Growth Factor Colony Stimulating Research Articles

Feasible Influence of G-CSF on Clinical Pregnancy Outcome in Oocyte Donation Cycles for Patients with Recurrent Implantation Failure.

Background and Objectives: The aim of our single-center cohort study was the determination of the influence of the intrauterine lavage of granulocyte colony-stimulating growth factor (G-CSF) on clinical pregnancy rate in patients with a history of implantation failure older than 40 years. Materials and Methods: The study was conducted in Ferticare Prague SE between May 2018 and June 2020. Overall, 115 patients were distributed into two arms, with 48 subjects in the experimental and 67 in the control arm. All women have had a previous history of unsuccessful history of infertility treatment with their own genetic material and at least one ineffective cycle with the donated oocytes. The experimental arm underwent the intrauterine lavage of 0.5 mL of pure G-CSF from 120 to 48 h prior to embryo transfer. Results: The clinical pregnancy rate was 63.3% in the experimental arm and 47.8% in the control arm (p = 0.097 for Pearsonߣs χ2, and p = 0.133 for Fisher's exact test). However, the mean endometrial thickness on the day of embryo transfer did not appear to be statistically different (p = 0.139). Only the difference in endometrium thickness growth was statistically significant (p = 0.023). The increase in pregnancy rate is still encouraging for the future, even if it is not significant. Conclusion: Our study suggests the trend of increased pregnancy rate after the intrauterine G-CSF lavage in the interval of 120-48 h prior to embryo transfer.

The role of granulocyte-macrophage colony-stimulating growth factor in inflammatory bowel diseases

Inflammatory bowel diseases, which include ulcerative colitis and Crohn's disease, are chronic immune-inflammatory diseases of the intestine that are increasing in prevalence and incidence worldwide. They are progressive, with the need for lifelong therapy, a high risk of surgical interventions and a decrease in the quality of life of patients. The results of clinical and population studies indicate that the possibilities of modern therapy for inflammatory bowel diseases have reached their maximum. Its effectiveness in achieving complete clinical and endoscopic remission, despite the use of genetically engineered biological drugs, is estimated at 35-40%, which is obviously insufficient. A possible solution to this problem could be the inclusion of granulocyte-macrophage colony-stimulating factors in treatment regimens for inflammatory bowel diseases in combination with glucocorticosteroids, cytostatics and biological therapy drugs. A review of a number of experimental and clinical studies that confirmed the clinical effectiveness of macrophage growth factors is the subject of this article.

Drug-induced pneumonitis risk in diffuse large B-cell/follicular lymphoma patients treated with R-CHOP-like regimen is associated with the use of granulocyte colony-stimulating growth factors.

Rituximab-based combinations are the standard of care in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Despite being on market for over 20 years, some of the adverse effects associated with the use of rituximab are not well known. Drug-induced interstitial pneumonitis (DIP) is a potentially fatal complication of the treatment. Granulocyte colony-stimulating factors (G-CSF) are supportive agents commonly used to prevent neutropenic infections. G-CSF are reported to have pulmonary toxicity, but the risk of DIP is greater when used in combination with other potentially pulmotoxic agents. In this retrospective study, we reported the G-CSF use and risk of DIP in 234 DLBCL patients and 87 FL patients receiving R-CHOP-type immunochemotherapy. In 72% of patients, the treatment included a G-CSF support. The overall incidence of treatment-induced pneumonitis was 6.9% in this patient group. All the DIP cases (n = 16) were among patients receiving G-CSF support (p = 0.03). Older age (over 60 years) and higher disease stage (Ann Arbor 3-4) also increased the risk of DIP. These findings suggest that the use of G-CSF increases the risk of DIP, when used in combination with rituximab-containing regimen.

Lurbinectedin in patients with small cell lung cancer with chemotherapy-free interval ≥30 days and without central nervous metastases

