Use Of Myeloid Growth Factors Research Articles

Assessment of the therapeutic use of myeloid growth factors in the treatment of patients with febrile neutropenia and gynecologic malignancies

Assessment of the therapeutic use of myeloid growth factors in the treatment of patients with febrile neutropenia and gynecologic malignancies

Efficacy of imetelstat on red blood cell (RBC)-transfusion independence (TI) in the absence of platelet transfusions or myeloid growth factors in IMerge.

6566 Background: In the IMerge trial (NCT02598661) of RBC transfusion-dependent (TD) patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory to or ineligible for erythropoiesis stimulating agents, imetelstat showed significant efficacy vs placebo (PBO) for 8-wk, 24-wk, and 1-y TI endpoints, with neutropenia and thrombocytopenia as the most common adverse events (Platzbecker. Lancet 2024). Supportive care was given to all pts as needed, per investigator discretion. Here we report RBC-TI rates in the absence of platelet transfusions or myeloid growth factor use. Separately, RBC-TI with mean central hemoglobin (Hb) rise of ≥1.5 g/d was assessed in all pts. Methods: Pts were randomized 2:1 to receive imetelstat (n=118) 7.5 mg/kg or PBO (n=60) Q4W IV until disease progression. Primary endpoint was 8-wk RBC-TI; 24-wk RBC-TI was a key secondary endpoint. Primary analysis cutoff was Oct 2022, with Oct 2023 cutoff for 1-y RBC-TI analyses. Results: Overall, 21/118 (18%) pts in the imetelstat group and 1/60 (2%) pts in the PBO group needed platelet transfusions; 41/118 (35%) and 2/60 (3%) pts received myeloid growth factors, respectively. Significantly higher percentages of pts achieved 8-wk, 24-wk, and 1-y RBC-TI with imetelstat vs PBO in the absence of either platelet transfusions or growth factor support (Table). In a separate analysis, 8-wk, 24-wk, and 1-y RBC-TI and concurrent Hb rise of ≥1.5 g/dL with imetelstat vs PBO occurred in 28% vs 2%, 23% vs 0%, and 17% vs 0% of pts, respectively (Table). Among responders, imetelstat increased median central Hb levels compared with PBO: 3.6 g/dL vs 0.8 g/dL for 8-wk, 4.2 g/dL vs 1.1 g/dL for 24-wk, and 5.2 g/dL vs 1.7 g/dL for 1-y RBC-TI. Conclusions: Results from this subanalysis confirm that pts who achieve RBC-TI with imetelstat do so without developing severe neutropenia and thrombocytopenia (functionally defined as needing myeloid growth factors or platelet transfusions, respectively), therefore not negating the clinical benefit of the drug. Imetelstat also led to significant rise in Hb levels in RBC-TI responders, particularly long-term responders. These data further support the efficacy of imetelstat in TD pts with LR-MDS. Clinical trial information: NCT02598661 . [Table: see text]

Dose modification rules and availability of growth factor support: A cross-sectional study of head-to-head cancer trials used for US FDA approval from 2009 to 2021

Aim of the studyDifferent drug modification rules or growth factor support guidance may affect the results in oncology randomised controlled trials. We aimed to estimate the prevalence of unequal rules for dose modification rules or the use of myeloid growth factors in head-to-head registration Food and Drug Administration trials. MethodsThis cross-sectional analysis included all head-to-head registration randomised controlled trials leading to a US Food and Drug Administration approval between 2009 and 2021. Trials examined anti-cancer drugs in the advanced or metastatic setting where a comparison could be made between arms regarding either dose modification rules or myeloid growth factors recommendations. Sixty-two registration trials met inclusion criteria. Information abstracted for each trial included tumour type, setting, phase, and type of sponsor. We assessed, according to pre-specified rules, imbalance in drug modification rules, myeloid growth factors recommendations or both. ResultsWe find 40 of 62 (65%) selected trials have unequal rules for dose medication, granulocyte colony-stimulating factor (G-CSF) use or both. Six trials (10%) had rules favouring the control arm, while 55% of selected trials (34/62) favoured the experimental arm. Among these, 50% (17/34) had unequal drug modification rules, 41% (14/34) had unequal G-CSF rules and 9% contained both (3/34). ConclusionWe find that 55% of trials testing anti-cancer drugs against each other used protocol rules that favoured the experimental arm. This leaves open the question of whether new molecules are truly superior to older molecules or if instead different outcomes are due to more aggressive dosing or growth factor support. Trials should utilise equal rules for dose medication and G-CSF support.

