Kostmann’s Neutropenia: A Case Report

Kostmann syndrome, or severe congenital neutropenia, is a rare condition in children marked by a neutrophil count of less than 500/mm3. This congenital agranulocytosis, an autosomal recessive genetic disorder, is often first identified by a neonatal infectious syndrome. The deficiency in neutrophils increases susceptibility to bacterial and fungal infections. Prior to the availability of hematopoietic growth factors, the disease was associated with significant morbidity and early mortality. We present the case of a 17-month-old boy who was admitted to the pediatric emergency department at Hassan II University Hospital in Fes with skin abscesses.

Efficacy and Safety Assessment of Antifungal Sequential Therapy from Micafungin to Liposomal Amphotericin B for Antibiotics-Refractory Febrile Neutropenia in Patients with Hematologic Malignancies

Invasive fungal infections are a major challenging problem in the management of febrile neutropenia (FN) in patients with hematologic malignancies. Liposomal amphotericin B (L-AmB) or micafungin (MCFG) has been widely used as a first-line empirical antifungal therapy for suspected fungal infection in such patients. However, there are several issues in patients receiving these agents: drug related toxicities for L-AmB and breakthrough fungal infections for MCFG. In order to make the best use of these 2 agents, we conducted a prospective study of sequential therapy from MCFG to L-AmB, and evaluated the efficacy and safety of this strategy in FN patients with hematologic malignancies. A total of 18 patients were enrolled, and 11 patients who fulfilled the protocol defined criteria were evaluated. Underlying diseases consisted of acute leukemia (n = 9), non-Hodgkin lymphoma (n = 1), and myelodysplastic syndrome (n = 1). Treatment success was achieved in 8 patients (72.7%). Drug-related adverse events occurred in 8 patients (72.7%). All of those adverse events except one case were below grade 2. Three patients required discontinuation of L-AmB. Although our empirical antifungal sequential therapy seems to be encouraging for antibiotics-refractory FN in patients with hematologic malignancies, further investigation in large-scale studies is warranted.

Current management of chemotherapy-induced neutropenia in adults:key points and new challenges

Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN.

A phase I study of different doses and frequencies of pegylated recombinant human granulocyte-colony stimulating factor(PEG rhG-CSF) in patients with standard-dose chemotherapy-induced neutropenia

Objective： The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor（PEG rhG-CSF） is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy.However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy.Methods：Eligible patients received 3-cycle chemotherapy every 3 weeks.No PEG rhG-CSF was given in the first cycle.Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3.In cycle 2,patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3,and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5,respectively.Escalating doses（30,60,100 and 200μg/kg）of PEG rhG-CSF were investigated.Results：A total of 26 patients were enrolled and received chemotherapy,in which 24 and 18 patients entered cycle 2 and cycle 3 treatment,respectively.In cycle 2,the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30,60,100 and 200 μg/kg was 66.67%,33.33%,22.22% and 0,respectively,with a median duration less than 1（0–2）d.No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts.Conclusions：The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported,as well as the safety.Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above.The single dose of 60 μg/kg,100 μg/kg and double half dose of 30 μg/kg were recommended to the phase Ⅱ study,hoping to find a preferable method for neutropenia treatment.

Application of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) for the prevention of neutropenia in triple negative breast cancer patients older than 65 years during adjuvant chemotherapy

