• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2453-2459
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• 2013

Bevacizumab has been approved for use in combination with chemotherapy to treat many types of cancer but associated neutropenic events, including febrile neutropenia, have been reported. To estimate the incidence and relative risk of neutropenic events in cancer patients treated with bevacizumab combination therapy, we searched PubMed, EMBASE, and Web of Science literature databases, as well as abstracts presented at the American Society of Clinical Oncology conferences, to identify relevant studies published from January 1966 to December 2011. Studies that compared bevacizumab plus chemotherapy or biological therapy with chemotherapy or biological therapy alone, and that had adequate safety data profiles, were selected for analysis. Statistical analyses were conducted to calculate the summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) using fixed- or random-effects models. A total of 22 clinical trials involving 15,056 patients were included in the analysis. The summary incidences of high-grade neutropenia (HGN) and high-grade febrile neutropenia (HGFN) in patients receiving bevacizumab was 27.3% (95% CI: 26.4%-28.3%) and 3.91% (95% CI: 3.51%-4.37%), respectively. The risks of HGN (RR=1.10; 95% CI: 1.02-1.19; P=0.02) and HGFN (RR=1.31; 95% CI: 1.08-1.59; P=0.005) were significantly increased in bevacizumab-treated patients, compared to those who did not receive bevacizumab. The RR of bevacizumab-associated HGN, but not HGFN, varied significantly with tumor types (P=0.005). The increased risk of bevacizumab-associated neutropenic events was dose-dependent, as the RR was greater at a dose of 5 mg/kg/week than at 2.5 mg/kg/week. Our findings suggest that bevacizumab addition to cancer therapy significantly increases the risk of serious neutropenic events, and this risk may be dose-dependent.

• The Journal of Internal Korean Medicine
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• v.28 no.1
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• pp.1-11
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• 2007

Objective : To study effects of Astragali radix on relieving neutropenia caused by cyclophosphamide. Method : We administered Astragali radixextracts for 7 days before injecting cyclophosphamide 200mg/kg to mice subcutaneously to cause neutropenia. The control group wasn't administered Astragali radix. One test group was administered Astragali radix extracts 500mg/kg and the other was administered 1000mg/kg. We observed WBC, neutrophil, lymphocyte, platelet, RBC, GOT, GPT, BUN, and creatine. Result : WBC, RBC, lymphocyte, neutrophil, and platelet improved more in mice administered Astragali radix extracts. Moreover, the 1000mg/kg group was more affected than the 500mg/kg group generally. GOT, GPT, BUN, and creatine weren't changed significantly compared with the control group. Conclusion : It is shown that Astragali radix extracts can relieve neutropenia induced by cyclophosphamide and we conclude that Astragali radix will be useful for cancer treatment.

• Korean Journal of Veterinary Research
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• v.55 no.4
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• pp.263-266
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• 2015

A 13-year-old, spayed, female Chihuahua dog was referred for evaluation of fever, lethargy, and dyspnea. Hematologic evaluation revealed severe neutropenia, thrombocytopenia, and mild anemia. The dog had been undergoing phenobarbital therapy for the past 7 weeks because of generalized seizures due to meningoencephalomyelitis of unknown etiology. After ruling out other possible causes of cytopenias, a tentative diagnosis was made of drug-induced blood cell dyscrasia. The neutropenia and thrombocytopenia resolved after discontinuation of phenobarbital (8 days and 15 days after discontinuation, respectively). This is the first case report in Korea to demonstrate blood dyscrasia associated with idiosyncratic adverse effects of phenobarbital.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2523-2526
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• 2012