Prevencija i lečenje febrilne neutropenije izazvane hemioterapijom - uloga mijeloidnih faktora rasta

Febrile neutropenia is a serious chemotherapy-related adverse event that can lead to complications and death and it could be a significant burden on the organization of the health care system. The risk for febrile neutropenia is determined by chemotherapy-induced myelosuppression and the presence of patient-related risk factors. In the literature, various patient-related risk factors are taken into consideration. It was suggested that the patient age is the one of the most important ones. If the estimated risk for the febrile neutropenia is high, prophylactic use of myeloid growth factors (granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor) is recommended. In patients with solid tumors and lymphomas it was shown that the prophylactic use of myeloid growth factors significantly reduces the incidence of febrile neutropenia, early mortality during chemotherapy and infection-induced mortality. In patients who develop febrile neutropenia, there is less evidence for the therapeutic use of myeloid growth factors compared to prophylactic use, although there is a clear benefit in reducing the time to neutrophil count recovery. There is a clear benefit for hospitalized patients, also, in reducing duration of hospitalization. In patients with febrile neutropenia who have not been previously treated with prophylactic myeloid factors, assessment of risk factors for the complications is advised. In patients with high-risk febrile neutropenia therapeutic use of growth should be considered.

Infections in cancer patients treated with immune checkpoint inhibitors: Data from randomized trials.

2637 Background: Febrile neutropenia and infections are well studied complications of chemotherapy (CT) and some targeted agents employed in oncology. Less is known about the risk of infection associated with the use of immune checkpoint inhibitors (ICIs) in cancer patients. The present systematic review and meta-analysis was performed to address this question in patients diagnosed with solid tumors enrolled in randomized trials employing ICIs as experimental treatment. Methods: The Cochrane Library, EMBASE, and Pubmed databases were searched from inception through December 1st, 2020. Randomized clinical trials comparing any ICI alone, with CT, or with other agents vs CT, placebo, or other agents in patients with solid tumors were included. Two independent reviewers used a standardized data extraction and quality assessment form. Discordant cases were discussed with a third independent investigator. The following information was extracted: baseline study characteristics, including the primary tumor, author, year of publication, type of trial, type of disease, and the type of therapy (experimental and control arms); and the incidence of any-grade (grades [G] 1–5), low-grade (G1–2), and high-grade (G3–4), fatal event (G5) infections, and type of event. Random or fixed-effect models were used according to the statistical heterogeneity. Results: 36 randomized clinical trials were deemed eligible. The total population reached 21451 patients. In the pooled analysis, the use of ICIs was associated with a similar risk of all-grade infections (relative risk, RR = 1.02; 95% CI 0.84–1.24; P = 0.85) compared to non-ICI treatments (G1-5 events: 9.6 vs. 8.3%). When the ICIs alone arms were compared to CT, the experimental arms were associated with a 42% less risk of all-grade infections (RR = 0.58, 95% CI 0.4–0.85; P = 0.01; N = 18 studies). Compared to CT, the combination of ICIs and CT increased the risk of all-grade infections (RR = 1.37, 95% CI 1.23–1.53; P < 0.01; N = 13 studies) and severe infections (RR = 1.52, 95% CI 1.17–1.96; P < 0.01; N = 12 studies). Fatal infections were similar in the experimental and control arms (0.5%). Conclusions: In patients with advanced solid tumors, when ICIs were administered with CT, the risk of all-grade and G3-5 infections was significantly increased. Compared to CT alone, ICIs were safer and their use should be recommended for frail patients. Further studies are required to identify high-risk patients and evaluate the need for CT dose reduction or prophylactic myeloid growth factors use.