Objective The aim of this study was to compare the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF)and recombinant human granulocyte colonystimulating factor(rhG-CSF)for the prevention of neutropenia in elderly breast cancer patients during adjuvant chemotherapy.Methods A total of 45 oncology inpatients with breast cancer,who received adjuvant chemotherapy and were older than 65 years from May 2017 to October 2018 in the General Hospital of the Northern Theater of the Chinese people’s Liberation Army,were included.Epirubivin Cyclophoshamide-Docetaxel(EC-T)sequential adjuvant chemotherapy was chosen.Forty-five patients were randomly divided into two groups;25 patients in the treatment group were treated with PEG-rhG-CSF and 20 patients in the control group were not treated with PEG-rhG-CSF,but only rhG-CSF.The experimental group was treated with the PEG-rhG-CSF at the end of chemotherapy for 24–48 h,with a 6 mg subcutaneous injection once per chemotherapy cycle.In the control group,rhG-CSF was administered after 48 h of chemotherapy,with a 100μg subcutaneous injection,1/d,d 1–7.The dosage could be increased step by step with the exacerbation of neutropenia.The primary aims of this study was to discover the incidence of leukopenia,neutropenia,neutrophilic fever,and adverse reactions in the two groups.Results The incidence of neutropenia,neutrophilic fever and adverse reactions decreased in the treatment group compared to the control group,but no significant difference existed between two groups(P>0.05).Patients in treatment group had a lower,but not statistically significant,incidence of adverse reactions(P>0.05).Conclusion Applying PEG-rhG-CSF could be effective in preventing neutropenia in elderly patients with postoperative adjuvant chemotherapy to treat breast cancer.It may effectively control the occurrence of neutropenia after chemotherapy and reduce the chance of infection.The incidence of side effects,such as fever and bone pain,was low.The adverse drug reactions were well tolerated by patients,which could ensure the smooth progress of chemotherapy.

Historical Cohort Study of the Efficacy and Safety of Piperacillin/Tazobactam Versus Fourth-Generation Cephalosporins for Empirical Treatment of Febrile Neutropenia in Patients with Hematological Malignancies

We retrospectively evaluated the efficacy and safety of the combination drug piperacillin/tazobactam (PIPC/TAZ) in comparison with those of fourth-generation cephalosporins (4th Cephs) as initial empirical treatment in hematological malignancies patients with febrile neutropenia (FN). Among 200 patients assessed in this study, 49 had received PIPC/TAZ and 151 4th Cephs. Patient background characteristics were comparable between the two treatment groups. The overall efficacy rate in those receiving 4th Cephs and PIPC/TAZ was 57.0% (86/151 patients) and 59.2% (29/49 patients), respectively, with no significant difference detected between the two treatment regimens (P = 0.78). Treat-ment did not need to be discontinued or interrupted due to development of adverse drug reactions in any of the patients. Therefore in this study the efficacy and safety of PIPC/TAZ as initial antimicrobial treatment for FN in patients with hematological malignancies were not inferior to those of 4th Cephs. Based on the preliminary data obtained in this study, we propose to conduct a multicenter, prospective, controlled study to compare PIPC/TAZ versus CFPM given as empirical antimicrobial treatment against FN in patients with hematological malignancies.

Neutropenia in colorectal cancer treated with oxaliplatin-based hyperthermic intraperitoneal chemotherapy: An observational cohort study

BACKGROUND The implications of neutropenia after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy(HIPEC)treatment have never been investigated.AIM To evaluate the occurrence of neutropenia and its effect on the risk of increased Clavien-Dindo morbidity as well as its effect on overall or disease-free survival.METHODS All patients with colorectal peritoneal metastases(1996-2015)completing cytoreductive surgery and oxaliplatin-based HIPEC treatment from a biinstitutional database(Uppsala and Sydney)were included in the study.Clavien-Dindo grade 3-4 morbidity differences between the neutropenia group vs nonneutropenia group were calculated and Kaplan-Meier curves with log rank test were rendered.Univariate and multivariable Cox regression models for diseasefree survival were implemented.RESULTS Two hundred and forty-six patients were identified–32 postoperative any-grade neutropenia patients and 214 non-neutropenia patients.The neutropenia group had more combination oxaliplatin+irinotecan treatment than the nonneutropenia group(66%vs 13%,P=0.0001).The neutropenia group was not associated with increased Clavien-Dindo grade 3-4 morbidity.Median overall survival was 53 mo vs 37 mo for the neutropenia and non-neutropenia group,P=0.07.Median disease-free survival was 16 mo vs 11 mo,respectively,P=0.02.Neutropenia was an independent prognostic factor for disease-free survival with hazard ratio:0.58,95%confidence interval:0.36-0.95,P=0.03.CONCLUSION 13%of patients developed neutropenia which was not associated with increased Clavien-Dindo grade 3-4 morbidity.Neutropenia was an independent positive prognostic factor for disease-free survival and was associated with more intense HIPEC treatment.This is in direct contrast to the current paradigm of decreasing the treatment intensity.