Introduction: Febrile neutropenia is a relatively frequent event in cancer patients treated with chemotherapy and improvement in absolute neutrophil count (ANC) has been linked directly to improved outcome. Evaluation of granulocyte colony stimulating factors (GCSFs) for treatment has shown reduced incidences of episodes of prolonged neutropenia and protracted hospitalization. To determine absolute neutrophil counts with GCSF in febrile neutropenic cancer patients admitted to a tertiary care centre and to co-relate the improvement in ANC with mortality and hospital discharge. Methods: A prospective cross sectional study was carried at an oncology ward at Aga Khan University hospital from January 2010 to June 2011. All adult patients who were admitted and treated with GCSF for chemotherapy induced febrile neutropenia were included. Multivariable regression was conducted to identify the factors related with poor outcomes. Results: A total of 131 patients with febrile neutropenia were identified with mean age of 43.2 (18-85) years, 79 (60%) being ${\leq}50$. Seventy-five (57%) had solid tumors and 56 (43%) hematological malignancies, including lymphoma. Fifty seven (43.5%) had an ANC less 100 cells/$mm^3$, 34 (26%) one between 100-300 cells/$mm^3$ and 40 (31%) an ANC greater than 300 cells/$mm^3$. Thirty (23%) patients showed ANC recovery in 1-3 days, and 74(56%) within 4-7 days. Thirteen (10%) patients showed no recovery. The overall mortality was 18 (13.7%) patients. The mean time for ANC recovery seen in hematological malignancies was 6.34 days whereas for solid tumors it was 4.88 days. Patients with ANC <100 cells/$mm^3$ were more likely to die than patients with ANC >300 cells/$mm^3$ by a factor of 4.3. Similarly patients >50 years of age were 2.7 times more likely to die than younger patients. Conclusion: Our study demonstrated that use of GCSF, in addition to intravenous antibiotics, in treatment of patients with chemotherapy induced febrile neutropenia accelerates neutrophil recovery, and shortens antibiotic therapy and hospitalization. We propose to risk classify the patients at the time of admission to evaluate the cost effectiveness of this approach in a resource constrained setup.

• Radiation Oncology Journal
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• v.13 no.1
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• pp.79-85
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• 1995

Purpose : To assess the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor(GM-CSF) in the neutropenia by radiotherapy. Materials and Methods : Eleven patients with various solid tumor were treated with a daily subcutaneous dose of GM-CSF(3-7microgram/kg) for 5days during the radiotherapy. Before and during the course of the study all the patients were monitored by the recording of physical examination, the complete blood count with differential and reticulocyte count and liver function test. Eight patients received prior or concurrent chemotherapy. Results : In 10 patients, the neutrophilic nadir was significantly elevated and the lenght of time that Patients had a neutrophil count below $10^3/mm^3$ a threshold known to be critical to acquiring infective complications was shortened following GM-CSF injection. A significant rise (two fold or greater) of neutrophil count was seen in 10 of 11 patients. In most patients, discontinuation of GM-CSF resulted in a prompt return of granulocyte counts toward baseline. However the neutrophil count remained elevated over $10^3/mm^3$ during radiation therapy, and radiotherapy delays were avoided. Other peripheral blood components including monocytes and platelets also increased after GM-CSF treatment. No significant toxicity was encountered with subcutaneous GM-CSF treatment. Conclusion : GM-CSF was well tolerated by subcutaneous route and induced improvement in the neutropenia caused by radiotherapy.

• Korean Journal of Clinical Pharmacy
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• v.13 no.2
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• pp.59-66
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• 2003

Filgrastim is used as an indispensable adjuvant drug to reduce the degree and duration of chemotherapy-induced neutropenia. The purpose of this research is to study the use of filgrastim by reviewing retrospective medical records of breast cancer patients who have been treated by filgtastim in the National Cancer Center. 84 patients have received 323 cycles of chemotherapy, of which 134 cycles were treated by filgrastim $(41.5\%)$. Among those 134 cycles, 34 were for prophylaxis $(21.6\%)$, and 100 for treatment of neutropenia $(74.6\%)$. The frequence of filgrastim usage was more than $50\%$ in frequency with regimens containing docetaxel. For prophylaxis, the median of filgrastim initiation was measured on the day of chemotherapy (-3rd-13th). For the treatment, on the other hand, the median appeared on the 9th day (4th-2lst) after chemotherapy, which showed very wide distribution. Time to filgrastim initiation ranged between the 7th and the 9th day after chemotherapy in docetaxel+doxorubicin combination regimen and docetaxel single regimen, whereas it showed after the 10th day in doxorubicin+cyclophosphamide combination regimens. For the treatment, 48 out of 61 patients $(73.8\%)$ in 63 cycles have experienced fever, had to visit the emergency room, required hospitalization, caused infection, transfusion, dosage reduction and schedule changes in spite of using filgrastim with chemotherapy. For prophylaxis, 11 out of 19 patients $(17.9\%)$ in 11 cycles have experienced the same results. In conclusion, the guideline of time to the initiation and the last is required for cost-effective administration of filgrastim because of the difference occurring ANC nadir, the severity and duration of neutropenia by chemotherapy regimens.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1115-1119
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• 2013