COVID-19 risk for patients undergoing anticancer treatment at the outpatient clinic of the National Cancer Institute of Milan: the COVINT study

BackgroundIn the midst of the COVID-19 pandemic, patients with cancer are regarded as a highly vulnerable population. Overall, those requiring hospital admission for treatment administration are potentially exposed to a...

Utilization of a clinical pathways decision support (CPDS) tool to guide myeloid growth factor usage in metastatic cancer.

302 Background: Myeloid growth factors (MGF) are used to prevent and treat febrile neutropenia caused by immunosuppressive therapy. In the curative setting, the use of a full dose-intensity chemotherapy plus an MGF are recommended based on the febrile neutropenic risk levels, as maintaining the full dose intensity has been shown to increase the chance of cure. In the metastatic setting, instead of administering an MGF to maintain dose-intensity, decreasing the dose and/or delaying the chemotherapy to allow recovery of the neutrophils is a reasonable alternative. This is supported by the American Society of Clinical Oncology (ASCO) where a review did not find data to support the use of MGFs to maintain dose-intensity in the treatment of metastatic cancer. In addition, no improvements in disease-free or overall survival were reported for any common cancer with the use of MGFs. New Century Health’s goal is to proactively educate and promote appropriate utilization of MGFs in the metastatic setting by incorporating several non-invasive questions into a Clinical Pathways Decision Support (CPDS) tool that aligns with ASCO’s recommendation (e.g. has a dose reduction/delay been attempted?). Methods: For a Medicare population, approved treatment requests involving the use of chemotherapy in metastatic cancer in the baseline period (baseline: January 2019 to May 2019, n = 606) were compared to requests approved in the implementation period (intervention: June 2019 to November 2019, n = 615). Two states were included in the analyses: Arizona (baseline: n = 200, intervention: n = 237) and Florida (baseline: n = 442, intervention: n = 422). Chi-square ( χ2) tests were performed to evaluate differences in requests during the baseline period as compared to the intervention period. Results: In Arizona, Florida, and total sample, treatment requests for MGF in metastatic cancer were lower in the intervention period as compared to the baseline period (Arizona: 21.52% vs. 28.50%, Florida: 18.48% vs. 23.98%, and total sample: 18.86% vs. 25.25%). In the total sample, the findings suggest that treatment requests for MGF in metastatic cancer were significantly lower in the intervention period as compared to the baseline period (χ2 = 7.25, p = .007). Conclusions: ASCO recommendations were incorporated into a CPDS tool to help align prescribing behavior. Real world data was used to help evaluate whether this change led a reduction in the utilization of MGFs in metastatic cancer. These findings suggest that such approaches can help guide providers to best practice.

Controversies Regarding Use of Myeloid Growth Factors in Leukemia.

This review focuses on the data supporting the use of myeloid growth factors (MGFs) in patients being treated for acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and hairy cell leukemia, for which neutropenia is a common complication of treatment. However, due to the lack of randomized trial data or conflicting results of clinical studies, comprehensive guidelines have been difficult to formulate. Moreover, to date, these diagnoses have not been addressed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MGFs. However, in most cases, the general principles have been included in the applicable NCCN Guidelines for each individual cancer site.

Myeloid Growth Factors, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology.

Myeloid growth factors (MGFs) are given as supportive care to patients receiving myelosuppressive chemotherapy to reduce the incidence of neutropenia. This selection from the NCCN Guidelines for MGFs focuses on the evaluation of regimen- and patient-specific risk factors for the development of febrile neutropenia (FN), the prophylactic use of MGFs for the prevention of chemotherapy-induced FN, and assessing the risks and benefits of MGF use in clinical practice.