Procalcitonin as a marker of infection in febrile neutropenia:A systematic review

Aim: Management of febrile neutropenia is challenged by lacking microbiological and clinical documentation of infection. Procalcitonin is emerging as a new promising biomarker of infection. We aimed to undertake a systematic review evaluating the diagnostic accuracy of procalcitonin as a marker of infection in febrile neutropenia. Methods: We performed a systematic re- view of the literature using the databases MEDLINE, EMBASE and Cochrane Library including a search of the grey literature (e.g. unpublished data, web sides of relevant societies). The methodological quality was assessed using predefined criteria. The relevant data were extracted and analyzed by two authors. Results: The literature search yielded a total of 193 studies of which nine were eligible for inclusion. There was a great variation in the quality of the methodological design. A notable heterogeneity exists regarding the studied populations and the definition of the reference standards. Among the nine included studies the sensitivity ranged from 42% to 72% and the specificity ranged from 64% - 89% at a cut off value ranging from 0.5 - 0.8 ng/ml. The studied endpoint was either microbiologically or clinically documented infection. Four studies found procalcitonin superior to Creactive protein in discriminating infection from the various other causes of fever. Conclusion: Procalcitonin appears to be a promising biomarker and might add new diagnostic information in the management of febrile neutropenia.

Association between Helicobacter Pylori Infection and Chronic Idiopathic Neutropenia

Summary： The possible association between Helicobacter pylori （H. pylori） infection and chronic idiopathic neutropenia （ClN） was investigated. A total of 78 subjects with CIN were recruited in this case-control study. As a control group, 40 subjects without ClN were selected for comparison with the case group. All participants were evaluated for the prevalence of H. pylori infection by 14C-urea breath test. The corrected splenic index （CSI） was calculated, and serum IL-6, IL-8, IL-10 and HsCRP levels were measured. The differences in CSI, serum IL-6, IL-8, IL-10 and HsCRP levels were compared between CIN patients and controls, as well as between subjects with and without H. pylori infection. The positive rate ofH. pylori was 87.18% in ClN group and 52.50% in control group, showing a significant difference （Fisher＇s exact, P=0.000）. CSI values, and serum IL-6 and HsCRP levels in H. pylori positive-CIN patients were significantly higher than those in negative subjects （Mann-whitney U-test, P=-0.016, P=0.001 and P=0.000 respectively）, while IL-10 level declined sig- nificantly in H, pylori negative-CIN patients （Mann-whimey U-test, P=0.000）. In control group, se- rum IL-6 and HsCRP levels in H. pylori positive individuals were also increased significantly （Mann-whitney U-test, P=0.000）, while IL-10 level declined （Mann-whimey U-test, P=0.018）. Mul- tivariate regression analysis revealed that H. pylori infection and IL-10 were significant risk factors for CIN with odds ratio （OR）： 3.09, 95.0% CI： 1.22-6.93; P=0.019, and OR： 0.17, 95.0% CI： 0.05-0.94; P=0.021, respectively. This prospective study confirmed the existence of an association between H. pylori infection and CIN, suggesting the screening for H. pylori infection and eradicating bacterium in positive cases seem appropriate and beneficial for those patients with CIN diagnosis.