ObjectivesThis report focuses on lurbinectedin activity and safety in a subgroup of small cell lung cancer (SCLC) patients from a Basket phase 2 study (Trigo et al. Lancet Oncology 2020;21:645–654) with chemotherapy-free interval (CTFI) ≥ 30 days. This pre-planned analysis was requested for obtaining regulatory approval of lurbinectedin in Switzerland. Materials and methodsPatients with extensive-stage SCLC, no central nervous system (CNS) metastases, and disease progression after platinum-containing therapy were included. Topotecan data from a contemporary, randomized, controlled phase 3 study (ATLANTIS) were used as indirect external control in a matched patient population (n = 98 patients). ResultsLurbinectedin showed a statistically significant higher overall response rate (ORR) by investigator assessment (IA) compared to topotecan subgroup (41.0 % vs. 25.5 %; p = 0.0382); higher ORR by Independent Review Committee (IRC) (33.7 % vs. 25.5 %); longer median duration of response (IA: 5.3 vs. 3.9 months; IRC: 5.1 vs. 4.3 months), and longer median overall survival (10.2 vs. 7.6 months). Grade ≥ 3 hematological abnormalities were remarkably lower with lurbinectedin: anemia 12.0 % vs. 54.1 %; leukopenia 30.1 % vs. 68.4 %; neutropenia 47.0 % vs. 75.5 %, and thrombocytopenia 6.0 % vs. 52.0 %. Febrile neutropenia was observed at a higher incidence with topotecan (6.1 % vs. 2.4 % with lurbinectedin) despite that the use of growth-colony stimulating factors was mandatory with topotecan. ConclusionWith the limitations of an indirect comparison, however using recent and comparable SCLC datasets, this post hoc analysis shows that SCLC patients with CTFI ≥ 30 days and no CNS metastases have a positive benefit/risk ratio with lurbinectedin, superior to that observed with topotecan.

Safety and Preliminary Efficacy of DFV890 in Adult Patients with Myeloid Diseases: A Phase 1b Study

Background and Significance: Patients (pts) with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) have a high unmet medical need, with limited standard-of-care therapeutic approaches, particularly after failure of response to first-line agents, and with allogeneic hematopoietic transplant as the only potential curative option. Through the production of interleukin (IL)-1β and IL-18, the NLRP3 inflammasome has been implicated as a major driver of inflammation associated with acute and chronic inflammatory diseases. The NLRP3 pathway is activated in hematopoietic stem and progenitor cells and in the marrow microenvironment in myeloid neoplasms such as MDS and CMML contributing to ineffective hematopoiesis and clonal progression (Hamarsheh 2020; Basiorka 2016). DFV890, a small molecule NLRP3 inhibitor, blocks IL-1β and IL-18 secretion and pyroptotic cell death in response to a wide variety of NLRP3-dependent danger signals, both in vitro and in vivo. Therefore, DFV890 may disrupt the smoldering inflammation and provide disease-modifying benefits to pts by improving hematopoiesis. Study Design and Methods: This is an open-label, phase 1b, multicenter study with a randomized dose-optimization part and a dose-expansion part consisting of two groups evaluating DFV890 in pts with very low, low, or intermediate risk MDS (LR-MDS) per revised International Prognostic Scoring System (IPSS-R) criteria and low or intermediate-1 risk CMML (LR-CMML) per CMML-specific Prognostic Scoring System (CPSS) criteria (NCT05552469). Eligible pts must be 18 years of age, with an Eastern Cooperative Oncology Group performance status ≤2, candidates for serial bone marrow assessments who are willing to undergo a bone marrow aspirate/biopsy during the trial, and meet one of the following: (a) IPSS-R-defined LR-MDS who failed to respond to or did not tolerate erythropoiesis-stimulating agents (ESAs) or luspatercept or hypomethylating agents (HMAs) and pts with del 5q who failed to respond to or did not tolerate lenalidomide; (b) CPSS-defined LR-CMML who failed to respond to or did not tolerate hydroxyurea or HMAs. Key exclusion criteria include treatment with systemic antineoplastic or any experimental therapies within 28 days (or 5 half-lives, whichever longer); unresolved treatment-related toxicities prior to the first dose of study treatment; previous treatment with agents targeting the NLRP3 inflammasome and the IL-1 pathways; prior use (≤1 week or 5 half-lives, whichever is longer) of hematopoietic colony-stimulating growth factors, thrombopoietin mimetics or ESAs; and concomitant medications, known to modulate cytochrome P450 enzymes. DFV890 is administered orally twice daily (bid) for a minimum of 24 weeks (6 cycles of treatment [1 cycle=28 days]) until treatment discontinuation. In the dose-optimization part, pts are randomized to receive either low dose or high dose bid and stratified by indications. The recommended dose (RD) determined from this part is further explored in the dose-expansion part to confirm safety and tolerability of DFV890 and explore preliminary efficacy. The primary objective is to assess safety (incidence and severity of adverse events, and dose-limiting toxicities) and tolerability to then determine the optimal RD for DFV980. Secondary objectives include assessment of DFV890 pharmacokinetics, evaluation of the preliminary efficacy of DFV890 on transfusion burden, and hematologic improvement: time to onset of transfusion independence; duration of response, best overall response, overall response rate, progression-free survival, and time to progression; and reduction in spleen volume (for CMML). Key exploratory objectives include patient perceptions of tolerability as measured by patient-reported outcomes; and determination of genetic characteristics and potential predictive markers of efficacy and/or resistance. The study is currently enrolling in Singapore, Hong Kong, and the USA with plans to treat approximately 80 pts. The first patient first visit was achieved on May 8, 2023.

