Efficacy of delayed pegfilgrastim administration following consolidation therapy with high-dose cytarabine (HiDAC) in acute myeloid leukemia (AML) patients

Efficacy of delayed pegfilgrastim administration following consolidation therapy with high-dose cytarabine (HiDAC) in acute myeloid leukemia (AML) patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Efficacy of delayed pegfilgrastim administration following consolidation therapy with high-dose cytarabine (HiDAC) in acute myeloid leukemia (AML) patients Spencer K. Yingling, Joshua Francis, Kelsea Seago, Salah Ud Din Safi, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3293532/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Apr, 2024 Read the published version in Supportive Care in Cancer → Version 1 posted 7 You are reading this latest preprint version Abstract Purpose : To study the effects of delaying pegfilgrastim administration following high-dose cytarabine (HiDAC) consolidation in AML patients on time to neutrophil count recovery, infectious complications, and survival. Methods : Single-center retrospective chart review of 55 patients receiving pegfilgrastim as early administration (within 72 hours) or delayed administration (after 72 hours) of HiDAC. Results : The difference in neutrophil recovery time was similar between the early and delayed groups (18 days versus 19 days, P<0.28). Infections were seen in four patients in the early administration group following chemotherapy compared to none in the delayed group (p=0.04). Febrile neutropenia rates were also decreased in the delayed administration group (23.1% versus 10.3%, p=0.28) as well as longer median survival (16 months versus 19 months, p=0.69) and overall survival (21 months versus 31 months, p=0.47). Conclusion : A difference in time to neutrophil recovery was not observed between the early and delayed administration groups yet decreased infectious complications may support the delayed of administration of pegfilgrastim in these patients. pegfilgrastim growth factors white blood cell growth factors high-dose cytarabine HiDAC timing Figures Figure 1 INTRODUCTION Acute myeloid leukemia (AML) is an aggressive malignancy requiring intensive chemotherapy to achieve durable responses. The cornerstone treatment consists of induction chemotherapy, including the combination of cytarabine and an anthracycline chemotherapy agent [ 1 , 2 ]. If the patient achieves remission, single agent high-dose cytarabine (HiDAC) is commonly utilized as a consolidation approach in some patient populations. This regimen results in severe and prolonged neutropenia, placing the patient at high risk for infectious complications [ 1 – 3 ]. Pegfilgrastim is a granulocyte colony-stimulating factor injectable medication commonly utilized to prevent neutropenia and decrease the duration of neutropenia in patients receiving intensive chemotherapy [ 4 ]. It is currently available as both a syringe or vial for immediate administration and as an on-body injector, which delivers the medication approximately 27 hours after it is applied [ 5 ]. Filgrastim is primarily eliminated renally, with a secondary mechanism of clearance being by white blood cells (WBC). The pegylated formulation of filgrastim prevents the renal clearance and primarily relies on the WBC for elimination. Therefore, a single dose of pegfilgrastim after chemotherapy will maintain therapeutic concentrations until it completes the task of neutrophil recovery, and then will self-eliminate [ 6 ]. As discussed previously, the role of pegfilgrastim is two-fold: to prevent neutropenia from occurring and to also shorten the duration of neutropenia that does occur. For treatment of patients will AML, the chemotherapy regimens are extremely myelosuppressive, and pegfilgrastim is unlikely to prevent neutropenia occurrence [ 7 ]. Therefore, we are focusing on decreasing the duration of neutropenia. Also, considering the expected median time to neutrophil recovery (> 500 cells/ µL) is 15 to 23 days, early administration of pegfilgrastim may not be optimal, as it would be in most other chemotherapy regimens [ 8 – 11 ]. We hypothesize that delayed administration may decrease some of the early clearance of pegfilgrastim by neutrophils still remaining after chemotherapy and will increase exposure later in the neutropenia course to facilitate neutrophil recovery. Filgrastim exerts a dose-dependent effect, so higher exposure could result in additional efficacy [ 4 , 12 ]. One study evaluating a similar concept using delayed administration of pegfilgrastim has been evaluated by Zwick et al. in patients with non-Hodgkin’s lymphoma. This study looks at two groups both receiving pegfilgrastim following cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) on either day 2 or day 4 of CHOP therapy. A significant reduction in the severity of leukocytopenias was observed when pegfilgrastim was administered on day 4 compared with earlier administration [ 6 ]. No current studies to our knowledge have evaluated delayed pegfilgrastim administration in other settings, including AML. The aim of the current study was to determine if delayed administration of pegfilgrastim following HiDAC for consolidation therapy in AML patients shortens duration of neutropenia (defined as absolute neutrophil count recovery to greater than 500 cells/µL). METHODS Patients The study was approved by the Institutional Review Board at WVU Medicine. AML patients aged 18 years and older who received HiDAC consolidation therapy and subsequent pegfilgrastim were included for analysis in this study. In order to remove variance in neutrophil recovery that occurs after multiple cycles of