Main Microbial Genres and Its Profile of Resistance and Sensitivity to Antimicrobials Used in the Treatment of Oncological Patients with Febril Neutropenia

Objective: To determine the main microbial genotypes and their antimicrobial resistance and susceptibility profile commonly used in the treatment of oncologic patients with febrile neutropenia, carried out through the review of the clinical histories of the patients’ medical records at the Hospital do Cancer de Muriaé-Fundacao Cristiano Varella. Methods: Quantitative research, determined the susceptibility profile of microorganisms in patients with febrile neutropenia from April 2007 to April 2008 by reviewing clinical histories of patients’ medical records at the referred hospital. Results: Of the total of 8 patients evaluated with Gram-negative microorganisms, 50% of the patients were female and 50% were male. Of the 18 patients evaluated with Gram-positive microorganisms 66% were female and 34% male. Gram-positive bacteria are prevalent and cause around 60% of documented bacteremias, although Gram-negative bacteria are more common in febrile neutropenic patientes. Conclusion: Exaggerated use of antimicrobials in hospitalized patients leads to the suppression of drug-sensitive microorganisms from the intestinal flora and promotes the persistence and growth of resistant bacteria. The antibiotic should be used in a curative manner with other therapeutic measures with the determined bacterial infection.

Isolated neutropenia caused by copper deficiency due to jejunal feeding and excessive zinc intake:A case report

BACKGROUND Percutaneous endoscopic gastrostomy with jejunal extension(PEG-J)is often used to treat patients with neurological impairment and difficulty in swallowing.However,these patients often develop copper deficiency.This report describes a case of isolated neutropenia,which is a rare manifestation of copper deficiency.CASE SUMMARY Our patient was a 19-year-old boy with neurological impairment and gastroesophageal reflux.He received PEG-J feeding,including an enteral supplement containing copper and zinc.However,as his serum zinc level was low(53μg/dL)at the age of 19 years and 2 mo,we changed to a zinc-rich supplement containing 22 mg/d of zinc and 1.0 mg/d of copper.The supplement comprised a mixture of isocal 1.0 junior(5 packs/d),Tezon[2 packs(250 mL)/d],and cocoa powder.Seven months later,he had neutropenia(606/mm^(3))with a serum copper level of 16μg/dL.There were no other manifestations of copper deficiency,including anemia.Copper deficiency and neutropenia both improved following the administration of cocoa powder and Tezon.CONCLUSION In patients receiving long-term PEG-J feeds,white blood cell counts,hemoglobin,and serum levels of copper and zinc should be regularly monitored.

Decreased incidence of febrile neutropenia in Michigan following masking and social distancing orders for the COVID-19 pandemic: A population based cohort study

BACKGROUND It has been theorized that 75%-80%of febrile neutropenia(FN)is caused by endogenous pathogens,while up to 20%of cases are thought to be caused by a viral infection.It is unknown if precautions such as masking and social distancing reduce the risk of FN in susceptible populations.AIM To determine whether coronavirus disease 2019(COVID-19)infection mitigation efforts,namely masking and social distancing,were associated with a reduction in the incidence of FN.METHODS This was a retrospective population based cohort study comparing the incidence of FN in the 13 mo prior to(Year 0)and 13 mo following(Year 1)the public health executive orders(PHEO)in Michigan.Data was queried for all emergency department(ED)visits from April 1,2019 to March 31,2021 from the National Syndromic Surveillance Program,a program which collects data that is voluntarily submitted by approximately 89%of Michigan EDs.The primary study outcome was the incidence of FN as a proportion of ED visits in the 13-mo before and 13-mo after COVID-19 mitigations efforts,namely masking and social distancing.We hypothesized that there would be a significant decrease in the incidence of FN in the period following the PHEO aimed at reducing the spread of the severe acute respiratory syndrome coronavirus 2 virus.RESULTS There was a total of 8979221 total ED visits captured during the study period.In Year 0 there were 5073081 recorded ED visits and 3906140 in Year 1.There was a significant reduction in the proportion of total ED visits with a diagnosis of FN,decreasing 13.3%across periods(0.15%vs 0.13%,P=0.036).In patients with a hematologic malignancy a more impressive reduction in the incidence of FN was evident following PHEO(22%vs 17%,P=0.02).CONCLUSION We found a significant association between social distancing and mask guidelines implemented on a large public scale with decreased rates of FN,particularly in those with a hematologic malignancy.These findings may be useful in the design of future research and recommendations regarding the prevention of FN.