Components of total cost of care in real-world patients with mPDAC who received first-line FOLFIRINOX or Gem/Abrax.

e16282 Background: FOLFIRINOX (FFX) and Gemcitabine/Abraxane (Gem/Abrax) are two recommended options for the treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC). There is limited research assessing differences in costs between real-world patients with mPDAC who received first-line (1L) FFX or Gem/Abrax. Methods: We used ICD-10 diagnosis codes to identify patients aged 65+ with mPDAC without end-stage renal disease in the 2018-2021 Medicare Parts A, B, and D 100% Research Identifiable Files (RIF) data. Total cost of care (TCOC) represents mean Medicare paid amounts and patient cost sharing. Lines of therapy (LOTs) were assigned based on therapies used. LOTs ended the day before a new chemotherapy began, 28 days after the last chemotherapy (if no new chemotherapy), or upon death. Study patients were treated with FFX or Gem/Abrax as a 1L therapy. Results: We identified 8,889 patients with mPDAC that received an 1L FFX regimen between 2018 and 2021 and 15,053 patients that received a Gem/Abrax regimen in the same period. Total cost of care was similar among the two cohorts ($7,187 per administration cycle among patients receiving FFX vs. $7,240 among those receiving Gem/Abrax in 1L). Patients receiving Gem/Abrax had higher chemotherapy costs ($2,980) than FFX ($406), however, patients receiving FFX had higher granulocyte colony-stimulating growth factor costs ($1,592 FFX vs. $293 Gem/Abrax) and higher Other Part B costs ($1,301 FFX vs. $876 Gem/Abrax). Inpatient costs were similar between FFX ($1,732) and Gem/Abrax ($1,615), while outpatient costs were higher for patients receiving FFX ($1,549) than patients receiving Gem/Abrax ($847). Conclusions: Among Medicare Fee-For-Service patients with mPDAC, patients receiving FOLFIRINOX (FFX) or Gemcitabine/Abraxane (Gem/Abrax) as a first-line therapy incurred similar costs of care overall, with different distributions across service categories. While therapy costs were lower among patients receiving generic FFX than those receiving branded Gem/Abrax, higher costs from supportive therapies offset those differences.

Selected pathological conditions affecting endometrial receptivity.

A summary of new knowledge on embryo implantation in dependence on quality of the endometrium. Literature review from August 2022 of the relevant publications in Web of Science, Scopus and PubMed/Medline databases, focused on “endometrial receptivity”, “polycystic ovary syndrome”, “endometriosis”, “SARS-CoV-2”. The receptive state of the endometrium is a result of physiological remodeling and immune system activity modulated by the microbio-me. This balance can be disturbed by myomas, polyps, sactosalpings, adenomyosis, endometriosis, polycystic ovary syndrome, infections. The effect of SARS-CoV-2 infection is being discussed. For a successful implantation, timing of transfer is crucial. The ultrasound examination is used conventionally. In specific cases, hysteroscopy and endometrium bio-psy are recommended. Histological and immunohistochemical evaluation is performed together with examination of microbio-me or transcriptome. To support the implantation, gestagenes are used, or metformin in the patients with polycystic ovary syndrome. In cases of a repeated implantation failure, the intrauterine infusion of mononuclear cells or platelet rich plasma is used, subcutaneous application of granulocyte colony stimulating growth factor, intravenous application of atosiban or intrauterine application of human chorionic gonadotropin. Recent research in the field of transcriptomics, proteomics and reproductive immunology uncovers the process of implantation more deeply and opens a new stage of the assisted reproduction.

Impacts of a Zwitterionic Peptide on its Fusion Protein.

Therapeutic proteins frequently need to be modified with high-molecular-weight molecules to improve their pharmacokinetic properties. The genetic linkage of therapeutic proteins to a high-molecular-weight zwitterionic peptide, termed EKP, offers a promising approach. As with any protein modification, EKP could impact the structural behavior and receptor binding properties of the linked therapeutic protein, thereby altering its bioactivity. To evaluate the effects of EKP on therapeutic proteins, we study the receptor binding properties of high-molecular-weight EKP linked to the growth colony-stimulating factor (GCSF) using the genetically based yeast display platform. We find that yeast-displayed EKP-GCSF and GCSF exhibits similar binding to its receptor GCSF-R, suggesting that EKP does not hinder receptor binding. Furthermore, yeast-displayed EKP-GCSF demonstrates protection against thermal denaturation compared to GCSF. Similarly, to study the structural effects of EKP on GCSF, we employ in silico modeling using alphaFold2 in conjunction with molecular dynamics (MD) simulations. Likewise, in silico modeling reveals that EKP does not alter the structural behavior of GCSF. Finally, we demonstrate the functional benefits of EKP, by which the EKP-GCSF fusion protein produced in Escherichia coli exhibits improved pharmacokinetics and prolonged bioactivity in vivo.

