Mirtazapine-induced neutropenic sepsis in an older person: a case report.

BACKGROUND: Mirtazapine is a frequently prescribed psychotropic drug for depression in older age. It is considered safe and has a side-effect profile uniquely favorable to an older person affected by reduced appetite, difficulty maintaining body weight, or insomnia. However, it is largely unknown that mirtazapine can cause a dangerous decline in neutrophil count. CASE PRESENTATION: We present a case of mirtazapine-induced severe neutropenia in a 91-year-old white British woman requiring drug withdrawal and granulocyte-colony stimulating factor administration. CONCLUSION: This case is of significance because mirtazapine is regarded as a safe, and often preferable, antidepressant in older age. However, this case demonstrates a rare, life-threatening side effect of mirtazapine and calls for greater pharmacovigilance when prescribing it. There is no previous report of mirtazapine-induced neutropenia requiring drug withdrawal and granulocyte-colony stimulating factor administration in an older person.

The effect of concomitant use of Colony-Stimulating factors on bleomycin pulmonary toxicity - A systematic review and meta-analysis.

BACKGROUND: Changes in the incidence of bleomycin pulmonary toxicity (BPT) as a result of adding colony-stimulating factors (CSF) to bleomycin regimens has been investigated in numerous studies. We performed a systematic review and meta-analysis to assess the outcomes of these studies. METHODS: A systematic search was performed using Pubmed, Scopus, Web of Science, and Embase on April 2021. Studies evaluating the incidence of BPT in patients receiving bleomycin with and without CSF were included. In addition, meta-analysis was performed by pooling odds ratios using R. RESULTS: Out of 340 obtained records, our qualitative and quantitative analysis included 3234 and 1956 patients from 22 and 14 studies, respectively. The quantitative synthesis showed that addition of CSF significantly increased the risk of BPT incidence (OR = 1.82, 95 % CI: 1.37-2.40, p < 0.0001; I2 = 10.7 %). Subgroup analysis did not show any association between continent, bleomycin dose, cancer type, type of study, and pulmonary function test with BPT incidence. CONCLUSION: This systematic review and meta-analysis showed that co-administration of CSF with bleomycin increases the incidence of BPT. The physicians need to consider this finding while deciding the best strategy for this cohort of patients.

Colony stimulating factors for prophylaxis of chemotherapy-induced neutropenia in children.

INTRODUCTION: Febrile neutropenia (FN) is one of the complications of chemotherapy that can increase the risk of infection and mortality. Granulocyte colony-stimulating factors (G-CSFs) are used in practice to prevent and treat episodes of neutropenia. The use of G-CSFs in children with cancer has not been studied much for primary prophylaxis of FN. AREAS COVERED: Current data suggest that G-CSFs have a similar pharmacokinetic profile in children and adults. Clinical trials published from 2002 to 2021 using G-CSFs in pediatric cancer patients were reviewed. All evaluated clinical trials used a dosage of 5 mcg/kg of filgrastim daily until neutrophil recovery or a single dose of 100 mcg/kg pegfilgrastim. Filgrastim demonstrated the benefit in decreasing the duration of fever, hospital stay, and antibiotic use in high-risk neuroblastoma patients. Pegfilgrastim showed similar efficacy in reducing the occurrence of FN and infections, with bone pain as an adverse effect. EXPERT OPINION: Filgrastim 5 mcg/kg/day or pegfilgrastim 100 mcg/kg single dose is appropriate when given at least 24 hours or after the chemotherapy in pediatric patients who weigh 45 kg or more. More prospective randomized trials are necessary to further investigate the efficacy and safety of G-CSFs in children with different types of cancer.

Colony-stimulating factor-1 receptor inhibition attenuates microgliosis and myelin loss but exacerbates neurodegeneration in the chronic cuprizone model.

