg-Neutropine, GEMA BIOTECH SAU biosimilar Peg-Filgrastim, is the first Peg-Filgrastim approved in LATAM for prevention of febrile neutropenia in patients treated with myelosuppressive chemotherapy. Methods: Study population: women with stage 2, 3 or 4 of breast cancer scheduled to receive 4 or 6 cycles of chemotherapy (with Taxane) at 3 weeks interval. Stratification was based on breast cancer stage. Study drug was administered subcutaneously in a 6 mg dose. The study was blind to the assessors. The primary endpoint was Duration of Severe Neutropenia (DSN, Absolute Neutrophil Count-ANC < 500/mm3) in the first cycle of chemotherapy. Secondary endpoints were incidence of severe neutropenia (SN), other efficacy measures, and incidence of ADRs. The non-inferiority margin for DSN was estimated in less than 1 day. Results: A total of 120 subjects were randomized 1:1, 58 were treated with Peg-Neutropine and 62 with Peg-Filgrastim (Roche). Efficacy: SN was developed in 52/283 (18,4%) cycles with Peg-Neutropine in 27 patients and 48/297 (16,2%) cycles with Peg-Filgrastim (Roche) in 20 patients (p=0,4836). In the first cycle, 16 patients with Peg-Neutropine and 11 patients with Peg-Filgrastim (Roche) developed SN. In per protocol analysis mean DNS in the first cycle was 0,78 ± 1,53 days for Peg-Neutropine group and 0,53±1,25 for Peg-Filgrastim (Roche) group (95% IC for the difference -0,26; 0,76). Per ITT analysis the mean DSN was 0,90±1,79 for Peg- Neutropine group and 0,50±1,21 for Peg-Filgrastim (Roche) group , (95% IC for the difference -0,15; 0,95). For all the efficacy secondary endpoints the differences were not statistically significant. Safety: 7 ADRs were developed by 3 subjects with Peg-Neutropine and 31 ADRs were developed by 10 subjects with Peg-Filgrastim (Roche). The most common reaction was myalgia, and other ADRs were arthralgia, asthenia, bone pain and acid sensitive syndrome. Conclusions: Based on the non-inferiority margin established we conclude that Peg-Neutropine is biosimilar to Peg-Filgrastim (Roche). Clinical trial information: NCT03404752.