Antioxidant and anti-inflammatory activities of Ganoderma resinaceum (Boud) fruiting bodies extracts

Introduction: Ganoderma resinaceum is used to treat oxidative and inflammatory-related diseases such as cardiovascular and liver diseases. Thus, this study aimed to evaluate the antioxidant and anti-inflammatory activities of different extracts from G. resinaceum fruiting bodies. Methods: Aqueous crude (GRT), mycelial (MYC), exopolysaccharide (EPS I, EPS II) and water-soluble polysaccharide-rich (GRP I and GRP II) extracts of G. resinaceum were assessed for their free radical scavenging and metal chelating ions assays. The in vitro anti-inflammatory activity was evaluated by stabilization of erythrocytes’ membranes and protein denaturation assays. For the in vivo study, paw oedema was induced by administration of κ-carrageenan (0.1 mL; 1%) to male Wistar rats aged 4 to 6 weeks. Animals were pre-treated with G. resinaceum extracts (125 mg/kg) and diclofenac sodium (20 mg/kg). Inflammatory cytokine and chemokine levels were determined, and histological analysis of paw tissue was performed. Results: G. resinaceum polysaccharide-rich extracts (GRP I and GRP II) showed the best bioactivities. They scavenged DPPH (1,1-diphenyl-2-picrylhydrazyl, ABTS (2,2-azino-bis-3- ethylbenzylthiazoline-6-sulfonic acid, and NO (nitric oxide) radicals, and chelated ferrous ions, stabilized murine erythrocyte membranes, and inhibited protein denaturation. At 125 mg/kg, GRP I and GRP II restored the microarchitecture with a weak infiltration of immune cells in the subcutaneous tissues. Moreover, they decreased the overproduction of proinflammatory cytokines growth colony-stimulating factor (G-CSF), interferon gamma (IFNγ), tumour necrosis factor alpha (TNFα), chemokines (eotaxin, fractalkine) and increased the levels of anti-inflammatory cytokines (IL-10, IL-12p70). Conclusion: G. resinaceum polysaccharide extracts could be potent antioxidant and antiinflammatory agents.

Comparison of standard versus low-dose valganciclovir regimens for cytomegalovirus prophylaxis in high-risk liver transplant recipients.

The purpose of this study was to compare the safety and efficacy of two valganciclovir (VGCV) institutional dosing protocols for cytomegalovirus (CMV) prophylaxis in liver transplant (LT) recipients with CMV serotype donor +/recipient- (D+/R-). This was a single-center review of CMV D+/R- adult LT recipients who received VGCV 450mg/day for 90 days (low-dose) or VGCV 900mg/day for 180 days (standard-dose). The primary outcome was incidence of CMV disease at 1 year. Secondary outcomes included rates of CMV syndrome, end-organ disease, breakthrough infection, and resistance. Neutropenia, early discontinuation of VGCV, growth colony stimulating factors use (G-CSF), biopsy-proven rejection (BPAR), graft loss, and death at 1 year were analyzed. Ninety-six CMV D+/R- LT recipients were included. Although no difference in CMV disease was observed (low-dose 26%vs. standard-dose 23%, p=0.71), 75% of CMV infections in the low-dose group presented with end-organ disease. Ganciclovir (GCV) resistance was observed only in the low-dose group (n=2). Significantly more patients in the standard-dose group developed neutropenia (low-dose 10%vs 60% standard-dose, p<0.001). In the standard-dose group, 29% required early discontinuation of VGCV (vs. 5% in the low-dose group, p<0.001), and 20% were treated with G-CSF. Both cohorts had similar rates of BPAR, graft loss, and death at 1 year. VGCV 900mg/day for 180 days had higher rates of hematologic adverse effects resulting in frequent treatment interruptions. However, the occurrence of two cases of GCV-resistant CMV disease raises concerns about routinely using low-dose VGCV prophylaxis.

A Phase 2, International, Multicenter, Prospective Clinical Trial of Subcutaneous Tbo-Filgrastim in Pediatric Patients with Solid Tumors Undergoing Chemotherapy