Multiple sclerosis (MS), especially in its progressive phase, involves early axonal and neuronal damage resulting from a combination of inflammatory mediators, demyelination, and loss of trophic support. During progressive disease stages, a microenvironment is created within the central nervous system (CNS) favoring the arrival and retention of inflammatory cells. Active demyelination and neurodegeneration have also been linked to microglia (MG) and astrocyte (AST)-activation in early lesions. While reactive MG can damage tissue, exacerbate deleterious effects, and contribute to neurodegeneration, it should be noted that activated MG possess neuroprotective functions as well, including debris phagocytosis and growth factor secretion. The progressive form of MS can be modeled by the prolonged administration to cuprizone (CPZ) in adult mice, as CPZ induces highly reproducible demyelination of different brain regions through oligodendrocyte (OLG) apoptosis, accompanied by MG and AST activation and axonal damage. Therefore, our goal was to evaluate the effects of a reduction in microglial activation through orally administered brain-penetrant colony-stimulating factor-1 receptor (CSF-1R) inhibitor BLZ945 (BLZ) on neurodegeneration and its correlation with demyelination, astroglial activation, and behavior in a chronic CPZ-induced demyelination model. Our results show that BLZ treatment successfully reduced the microglial population and myelin loss. However, no correlation was found between myelin preservation and neurodegeneration, as axonal degeneration was more prominent upon BLZ treatment. Concomitantly, BLZ failed to significantly offset CPZ-induced astroglial activation and behavioral alterations. These results should be taken into account when proposing the modulation of microglial activation in the design of therapies relevant for demyelinating diseases. Cover Image for this issue: https://doi.org/10.1111/jnc.15394.

Nested Case-Control Study Utilizing MID-NET® on Thrombocytopenia Associated With Pegfilgrastim in Patients Treated With Antineoplastic Agents.

Although several spontaneous case reports on the occurrence of thrombocytopenia in patients treated with human granulocyte colony-stimulating factor (G-CSF) preparations have been accumulated, its actual causality is still unclear. To investigate the association between G-CSF preparations (filgrastim, nartograstim, lenograstim, and pegfilgrastim) available in Japan and thrombocytopenia in patients treated with antineoplastic agents, a nested case-control study was conducted using the Medical Information Database NETwork (MID-NET®) with the cohort of the Japanese population taking antineoplastic agents between 2009 and 2018. A case of thrombocytopenia was defined as a patient who had decreased platelet counts (< 50,000/mm3 ). We identified a maximum of 10 controls for each case matched on the index date. Adjusted odds ratios (aORs) and their 95% confidence intervals (CIs) of thrombocytopenia for the use of G-CSF preparations compared with nonuse were estimated using conditional logistic regression. From the cohort in which 33,124 patients were included, 733 cases and 5,592 controls were identified. Compared with the nonuse of G-CSF preparations, the use of any G-CSF preparations increased the risk of thrombocytopenia (aOR: 5.7, 95% CI: 4.3-7.5). More detailed analysis showed that a distinctive increased risk was observed when pegfilgrastim was prescribed at 2-7 days before the index date (aOR: 7.4 95% CI: 2.0-28.1). Associations of the other G-CSF preparations with thrombocytopenia were unclear due to the inconsistent results among different analyses. A significantly increased risk of thrombocytopenia associated with pegfilgrastim was identified, leading to a revision of precautions in the package inserts of pegfilgrastim as a regulatory safety action.

Should we screen patients with hematologic malignancies for COVID-19?

The coronavirus disease (COVID-19) pandemic has posed several challenges to the hematology community to re-organize the medical care of patients with hematologic malignancies. Whereas the oncology societies favored a more or less conservative approach which considered the possibility of delaying treatment administration on a case-by-case basis, the hematology community guidelines were less stringent and recommended adequate individualized regimens. As countries are de-escalating the lockdown and the medical community is unable to foresee the end of the current outbreak will and whether the pandemic would eventually come back as a seasonal infection, there is interest in screening of patients with hematology malignancies with COVID-19 instead of limiting access to curative treatments. The rapidly accumulating knowledge about COVID-19 allows a better understanding of the diagnostic tools that may be potentially used in screening. Herein, we briefly review the pathophysiology of COVID-19, the rationale of screening of patients with hematologic malignancies, tools for screening, and available guidelines.

Use of Hematopoietic Growth Factors and Risk of Thromboembolic and Pulmonary Toxicities in Elderly Patients with Advanced Ovarian Cancer.

