A randomized, multicenter phase III Study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer.

BACKGROUND: F-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®). METHODS: This was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated. RESULTS: The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 - 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim. CONCLUSIONS: A single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04174599, on 22/11/2019.

Forty years of human G-CSF: A short history in time.

Human G-CSF was identified in 1984 at Memorial Sloan-Kettering Cancer Centre, New York. Based on these findings, recombinant G-CSF was developed by Amgen, Thousand Oaks. In 1987, clinical trials began using recombinant G-CSF in cancer patients following chemotherapy to reduce the duration of neutropenia and in patients with congenital neutropenia (CN) to increase the number of neutrophils. It has changed the quality of life for many cancer patients and saved the lives of many patients with (CN).

Biosimilar underutilization alone does not foretell a broken biologics market.

Biosimilars offer the potential for cost savings and expanded access to biologic products; however, there are concerns regarding the rate of biosimilar uptake. We assessed the relationship between biosimilar and originator pricing, coverage, and market share by describing four case studies that fall into two categories: (1) sole preferred coverage strategy (ie, aim is to have originator product preferred; biosimilar(s) non-preferred), defined as steep average sales price (ASP) reductions for originator products (decline in net prices by at least 50% following the introduction of biosimilar competition by 2022) and (2) non-sole preferred coverage strategy (ie, aim is to have originator product preferred alongside biosimilar products), defined as moderate ASP reductions for originator products with (net prices did not decline by at least 50% of its pre-biosimilar competition value). We found that originators with sole preferred coverage strategies maintained formulary preference and market share relative to originators with non-sole preferred coverage strategies. Regardless of strategy, the market-weighted ASP for all four product families (originator and biosimilars) declined significantly in the years following the introduction of biosimilars, suggesting that biosimilar uptake alone may not be a complete measure of whether the biosimilar market is facilitating competition and lowering prices.

Balancing Benefits and Risks: A Literature Review on Hypersensitivity Reactions to Human G-CSF (Granulocyte Colony-Stimulating Factor).

Human granulocyte colony-stimulating factor (G-CSF) is a granulopoietic growth factor used in the treatment of neutropenia following chemotherapy, myeloablative treatment, or healthy donors preparing for allogeneic transplantation. Few hypersensitivity reactions (HRs) have been reported, and its true prevalence is unknown. We aimed to systematically characterize G-CSF-induced HRs while including a comprehensive list of adverse reactions. We reviewed articles published before January 2024 by searching in the PubMed, Embase, Cochrane Library, and Web of Science databases using a combination of the keywords listed, selected the ones needed, and extracted relevant data. The search resulted in 68 entries, 17 relevant to our study and 7 others found from manually searching bibliographic sources. A total of 40 cases of G-CSF-induced HR were described and classified as immediate (29) or delayed (11). Immediate ones were mostly caused by filgrastim (13 minimum), with at least 9 being grade 5 on the WAO anaphylaxis scale. Delayed reactions were mostly maculopapular exanthemas and allowed for the continuation of G-CSF. Reactions after first exposure frequently appeared and were present in at least 11 of the 40 cases. Only five desensitization protocols have been found concerning the topic at hand in the analyzed data. We believe this study brings to light the research interest in this topic that could benefit from further exploration, and propose regular updating to include the most recently published evidence.

Atraumatic splenic rupture secondary to granulocyte-colony stimulating factor medication exposure.

Hematopoietic hormones such as granulocyte-colony stimulating factors are commonly used prevent neutropenia in patients undergoing chemotherapy and to prepare patients for bone marrow donations. In rare cases, splenic injury can result from exposure to this medication. We present the case of a 30-year-old man who presented to the emergency department the day after a bone marrow donation procedure complaining of severe, acute onset left upper quadrant abdominal pain, radiating to the shoulder. Neither the patient nor his family reported any abdominal trauma prior to or following the marrow donation procedure. An initial bedside ultrasound examination was positive for peritoneal fluid and distortion of the normal splenic architecture, raising suspicion for possible intraabdominal or splenic injury. An emergent confirmatory CT with contrast of the abdomen confirmed the initial ultrasound examination suspicion of an atraumatic splenic rupture and with evidence of venous bleeding but without active arterial extravasation. An emergent trauma surgery consultation was placed, and he underwent embolization with an uneventful recovery. This case report highlights the need for a high index of suspicion for atraumatic splenic rupture in patients exposed to these types of granulocyte-colony stimulating factors.