Background: Chemotherapy (CT)-induced neutropenia is a common complication from chemotherapy, limiting optimal dosing and treatment. Tbo-filgrastim (GRANIX®) is a non-glycosylated recombinant methionyl human granulocyte colony-stimulating growth factor manufactured by recombinant DNA technology. It is indicated to reduce the duration of severe neutropenia (SN) in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia (FN). It is approved under a biologic license application in the United States. This phase 2, multicenter, open-label study investigated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and immunogenicity of tbo-filgrastim in pediatric patients receiving at least 1 cycle of myelosuppressive CT.Methods: Patients ages 1 mo to <16 y with solid tumors without bone marrow involvement were administered tbo-filgrastim 5 µg/kg/body weight once daily subcutaneously. Tbo-filgrastim administration was started at approximately 24 hours (±3 hours) after the end of the last CT treatment. Daily dosing with tbo-filgrastim continued until the expected neutrophil nadir was passed and the neutrophil count had recovered to 2.0 × 109/L but not longer than 14 consecutive days. Patients were stratified into three age groups: infants (1 mo to <2 y), children (2 to <12 y), and adolescents (12 to <16 y). The CT regimens included at least one of the following: etoposide, doxorubicin, ifosfamide, or cyclophosphamide. The primary endpoint was the safety of tbo-filgrastim; secondary objectives were to assess the PK, PD (incidence and duration of SN, defined as absolute neutrophil count <0.5x109/L), and efficacy (incidence of FN). Immunogenicity was also assessed.Results: Fifty patients (2 infants, 30 children, and 18 adolescents) were administered a single daily dose of tbo-filgrastim. The most common cancers were rhabdomyosarcoma (14%), neuroblastoma (14%), Ewing tumors (12%), and osteosarcoma (12%). The mean (SD) number of doses administered were 9.2 (2.83) in children and 7.3 (1.88) in adolescents. Twelve and 14 doses, respectively, were administered to each infant. Serious treatment-emergent adverse events (TEAEs) were reported in 24% of patients (Table). The most common serious TEAEs were FN (12%, 4 children, 2 adolescents), anemia (8%, 4 children) and thrombocytopenia (8%, 2 children, 2 adolescents), increased alanine aminotransferase (ALT) and increased aspartate aminotransferase (AST) (6% each). The majority of grade 3 and 4 events, per Common Terminology Criteria for Adverse Events (NCI CTCAE), were in the hematologic system organ class. Nine patients (18%) experienced treatment-related TEAEs. The most common treatment-related TEAEs were musculoskeletal and connective tissue disorders (4/50, 8%) and were of NCI CTCAE grade 1 severity. Two patients (2/50, 4%) had increases in liver function enzymes considered to be related to tbo-filgrastim and CT by the investigator. No clinical symptoms were observed with these events, which resolved by the end of the study. No deaths or study withdrawal occurred during the study. PK parameters of exposure were comparable between age groups as shown by the overlap of tbo-filgrastim serum concentrations (Figure). The incidence of SN was 52% (26/50; 95% CI 0.374-0.663). The mean (SD) duration of SN was 1.8 (2.21) d. The incidence of FN was 26% (13/50; 95% CI 0.146-0.403). Immunogenicity assessments found that none of the patients had an antidrug antibody response after tbo-filgrastim treatment.Conclusion: A daily dose of tbo-filgrastim 5 μg/kg/body weight administered to pediatric patients with solid tumors without bone marrow involvement demonstrated a safety profile consistent with the safety profile in adult patients. No immunogenic response was observed in this population. The increases in liver function enzymes were considered related to both tbo-filgrastim and CT by the investigator. The sponsor assessed these events to be related to CT and concomitant medications and not related to tbo-filgrastim. The incidence of FN was on the lower end of the range in the literature. PD variables of the incidence and duration of SN provide supportive results of the efficacy of tbo-filgrastim in pediatric cancer patients. [Display omitted] DisclosuresBias:Teva ratiopharm: Employment, Equity Ownership. Lammerich:Teva ratiopharm: Employment, Equity Ownership. Roth-Ben Arie:Teva Pharmaceuticals Industries: Employment. Zou:Teva Pharmaceuticals: Employment, Equity Ownership. Buchner:Teva ratiopharm: Employment, Equity Ownership.

Evaluation of Engraftment and Adverse Effects of Granulocyte Colony Stimulating Factor versus PEG Granulocyte Colony Stimulating Factor in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation (HSCT) is an effective treatment for many hematological malignancies. Engraftment is the foremost step in the autologous hematopoietic stem cell transplantation (AHSCT) process in which different granulocyte colony-stimulating factors with various administration are used. In this study, we evaluated and compared the efficacy and side effects of two forms of recombinant granulocyte colony-stimulating growth factors (GCSF) ,GCSF and Peg GCSF, In this randomized clinical trial, 60 consecutive patients with multiple myeloma, Hodgkin's and non-Hodgkin's lymphoma who underwent AHSCT were included, the average age of the patients was 55; the patients were then divided into two groups so the comparison of efficacy and side effects between the two methods become achievable. The local ethical committee approved the study with the code of SB2019:210291, and the Helsinki declaration was respected across the study. In the first group, patients received peg GCSF at a dose of 6 mg on day five, and the second group received GCSF started with 5μg/kg from day 5. We compared engraftment time and adverse effects in the two groups. Our study demonstrated no difference between the two groups regarding need for transfusion and infection complications; also, the two groups did not differ in terms of the flue-like syndrome, the type of infection and the recorded number of febrile neutropenia. Mean leukocyte engraftment days were 10.97 ± 1 and 11.1 ± 1.1 that was similar in both groups (P=0.328). Mean platelet engraftment days were 11.03 ± 2.4 and 11.1 ± 2.4 without significant difference (P=0.714).it was concluded that Pegfilgrastimhas the same efficacy and safety profile in comparison to Filgrastim. Therefore, since Pegfilgrastim has a easier method of injection and can simplify the HSCT process.