Background: Febrile neutropenia (FN) is a serious complication following chemotherapy and is associated with significant mortality and financial expenditure. The aim of this study was to evaluate risk factors for longer length of stay (LOS) and mortality and cost of treatment among hospitalized adults with cancer who developed febrile neutropenia in Thailand. Materials and Methods: Information on illness of inpatients and casualties came from hospitals nationwide and from hospital withdrawals from the 3 health insurance schemes in fiscal 2010. The data covered 96% of the population and were analyzed by age groups, hospital level, and insurance year schemes in patients with febrile neutropenia. Results: A total of 5,809 patients were identified in the study. The mortality rate was 14%. The median LOS was 8.67 days and 69% of patients stayed for longer than 5 days. On bivariate analysis, age, cancer type, and infectious complications (bacteremia/sepsis, hypotension, fungal infections, and pneumonia) were significantly associated with longer LOS and death. On multivariate analysis, acute leukemia and infectious complications were linked with longer LOS and death significantly. The median cost of hospitalized FN was THB 33,686 (USD 1,122) with the highest cost observed in acute leukemia patients. Conclusions: FN in adult patients results in significant mortality in hospitalized Thai patients. Factors associated with increased mortality include older age (>70), acute leukemia, comorbidity, and infectious complications.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5945-5950
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• 2015

A 6-year retrospective cohort study was conducted among Thai hematologic malignancy (HM) patients receiving intensive chemotherapy. Of the 145 eligible patients receiving 893 chemotherapy sessions, 46.9% were female, median age was 52 years, and the most common HM diagnosis was diffuse large B-cell lymphoma (46.2%). Febrile neutropenia (FN) occurred in 14.9% of chemotherapy sessions with an incidence of 24.8 per 1,000 chemotherapy cycles per year. Independent factors associated with FN were receiving the first chemotherapy cycle [adjusted hazard ratio (aHR) 4.1], having hemoglobin ${\leq}100g/L$ (aHR 3.7) and platelet ${\leq}140,000/{\mu}L$ (aHR 2.7) on chemotherapy day and receiving acute myeloid leukemia regimens (aHR 20.8). Granulocyte colony stimulating factor was significantly associated with reduced rate of FN when given in those receiving CHOP regimen. With the median follow-up time of 16 months, the overall survival time was significantly longer in patients without FN than those with FN (61.7 vs. 20.8 months; p<0.001).

• Clinical and Experimental Pediatrics
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• v.46 no.10
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• pp.966-971
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• 2003

Purpose : It is now well established that infection and inflammation play an important role in the pathogenesis of ischemic brain damage. The loss of neutrophils from systemic circulation is an associated finding in injury mediated by granulocyte. Periventricular leukomalacia(PVL) caused by ischemia is the principal form of brain injury in premature infants. This study was conducted to evaluate whether the low neutrophil count is associated with periventricular leukomalacia(PVL) in premature infants. Methods : Retrospective review of medical records was undertaken. Subjects were premature infants with a birth weight of less than 1,500 gm, admitted to the Neonatal Intensive Care Unit of Kyungpook University Hospital. A complete blood count of peripheral blood was done within the 1st hour of life. Neutropenia was defined as absolute neutrophil count < $1,500/mm^3$, PVL as increased periventricular echodensities followed by cyst formation on ultrasonography or corresponding signs on brain MRI. Results : Thirteen infants out of a total population of 37 revealed neutropenia. Respiratory distress syndrome and requirement for respiratory support were not different between infants with neutropenia( neutropenia group) and infants without neutropenia(control group). Intraventricular hemorrhage (IVH) and grade 3 and 4 IVH were more frequent in neutropenia group(P<0.05). There was no statistically significant increase of PVL in neutropenia group. The neutrophil count was $18,760.0{\pm}10,266.1/mm^3$, $7,272.0{\pm}7,435.0/mm^3$ infants with PVL and $11,131.7{\pm}3,386.5/mm^3$, $2,407.5{\pm}1,933.1/mm^3$ in infants without PVL, respectively. The frequency of mechanical ventilation and artificial surfactant therapy was higher in infants with PVL compared with infants without PVL, but statistical analysis was not performed due to small number of subjects. Conclusion : A low number of neutrophils in the systemic circulation was not associated with an increased risk of PVL in premature infants.

• The Journal of Korea Assosiation for Disability and Oral Health
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• v.4 no.1
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• pp.32-36
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• 2008

Congenital neutropenia or Kostmann syndrome is an inherited disorder manifesting in infancy and characterized by severe bacterial infections. The myelodysplastic syndromes(MDS) are a group of stem cell disorders characterized by a reduction in one or more elements of the peripheral blood. This paper reports a case of Kostmann syndrome and MDS with oral complications such as generalized gingivitis and periodontitis, oral mucosal ulcer, petechiae. The features of these syndromes are reviewed and their oral manifestations and significance to dental management outlined.