Predicting neutropenia risk in patients with cancer using electronic data.

Clinical guidelines recommending the use of myeloid growth factors are largely based on the prescribed chemotherapy regimen. The guidelines suggest that oncologists consider patient-specific characteristics when prescribing granulocyte-colony stimulating factor (G-CSF) prophylaxis; however, a mechanism to quantify individual patient risk is lacking. Readily available electronic health record (EHR) data can provide patient-specific information needed for individualized neutropenia risk estimation. An evidence-based, individualized neutropenia risk estimation algorithm has been developed. This study evaluated the automated extraction of EHR chemotherapy treatment data and externally validated the neutropenia risk prediction model. A retrospective cohort of adult patients with newly diagnosed breast, colorectal, lung, lymphoid, or ovarian cancer who received the first cycle of a cytotoxic chemotherapy regimen from 2008 to 2013 were recruited from a single cancer clinic. Electronically extracted EHR chemotherapy treatment data were validated by chart review. Neutropenia risk stratification was conducted and risk model performance was assessed using calibration and discrimination. Chemotherapy treatment data electronically extracted from the EHR were verified by chart review. The neutropenia risk prediction tool classified 126 patients (57%) as being low risk for febrile neutropenia, 44 (20%) as intermediate risk, and 51 (23%) as high risk. The model was well calibrated (Hosmer-Lemeshow goodness-of-fit test = 0.24). Discrimination was adequate and slightly less than in the original internal validation (c-statistic 0.75 vs 0.81). Chemotherapy treatment data were electronically extracted from the EHR successfully. The individualized neutropenia risk prediction model performed well in our retrospective external cohort.

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.

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 America...

Importance of Risk Factors for Febrile Neutropenia Among Patients Receiving Chemotherapy Regimens Not Classified as High-Risk in Guidelines for Myeloid Growth Factor Use.

Clinical practice guidelines recommend prophylaxis in patients with cancer receiving a colony-stimulating factor (CSF) when the risk of febrile neutropenia (FN) is high (>20%). For patients receiving chemotherapy regimens not documented as high-risk, the decision regarding CSF prophylaxis use can be challenging, because some patients may be at high risk based on a combination of the regimen and individual risk factors. A retrospective cohort design and US private health care claims data were used. Study subjects received chemotherapy regimens classified as "low" or "intermediate," or unclassified, in terms of FN risk, and were stratified by cancer and regimen. For each subject, the first chemotherapy course, and each cycle and FN episode within the course, were identified. FN incidence proportions were estimated by the presence and number of risk factors and chronic comorbidities. Across the 17 tumor/regimen combinations considered (n=160,304 in total), 74% to 98% of patients had 1 or more risk factor for FN and 41% to 89% had 2 or more. Among patients with 1 or more risk factor, FN incidence ranged from 7.2% to 29.0% across regimens, and the relative risk of FN (vs those without risk factors) ranged from 1.1 (95% CI, 0.8-1.3) to 2.2 (95% CI, 1.5-3.0). FN incidence increased in a graded and monotonic fashion with the number of risk factors and comorbidities. In this retrospective evaluation of patients with cancer receiving chemotherapy regimens not classified as high-risk for FN in US clinical practice, most patients had 1 or more FN risk factor and many had 2 or more. FN incidence was found to be elevated in these patients, especially those with multiple risk factors.

Management of chemotherapy-induced neutropenia: measuring quality, cost, and value.