1702. Assessing the Safety and Efficacy of Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Solid Organ Transplant Recipients on Hemodialysis

BackgroundValganciclovir is the standard of care used for the prevention of Cytomegalovirus (CMV) infections among solid organ transplant (SOT) recipients. Currently there is minimal guidance for prophylaxis in SOT recipients undergoing intermittent hemodialysis (IHD). At Mount Sinai Hospital (MSH), the current practice for CMV prophylaxis in SOT recipients on IHD is valganciclovir 450 mg every other day (Q48H) or three-times weekly (TIW). This study aims to evaluate the safety and effectiveness of these dosing regimens in SOT recipients on IHD.MethodsA single-center, retrospective chart review study was conducted among all MSH SOT recipients on valganciclovir 450 mg Q48H or TIW for CMV prophylaxis and undergoing IHD for at least 30 days. The primary study outcome was the safety of using these valganciclovir doses determined by the incidence of leukopenia, thrombocytopenia, and the administration of growth colony stimulating factor (GCSF). The secondary outcome were the incidences of CMV viremia and CMV disease while on prophylaxis.ResultsEighteen transplant encounters satisfied the inclusion and exclusion criteria. The majority were liver (7, 38.9%) and kidney (5, 27.8%) transplants. Thirteen (72.2%) recipients were on valganciclovir 450 mg Q48H dosing, while 5 (27.8%) were on valganciclovir 450 mg TIW dosing. Both the mean platelet count nadir (131 ± 93 vs 161 ± 115) and mean white blood cell count nadir (3.4 ± 2.5 vs 5.1 ± 3.8) were lower in the Q48H regimen. Four patients (22.2%) in the Q48H regimen group required GCSF vs none (0.0%) in the TIW regimen. No patient had a detectable CMV viral load while on either prophylactic dose. Two (11.1%) CMV high risk patients on the every other day dosing regimen and one (5.6%) CMV moderate risk patient on the three times weekly regimen developed CMV viremia about 2-3 months after their prophylaxis was stopped.Table 1. Baseline Demographics. Table 2. Primary Outcomes Table 3. Secondary Outcomes ConclusionValganciclovir 450 mg TIW may be safer than and as efficacious as Q48H dosing for prophylaxis in SOT recipients on chronic IHD. This data supports the use of three times weekly dosing as standardized practice at MSH, however more data is necessary to determine a conclusive result.Disclosures All Authors: No reported disclosures

ASSESSING THE UTILITY OF A CYTOKINE IN THE DIAGNOSIS OF CERVICAL INTRAEPITHELIAL NEOPLASM AMONG WOMEN IN BENIN CITY, NIGERIA

Cervical cancer has been recognized as the fourth commonest cancer worldwide with 70 % of deaths from cases occurring from developing countries. The mortality rate among women in Nigeria can be drastically reduced by early specific diagnosis of premalignant lesions. Although Cytokines are not routinely used as diagnostic markers for cervical cancer, this study investigated the strength of Granulocyte Monocyte Colony Stimulating growth Factor (GM-CSF) as an indicator in the prediction of Cervical Intraepithelial Neoplasm (CIN). The study was carried out at the Department of Obstetrics and Gynaecology, University of Benin Teaching Hospital Benin City and Department of Chemical Pathology, Edo University Iyamho, Edo state Nigeria, between August, 2017 and January 2019. It was a cross-sectional prospective study. A total of 197 female participants were recruited for this study. Based on histological diagnosis they were grouped as; Negative, CIN 1, CIN 2 and CIN 3. Venous blood was obtained from participants and serum GM-CSF levels were determined using standardized laboratory methods. The results showed a statistically significant elevation of serum GM-CSF in participants with CIN lesions (56.27±1.21ng/ml) compared to those without (33.43±3.03ng/ml). The study also suggests a 56.3% sensitivity and a 95.3% specificity of GM-CSF marker to CIN with an Area under the Curve (AUC) of 0 .907, p&lt;0.001 from the Receivers Operator Curve (ROC). This research suggests the use of GM-CSF as a good marker for screening of those at risk of cervical cancer because of its high prospect to reduce the incidence of false positives. However, because of the low sensitivity, it is recommended that GM-CSF be used as a CIN diagnostic tool in combination with the standard Pap smear test.