chemotherapy, only the first cycle of HiDAC for consolidation was used for study inclusion. Only patients receiving the traditional HiDAC regimen (1 to 3gm/m 2 every 12 hours for 2 doses on days 1, 3, and 5) were included in the analysis [ 3 ]. Patients remained eligible if concomitant fms-like tyrosine kinase 3 (FLT3) agents were administered. Patients were excluded if not in a complete remission at the initiation of HiDAC or if the patient received filgrastim in addition to pegfilgrastim. Furthermore, in order to best determine the date of count recovery, patients must have had documentation of at least twice weekly labs including neutrophil counts to be included in the analysis. Study Design Patients were stratified into an early (within 72 hours of last dose of cytarabine) or delayed (> 72 hours) pegfilgrastim administration group for analysis. For those receiving the on-body injector formulation, the date of pegfilgrastim was calculated at 27 hours (one day) following charted administration date. The primary objective of this study was to determine if administration time of pegfilgrastim relative to completion of HiDAC consolidation therapy affected the time to neutrophil recovery. Secondary objectives included the incidence of infection, number of febrile neutropenia events, infection-related mortality, progression-free survival (PFS) and overall survival (OS) rates compared between both administration groups. Statistical Analysis Descriptive statistical analyses were performed to summarize the baseline data and to describe the clinical outcomes of including summary tables, proportions, median, means, and standard deviations. Wilcoxon rank test and Fisher exact test were used in the data analysis on continuous variables and categorical variables, respectively. Kaplan-Meier method and log-rank test were used to assess the time-to-event outcomes including overall survival and progression-free survival. Analyses were considered statistically significant if p < 0.05. All statistical analyses were performed using statistical software R software (R Foundation for Statistical Computing, Vienna, Austria; URL http://www.R-project.org/ ). RESULTS From April 2009 to October 2018, 57 patients were eligible for inclusion into this study. Patients were assigned to either the early or delayed administration group based on the date of pegfilgrastim administration documented. Patient characteristics are described in Table I. There were no significant differences between the two groups. All patients received antibacterial (quinolone), antiviral (acyclovir), and antifungal (triazole) prophylaxis starting with chemotherapy and continued throughout the duration of neutropenia as standard of care at our center in both groups. Table II displays the full details of the study outcomes. The difference in neutrophil recovery time between the early and delayed group showed comparable times to recovery (18 days versus 19 days, p = 0.28). There were more infections seen in the early administration group (14.8% versus 0%, p = 0.04). The median PFS and OS were similar between the two groups. Kaplan-Meier analysis of PFS and OS are shown in Figures IA and IB. DISCUSSION Supporting evidence to guide the optimal administration time of pegfilgrastim following HiDAC consolidation therapy for AML patients is unavailable. Most administration practice is based on extrapolation of pegfilgrastim in other oncology chemotherapy treatment regimens and protocols, which may not be accurate. Based on the pharmacokinetics, mechanism of action, and elimination profile of pegfilgrastim, it is hypothesized that delaying the administration following an extremely myelosuppressive chemotherapy regimen, such as HiDAC, may be reasonable and could improve neutropenia complications. Our study found similar durations of neutropenia with delayed administration, but we found a significant decrease in infections within the delayed administration group. Although neutrophil recovery was the primary endpoint in our study, it is probably not the most accurate measurement of effect due to limitations in accuracy of this endpoint. A major limitation in assessing neutrophil recovery in this study was that many of these patients were outpatient at the time of blood count recovery. Our standard outpatient laboratory monitoring is twice weekly making it difficult to clearly capture the precise day of neutrophil recovery. Therefore, we believe the secondary endpoint, infectious complications, is less affected by these limitations and may be a better predictor of benefit. Likewise, it is also difficult to assess impact on PFS and OS given the smaller sample size and many confounding factors for these endpoints. We arbitrarily picked the 72-hour time frame to define delayed pegfilgrastim administration. We felt this was an adequate amount of time to see reductions in peripheral blood neutrophil counts and to allow for less pegfilgrastim clearance in the early phase. The ideal definition for delayed administration needs further evaluated. Delayed administration also serves to benefit patient convenience in many cases. HiDAC chemotherapy is commonly administered in the inpatient setting, with return visits after discharge for pegfilgrastim administrations. Next-day visits are typically unnecessary, other than to receive the pegfilgrastim administration, and delaying pegfligrastim to a regularly scheduled appointment for laboratory monitoring decreases travel and hospital visits for the patient. This can have significant implications for patient satisfaction, quality of life, and healthcare resource utilization. CONCLUSION Delayed administration of pegfilgrastim in HiDAC