OBJECTIVE: To evaluate the risk of thromboembolic and pulmonary toxicities associated with hematopoietic growth factor (HGF) use (i.e., erythropoietin-stimulating agent [ESA] and/or colony-stimulating factor [CSF]) in a community-dwelling cohort of elderly patients with advanced ovarian cancer. METHODS: We studied 8,188 women, 65 years and older from the Surveillance, Epidemiology and End Results-Medicare linked database, diagnosed from January 1, 2000 to December 31, 2009. Patients were categorized into five groups: no chemotherapy and no ESA/CSF (n = 2,616), chemotherapy but no ESA/CSF (n = 1,854), ESA only (n = 1,313), CSF only (n = 743), and ESA + CSF (n = 1,662). We reported the cumulative incidence of toxicities for 2, 6, and greater than 6 months, and the incidence density for the overall follow-up. Cox-proportional hazards regression was performed to determine risk of toxicities. RESULTS: Of the 5,572 patients receiving chemotherapy, 66.7% (n = 3,718) received HGF supportive treatment, 29.8% received ESA + CSF, 23.6% received ESA only, and 13.3% received CSF only. Patients who received chemotherapy and also ESA + CSF had a 14.1% cumulative incidence of thromboembolic event (TEE) at 6 months of follow-up compared with 8.0% in those who received chemotherapy without growth factor and 3.2% in those with neither chemotherapy nor growth factor. Those with chemotherapy who received ESA + CSF had a significantly higher risk of TEE (adjusted hazard ratio, 1.22; 95% confidence interval, 1.01-1.47) as compared with patients with chemotherapy and no ESA/CSF, although patients aged 85 years and older may experience up to a five-fold increased risk. The risk of pulmonary toxicities did not significantly differ by HGF use. CONCLUSIONS: An increased risk of TEEs was observed in elderly patients with ovarian cancer who received ESA + CSF. The risk-benefit ratio for administering HGF should be carefully evaluated, especially among those 85 years and older.

Real-World Conundrums and Biases in the Use of White Cell Growth Factors.

We present the 2015 American Society of Clinical Oncology (ASCO) white cell growth factors, or colony-stimulating factor (CSF), guidelines, updated from 2006. One new indication has been added-dose-intense chemotherapy for bladder cancer-to accompany the existing use for dose-dense breast cancer chemotherapy. Colony-stimulating factors remain appropriate for any regimen where the risk of febrile neutropenia is about 20% per cycle and dose reduction is not appropriate. Based on new evidence from multiple trials, CSF use is no longer indicated in treatment of lymphoma unless there are special risk factors. The United States accounts for 78% of the sales of CSF. The panel approved the use of all biosimilars, but the cost savings will be small as the price is about 80% of the branded CSFs. More biosimilars at lower cost are awaited. Methods to reduce use without harm to patients, by requiring justification according to accepted guidelines, are ongoing.

Issues on the Use of White Blood Cell Growth Factors in Oncology Practice.

Appropriate use of myeloid growth factors may reduce the risk of neutropenic complications including febrile neutropenia (FN) in patients receiving cancer chemotherapy. The recently updated American Society of Clinical Oncology (ASCO) Guidelines on the Use of the White Blood Cell Growth Factors recommends routine prophylaxis with these agents starting in the first cycle when the risk of FN is 20% or greater. However, the risks for neutropenic complications and the risk of serious adverse consequences from FN vary considerably with different chemotherapy regimens as well as other disease-, treatment-, and patient-specific risk factors. Considerably more information is now available on the major risk factors for FN. Multivariable risk models combining factors look promising but require further validation. Most clinical studies of myeloid growth factor prophylaxis assessed relative risk (RR) of FN but were not powered to evaluate the effect of prophylaxis on disease-free or overall survival. Accumulating evidence suggests, however, that the appropriate use of these agents in selected patients may improve both short-term and long-term survival by reducing the immediate risk of mortality accompanying patients with high-risk disease developing FN as well as improving disease-free and overall survival by enabling the delivery of full dose intensity chemotherapy and reducing the risk of disease recurrence in patients treated with curative intent. Further studies to evaluate risk factors and models for FN are needed to guide clinical and shared decision making for the optimal personalized use of these agents and offer patients at increased risk the best chance of long-term disease control.

Associations between hematopoietic growth factors and risks of venous thromboembolism, stroke, ischemic heart disease and myelodysplastic syndrome: findings from a large population-based cohort of women with breast cancer.