Applying Multinational Association of Supportive Care of Cancer Index Score for Identifying Febrile Neutropenia Patients at High Risk of Complications at Tertiary Care Hospital, Pakistan

Introduction: Multinational Association of Supportive Care of Cancer (MASCC) index score is a clinical tool to predict outcomes in Febrile Neutropenia patients. This risk-index score has been authenticated in international trials however local data is deficient. We aimed to determine hospital based incidence rate of serious complications in admitted chemotherapy induced febrile neutropenia patients presenting to a tertiary care hospital. We also aimed to compare proportions of serious medical complications in patients having MASCC score Methods: A hospital based prospective close cohort study was designed and conducted at Oncology wards of The Aga Khan University from February to August 2014. Total of 88 patients, aged 16 and above, with chemotherapy induced febrile neutropenia were identified and divided on the basis of MASCC Score into low or high risk {exposure} groups. Follow up was done from day of admission (day zero) to discharge. Outcome was assessed in terms of development of serious complications. Hospital based incidence rate was estimated. The associations between outcome and qualitative variables were evaluated by using Pearson Chi-square and Fisher’s exact test. Results: Hospital based incidence rate of febrile neutropenia admission was 5.98%, 95%CI [4.88% - 7.08%]. Out of 88 patients with chemotherapy induced febrile neutropenia 85.2% patients were in the high risk group and 14.8% in the low risk group. Serious complications were found in 21.33% and no patients in high and low risk group respectively. Age > 60 (p = 0.039), MASCC score Conclusion: MASCC risk-index score is a useful tool to identify patients at low risk of complications. Hospital based incidence rate of serious complications was 18.2%.

Clinical research in febrile neutropenia in cancer patients: Past achievements and perspectives for the future

Febrile neutropenia(FN) is responsible for significant morbidity and mortality. It can also be the reason for delaying or changing potentially effective treatments and generates substantial costs. It has been recognized for more than 50 years that empirical administration of broad spectrum antibiotics to patients with FN was associated with much improved outcomes; that has become a paradigm of management. Increase in the incidence of microorganisms resistant to many antibiotics represents a challenge for the empirical antimicrobial treatment and is a reason why antibiotics should not be used for the prevention of neutropenia. Prevention of neutropenia is best performed with the use of granulocyte colonystimulating factors(G-CSFs). Prophylactic administration of G-CSFs significantly reduces the risk of developing FN and consequently the complications linked to that condition; moreover, the administration of G-CSF is associated with few complications, most of which are not severe. The most common reason for not using G-CSF as a prophylaxis of FN is the relatively high cost. If FN occurs, in spite of prophylaxis, empirical therapy with broad spectrum antibiotics is mandatory. However it should be adjusted to the risk of complications as established by reliable predictive instruments such as the Multinational Association for Supportive Care in Cancer. Patients predicted at a low level of risk of serious complications, can generally be treated with orally administered antibiotics and as out-patients. Patients with a high risk of complications should be hospitalized and treated intravenously. A short period of time between the onset of FN and beginning of empirical therapy is crucial in those patients. Persisting fever in spite of antimicrobial therapy in neutropenic patients requires a special diagnostic attention, since invasive fungal infection is a possible cause for it and might require the use of empirical antifungal therapy.