patients appears safe and reasonable to improve patient convenience. There was no change in neutrophil recovery time compared to early administration, but it did have a significant reduction in infectious complications and may have clinical benefits in these patients. Statements and Declarations Conflicts of Interest: No relevant conflicts of interest to disclose by any authors. All authors have made substantial contributions to the conception/design of the project, data analysis and interpretation, and manuscript draft and review. All others consent to publication in Supportive Care in Cancer. Funding: The authors did not receive support from any organization for the submitted work. Competing interests: The authors have no competing interests to declare that are relevant to the content of this article. Author contributions: All authors have made substantial contributions to the conception/design of the project, data analysis and interpretation, and manuscript draft and review. Ethics approval: This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the Investigational Review Board at WVU Hospitals. Consent to participate: Not applicable – research was retrospective in nature. Consent for publication: All authors grant final approval of the manuscript draft for publication. References Dombret H, Gardin C. An update of current treatments for adult acute myeloid leukemia. Blood. 2016;127(1):53–61. https://doi:10.1182/blood-2015-08-604520 Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345–1377. https://doi:10.1182/blood.2022016867 Bloomfield CD, Lawrence D, Byrd JC, et al. Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype. Cancer Res. 1998;58(18):4173–9. PMID: 9751631. Petros, WP. Pharmacokinetics and administration of colony-stimulating factors. Pharmacotherapy. 1992;12: 32S-38S. https://doi.org/10.1002/j.1875-9114.1992.tb02680 Neulasta® OnPro® [package insert]. Thousand Oaks, CA: Amgen Inc; 2018. Zwick C, Hartmann F, Zeynalova S, et al. Randomized comparison of pegfilgrastim day 4 versus day 2 for the prevention of chemotherapy-induced leukocytopenia. Annals of Oncology. 2011;22(8):1872–1877. https://doi.org/10.1093/annonc/mdq674 Ottmann OG, Bug G, Krauter J. Current status of growth factors in the treatment of acute myeloid and lymphoblastic leukemia. Semin Hematol. 2007;44(3):183–192. https://doi:10.1053/j.seminhematol.2007.04.007 Böhm A, Piribauer M, Wimazal F, et al. High dose intermittent ARA-C (HiDAC) for consolidation of patients with de novo AML: A single center experience. Leuk Res. 2005;29(6):609–615. https://doi:10.1016/j.leukres.2004.10.009 Jaramillo S, Benner A, Krauter J, et al. Condensed versus standard schedule of high-dose cytarabine consolidation therapy with pegfilgrastim growth factor support in acute myeloid leukemia. Blood Cancer J. 2017;7(5):e564. https://doi:10.1038/bcj.2017.45 Kam G, Yiu R, Loh Y, et al. Impact of pegylated filgrastim in comparison to filgrastim for patients with acute myeloid leukaemia (AML) on high-dose cytarabine (HIDAC) consolidation chemotherapy. Support Care Cancer. 2015;23(3):643–649. https://doi:10.1007/s00520-014-2417-7 Sierra J, Szer J, Kassis J, et al. A single dose of pegfilgrastim compared with daily filgrastim for supporting neutrophil recovery in patients treated for low-to-intermediate risk acute myeloid leukemia: Results from a randomized, double-blind, phase 2 trial. BMC Cancer. 2008;8:195. https://doi:10.1186/1471-2407-8-195 van Der Auwera P, Platzer E, Xu ZX, et al. Pharmacodynamics and pharmacokinetics of single doses of subcutaneous pegylated human G-CSF mutant (ro 25-8315) in healthy volunteers: Comparison with single and multiple daily doses of filgrastim. Am J Hematol. 2001;66(4):245–251. https://doi:10.1002/ajh.1052 Tables Table I. Baseline patient characteristics Characteristic Early administration (n=26) Delayed administration (n=29) P-value Age , median (range) 45 (24-65) 53 (23-69) 0.27 Male , n (%) 11 (42.3) 14 (48.3) 0.79 BMI , median (range) 27.8 (20.4-61.8) 25.8 (15.8-44.3) 0.24 Baseline bilirubin (mg/dL) , median (range) 0.5 (0.2-1.1) 0.5 (0.3-1.1) 0.65 Baseline serum creatinine (mg/dL) , median (range) 0.75 (0.46-2.48) 0.75 (0.58-1.50) 0.61 Treatment-related AML , n (%) 1 (3.8) 0 (0) 0.47 Underlying MDS/MPD , n (%) 5 (19.2) 2 (6.9) 0.24 Prior allo-HSCT 1 (3.8) 1 (3.4) 1.00 ELN risk classification , n (%) Favorable 7 (26.9) 6 (20.7) 0.87 Intermediate 14 (53.8) 13 (44.8) Adverse 5 (19.2) 7 (24.1) ECOG performance status , n (%) 0 3 (11.5) 8 (27.6) 0.85 1 14 (53.8) 13 (44.8) 2 4 (15.4) 3 (10.3) 3 1 (3.8) 1 (3.4) Unknown 4 (15.4) 4 (13.8) Prior therapies , median (range)† 1 (1-3) 1 (1-2) 0.56 Days from last dose cytarabine to pegfilgrastim administration , median (range) 2 (1-2) 4 (3-9) <0.001 Cytarabine dose , n (%) 1 g/m 2 7 (26.9) 3 (10.3) 0.33 1.5 g/m 2 6 (23.1) 9 (31.0) 2 g/m 2 0 (0) 1 (3.4) 3 g/m 2 13 (50.0) 16 (55.2) Concomitant FLT3 agent , n (%) 2 (7.7) 2 (6.9) 1.00 †All patients received cytarabine + anthracycline induction Abbreviations: BMI, body mass index; AML, acute myeloid leukemia; MDS/MPD, myelodysplastic syndrome/myeloproliferative disorder; Allo-HSCT, allogenic hematopoietic stem cell transplant; ELN, European LeukemiaNet; ECOG, Eastern Cooperative Oncology Group; HiDAC, high-dose cytarabine; FLT3, FMS-like tyrosine kinase 3 Table II. Study endpoints Early administration (n=26) Delayed administration (n=29) P-value Time to neutrophil recovery in days , median (range) 18 (15-36) 19 (17-39) 0.28 Infections , n (%) 4 (14.8) 0 (0) 0.04 Pneumonia 1 (3.8) 0 (0) 0.47 Bacteremia 2 (7.7) 0 (0) 0.22 Urinary Tract Infection 1 (3.8) 0 (0) 0.47 Febrile neutropenia 6 (23.1) 3 (10.3) 0.28 Infection-related