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1.
Efficacy and safety of biosimilar Peg-filgrastim after autologous stem cell transplant in myeloma and lymphoma patients: a comparative study with biosimilar Filgrastim, Lenograstim, and originator Peg-filgrastim
Marchesi, F., Terrenato, I., Papa, E., Tomassi, M., Falcucci, P., Gumenyuk, S., Palombi, F., Pisani, F., Renzi, D., Romano, A., et al
Annals of hematology. 2024
Abstract
Data about biosimilar Peg-filgrastim (bioPEG) in autologous stem cell transplant (ASCT) are still scarce. The aim of this study has been to assess efficacy and safety of bioPEG among lymphoma and myeloma patients undergoing ASCT, comparing these data with historical controls receiving other G-CSFs. Furthermore, an economic evaluation has been included to estimate the savings by using bioPEG. This is a prospective cohort study comparing lymphoma and myeloma patients undergoing ASCT and receiving bioPEG (n = 73) with three historical consecutive cohorts collected retrospectively who received other G-CSFs (Lenograstim - Leno - n = 101, biosimilar Filgrastim - bioFIL n = 392, and originator Peg-filgrastim - oriPEG n = 60). We observed a significantly shorter time to neutrophils and platelet engraftment (p < 0.001) in patients treated with bioPEG and oriPEG. Moreover, patients who received bioPEG showed a shorter hospitalization time (p < 0.001) and a lower transfusion need (p < 0.001). We did not observe any significant difference in terms of transplant-related mortality, mucositis, and diarrhea among the four groups. No serious adverse events were associated with bioPEG. Similar data were obtained after running a stratified analysis for lymphomas and myeloma separately conducted by using a propensity score matching. The average total cost per patient of bioPEG was € 18218.9 compared to € 23707.8, € 20677.3 and € 19754.9 of Leno, oriPEG, and bioFIL, respectively. In conclusion, bioPEG seems to be as effective as the originator and more effective than short-acting G-CSFs in terms of post-transplant engraftment in myeloma and lymphoma patients undergoing ASCT. Moreover, bioPEG was cost-effective when compared with the other G-CSFs.
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2.
Revisiting the utility of G-CSF post-autologous hematopoietic stem cell transplantation for outpatient-based transplants
Portuguese, A. J., Holmberg, L., Hill, G. R., Lee, S. J., Green, D. J., Mielcarek, M., Gooley, T., Yeh, A. C.
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND The use of granulocyte colony-stimulating factor (G-CSF) after autologous stem cell transplant (ASCT) has been shown to reduce time to neutrophil engraftment as well as duration of hospitalization post-transplant. However, prior studies have focused on inpatient-based transplants, where patients are routinely admitted for conditioning and frequently remain hospitalized until signs of neutrophil recovery. Given improvements in post-transplant care, an increasing number of patients, particularly those receiving ASCT for multiple myeloma, are now being transplanted in an outpatient setting. OBJECTIVE We hypothesize that the routine use of G-CSF for outpatient-based ASCT may not result in the same benefit with respect to reduction of duration of hospitalization and therefore should be reconsidered in this setting. STUDY DESIGN We performed a retrospective cohort study of 633 patients with multiple myeloma (MM; n=484) and non-Hodgkin lymphoma (NHL; n=149) who were transplanted consecutively between 9/2018 and 2/2023. Outpatient ASCT comprised 258 (53%) of MM and no NHL cases. Starting September 2021, post-transplant G-CSF was incorporated into the supportive care regimen for all ASCTs. There were 410 (309 MM, 101 NHL) and 223 patients (175 MM, 48 NHL) transplanted in the pre- and post-G-CSF policy periods, respectively. The primary outcome focused on the duration of hospitalization within the first 30 days following graft infusion. RESULTS As expected, after implementation of the G-CSF policy, the time to neutrophil engraftment was reduced among patients with MM (mean -2.8 days, p<.0001) and NHL (mean -2.9 days, p<.0001). However, among patients with MM, roughly half of whom underwent outpatient-based ASCT, the inpatient duration during the first 30 days was not reduced after G-CSF implementation (p=.40). Comparatively, the inpatient duration (mean -1.8 days, p=.030) was reduced among patients with NHL, all of whom were electively admitted for ASCT. CONCLUSIONS For patients with MM at an outpatient-based transplant center, incorporation of G-CSF post-ASCT resulted in reduced time to neutrophil engraftment but did not significantly reduce the time spent in the inpatient setting through day +30.
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3.