Clinical Pathological Correlation Quiz: A 7-Month-Old Girl with Congenital Neutropenia and Increased Bone Morrow “Blasts”

Persistent Neutropenia in a child presents a wide differential diagnosis, spanning the spectrum of benign disorders (such as congenital neutropenia, cyclic neutropenia, etc.) to malignant processes (such as myelodysplasia or acute leukemia). The morphologic findings in the bone marrow of a patient with neutropenia may show considerable overlap with those seen in hematopoietic malignancies. We present herein a case that demonstrates this overlap and discuss features that can help in avoiding diagnostic pitfalls.

Perioperative care following strabismus surgery for the patient with severe congenital neutropenia

A 10-year-old girl presented with esotropia. She had 35 prism diopters of esodeviation at far and near with left inferior oblique muscle overaction (+3). Cycloplegic refraction was +0.5D OD and +0.75D OS, and visual acuity was 20/25 in each eye. The patient was being treated with G-CSF (Leufokine?) due to her severe congenital neutropenia (WBC 3350, neutrophil 7.3%, and ANC 170/ul). Despite of low ANCs, we decided to perform a surgery because the patient and her parents strongly wanted it. Prophylactic topical antibiotics (Cravit?, levofloxacin 0.5%) were applied four times a day for three days prior to the surgery. We sterilized the periocular skin with povidone-iodine 10% and placed povidone-iodine 5% drops in the cul-de-sac preoperatively. Strabismus surgery was performed. After surgery, profuse irrigation with the entire bottle of topical antibiotics (Vigamox?, moxifloxacin hydrochloride 0.5%) was performed for each eye. We prescribed topical and highly potent systemic antibiotics for 1 week. This is the first case report to describe the successful perioperative antisepsis care following strabismus surgery for a patient with severe congenital neutropenia. Prevention of postoperative infection in granulocytopenic patients could be achieved using antibiotic agents which provide the greatest spectrum of coverage against both Gram-positive and Gram-negative infections.

A Parameter Estimation Model of G-CSF: Mathematical Model of Cyclical Neutropenia

We investigate the FFT (Fast Fourier Transform) model and G-CSF (granulocyte colony-stimulating factor) treatment of CN (Cyclical Neutropenia). We collect grey collies and normal dog’s data from CN and analyze the G-CSF treatment. The model develops the dynamics of circulating blood cells before and after the G-CSF treatment. This is quite natural and useful for the collection of laboratory data for investigation. The proposed interventions are practical. This reduces the quantity of G-CSF required for potential maintenance. This model gives us good result in treatment. The changes would be practical and reduce the risk side as well as the cost of treatment in G-CSF.

Garenoxacin Prophylaxis for Febrile Neutropenia after Chemotherapy in Hematological Malignancies

Background: Febrile neutropenia is one of the most serious adverse events in patients with hematological malignancies and chemotherapy. The routine use of fluoroquinolone prophylaxis in patients with hematological malignancies is controversial. Therefore, we prospectively evaluated the efficacy and safety of prophylactic use of garenoxacin for febrile neutropenia. Patients and Methods: Consecutive adult patients with hematological malignancies who were at risk for chemotherapy-induced neutropenia lasting more than seven days were eligible for present study. They received oral garenoxacin (400 mg daily) from the neutrophil count decreased to less than 1000/μl and continued until the neutropenia had resolved. The primary endpoint was incidence of febrile neutropenia, and the secondary endpoints were the type and incidence of adverse events. Results: We enrolled 46 consecutive patients (median age, 59 years). The underlying diseases comprised acute myeloid leukemia (n = 17), acute lymphoblastic leukemia (n = 3), malignant lymphoma (n = 23), and multiple myeloma (n = 3). There were 23 febrile neutropenia episodes and 2 episodes of bacteremia. There were no grade 3 or 4 adverse events;however serum creatinine levels were significantly elevated after garenoxacin administration. The overall prophylactic efficacy of garenoxacin was 50%, and there were no infection-related deaths. Conclusions: Prophylactic use of garenoxacin is effective and safe in patients with hematological malignancies. (Clinical trial registration number: UMIN000004979).