mortality 0 (0) 0 (0) 1.00 Progression-free survival in months , median (range) 16 (3-105+) 19 (0-108+) 0.69 Overall survival in months , median (range) 21 (3+-105+) 31 (7-108+) 0.47 +Indicates ongoing survival data at the time of study inclusion Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 09 Apr, 2024 Read the published version in Supportive Care in Cancer → Version 1 posted Editorial decision: Revision requested 03 Dec, 2023 Reviews received at journal 07 Nov, 2023 Reviewers agreed at journal 30 Oct, 2023 Reviewers invited by journal 29 Oct, 2023 Editor assigned by journal 21 Sep, 2023 Submission checks completed at journal 25 Aug, 2023 First submitted to journal 24 Aug, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3293532","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":228838861,"identity":"e05798a2-90cb-4ec1-9811-57bb8d3eb6be","order_by":0,"name":"Spencer K. 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Hash marks on curves represent censored data. The median progression-free survival was 16 months in the early administration group and 19 months in the delayed administration group.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3293532/v1/d6059d236c8fc0b73ea74026.png"},{"id":54712659,"identity":"43a2041a-ba5b-4ddf-b4ad-a4ac5379def2","added_by":"auto","created_at":"2024-04-15 15:11:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":482862,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3293532/v1/d9b07491-c154-47b8-9b7f-b736a2b4f82c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy of delayed pegfilgrastim administration following consolidation therapy with high-dose cytarabine (HiDAC) in acute myeloid leukemia (AML) patients","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAcute myeloid leukemia (AML) is an aggressive malignancy requiring intensive chemotherapy to achieve durable responses. The cornerstone treatment consists of induction chemotherapy, including the combination of cytarabine and an anthracycline chemotherapy agent [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. If the patient achieves remission, single agent high-dose cytarabine (HiDAC) is commonly utilized as a consolidation approach in some patient populations. This regimen results in severe and prolonged neutropenia, placing the patient at high risk for infectious complications [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePegfilgrastim is a granulocyte colony-stimulating factor injectable medication commonly utilized to prevent neutropenia and decrease the duration of neutropenia in patients receiving intensive chemotherapy [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. It is currently available as both a syringe or vial for immediate administration and as an on-body injector, which delivers the medication approximately 27 hours after it is applied [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Filgrastim is primarily eliminated renally, with a secondary mechanism of clearance being by white blood cells (WBC). The pegylated formulation of filgrastim prevents the renal clearance and primarily relies on the WBC for elimination. Therefore, a single dose of pegfilgrastim after chemotherapy will maintain therapeutic concentrations until it completes the task of neutrophil recovery, and then will self-eliminate [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs discussed previously, the role of pegfilgrastim is two-fold: to prevent neutropenia from occurring and to also shorten the duration of neutropenia that does occur. For treatment of patients will AML, the chemotherapy regimens are extremely myelosuppressive, and pegfilgrastim is unlikely to prevent neutropenia occurrence [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Therefore, we are focusing on decreasing the duration of neutropenia. Also, considering the expected median time to neutrophil recovery (\u0026gt;\u0026thinsp;500 cells/ \u0026micro;L) is 15 to 23 days, early administration of pegfilgrastim may not be optimal, as it would be in most other chemotherapy regimens [\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. We hypothesize that delayed administration may decrease some of the early clearance of pegfilgrastim by neutrophils still remaining after chemotherapy and will increase exposure later in the neutropenia course to facilitate neutrophil recovery. Filgrastim exerts a dose-dependent effect, so higher exposure could result in additional efficacy [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOne study evaluating a similar concept using delayed administration of pegfilgrastim has been evaluated by Zwick et al. in patients with non-Hodgkin\u0026rsquo;s lymphoma. This study looks at two groups both receiving pegfilgrastim following cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) on either day 2 or day 4 of CHOP therapy. A significant reduction in the severity of leukocytopenias was observed when pegfilgrastim was administered on day 4 compared with earlier administration [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. No current studies to our knowledge have evaluated delayed pegfilgrastim administration in other settings, including AML.\u003c/p\u003e \u003cp\u003eThe aim of the current study was to determine if delayed administration of pegfilgrastim following HiDAC for consolidation therapy in AML patients shortens duration of neutropenia (defined as absolute neutrophil count recovery to greater than 500 cells/\u0026micro;L).