Treatment-associated neutropenia continues to represent the most common dose-limiting toxicity of cancer chemotherapy. It often leads to fever and infection, prompting hospitalization and occasionally resulting in serious morbidity, and even mortality, despite modern broad-spectrum antibiotic treatment and supportive care. Neutropenia and its complications may also lead to chemotherapy dose reductions, treatment delays, or early treatment termination, compromising disease control and the potential for cure. NCCN Clinical Practice Guidelines in Oncology recommend administration of primary prophylaxis with a myeloid growth factor in patients receiving regimens associated with a high risk for febrile neutropenia, and consideration of prophylaxis in patients receiving lower-risk regimens who have other risk factors that might place them at higher risk for febrile neutropenia. Although these agents have been shown to be effective and safe in numerous randomized controlled trials, they are expensive and contribute significantly to increasing health care costs. Regulatory agencies and guideline organizations do not currently address the issue of cost. However, with the relentless increase in health care use and current efforts to reform health care, it has become increasingly important to assess both the cost and the net benefit of interventions related to an episode of care in order to compare the overall value of therapeutic options. This article defines and discusses the intersection of quality, costs, and value in the context of prophylactic myeloid growth factor use in patients with cancer receiving myelosuppressive chemotherapy.

Incidence of Febrile Neutropenia Among Patients Receiving Chemotherapy Regimens Not Classified As High-Risk in Guidelines for Myeloid Growth Factor Use: Importance of “Risk Factor Stacking”

Background: Clinical practice guidelines recommend primary prophylactic colony-stimulating factor (CSF) when risk of febrile neutropenia (FN) is ≥20%. Evaluating FN risk among patients who receive regimens that are not documented as high risk in guidelines can be challenging, as some patients may be at a high risk based on a combination of the regimen and their risk factors.Methods: A retrospective cohort design and data from two US private healthcare claims repositories (2003-2012) were employed. The study population comprised cancer patients aged ≥18 years who initiated a course of chemotherapy with a regimen classified as “low” or “intermediate”, or that was unclassified, in terms of FN risk based on guidelines for CSF use. For each subject, the first qualifying chemotherapy course, and each cycle and FN episode within the course, was identified; use of CSF prophylaxis also was identified. FN was ascertained using diagnosis codes for neutropenia, fever, and/or infection; for FN requiring outpatient care only, receipt of intravenous antimicrobials also was required. FN incidence proportion was evaluated during the course within cohorts stratified by tumor type and regimen, for all patients in each cohort and by FN risk factor. Risk factors documented in guidelines and the published literature, and listed in the Table herein were evaluated during the 12-month pre-chemotherapy period. Unadjusted relative risks of FN for patients with versus without risk factors, and by the number of risk factors (i.e., “risk factor stacking”), were estimated. Only results for the five most frequently observed tumor/regimen combinations are reported herein.Results: Among patients with one of the five most frequently observed tumor/regimen combinations (n=84,252), 74-97% had ≥1 risk factor for FN and 42-88% had ≥2 (Table). Among patients with ≥1 risk factor, FN incidence ranged from 11-25% (relative risk vs. those without risk factors, 1.4-2.1), and increased in a graded and monotonic fashion with the number of risk factors present (Figure).Conclusion: In this retrospective evaluation of nearly 85,000 cancer patients receiving chemotherapy regimens not classified as high-risk for FN in US clinical practice, the large majority had at least one risk factor for FN and many had two or more. FN incidence was found to be markedly elevated in these patients, especially those with multiple risk factors (i.e., “risk factor stacking”). [Display omitted] [Display omitted] DisclosuresWeycker:Amgen: Research Funding. Li:Amgen: Employment, Equity Ownership. Barron:Amgen: Employment, Equity Ownership. Wu:Amgen: Research Funding. Morrow:Amgen: Employment, Equity Ownership. Xu:Amgen: Employment, Equity Ownership. Reiner:Amgen: Employment, Equity Ownership. Garcia:Amgen: Employment, Equity Ownership. Mhatre:Amgen: Employment. Lyman:Amgen: Research Funding.

Myeloid growth factor utilization in a commercial and Medicare population: Phase 1 of a quality improvement initiative.