Evaluation of Prophylaxis with Norfloxacin and Ceftriaxone versus Ciprofloxacin during the Period of Neutropenia after Haematopoietic Stem Cell Transplantation:Retrospective Analysis of Two Sequencial Cohorts

Background: The aim of this study was to evaluate the occurrence of febrile neutropenia (FN) during aplasia after haematopoietic stem cell transplantation (HSCT) in patients who received anti-bacterial prophylaxis with norfloxacin/ceftriaxone or ciprofloxacin, between September 2006 and May 2009. Methods: We retrospectively examined all patients undergoing HSCT at S?o Paulo Hospital during the study period. Results: Of the 107 studied patients, 71 (66.3%) were included in the analysis. The exclusion criteria were as follows: occurrence of fever or infection before the transplantation (17), prophylactic use of norfloxacin (6), fever of probable non-infectious aetiology (2), and absence of prophylaxis during the aplasia period (11). Thirty-eight patients received norfloxacin and ceftriaxone as prophylaxis (Group I) and 33 received ciprofloxacin (Group II). The groups were comparable with respect to age, underlying diseases, comorbidities, and status of the underlying disease. Patients in Group II used antibiotics in a significantly higher frequency than those in Group I (66.7% vs 33.8%, p = 0.017), for 30 days before transplantation. The number of previous hospitalisations, length of hospitalisation until transplantation, type of transplant, progenitor cells used, number of CD34 cells infused, type of conditioning, and graft-versus-host disease prophylaxis were similar in both groups. After the transplantation, 28.9% and 39.4% of the patients in Groups I and II, respectively, presented Grade III and IV mucositis (p = 0.448). Neutropenia of <500 neutrophils/mm3 lasted an average of 9.5 and 9.3 days in Groups I and II, whereas neutropenia of <100 neutrophils/mm3 lasted between 6.6 and 5.7 days. FN occurred in 78.9% of patients in Group I and 81.8% in Group II, with no significant difference in the classification of these episodes. Six patients (15.8%) in Group I and five (15.2%) in Group II had bacteraemia. All patients who did not receive prophylaxis developed FN. Conclusions: The high incidence and classification of FN episodes were similar between groups;however, the frequency was lower than in those patients who did not receive prophylaxis.

PEG-rhG-CSF用于中、高中性粒细胞减少性发热风险癌症患者一级预防与二级预防的药物经济学评价

目的评价聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)用于中、高中性粒细胞减少性发热(FN)风险的癌症患者一级预防与二级预防的经济性。方法从中国全社会角度出发,采用TreeAge软件构建决策分析模型。主要状态包括一级预防、二级预防、相对剂量强度≥85%和相对剂量强度<85%。模型参数包括FN发生的风险、FN住院概率、相关癌症死亡概率、相关癌症效用值、直接医疗成本与间接医疗成本等。模型周期为21 d。研究时间范围为70年。主要结果包括总成本、抗感染成本、生命年、质量调整寿命年(QALY)和增量成本效果比。对结果进行了单因素敏感性和概率敏感性分析以评估结果的稳健性;并进行不同时间范围的情景分析。结果基线分析结果显示,与二级预防组相比,一级预防组患者多获得0.84个QALYs,并少支付39373元,节约总的抗感染成本为32311元,增量成本效果比为-46722元/QALY,一级预防组为绝对优势方案。情景分析结果显示,一级预防组与二级预防组相比,在任何研究时间范围都是绝对优势方案。当中国意愿支付阈值为257094元/QALY时,单因素和概率敏感性分析结果显示一级预防组具有成本效果的概率为100%。结论与二级预防相比,PEG-rhG-CSF用于中、高FN风险的癌症患者的一级预防是具有经济性的。