Evaluation of a Quality Improvement Process for Health-System Retention of Long Acting Growth Factors Prescriptions in the Pediatric Oncology Population.

OBJECTIVE: Granulocyte-colony stimulating factor (GCSF) products are often used in pediatric patients with malignant diagnoses to reduce the time that the patient is neutropenic. Long-acting GCSF products have been shown to be non-inferior to daily dosing of GCSF products, and are becoming more desired by patients and families. Insurance companies often require a prior authorization prior to approving the use of the long-acting GCSF products. This process has proven challenging leading to treatment delays and missed doses. The purpose of this study is to evaluate a quality improvement process for the prescribing and dispensing of long-acting GCSF to better serve pediatric patients within a single health care system. METHODS: This is a single-center, retrospective chart review with the purpose of collecting data to compare prescription retention before and after the improvement intervention. Study timeline includes all doses of long-acting GCSF prescribed for pediatric oncology patients between June 2020-June 2021 compared with July 2021-March 2022. On June 30, 2021, educational information was provided to the appropriate stakeholders regarding the change in practice. RESULTS: A total of 31 patients were included in the review, with 22 patients prior to the intervention (115 prescriptions), and 9 patients after the intervention (43 prescriptions). There was a 37.8% increase in health system prescription retention (15.7% vs 53.5%). CONCLUSIONS: Pharmacist directed long-acting GCSF prescription destination and a dedicated prior-authorization team led to an increase in prescription retention for patients regardless of payer mandated outpatient pharmacy.

A global assessment of hemostatic function of healthy allogeneic stem cell donors undergoing apheresis by rotational thromboelastometry.

INTRODUCTION: Peripheral blood stem cell (PBSC) collection via apheresis requires the administration of granulocyte colony-stimulating factor (filgrastim) to stem cell donors. Several reports have shown that filgrastim administration and apheresis procedure induce a hypercoagulable state across PBSC collection, which might predispose certain donors to thrombotic complications. METHODS: We evaluated the hemostatic functions of healthy allogeneic stem cell donors by rotational thromboelastometry (ROTEM). Blood samples from healthy donors (n = 30) were collected at defined time points: before filgrastim (baseline), on the day of apheresis before and after the procedure, and 1 week after apheresis. RESULTS: The results indicated that hemostatic changes are temporary since all parameters in both EXTEM and INTEM assays are restored to their initial values 1 week after the apheresis. CONCLUSION: We concluded that stem cell apheresis does not induce a hypercoagulable state in healthy donors. This is the first study evaluating the hemostatic functions of stem cell donors by ROTEM.

Filgrastim biosimilar (EP2006): A review of 15 years' post-approval evidence.

Filgrastim is approved for several indications, including reduction of the incidence and duration of chemotherapy-induced neutropenia and for stem cell mobilization. The filgrastim biosimilar, EP2006, has been available in Europe since 2009, and in the United States since 2015. In this time, preclinical and clinical data used to support the approval of EP2006 have been published. These data established the biosimilarity of EP2006 to reference filgrastim in terms of structure, pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity. Additional real-world evidence studies have also demonstrated equivalent efficacy and safety of EP2006 compared with reference filgrastim, both in the reduction of neutropenia and in stem cell mobilization in clinical practice. This review summarizes these preclinical, clinical, and real-world data, as well as the available cost-effectiveness data, for EP2006 since its approval 15 years ago.

Efficacy and safety of biosimilar Peg-filgrastim after autologous stem cell transplant in myeloma and lymphoma patients: a comparative study with biosimilar Filgrastim, Lenograstim, and originator Peg-filgrastim.