242 Background: Some clinical practice guidelines encourage the judicial use of myeloid growth factors (MGFs) in the prevention of chemotherapy-induced febrile neutropenia (FN) because of efficacy and safety concerns. For example, the ASCO guidelines state that a dose reduction of myelosuppressive chemotherapy in patients with incurable disease rather than prescribing a MGF for secondary prophylaxis is a reasonable alternative. Because there is wide variation in MGF prescribing, New Century Health (NCH) conducted a quality improvement analysis of MGF requests in a commercial and Medicare population. The objectives are to: (1) describe the cohort demographics, (2) identify areas of improvement to promote cost-effective use, and (3) measure the economic impact from interventions. Methods: MGF authorization requests for oncology indications to NCH in 2013 were analyzed for cohort demographics: age, weight, tumor diagnosis, and treatment intention (e.g., metastatic/palliative, curative, etc.). Requests were analyzed for concurrent use with chemotherapy, approval status of the request (including reason for withdrawal), and cost saving associated with interventions. Results: There were 7,958 requests for a MGF; 81% were for pegfilgrastim and 19% for filgrastim. Average age of the cohort was 66 years, weight-based dosing (>70 kg) was appropriate in 43% of patients receiving 300 mcg and 72% of patients receiving 480 mcg. MGFs were most commonly requested in: breast (18%), lung (17%), lymphoma (14%), and gynecologic (8%) tumors. 40% of requests were for metastatic/recurrent disease and 38% for curative intent. 6,724 (84%) of requests were authorized based on established-use criteria. The main reason for not authorizing was lack of compendia support for both primary and secondary prophylaxis; this resulted in approximately $3.5 million in cost savings. Conclusions: There is opportunity to improve efficiency of MGFs use in this population through a dose rounding protocol and by promoting chemotherapy dose reductions, as advocated by the ASCO guidelines. Further analysis will assess the concordance of MGF use with guidelines, specifically in regard to chemotherapy regimens and their risk of FN.

The absolute lymphocyte/monocyte ratio recovery during ABVD treatment cycles is not significantly impacted by the use of myeloid growth factors and predicts clinical outcomes in classical Hodgkin lymphoma regardless of their use

The absolute lymphocyte/monocyte ratio recovery during ABVD treatment cycles is not significantly impacted by the use of myeloid growth factors and predicts clinical outcomes in classical Hodgkin lymphoma regardless of their use

Adverse Events During Intensive Induction Chemotherapy For Acute Myeloid Leukemia (AML) Or High-Grade Myelodysplastic Syndromes (MDS)