\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003e The study was approved by the Institutional Review Board at WVU Medicine. AML patients aged 18 years and older who received HiDAC consolidation therapy and subsequent pegfilgrastim were included for analysis in this study. In order to remove variance in neutrophil recovery that occurs after multiple cycles of chemotherapy, only the first cycle of HiDAC for consolidation was used for study inclusion. Only patients receiving the traditional HiDAC regimen (1 to 3gm/m\u003csup\u003e2\u003c/sup\u003e every 12 hours for 2 doses on days 1, 3, and 5) were included in the analysis [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Patients remained eligible if concomitant fms-like tyrosine kinase 3 (FLT3) agents were administered. Patients were excluded if not in a complete remission at the initiation of HiDAC or if the patient received filgrastim in addition to pegfilgrastim. Furthermore, in order to best determine the date of count recovery, patients must have had documentation of at least twice weekly labs including neutrophil counts to be included in the analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003ePatients were stratified into an early (within 72 hours of last dose of cytarabine) or delayed (\u0026gt;\u0026thinsp;72 hours) pegfilgrastim administration group for analysis. For those receiving the on-body injector formulation, the date of pegfilgrastim was calculated at 27 hours (one day) following charted administration date. The primary objective of this study was to determine if administration time of pegfilgrastim relative to completion of HiDAC consolidation therapy affected the time to neutrophil recovery. Secondary objectives included the incidence of infection, number of febrile neutropenia events, infection-related mortality, progression-free survival (PFS) and overall survival (OS) rates compared between both administration groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eDescriptive statistical analyses were performed to summarize the baseline data and to describe the clinical outcomes of including summary tables, proportions, median, means, and standard deviations. Wilcoxon rank test and Fisher exact test were used in the data analysis on continuous variables and categorical variables, respectively. Kaplan-Meier method and log-rank test were used to assess the time-to-event outcomes including overall survival and progression-free survival. Analyses were considered statistically significant if p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. All statistical analyses were performed using statistical software R software (R Foundation for Statistical Computing, Vienna, Austria; URL \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.R-project.org/\u003c/span\u003e\u003cspan address=\"http://www.R-project.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eFrom April 2009 to October 2018, 57 patients were eligible for inclusion into this study. Patients were assigned to either the early or delayed administration group based on the date of pegfilgrastim administration documented. Patient characteristics are described in Table I. There were no significant differences between the two groups. All patients received antibacterial (quinolone), antiviral (acyclovir), and antifungal (triazole) prophylaxis starting with chemotherapy and continued throughout the duration of neutropenia as standard of care at our center in both groups. Table II displays the full details of the study outcomes. The difference in neutrophil recovery time between the early and delayed group showed comparable times to recovery (18 days versus 19 days, p\u0026thinsp;=\u0026thinsp;0.28). There were more infections seen in the early administration group (14.8% versus 0%, p\u0026thinsp;=\u0026thinsp;0.04). The median PFS and OS were similar between the two groups. Kaplan-Meier analysis of PFS and OS are shown in Figures IA and IB.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eSupporting evidence to guide the optimal administration time of pegfilgrastim following HiDAC consolidation therapy for AML patients is unavailable. Most administration practice is based on extrapolation of pegfilgrastim in other oncology chemotherapy treatment regimens and protocols, which may not be accurate. Based on the pharmacokinetics, mechanism of action, and elimination profile of pegfilgrastim, it is hypothesized that delaying the administration following an extremely myelosuppressive chemotherapy regimen, such as HiDAC, may be reasonable and could improve neutropenia complications. Our study found similar durations of neutropenia with delayed administration, but we found a significant decrease in infections within the delayed administration group.\u003c/p\u003e \u003cp\u003eAlthough neutrophil recovery was the primary endpoint in our study, it is probably not the most accurate measurement of effect due to limitations in accuracy of this endpoint. A major limitation in assessing neutrophil recovery in this study was that many of these patients were outpatient at the time of blood count recovery. Our standard outpatient laboratory monitoring is twice weekly making it difficult to clearly capture the precise day of neutrophil recovery. Therefore, we believe the secondary endpoint, infectious complications, is less affected by these limitations and may be a better predictor of benefit. Likewise, it is also difficult to assess impact on PFS and OS given the smaller sample size and many confounding factors for these endpoints.