INDICES OF VASCULAR - ENDOTHELIAL AND GRANULOCYTIC COLONYSTIMULATING GROWTH FACTORS IN PATIENTS SUFFERING FROM CHRONIC OBSTRUCTIVE PULMONARY DISEASE WITH CONCOMITANT CHRONIC PANCREATITIS IN THE DYNAMICS OF THERAPY

Purpose. Estimation of the level of the circulatory vascular-endothelial growth factor(VEGF) and granulocytic colony-stimulating growth factor (GCSF) in patients sufferingfrom chronic obstructive lung disease (COLD) with concomitant chronic pancreatitis(CP) in the dynamics of therapy.Material and methods. Investigation of 52 patients with COLD B-C groups, where theobstruction degree corresponded to COLD 1-2 with a low risk and more pronouncedsymptomatics (B), and also COLD 3 with a high risk but less pronounced symptomatics(C), - I group, 60 CP patients with corresponding characteristics of groups with concomitant COLD (II group) and 19 practically healthy persons as a referent group wascarried out. Patients of II group were divided into 3 subgroups according to theobtained treatment. Patients of IA subgroup (19 persons) received basic therapy according to the MPH order of Ukraine №555 dated from 27.06.2013. 23 patients, whoreceived "Essentsiale forte H" two capsules thrice a day during 1/12, except generallyaccepted treatment, constituted IB subgroup. In patients of IB subgroup (18 patients) thebasic treatment was combined with additional administration of kvertsetin in a dose of1.0 g thrice a day during 14 days.Results. Thus, in patients of II group VEGF level (median and 80% interprocentilerange) was 203 pg/ml [104,3 - 391, 68 pg/ml], that differed from healthy persons (p&lt;0,05).This index fluctuated from 104 to 195, 84 pg/ml, and median was equaled to 172, 92pg/ml in patients without concomitant pathology of the pancreas. In practically healthypersons it constituted 28, 7 [15, 07 - 44, 39] pg/ml accordingly. As to G-CSF its concentration was various in patients of both groups in comparison with the group ofpractically healthy persons. Differences between groups of patients were not revealed.Thus, this index fluctuated from 21 to 93, 3 pg/ml, median constituted 26, 2 pg/ml inpatients of II group, and in patients of III group it was 23-93, 3 pg/ml and median - 27, 9pg.ml.Conclusions. An increase of the circulating VEGF level at COLD exacerbation withconcomitant CP is probably associated with the systemic response syndrome to inflammatory process. CP presence deteriorates the indices of the endothelium functioning.

A randomized multicenter phase II trial of mecapegfilgrastim single administration versus granulocyte colony-stimulating growth factor on treating chemotherapy-induced neutropenia in breast cancer patients.

This study aimed to evaluate the efficacy and safety of mecapegfilgrastim (HHPG-19K) with different doses compared to granulocyte colony-stimulating growth factor (G-CSF) in treating chemotherapy-induced neutropenia in breast cancer patients. A total of 182 breast cancer patients were enrolled in this multi-center, randomized, phase II trial and developed neutropenia after first cycle chemotherapy. Patients were then assigned as 1:1:1 ratio to receive 100 µg/kg HHPG-19K single injection (HHPG-19K-N group), 150 µg/kg HHPG-19Ksingle injection (HHPG-19K-H group) and 5 µg/kg G-CSF daily injection (G-CSF group) at day 3 of the second cycle (cycle 2) chemotherapy. The primary endpoint was incidence of grade ≥3 neutropenia during cycle 2. Study drug-related adverse events during cycle 2 were recorded for safety assessment. During cycle 2 chemotherapy, both HHPG-19K-N and HHPG-19K-H groups exhibited lower incidence of grade ≥3 neutropenia compared with G-CSF group, while no difference was observed between HHPG-19K-N and HHPG-19K-H groups. Also, better outcomes were observed in HHPG-19K-N and HHPG-19K-H groups compared with G-CSF group regarding to grade 4 neutropenia, duration of grade ≥3 neutropenia, duration of grade 4 neutropenia, incidence of febrile neutropenia (FN) and rescue application of G-CSF, time to ANC recovery, while no difference of these outcomes between HHPG-19K-N and HHPG-19K-H groups was observed. For safety analysis, the incidences of hematologic and non-hematologic adverse events were similar among the 3 groups. HHPG-19K presents with better clinical efficacy as well as equal tolerance compared with G-CSF in treating chemotherapy-induced neutropenia in breast cancer patients.

The toxicity profile of TAS-102. Practical considerations about neutropenia.