[Effect and safety of pegylated recombinant human G-CSF on hematopoietic reconstitution after autologous hematopoietic stem cell transplantation in lymphoma patients]
Shen, Y. G., Ji, M. M., Zheng, Z., Tang, W., Zhao, W. L.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. 2022;43(11):940-945
Abstract
Objective: Efficacy and safety analysis of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in promoting hematopoietic recovery after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with lymphoma. Methods: A total of 149 patients after auto-HSCT in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled in this study from April 2016 to December 2021. There were 75 cases in the PEG-rhG-CSF group who were given a single subcutaneous dose of 100 µg/kg on the first day and +8 d, while 74 cases in the rhG-CSF group were given a dose of 5-10 µg·kg(-1)·d(-1) by subcutaneous injection from +1d continuing to an absolute value of neutrophil (ANC) of more than 1.5×10(9)/L. Results: ①The time of grade 3/4 agranulocytosis and neutrophil implantation in the PEG-rhG-CSF group were significantly different from that in rhG-CSF group (P=0.010, 0.030, 0.007) . There were no significant differences in the platelet implantation time, anemia incidence and duration, and platelet and red blood cell infusion within 1 month after transplantation between groups. ②The agranulocytosis with fever incidence in PEG-rhG-CSF group was similar to that in rhG-CSF group (84.0% vs 82.4% , P=0.798) , but the duration was shorter in the PEG-rhG-CSF group (4.0 d vs 5.5 d, P=0.005) . ③The incidence of infection in the PEG-rhG-CSF and the rhG-CSF groups were 22.7% (17/75) and 31.1% (23/74) , respectively (P=0.247) , and the bloodstream infection incidence were 5.3% (4/75) and 9.5% (7/74) , respectively (P=0.336) . ④The PEG-rhG-CSF group and rhG-CSF group's mean length of hospital stay were 31.5 (23-43) days and 37 (25-75) days, respectively (P<0.001) . ⑤The PEG-rhG-CSF group and rhG-CSF group's disease-free survival rates were (96.4±2.5) % and (94.7±2.6) % (P=0.638) , respectively, and the OS rates were 100.0% and (98.6±1.3) % (P=0.312) , respectively. Conclusion: PEG-rhG-CSF application after auto-HSCT in patients with lymphoma can promote hematopoietic granulocyte reconstruction and shorten hospital stay, but has no significant effect on the incidence of infection, disease-free survival, and overall survival after transplantation.
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Efficacy and cost of G-CSF derivatives for prophylaxis of febrile neutropenia in lymphoma and multiple myeloma patients underwent autologous hematopoietic stem cell transplantation
Wang, X., Ren, J., Liang, X., He, P.
Hematology (Amsterdam, Netherlands). 2021;26(1):950-955
Abstract
OBJECTIVES To compare the efficacies and costs between pegfilgrastim and filgrastim prophylaxis for FN post-ASCT for lymphoma and multiple myeloma patients. METHODS 43 patients who received pegfilgrastim (6 mg) were compared to a retrospective cohort of 129 patients that had received filgrastim post-ASCT. Hematopoietic recovery time, FN incidence and treatment costs were assessed and compared. RESULTS The mean time to absolute neutrophil count engraftment was 8.72?±?2.38 days for the prospective pegfilgrastim group and 9.87?±?3.13 days for the retrospective filgrastim group (P?=?0.027). The incidence of FN was 18.60% and 50.39% in prospective pegfilgrastim and retrospective filgrastim groups, respectively (P?=?0.000). The mean cost of filgrastim was $617.22?±?37.87, compared with $525.78 for pegfilgrastim (P?=?0.032). DISCUSSION Convenience, effectiveness, and safety of prophylaxis for FN in the prospective pegfilgrastim group were significantly improved compared to the retrospective filgrastim group in ASCT patients. CONCLUSION Pegfilgrastim prophylaxis was more effective and convenient than filgrastim for FN prophylaxis in patients post-ASCT, especially for MM patients.
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Flat-dose granulocyte colony-stimulating factor evaluation after autologous hematopoietic stem cell transplant in multiple myeloma patients: Does one dose fit all?
Kim, O. M., Jared, J. R., Hennes, E. R., Ninos, C. L., Przybylski, D. J., Callander, N. S.