Data about biosimilar Peg-filgrastim (bioPEG) in autologous stem cell transplant (ASCT) are still scarce. The aim of this study has been to assess efficacy and safety of bioPEG among lymphoma and myeloma patients undergoing ASCT, comparing these data with historical controls receiving other G-CSFs. Furthermore, an economic evaluation has been included to estimate the savings by using bioPEG. This is a prospective cohort study comparing lymphoma and myeloma patients undergoing ASCT and receiving bioPEG (n = 73) with three historical consecutive cohorts collected retrospectively who received other G-CSFs (Lenograstim - Leno - n = 101, biosimilar Filgrastim - bioFIL n = 392, and originator Peg-filgrastim - oriPEG n = 60). We observed a significantly shorter time to neutrophils and platelet engraftment (p < 0.001) in patients treated with bioPEG and oriPEG. Moreover, patients who received bioPEG showed a shorter hospitalization time (p < 0.001) and a lower transfusion need (p < 0.001). We did not observe any significant difference in terms of transplant-related mortality, mucositis, and diarrhea among the four groups. No serious adverse events were associated with bioPEG. Similar data were obtained after running a stratified analysis for lymphomas and myeloma separately conducted by using a propensity score matching. The average total cost per patient of bioPEG was € 18218.9 compared to € 23707.8, € 20677.3 and € 19754.9 of Leno, oriPEG, and bioFIL, respectively. In conclusion, bioPEG seems to be as effective as the originator and more effective than short-acting G-CSFs in terms of post-transplant engraftment in myeloma and lymphoma patients undergoing ASCT. Moreover, bioPEG was cost-effective when compared with the other G-CSFs.

Filgrastim-induced hemophagocytic lymphohistiocytosis in a patient with mantle cell lymphoma: A case report.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease potentially induced by various causes. Very few reports have described HLH induced by granulocyte colony-stimulating factor (G-CSF) and those few previous reports have uniformly indicated that continuing G-CSF is unfeasible once HLH has been induced. A 52-year-old Japanese man who had been diagnosed with mantle cell lymphoma with systemic and central nervous system involvements received rituximab, hyper-fractionated cyclophosphamide, vincristine, Adriamycin and dexamethasone (R-HCVAD)/methotrexate and cytarabine. During the second cycle of R-HCVAD, the patient developed severe back pain, thrombocytopenia, elevated serum lactate dehydrogenase and ferritin levels, and hemophagocytosis in the bone marrow. Complete remission (CR) of mantle cell lymphoma was confirmed on whole-body computed tomography, brain magnetic resonance imaging, and bone marrow biopsy. The patient was diagnosed with HLH induced by filgrastim. HLH recovered with intravenous methylprednisolone at 1 g/day for 3 days, followed by oral prednisolone tapered off over 5 days. The patient continued chemotherapy with a change in the G-CSF formulation from filgrastim to lenograstim and prophylactic administration of corticosteroids. He safely completed scheduled chemotherapy without recurrence of HLH and successfully maintained CR of lymphoma. Although rare, G-CSF potentially induces HLH. Changing the G-CSF formulation and steroid prophylaxis may allow safe continuation of G-CSF.

The Impact of Biosimilar Use on Total Cost of Care and Provider Financial Performance in the Medicare Oncology Care Model: A Population-Based Simulation Study.

INTRODUCTION: Payment for oncology care is increasingly moving from fee-for-service to value-based payment (VBP). VBPs are agreements in which providers are held accountable for total cost of care (TCOC) through risk-sharing arrangements with payers that tie reimbursement levels to TCOC benchmarks. Oncology biosimilars may play an important role in managing financial risk in the VBPs like Medicare's Oncology Care Model (OCM), but there has been limited research in this area. The objective of this study is to estimate the impact of biosimilar adoption on TCOC and oncology provider financial performance under the terms of the Medicare OCM. METHODS: We conducted a population-based simulation study using the Medicare Limited Data Set (LDS) and the methodology of Medicare's OCM. The primary outcome was the simulated average change in TCOC per 6-month episode of care attributable to use of biosimilars as an alternative to reference products. The study population consisted of episodes of care in 2020 and using the reference product or corresponding biosimilar for bevacizumab, rituximab, trastuzumab, epoetin alfa, filgrastim, or pegfilgrastim. TCOC was calculated for each episode of care with use of reference products only and compared with TCOC with corresponding biosimilars. The simulation calculated TCOC outcomes in cohorts of 100 episodes sampled from the Medicare LDS study population using a Monte Carlo simulation with 10,000 iterations. RESULTS: Among the total of 8281 6-month oncology care episodes identified in the study period (initiating January 2020 to July 2020) in Medicare claims, 1586 (19.2%) episodes met OCM and study criteria and were included. Applying the simulation methods to these observed episodes, biosimilar substitution reduced mean TCOC per episode by $1193 (95% CI $583-1840). The cost reduction from biosimilars represented 2.4% of the average TCOC benchmark and led to a 15% reduction in the risk of providers needing to pay recoupments to Medicare for exceeding TCOC benchmarks. CONCLUSIONS: On the basis of our simulation study using observed Medicare claims and OCM criteria, we found that biosimilar substitution for reference products can significantly lower episode TCOC and improve provider financial performance under the terms of the largest value-based payment model implemented to date.