PURPOSE: To determine the risk of venous thromboembolism (VTE), stroke, ischemic heart disease, and myelodysplastic syndrome (MDS) in association with the receipt of colony-stimulating factors (CSFs) and/or erythropoiesis-stimulating agents (ESAs) in women with breast cancer. METHODS: We studied 77,233 women with breast cancer aged ≥65 in 1992-2009 from the Surveillance, Epidemiology, and End Results-Medicare linked data with up to 19 years of follow-up. RESULTS: Incidence of VTE increased from 9 cases in women receiving no chemotherapy and no CSFs/ESAs to 22.79 cases per 1,000 person-years in those receiving chemotherapy with CSFs and ESAs. Women with chemotherapy who received both CSFs and ESAs (adjusted hazard ratio and 95 % confidence interval 2.01, 1.80-2.25) or received ESAs without CSFs (2.03, 1.74-2.36) were twice as likely to develop VTE than those receiving no chemotherapy and no CSFs/ESAs, whereas those receiving CSF alone without ESA were 64 % more likely to have VTE (1.64, 1.45-1.85). Risk of MDS was significantly increased by fivefold in patients receiving ESA following chemotherapy. CONCLUSIONS: Receipts of CSFs and ESAs were significantly associated with an increased risk of VTE in women with breast cancer. Use of ESAs was significantly associated with substantially increased risks of MDS. These findings support those of previous studies.

Risks of Venous Thromboembolism, Stroke, Heart Disease, and Myelodysplastic Syndrome Associated With Hematopoietic Growth Factors in a Large Population-Based Cohort of Patients With Colorectal Cancer.

PURPOSE: To determine the relationship between the receipt of colony-stimulating factors (CSFs) with erythropoiesis-stimulating agents (ESAs) and the risk of developing venous thromboembolism (VTE), stroke, heart disease, and myelodysplastic syndrome (MDS) in patients with colorectal cancer. METHODS: We studied 80,925 patients diagnosed with colorectal cancer at age ≥ 65 years in 1992-2009 from the nationwide 16 areas of the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data. Cumulative incidence and the time to events Cox hazard regressions were used to explore the risks of outcomes in association with the receipt of CSFs and ESAs. RESULTS: Patients who received chemotherapy (CT) with both CSF and ESA were 58% more likely to develop VTE than those who received CT without CSF and ESA (hazard ratio, 1.58; 95% confidence interval, 1.43-1.76). The risk of stroke appeared to be not associated with the use of CSF and ESA, whereas the risk of heart disease was only significantly elevated in those patients who did not receive CT but received ESA. The risk of acute myeloid leukemia or MDS was significantly increased 4- to 9-fold in patients who received ESA, regardless of receipt of CT or CSF. CONCLUSION: The use of ESAs was significantly associated with a substantially increased risk of MDS in patients with colorectal cancer. The use of CSFs and ESAs was also significantly associated with a moderately increased risk of VTE and a slightly elevated risk of heart disease.

Genetic variability in drug transport, metabolism or DNA repair affecting toxicity of chemotherapy in ovarian cancer.

BACKGROUND: This study aimed to determine whether single nucleotide polymorphisms (SNPs) in genes involved in DNA repair or metabolism of taxanes or platinum could predict toxicity or response to first-line chemotherapy in ovarian cancer. METHODS: Twenty-six selected SNPs in 18 genes were genotyped in 322 patients treated with first-line paclitaxel-carboplatin or carboplatin mono-therapy. Genotypes were correlated with toxicity events (anemia, neutropenia, thrombocytopenia, febrile neutropenia, neurotoxicity), use of growth factors and survival. RESULTS: The risk of anemia was increased for variant alleles of rs1128503 (ABCB1, C > T; p = 0.023, OR = 1.71, 95% CI = 1.07-2.71), rs363717 (ABCA1, A > G; p = 0.002, OR = 2.08, 95% CI = 1.32-3.27) and rs11615 (ERCC1, T > C; p = 0.031, OR = 1.61, 95% CI = 1.04-2.50), while it was decreased for variant alleles of rs12762549 (ABCC2, C > G; p = 0.004, OR = 0.51, 95% CI = 0.33-0.81). Likewise, increased risk of thrombocytopenia was associated with rs4986910 (CYP3A4, T > C; p = 0.025, OR = 4.99, 95% CI = 1.22-20.31). No significant correlations were found for neurotoxicity. Variant alleles of rs2073337 (ABCC2, A > G; p = 0.039, OR = 0.60, 95% CI = 0.37-0.98), rs1695 (ABCC1, A > G; p = 0.017, OR = 0.55, 95% CI 0.33-0.90) and rs1799793 (ERCC2, G > A; p = 0.042, OR = 0.63, 95% CI 0.41-0.98) associated with the use of colony stimulating factors (CSF), while rs2074087 (ABCC1, G > C; p = 0.011, OR = 2.09, 95% CI 1.18-3.68) correlated with use of erythropoiesis stimulating agents (ESAs). Homozygous carriers of the rs1799793 (ERCC2, G > A) G-allele had a prolonged platinum-free interval (p = 0.016). CONCLUSIONS: Our data reveal significant correlations between genetic variants of transport, hepatic metabolism, platinum related detoxification or DNA damage repair and toxicity or outcome in ovarian cancer.