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2020;:1078155220968611
Abstract
INTRODUCTION The current recommended granulocyte-colony stimulating factor (G-CSF) dose after autologous hematopoietic stem cell transplant (autoHSCT) in multiple myeloma patients is 5 mcg/kg/day administered subcutaneously until engraftment. Recently, our institution changed practice from weight-based to flat-dose G-CSF. The purpose of this study was to assess the impact of flat-dose G-CSF on time to engraftment among multiple myeloma patients of different weight groups. METHODS Retrospective chart review was completed for adult patients with multiple myeloma who underwent autoHSCT from March 2018 through August 2019. Data collected included time to neutrophil engraftment, total length of hospitalization, length of stay post-transplant, time to platelet engraftment, use of intravenous fluconazole or acyclovir, parenteral nutrition use, incidence of febrile neutropenia, antibiotic use, and death. Differences in outcomes were compared between patients ≤80 kg versus those >80 kg. A secondary analysis was completed for patients ≤100 kg versus those >100 kg. RESULTS There was no difference in time to neutrophil engraftment between weight groups (≤80 kg versus >80 kg: median = 12 days, p = 0.22; ≤100 kg versus >100 kg: median = 12 days, p = 0.52). There was a significant difference in intravenous fluconazole and acyclovir use between groups, with more use in the lower weight groups (≤80 kg versus >80 kg: 12 patients versus 10 patients p = 0.02; ≤100 kg versus >100 kg: 19 patients versus 3 patients p = 0.04). No significant differences were found for any other outcomes. CONCLUSION Utilizing a flat-dose of G-CSF for patients after autoHSCT does not appear to negatively affect patient outcomes. Institutions may benefit from using the 300 mcg dose of G-CSF for multiple myeloma patients after autoHSCT.
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The avoidance of G-CSF and the addition of prophylactic corticosteroids after autologous stem cell transplantation for multiple myeloma patients appeal for the at-home setting to reduce readmission for neutropenic fever
Rodríguez-Lobato, L. G., Martínez-Roca, A., Castaño-Díez, S., Palomino-Mosquera, A., Gutiérrez-García, G., Pedraza, A., Suárez-Lledó, M., Rovira, M., Martínez, C., Fernández de Larrea, C., et al
PloS one. 2020;15(11):e0241778
Abstract
BACKGROUND Autologous stem cell transplantation (ASCT) remains the standard of care for young multiple myeloma (MM) patients; indeed, at-home ASCT has been positioned as an appropriate therapeutic strategy. However, despite the use of prophylactic antibiotics, neutropenic fever (NF) and hospital readmissions continue to pose as the most important limitations in the outpatient setting. It is possible that the febrile episodes may have a non-infectious etiology, and engraftment syndrome could play a more significant role. The aim of this study was to analyze the impact of both G-CSF withdrawal and the addition of primary prophylaxis with corticosteroids after ASCT. METHODS Between January 2002 and August 2018, 111 MM patients conditioned with melphalan were managed at-home beginning +1 day after ASCT. Three groups were established: Group A (n = 33) received standard G-CSF post-ASCT; group B (n = 32) avoided G-CSF post-ASCT; group C (n = 46) avoided G-CSF yet added corticosteroid prophylaxis post-ASCT. RESULTS The incidence of NF among the groups was reduced (64%, 44%, and 24%; P<0.001), with a non-significant decrease in hospital readmissions as well (12%, 6%, and 2%; P = 0.07). The most important variables identified for NF were: HCT-CI >2 (OR 6.1; P = 0.002) and G-CSF avoidance plus corticosteroids (OR 0.1; P<0.001); and for hospital readmission: age =60 years (OR 14.6; P = 0.04) and G-CSF avoidance plus corticosteroids (OR 0.07; P = 0.05). CONCLUSIONS G-CSF avoidance and corticosteroid prophylaxis post ASCT minimize the incidence of NF in MM patients undergoing at-home ASCT. This approach should be explored in a prospective randomized clinical trial.
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The use of granulocyte colony stimulating factor after autologous hematopoietic stem cell transplantation
Farkas, F., Mistrik, M., Batorova, A.
Bratislavske lekarske listy. 2019;120(9):668-672
Abstract
Restrospective study to evaluate the efficacy of early vs. delayed initiation of G-CSF after autologous hematopoietic stem cell transplantation (AHSCT) in patients with lymphoid malignancies. BACKGROUND Granulocyte colony stimulating factor (G-CSF) is commonly used after AHSCT to accelerate stem cell engraftment to minimize the morbidity and mortality associated with prolonged neutropenia. However, there is no consensus on the optimal timing of G-CSF after HSCT. METHODS A total of 117 patients with lymphoid malignancies who underwent AHSCT were included. All patients received G-CSF (filgrastim 5 mug/kg s.c.) daily after AHSCT (43 patients on day 6-8 and 74 patients on day 3 or 4). All patients received standard conditioning regimen for the underlying disease, and standard supportive treatment, including treatment of febrile neutropenia. RESULTS The incidence of severe neutropenia was 81 % vs 17 %, and very severe neutropenia 61 % vs 4 % in the delayed and early G-CSF groups, respectively (p < 0.0001). The rate of fungal infection was higher in the group of patients who received delayed G-CSF (p < 0.005). CONCLUSION An early administration of G-CSF after AHSCT (on day 3 or 4) accelerates neutophil engraftment; decreases the incidence of severe neutropenia and the risk of infectious complications (especially fungal infections) (Tab. 1, Fig. 3, Ref. 22).