Aggregation of human plasma and of human blood induced in vitro by filgrastim originator product; effect of PEGylation.

We herein report that filgrastim product Neupogen® and the filgrastim formulation buffer induced aggregate formation when mixed in vitro with human plasma, and formation of large membranous erythrocyte aggregates when mixed with human blood, similar to the aggregation induced by pegfilgrastim and by pegfilgrastim buffer [T. Arvinte, E. Poirier, N. Ersayin, G. Darpin, A. Cudd, J. Dowd, S. Brokx, Aggregation of human plasma and of human blood induced in vitro by pegfilgrastim originator formulation buffer and pegfilgrastim products, Eur. J. Pharmaceut. Biopharmaceut. (2023), doi: 10.1016/j.ejpb.2023.10.019]. The data identify the filgrastim buffer (which is practically the same in filgrastim and pegfilgrastim products) as the main driver of human plasma and blood aggregation. Kinetic experiments showed differences in the extent of plasma aggregation induced by a filgrastim product manufactured in EU and one manufactured in USA. Human donor variability in the plasma aggregation induced by filgrastim was observed. To study the effect of PEGylation of the filgrastim protein on plasma aggregation we compared filgrastim (Neupogen®) with pegfilgrastim (Neulasta®) solutions at the same protein concentration. These data show that PEGylation has a beneficial effect in inhibiting to an extent plasma aggregation. Interestingly, 20 kDa polyethylene glycol in the filgrastim buffer induced more plasma aggregation compared to the buffer, similar to the aggregation induced by pegfilgrastim. For intravenous infusion filgrastim solutions (300 µg/ml, vials only) may be diluted in 5 % dextrose from a concentration of 300 µg/ml to 5 µg/ml. Aggregation of human plasma was also induced by filgrastim solutions diluted in 5 % dextrose to 50 µg/ml, 15 µg/ml and 5 µg/ml filgrastim, as well as by the filgrastim buffer similarly diluted in 5 % dextrose (1:6, 1:20 and 1:60 dilution). These data show that filgrastim solutions used for intravenous administration in patients induce human plasma aggregation in vitro. Such aggregation phenomena may be related to known infusion side effects of filgrastim therapy.

Granulocyte Colony-Stimulating Factor (Neupogen®; Filgrastim) Accelerates Neutrophil Recovery in a Rodent Model of Sulfur Mustard-Induced Hematologic Toxicity.

OBJECTIVE: Evidence of myelosuppression has been negatively correlated with patient outcomes following cases of high dose sulfur mustard (SM) exposure. These hematologic complications can negatively impact overall immune function and increase the risk of infection and life-threatening septicemia. Currently, there are no approved medical treatments for the myelosuppressive effects of SM exposure. METHODS: Leveraging a recently developed rodent model of SM-induced hematologic toxicity, post-exposure efficacy testing of the granulocyte colony-stimulating factor drug Neupogen® was performed in rats intravenously challenged with SM. Before efficacy testing, pharmacokinetic/pharmacodynamic analyses were performed in naïve rats to identify the apparent human equivalent dose of Neupogen® for efficacy evaluation. RESULTS: When administered 1 d after SM-exposure, daily subcutaneous Neupogen® treatment did not prevent the delayed onset of hematologic toxicity but significantly accelerated recovery from neutropenia. Compared with SM controls, Neupogen®-treated animals recovered body weight faster, resolved toxic clinical signs more rapidly, and did not display transient febrility at time points generally concurrent with marked pancytopenia. CONCLUSIONS: Collectively, this work corroborates the results of a previous pilot large animal study, validates the utility of a rodent screening model, and provides further evidence for the potential clinical utility of Neupogen® as an adjunct treatment following SM exposure.