Myeloid growth factors.

Febrile neutropenia, a common side effect of myelosuppressive chemotherapy in patients with cancer, can result in prolonged hospitalization and broad-spectrum antibiotic use, often prompting treatment delays or dose reductions of drug regimens. Prophylactic use of myeloid growth factors (mainly the colony-stimulating factors filgrastim and pegfilgrastim) in patients of heightened risk can reduce the severity and duration of febrile neutropenia. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Myeloid Growth Factors provide recommendations on the use of these agents mainly in the oncology setting based on clinical evidence and expert consensus. This version includes revisions surrounding the issue of timing of pegfilgrastim administration. It also includes new sections on tbo-filgrastim, a recently approved agent that is biologically similar to filgrastim, and the role of myeloid growth factors in the hematopoietic cell transplant setting.

Colony stimulating factors (including erythropoietin, granulocyte colony stimulating factor and analogues) for stroke.

BACKGROUND: Colony stimulating factors (CSFs), also called haematopoietic growth factors, regulate bone marrow production of circulating red and white cells, and platelets. Some CSFs also mobilise the release of bone marrow stem cells into the circulation. CSFs have been shown to be neuroprotective in experimental stroke. OBJECTIVES: To assess (1) the safety and efficacy of CSFs in people with acute or subacute ischaemic or haemorrhagic stroke, and (2) the effect of CSFs on circulating stem and blood cell counts. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched September 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 4), MEDLINE (1985 to September 2012), EMBASE (1985 to September 2012) and Science Citation Index (1985 to September 2012). In an attempt to identify further published, unpublished and ongoing trials we contacted manufacturers and principal investigators of trials (last contacted April 2012). We also searched reference lists of relevant articles and reviews. SELECTION CRITERIA: We included randomised controlled trials recruiting people with acute or subacute ischaemic or haemorrhagic stroke. CSFs included stem cell factor (SCF), erythropoietin (EPO), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage-colony stimulating factor (M-CSF, CSF-1), thrombopoietin (TPO), or analogues of these. The primary outcome was functional outcome at the end of the trial. Secondary outcomes included safety at the end of treatment, death at the end of follow-up, infarct volume and haematology measures. DATA COLLECTION AND ANALYSIS: Two review authors (TE and NS) independently extracted data and assessed trial quality. We contacted study authors for additional information. MAIN RESULTS: We included a total of 11 studies involving 1275 participants. In three trials (n = 782), EPO therapy was associated with a significant increase in death by the end of the trial (odds ratio (OR) 1.98, 95% confidence interval (CI) 1.19 to 3.3, P = 0.009) and a non-significant increase in serious adverse events. EPO significantly increased the red cell count with no effect on platelet or white cell count, or infarct volume. Two small trials of carbamylated EPO have been completed but have yet to be reported. We included eight small trials (n = 548) of G-CSF. G-CSF was associated with a non-significant reduction in early impairment (mean difference (MD) -0.4, 95% CI -1.82 to 1.01, P = 0.58) but had no effect on functional outcome at the end of the trial. G-CSF significantly elevated the white cell count and the CD34+ cell count, but had no effect on infarct volume. Further trials of G-CSF are ongoing. AUTHORS' CONCLUSIONS: There are significant safety concerns regarding EPO therapy for stroke. It is too early to know whether other CSFs improve functional outcome.

Biosimilars: are they ready for primetime in the United States?