TAS-102 represents an important therapeutic resource for patients with metastatic refractory colorectal cancer. Albeit generally well tolerated, clinically relevant neutropenia may interfere with the regular delivery of full-dose cycles with a possible detrimental effect on the dose-intensity. Judicious and personalized use of colony-stimulating growth factors as well as alterative schedules of drug delivery could mitigate neutropenia, so contributing to an even better therapeutic index of the drug.

Concentration of colony-stimulating growth factor (CSF) in uterine flushing as prognostic criterion of IVF cycle outcome in patients with recurrent implantation failure

Concentration of colony-stimulating growth factor (CSF) in uterine flushing as prognostic criterion of IVF cycle outcome in patients with recurrent implantation failure

Chemical Stability of Plerixafor after Opening of Single-Use Vial.

The addition of the immunostimulant plerixafor to the current standard-of-care regimens of granulocyte colony-stimulating growth factor with or without chemotherapy has improved clinical results in terms of successful stem cell mobilization and the outcomes of stem cell transplant in various settings. With this medical innovation has come an added financial cost for institutions where stem cell transplants are routinely performed, and there may be a further financial burden when the contents of partial vials of the drug are wasted, given that plerixafor vials (Mozobil, Sanofi-Aventis Canada Inc) are currently deemed suitable only for single use. To determine whether the portion of plerixafor remaining in an opened vial of the Mozobil product after administration of a single dose is chemically stable, by comparison with the original product. Stability testing of partial drug contents of an opened vial, stored at room temperature or under refrigeration (4°C), was conducted using liquid chromatography-tandem mass spectrometry analysis. The mean concentration of plerixafor (μmol/L), standard deviation, coefficient of variation, and bias were determined on days 2, 3, 11, 17, 24, and 31. Method validation included determination of precision, sensitivity, recovery, dilution linearity, and carryover. Throughout the 4-week testing period, measured plerixafor concentration in aliquots stored at room temperature and under refrigeration, tested in series over time, appeared similar. The mean residual drug concentration after initial opening was slightly, but not significantly, higher for the sample designated for storage at room temperature than the one designated for refrigerated storage (40.4 versus 39.9 μmol/L; p = 0.37). Residual plerixafor after initial opening of a vial of the Mozobil product remained chemically stable for at least 2 weeks both at room temperature and under refrigeration. The results of this study provide in vitro evidence to support multiple uses, instead of single use, of vials of this drug in an aseptic, controlled environment.

Evaluation of Hematopoietic Stem Cell Mobilization Rates with Early Plerixafor Administration for Adult Stem Cell Transplantation

The addition of plerixafor to high-dose colony-stimulating growth factor has been shown to improve stem cell mobilization rates in autologous transplant patients with multiple myeloma and non-Hodgkin lymphoma. This study evaluates the change in administration time of plerixafor to determine if cell mobilization rates are similar between the US Food and Drug Administration–approved administration time of 11 hours before apheresis and an earlier administration time of 16 hours before apheresis. Medical records of patients age ≥ 18 years undergoing autologous stem cell transplantation requiring the use of plerixafor after at least 4 days of granulocyte colony-stimulating factor therapy to complete stem cell mobilization from January 1, 2010 through September 30, 2014 were retrospectively reviewed. The primary outcome was CD34+ cell mobilization success rates when plerixafor was administered 11 ± 2 hours (standard administration group) compared with 16 ± 2 hours before cell apheresis (early administration group), as defined as collection of ≥2 × 106 CD34+ cells/kg. Secondary outcomes included the number of plerixafor therapy days required to collect a total of ≥2 × 106 CD34+ cells/kg, the number of apheresis cycles required to achieve ≥2 × 106 CD34+ cells/kg, the median CD34+ cells/kg collected in each apheresis session, and the rates of reported adverse events that occurred in the standard administration time group compared with the early administration time group. Of the 197 patients included, 114 patients received plerixafor 11 ± 2 hours before apheresis and 83 patients received plerixafor 16 hours ± 2 hours before apheresis. Ninety-four percent of patients in the early administration group achieved successful stem cell mobilization compared with 81.6% in the standard administration group (P = .0111). The median number of plerixafor days to reach the collection goal of ≥2 × 106 CD34+ cells/kg was 1 day for each group (P = .323), and the median number of apheresis days to reach the collection goal was 2 days for the standard administration group compared with 1 day for the early administration group (P = .0156). Most adverse events were similar between the 2 groups except for fever, which occurred in 4.8% of the patients in the early administration group and none of the patients in the standard administration group. This study demonstrates plerixafor effectively mobilizes peripheral blood stem cells when given at an early administration time of 16 hours before apheresis compared with standard administration of 11 hours before apheresis. However, further prospective studies could strengthen these results.