Recurrence of Large-Vessel Vasculitis Induced by Multiple Types of Granulocyte Colony-Stimulating Factor Preparation in Patient with Large-Cell Neuroendocrine Lung Carcinoma: A Case Report.

With the increased use of granulocyte colony-stimulating factor (G-CSF) preparations, there is concern about the increase in G-CSF-associated large-vessel vasculitis; however, there have been no previous reports of vasculitis caused by multiple types of G-CSF preparations. We experienced a case of drug-induced large-vessel vasculitis caused by two different G-CSF products, which was difficult to diagnose. When treating patients with a history of large-vessel vasculitis caused by pegfilgrastim, we need to pay attention to its recurrence when using other G-CSF preparations.

Cost-effectiveness of granulocyte colony-stimulating factors (G-CSFs) for the prevention of febrile neutropenia (FN) in patients with cancer.

PURPOSE: Clinical practice guidelines recommend the use of all approved granulocyte colony-stimulating factors (G-CSFs), including filgrastim and pegfilgrastim, as primary febrile neutropenia (FN) prophylaxis in patients receiving high- or intermediate-risk regimens (in those with additional patient risk factors). Previous studies have examined G-CSF cost-effectiveness by cancer type in patients with a high baseline risk of FN. This study evaluated patients with breast cancer (BC), non-small cell lung cancer (NSCLC), or non-Hodgkin's lymphoma (NHL) receiving therapy who were at intermediate risk for FN and compared primary prophylaxis (PP) and secondary prophylaxis (SP) using biosimilar filgrastim or biosimilar pegfilgrastim in Austria, France, and Germany. METHODS: A Markov cycle tree-based model was constructed to evaluate PP versus SP in patients with BC, NSCLC, or NHL receiving therapy over a lifetime horizon. Cost-effectiveness was evaluated over a range of willingness-to-pay (WTP) thresholds for incremental cost per quality-adjusted life year (QALY) gained. Sensitivity analyses evaluated uncertainty. RESULTS: Results demonstrated that using biosimilar filgrastim as PP compared to SP resulted in incremental cost-effectiveness ratios (ICERs) well below the most commonly accepted WTP threshold of €30,000. Across all three countries, PP in NSCLC had the lowest cost per QALY, and in France, PP was both cheaper and more effective than SP. Similar results were found using biosimilar pegfilgrastim, with ICERs generally higher than those for filgrastim. CONCLUSIONS: Biosimilar filgrastim and pegfilgrastim as primary prophylaxis are cost-effective approaches to avoid FN events in patients with BC, NSCLC, or NHL at intermediate risk for FN in Austria, France, and Germany.

Assessing the Optimal Regimen: A Systematic Review and Network Meta-Analysis of the Efficacy and Safety of Long-Acting Granulocyte Colony-Stimulating Factors in Patients with Breast Cancer.

Patients with breast cancer undergoing chemotherapy are susceptible to prolonged and severe neutropenia. Multiple biosimilars of long-acting granulocyte colony-stimulating factors (LA-G-CSFs) have been newly developed to prevent this disease. Nonetheless, which LA-G-CSF regimen has the optimal balance of efficacy and safety remains controversial. Moreover, there is a lack of evidence supporting clinical decisions on LA-G-CSF dose escalation in poor conditions. PubMed, Embase, Cochrane Library, Web of Science, and several Chinese databases were searched (December 2022) to collect randomized controlled trials (RCTs) about LA-G-CSFs preventing chemotherapy-induced neutropenia in breast cancer patients. No restrictions were imposed on language. A Bayesian network meta-analysis was performed. We assessed the incidence of severe neutropenia (SN) and febrile neutropenia (FN), the duration of SN (DSN), and the absolute neutrophil account recovery time (ANCrt) for efficacy, while the incidence of severe adverse events (SAE) was assessed for safety. The study was registered in PROSPERO (CRD42022361606). A total of 33 RCTs were included. Our network meta-analysis demonstrated that lipegfilgrastim 6 mg and eflapegrastim 13.2 mg outperformed other LA-G-CSFs with high efficacy rates and few safety concerns (SUCRA of lipegfilgrastim 6 mg: ANC rt 95.2%, FN 97.4%; eflapegrastim 13.2 mg: FN 87%, SN 89.3%). Additionally, 3.6 mg, 4.5 mg, 6 mg, and 13.2 mg dosages all performed significantly better than 1.8 mg in reducing the duration of SN (3.6 mg: DSN, SMD -0.68 [-1.13, -0.22; moderate]; 4.5 mg: -0.87 [-1.57, -0.17; low]; 6 mg: -0.89 [-1.49, -0.29; moderate]; 13.2 mg: -1.02 [1.63, -0.41; high]). Increasing the dosage from the guideline-recommended 6 mg to 13.2 mg can reduce both the duration and incidence of SN (SMD -0.13 [-0.24 to -0.03], RR 0.65 [0.43 to 0.96], respectively), with no significant difference in SAE. For patients with breast cancer, lipegfilgrastim 6 mg and eflapegrastim 13.2 mg might be the most effective regimen among LA-G-CSFs. Higher doses of LA-G-CSF may enhance efficacy without causing additional SAEs.