\u003c/p\u003e \u003cp\u003eWe arbitrarily picked the 72-hour time frame to define delayed pegfilgrastim administration. We felt this was an adequate amount of time to see reductions in peripheral blood neutrophil counts and to allow for less pegfilgrastim clearance in the early phase. The ideal definition for delayed administration needs further evaluated. Delayed administration also serves to benefit patient convenience in many cases. HiDAC chemotherapy is commonly administered in the inpatient setting, with return visits after discharge for pegfilgrastim administrations. Next-day visits are typically unnecessary, other than to receive the pegfilgrastim administration, and delaying pegfligrastim to a regularly scheduled appointment for laboratory monitoring decreases travel and hospital visits for the patient. This can have significant implications for patient satisfaction, quality of life, and healthcare resource utilization.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eDelayed administration of pegfilgrastim in HiDAC patients appears safe and reasonable to improve patient convenience. There was no change in neutrophil recovery time compared to early administration, but it did have a significant reduction in infectious complications and may have clinical benefits in these patients.\u003c/p\u003e"},{"header":"Statements and Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u0026nbsp;\u003c/strong\u003eNo relevant conflicts of interest to disclose by any authors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAll authors have made substantial contributions to the conception/design of the project, data analysis and interpretation, and manuscript draft and review. All others consent to publication in \u003cem\u003eSupportive Care in Cancer.\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e The authors did not receive support from any organization for the submitted work.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors have no competing interests to declare that are relevant to the content of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e All authors have made substantial contributions to the conception/design of the project, data analysis and interpretation, and manuscript draft and review.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the Investigational Review Board at WVU Hospitals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e Not applicable \u0026ndash; research was retrospective in nature.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e All authors grant final approval of the manuscript draft for publication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDombret H, Gardin C. An update of current treatments for adult acute myeloid leukemia. Blood. 2016;127(1):53\u0026ndash;61. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi:10.1182/blood-2015-08-604520\u003c/span\u003e\u003cspan address=\"https://doi:10.1182/blood-2015-08-604520\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eD\u0026ouml;hner H, Wei AH, Appelbaum FR, et al. 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Am J Hematol. 2001;66(4):245\u0026ndash;251. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi:10.1002/ajh.1052\u003c/span\u003e\u003cspan address=\"https://doi:10.1002/ajh.1052\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable I.\u003c/strong\u003e Baseline patient characteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEarly\u003c/strong\u003e \u003cstrong\u003eadministration\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(n=26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDelayed\u003c/strong\u003e \u003cstrong\u003eadministration\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(n=29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e45 (24-65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e53 (23-69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" valign=\"top\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e11 (42.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e14 (48.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" valign=\"top\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI\u003c/strong\u003e, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e27.8 (20.4-61.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e25.8 (15.8-44.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" valign=\"top\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline bilirubin (mg/dL)\u003c/strong\u003e, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e0.5 (0.2-1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e0.5 (0.3-1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" valign=\"top\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline serum creatinine (mg/dL)\u003c/strong\u003e, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e0.75 (0.46-2.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e0.75 (0.58-1.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" valign=\"top\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment-related AML\u003c/strong\u003e, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" valign=\"top\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnderlying MDS/MPD\u003c/strong\u003e, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e5 (19.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e2 (6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" valign=\"top\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrior allo-HSCT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" valign=\"top\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eELN risk classification\u003c/strong\u003e, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003eFavorable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e7 (26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e6 (20.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" rowspan=\"3\"\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.107142857142854%\" valign=\"top\"\u003e\n \u003cp\u003eIntermediate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.214285714285715%\" valign=\"top\"\u003e\n \u003cp\u003e14 (53.