BackgroundIntensive chemotherapy for adults with newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) is associated with a considerable risk of morbidity and mortality, commonly due to infections and bleeding. Little information is available on pre-treatment risk factors that predispose to these complications. Here, we investigated the relationship between baseline peripheral blood counts and (a) subsequent adverse events and (b) duration of neutropenia following administration of induction chemotherapy at our institution over the last decade for newly diagnosed AML/MDS undergoing curative-intent induction chemotherapy. Patients and MethodsWe retrospectively analyzed 205 consecutive adults receiving 7 + 3-like treatment regimens. Daily blood counts were recorded from initiation of chemotherapy until the day of neutrophil recovery (defined as an absolute neutrophil count [ANC] greater than or equal to 500 cells/µL). Adverse events (fever, infection, bacteremia, transfer to the intensive care unit, and death) were recorded until day 35 or administration of additional chemotherapy, whichever came first. Cytogenetic risk was classified based on revised MRC/NCRI criteria. Associations between baseline patient characteristics and adverse events were assessed using Kaplan-Meier survival curves with a log-rank test (for two groups) or log-rank test for trend (for three or more groups); patients requiring salvage therapy for persistent disease were censored on the day such therapy was initiated. Cox proportional hazards models were used to estimate the hazard ratio (HR) for the associations between age, gender, disease type, cytogenetic risk and adverse outcomes in univariate and multivariate analyses. ResultsThe median age of our study cohort was 53 (range: 18 to 81) years. Sixty-six percent of the patients had de novo AML. Cytogenetic risk was favorable in 14%, intermediate in 60%, and adverse in 24%. Among all patients, the complete remission (CR) rate was 75%, while 2% died before response could be assessed (range: day 13 to 28) and 23% were refractory. When analyzed as a continuous variable, the baseline neutrophil count was statistically significantly associated with fever (HR=0.97 [95% confidence interval: 0.95-0.999] for each increase of 1000 cells/µL, P=0.04) and infection (HR=0.92 [0.87-0.98], P=0.01), but not bacteremia (HR=0.95 [0.89-1.01], P=0.10) or requirement for intensive care unit (ICU) care (HR=1.00 [0.93-1.07], P=0.99). For subsequent analyses, we dichotomized the study cohort based on pre-treatment ANC and compared patients with baseline ANC<500/µL (n=75) with those with ANC greater than or equal to 500/µL (n=130). As shown in Figure 1, baseline ANC<500/µL was associated with the development of fever (P=0.022), documented infection (P<0.001), bacteremia (P<0.001), and death (P=0.035) [Figure 1] but not requirement for ICU care (P=0.39). In patients who achieved CR with 1 course of therapy without myeloid growth factor support, baseline ANC<500/µL was associated with delayed neutrophil count recovery (P<0.0001). In addition to low baseline ANC, we also found that low baseline monocyte and lymphocyte counts were associated with increased risk of documented infection or bacteremia. After adjustment for age, gender, disease type, and cytogenetic risk, the risk of documented infection or bacteremia was 2.71 (1.78-4.12)-fold and 2.11 (1.26-3.55)-fold higher in patients with baseline ANC<500/µL. Having demonstrated that baseline ANC<500/µL was associated with both duration of neutropenia and the development of adverse events and death, we wondered whether this patient subset could be suitable for the targeted use of myeloid growth factors. To investigate this, we evaluated whether those with 0% bone marrow blasts at first post-treatment assessment were also more susceptible to adverse events after day 14. Indeed, this was the case for infection (P=0.0140) and bacteremia (P=0.0023). ConclusionOur studies identify pre-treatment ANC<500/µL as a risk factor for both infection-associated adverse events, including death, and longer duration of neutropenia. If validated, these results would provide the rationale for the risk-adapted testing of myeloid growth factor support in patients with AML/MDS with pre-treatment ANC< 500/µL when undergoing curative-intent induction chemotherapy. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

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.

A Case Report: Neutropenia Grade IV and Febrile Neutropenia in a Metastatic Breast Cancer Patient Treated With Palliative Chemotherapy Cyclophosphamide/Myocet

Febrile neutropenia is a major toxicity of myelosuppressive chemotherapy. It is a potentially fatal complication which leads to increase in morbidity, mortality and treatment costs. Myeloid growth factors (colony-stimulating factors - CSFs) can effectively reduce the incidence of severe neutropenia in patients treated with high-risk chemotherapy regimens in both curative and palliative therapy. We present a case of the 45-year-old metastatic breast cancer patient treated with palliative chemotherapy cyclophosphamide/Myocet who repeatedly presented with severe neutropenia, including febrile neutropenia after the second cycle of chemotherapy. Grade IV neutropenia was successfully managed with the combination of antibiotic and antimycotic drugs administered together with filgrastim. The second cycle of chemotherapy was complicated with a febrile neutropenia episode despite previous prophylactic use of pegfilgrastim. There was a complete restitution in white blood count after ten days of antibiotic and antimycotic therapy (without additional use of CSF). However, the chemotherapy had to be reduced by 25% since the third cycle and Myocet monotherapy was used since the fourth cycle. With the prophylactic use of five doses of filgrastim there was no adverse event of myelotoxicity in the fifth and sixth cycle. This case demonstrates the development of myelotoxicity in chemotherapy treated patient and the use of myeloid growth factors for the prevention and treatment of febrile neutropenia. A dose reduction was required despite the use of GSF.