Comparing the effectiveness of biosimilar filgrastim (Nivestim®) versus original filgrastim (Neupogen®) for stem cell mobilization in adult and pediatric healthy donors.

INTRODUCTION: Filgrastim is used for the mobilization of stem cells in healthy donors. Though several biosimilar filgrastim products have been approved, there is limited literature evaluating biosimilar products for stem cell mobilization. Therefore, we conducted this study to compare the effectiveness of the original filgrastim, Neupogen®, to the biosimilar product, Nivestim®, for stem cell mobilization(SCM) in healthy donors. METHODS: This was a retrospective study that included all healthy donors: adults and pediatrics, who received Neupogen® or Nivestim® for stem cell mobilization between 2014 and 2016 at a comprehensive cancer center. Donors received filgrastim at a dose of 5 mcg/kg every 12 h for 4 days to achieve the target CD34 + cell count of 5-10 × 106 CD34 + /kg of recipient body weight. Additional doses of filgrastim were administered and/or the dose increased if target CD34 + was not achieved. The primary endpoint was the number of doses required to achieve the target CD34 + cell count. RESULTS: Over the study period, 89 donors received Neupogen® and 68 received Nivestim®. The median age of donors was 19.5 years (3-64) in the Nivestim® group and 15 years (2-16) in the Neupogen® group. The median number of doses required for SCM was eight doses (6-10) in the Nivestim group and eight (6-16) in the Neupogen® group. CONCLUSION: Biosimilar Nivestim® was as effective as the original, Neupogen®, for stem cell mobilization for healthy adult and pediatric donors. Larger randomized studies are necessary to evaluate the safety and transplant outcomes of the use of Nivestim®.

As-Required Filgrastim for Late-Onset Neutropenia Complicating Long-Term Clozapine Treatment: a Case Report.

Clozapine is considered the most effective antipsychotic for schizophrenia, but it can cause neutropenia and even agranulocytosis. We describe the first case in Hong Kong involving the use of filgrastim, a recombinant form of human granulocyte colony-stimulating factor, to enable clozapine continuation therapy for a severely ill patient with treatment-resistant schizoaffective disorder who developed recurrent neutropenia after almost 20 years of continuous clozapine therapy. Therefore, clinical vigilance is important, regardless of clozapine treatment duration. Filgrastim can facilitate long-term clozapine therapy in patients with clozapine-induced neutropenia.

Successful treatment of 5-fluorouracil toxicosis with hemodialysis.

OBJECTIVE: To describe the successful treatment of lethal dose 5-fluorouracil (5-FU) toxicosis using hemodialysis. CASE SUMMARY: A 4-month-old intact female Golden Retriever was presented to the emergency department after ingesting 20 g of 5% 5-FU cream. The puppy developed refractory seizures and became comatose with uncontrolled tonic-clonic convulsions. Because of the low molecular weight and minimal protein binding of 5-FU, a single hemodialysis treatment was employed for detoxification. The puppy improved clinically posttreatment and was successfully discharged 3 days after admission. Postingestion leukopenia and neutropenia occurred but were responsive to treatment with filgrastim. The puppy is neurologically normal and has no lasting effects 1 year postingestion. NEW OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge, this is the first reported case in veterinary medicine of a potentially fatal 5-FU ingestion that has been treated with intermittent hemodialysis.