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.678571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e13 (44.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.107142857142854%\" valign=\"top\"\u003e\n \u003cp\u003eAdverse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.214285714285715%\" valign=\"top\"\u003e\n \u003cp\u003e5 (19.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.678571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e7 (24.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eECOG performance status\u003c/strong\u003e, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e3 (11.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e8 (27.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" rowspan=\"5\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.107142857142854%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.214285714285715%\" valign=\"top\"\u003e\n \u003cp\u003e14 (53.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.678571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e13 (44.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.107142857142854%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.214285714285715%\" valign=\"top\"\u003e\n \u003cp\u003e4 (15.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.678571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e3 (10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.107142857142854%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.214285714285715%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.678571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.107142857142854%\" valign=\"top\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.214285714285715%\" valign=\"top\"\u003e\n \u003cp\u003e4 (15.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.678571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e4 (13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrior therapies\u003c/strong\u003e, median (range)\u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" valign=\"top\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDays from last dose cytarabine to pegfilgrastim\u003c/strong\u003e \u003cstrong\u003eadministration\u003c/strong\u003e, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e2 (1-2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e4 (3-9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCytarabine dose\u003c/strong\u003e, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e1 g/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e7 (26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e3 (10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" rowspan=\"4\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.107142857142854%\" valign=\"top\"\u003e\n \u003cp\u003e1.5 g/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.214285714285715%\" valign=\"top\"\u003e\n \u003cp\u003e6 (23.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.678571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e9 (31.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.107142857142854%\" valign=\"top\"\u003e\n \u003cp\u003e2 g/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.214285714285715%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.678571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.107142857142854%\" valign=\"top\"\u003e\n \u003cp\u003e3 g/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.214285714285715%\" valign=\"top\"\u003e\n \u003cp\u003e13 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.678571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e16 (55.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.65493910690122%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eConcomitant FLT3 agent\u003c/strong\u003e, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.10960757780785%\" valign=\"top\"\u003e\n \u003cp\u003e2 (7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.16914749661705%\" valign=\"top\"\u003e\n \u003cp\u003e2 (6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.066305818673884%\" valign=\"top\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u0026dagger;All patients received cytarabine + anthracycline induction\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eAbbreviations: BMI, body mass index;\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eAML, acute myeloid leukemia; MDS/MPD, myelodysplastic syndrome/myeloproliferative disorder; Allo-HSCT, allogenic hematopoietic stem cell transplant; ELN, European LeukemiaNet; ECOG, Eastern Cooperative Oncology Group; HiDAC, high-dose cytarabine; FLT3, FMS-like tyrosine kinase 3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable II.\u003c/strong\u003e \u003cstrong\u003eStudy endpoints\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.1358024691358%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.864197530864196%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEarly\u003c/strong\u003e \u003cstrong\u003eadministration\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(n=26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDelayed\u003c/strong\u003e \u003cstrong\u003eadministration\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(n=29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.1358024691358%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime to neutrophil recovery in days\u003c/strong\u003e, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.864197530864196%\" valign=\"top\"\u003e\n \u003cp\u003e18 (15-36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e19 (17-39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.1358024691358%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eInfections\u003c/strong\u003e, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.864197530864196%\" valign=\"top\"\u003e\n \u003cp\u003e4 (14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.1358024691358%\" valign=\"top\"\u003e\n \u003cp\u003ePneumonia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.864197530864196%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.1358024691358%\" valign=\"top\"\u003e\n \u003cp\u003eBacteremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.864197530864196%\" valign=\"top\"\u003e\n \u003cp\u003e2 (7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.1358024691358%\" valign=\"top\"\u003e\n \u003cp\u003eUrinary Tract Infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.864197530864196%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.1358024691358%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFebrile neutropenia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.864197530864196%\" valign=\"top\"\u003e\n \u003cp\u003e6 (23.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e3 (10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.1358024691358%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eInfection-related mortality\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.864197530864196%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.1358024691358%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eProgression-free survival in months\u003c/strong\u003e, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.864197530864196%\" valign=\"top\"\u003e\n \u003cp\u003e16 (3-105+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e19 (0-108+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.1358024691358%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall survival in months\u003c/strong\u003e, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.864197530864196%\" valign=\"top\"\u003e\n \u003cp\u003e21 (3+-105+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e31 (7-108+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0%\" valign=\"top\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e+Indicates ongoing survival data at the time of study inclusion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"pegfilgrastim, growth factors, white blood cell growth factors, high-dose cytarabine, HiDAC, timing","lastPublishedDoi":"10.21203/rs.3.rs-3293532/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3293532/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cu\u003ePurpose\u003c/u\u003e: To study the effects of delaying pegfilgrastim administration following high-dose cytarabine (HiDAC) consolidation in AML patients on time to neutrophil count recovery, infectious complications, and survival.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eMethods\u003c/u\u003e: Single-center retrospective chart review of 55 patients receiving pegfilgrastim as early administration (within 72 hours) or delayed administration (after 72 hours) of HiDAC.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eResults\u003c/u\u003e: The difference in neutrophil recovery time was similar between the early and delayed groups (18 days versus 19 days, P\u0026lt;0.28). Infections were seen in four patients in the early administration group following chemotherapy compared to none in the delayed group (p=0.04). Febrile neutropenia rates were also decreased in the delayed administration group (23.1% versus 10.3%, p=0.28) as well as longer median survival (16 months versus 19 months, p=0.69) and overall survival (21 months versus 31 months, p=0.47).\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConclusion\u003c/u\u003e: A difference in time to neutrophil recovery was not observed between the early and delayed administration groups yet decreased infectious complications may support the delayed of administration of pegfilgrastim in these patients.\u003c/p\u003e","manuscriptTitle":"Efficacy of delayed pegfilgrastim administration following consolidation therapy with high-dose cytarabine (HiDAC) in acute myeloid leukemia (AML) patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-08-31 14:17:51","doi":"10.21203/rs.3.rs-3293532/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2023-12-03T20:08:55+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-11-07T18:56:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"30a0ad38-daf5-4df7-8624-a85dcee9272a","date":"2023-10-30T16:42:59+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-10-29T20:57:10+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-09-21T14:00:12+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-08-25T09:41:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"Supportive Care in Cancer","date":"2023-08-24T18:04:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"1f2c7e12-c335-4ad4-a765-0dedf0f44fd7","owner":[],"postedDate":"August 31st, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-04-15T15:04:03+00:00","versionOfRecord":{"articleIdentity":"rs-3293532","link":"https://doi.org/10.1007/s00520-024-08480-9","journal":{"identity":"supportive-care-in-cancer","isVorOnly":false,"title":"Supportive Care in Cancer"},"publishedOn":"2024-04-09 15:00:49","publishedOnDateReadable":"April 9th, 2024"},"versionCreatedAt":"2023-08-31 14:17:51","video":"","vorDoi":"10.1007/s00520-024-08480-9","vorDoiUrl":"https://doi.org/10.1007/s00520-024-08480-9","workflowStages":[]},"version":"v1","identity":"rs-3293532","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3293532","identity":"rs-3293532","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}