The introduction of alternative versions of biologic products, also known as biosimilars, into the United States market has been gaining increasing visibility as patents for many agents are nearing expiration. Unlike generics, which are regulated under the Hatch-Waxman legislation passed in 1984, the approval process for biosimilars in the United States has not been defined. In 2004, the European Union established a regulatory pathway for these agents, and the FDA is now following suit. The economic implications are large, with $66.9 billion spent on the top 20 biologics in 2009. Of the top 10 biologics, 6 are routinely used in oncology. As the regulatory requirements are debated, several critical issues must be resolved. The most obvious is that the agents must be shown to be comparable to the original biologic they intend to replace. Knowledge of pharmacokinetic parameters alone will not be adequate, but the amount of clinical data required by the FDA remains unclear. The regulations will define the ease with which a biosimilar can be brought to market, and the associated costs of trials will influence the ultimate price of the medications. Balancing the needs of the relevant stakeholders is critical to ensure patient safety while controlling costs, improving access, and encouraging innovation. This is not an easy balance to strike.

Hematopoietic growth factors in myelodysplastic syndromes.

Hematopoietic growth factors (HGFs) continue to be the most widely prescribed class of medications for patients with myelodysplastic syndromes (MDS), despite the advent of disease-modifying therapies for MDS (eg, azacitidine, decitabine, and lenalidomide) and the current absence of an MDS-specific US Food and Drug Administration (FDA)-approved indication for any of the HGFs. Erythropoiesis-stimulating agents (ESAs: epoetin alfa, darbepoetin alfa), myeloid growth factors (MGFs: filgrastim, pegfilgrastim, sargramostim), and the newest group of HGFs, thrombopoiesis-stimulating agents (TSAs: romiplostim, eltrombopag), can increase peripheral blood counts in some patients, and may ameliorate some of the signs and symptoms of MDS-associated bone marrow failure. Although HGFs are generally considered "supportive care" measures, recent data suggest that HGFs may alter the natural history of disease in MDS, either for better or worse. This review examines data on the safety and effectiveness of HGFs for patients with MDS.

Comparative effectiveness of colony-stimulating factors for febrile neutropenia: a retrospective study.

BACKGROUND: Granulocyte colony stimulating factors (G-CSFs) decrease the incidence of febrile neutropenia (FN) in cancer patients receiving myelosuppressive chemotherapy. There are two G-CSFs (pegfilgrastim and filgrastim) that differ in dosing schedules from which oncologists may prescribe. OBJECTIVES: This study aimed to compare the effectiveness of prophylactic pegfilgrastim and filgrastim on the risk of hospitalizations. The secondary objective was to compare the effectiveness of the timing of initiation (prophylactic versus delayed). METHODS: A retrospective study of administrative claims from US commercial payers included adult patients with Non-Hodgkin's lymphoma, breast, or lung cancer, treated with chemotherapy between July 2004 and January 2008. For these patients, the first course of chemotherapy and each unique cycle with use of G-CSF was identified and designated 'prophylaxis' if used within the first 5 days of each cycle, or 'delayed', if after day 5. The risk of neutropenia-related and all-cause hospitalization was evaluated for the pegfilgrastim and filgrastim prophylaxis cohorts and for the prophylaxis and delayed G-CSF initiation cohorts. RESULTS: Among 5,571 patient-cycles identified, 88.9% and 11.1% used pegfilgrastim and filgrastim respectively. The rate of neutropenic hospitalization was 1.1% for pegfilgrastim prophylaxis and 3.5% for filgrastim prophylaxis (P = 0.001). Compared to chemotherapy cycles with filgrastim prophylaxis, those with pegfilgrastim prophylaxis had decreased risk of neutropenia-related (adjusted odds ratio (OR) = 0.38, 95% confidence interval (CI) 0.17-0.83) and all-cause hospitalization (adjusted OR = 0.51, 95% CI 0.31-0.84). The neutropenic hospitalization rate was 1.2% for G-CSF prophylactic initiation and 3.7% for delayed G-CSF initiation (P < 0.001). Chemotherapy cycles with prophylactic initiation of either G-CSF had decreased risk of neutropenia-related (adjusted OR = 0.34, 95% CI 0.21-0.56) and all-cause hospitalization (adjusted OR = 0.67, 95% CI 0.49-0.91) compared with delayed initiation of G-CSF. CONCLUSIONS: Pegfilgrastim prescribed as prophylaxis resulted in lower risk of neutropenia-related and all-cause hospitalizations compared to filgrastim prophylaxis. This reduction was similar for prophylactic G-CSF initiation when compared to delayed G-CSF initiation.