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Autologous Stem Cell Transplantation for Multiple Myeloma: Growth Factor Matters
Chen, J., Pan, J., Zhan, T., Tuazon, S., Saini, N., O'Hara, W., Filicko-O'Hara, J., Klumpp, T., Kasner, M., Carabasi, M., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
Engraftment syndrome (ES) is a known complication of autologous hematopoietic stem cell transplant during neutrophil recovery. There is a limited amount of data available comparing the incidence of ES with post-transplant G-CSF versus GM-CSF, specifically in patients with multiple myeloma. Our retrospective review of 156 patients at a single center showed that GM-CSF was associated with a higher incidence of ES compared with G-CSF (32% vs. 8% of patients, p<0.001) and that development of ES was associated with 32.9% (p<0.001) longer hospital stay. This suggests that the choice of growth factor could possibly contribute to the development of ES and the associated costs of increased medical care.
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A comparative effectiveness study of lipegfilgrastim in multiple myeloma patients after high dose melphalan and autologous stem cell transplant
Martino, M., Gori, M., Tripepi, G., Recchia, A. G., Cimminiello, M., Provenzano, P. F., Naso, V., Ferreri, A., Moscato, T., Console, G., et al
Annals of hematology. 2019
Abstract
G-CSF administration after high-dose chemotherapy and autologous stem cell transplantation (ASCT) has been shown to expedite neutrophil recovery. Several studies comparing filgrastim and pegfilgrastim in the post-ASCT setting concluded that the two are at least equally effective. Lipegfilgrastim (LIP) is a new long-acting, once-per-cycle G-CSF. This multicentric, prospective study aimed to describe the use of LIP in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation (ASCT) and compare LIP with historic controls of patients who received short-acting agent (filgrastim [FIL]). Overall, 125 patients with a median age of 60 years received G-CSF after ASCT (80 patients LIP on day 1 post-ASCT and 45 patients FIL on day 5 post-ASCT). The median duration of grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 x 10 [9]/L) was 5 days in both LIP and FIL groups, whereas the median number of days to reach ANC ≥ 0.5 x 10 [9]/L was 10% lower in the LIP than in the FIL group (10 vs 11 days), respectively. Male sex was significantly associated with a faster ANC ≥ 0.5 x 10 [9] L response (p = 0.015). The incidence of FN was significantly lower in the LIP than in the FIL group (29% vs 49%, respectively, p = 0.024). The days to discharge after ASCT infusion were greater in patients with FN (p < 0.001). The study indicates that LIP had a shorter time to ANC recovery and is more effective than FIL for the prevention of FN in the ASCT setting.
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10.
Granulocyte colony-stimulating factor utilization postautologous hematopoietic stem cell transplant in multiple myeloma patients: Does one size fit all?
Jackson, E. R., Jared, J. R., Piccolo, J. K., Woo, K. M., Mably, M. S., Reed, M. P., Callander, N. S.
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2018;:1078155218781888
Abstract
Purpose To evaluate a single institution's experience with granulocyte colony-stimulating factor after autologous hematopoietic stem cell transplant in myeloma patients to identify populations that benefit most from granulocyte colony-stimulating factor administration. Methods Retrospective chart reviews were conducted on patients 18+ years with multiple myeloma that underwent autologous hematopoietic stem cell transplant at UW Health from January 2012 to May 2016. Data collection included demographics, length of stay, time to engraftment, Eastern Cooperative Oncology Group performance status score, and hematopoietic cell transplantation-comorbidity index. The primary outcome was days from transplant to engraftment, defined as absolute neutrophil count > 500/mm(3) for two consecutive days or absolute neutrophil count > 1000/mm(3) once. A subset analysis was performed on patients whose date of engraftment was known. Results In total, 216 individual patients were included in the full cohort and 122 patients included in the subset analysis. Median time to engraftment between patients administered granulocyte colony-stimulating factor and the nongranulocyte colony-stimulating factor group was 12 versus 19 days (P < 0.001) in the full cohort and 12 versus 14 days (P < 0.001) in the subset analysis. The average length of stay posthematopoietic stem cell transplant in the granulocyte colony-stimulating factor group was 15 days versus 17 days in the nongranulocyte colony-stimulating factor group (P = 0.026) in the subset analysis. Additionally, no difference in time to engraftment was seen when stratified by age, Eastern Cooperative Oncology Group performance status score, or hematopoietic cell transplantation-comorbidity index. Conclusion Our study supports use of granulocyte colony-stimulating factor posthematopoietic stem cell transplant in myeloma patients to decrease time to engraftment and length of stay. Consideration should be given to utilization in all patients in this population posthematopoietic stem cell transplant. Further research is needed to identify the populations that benefit most from granulocyte colony-stimulating factor administration.