-
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.
-
2.
The Effect of Granulocyte Colony-Stimulating Factor (G-CSF) on Early Complications and Graft-Versus-Host Disease (GVHD) in Allogeneic Stem Cell Transplantation (ASCT) Recipients
Aydın Kaynar, L., Özkurt, Z. N.
Cureus. 2023;15(9):e46105
Abstract
Objectives Granulocyte colony-stimulating factor (G-CSF) is commonly used to accelerate neutrophil recovery after allogeneic stem cell transplantation (ASCT) in most transplant centers. There was no consensus on the optimal use of G-CSF after ASCT. Although we use G-CSF to minimize morbidity and mortality, G-CSF can increase the risk of graft-versus-host disease (GVHD). In our study, we want to show the effect of prophylactic G-CSF on infection frequency, neutrophil and platelet engraftment, the duration of neutropenia, the development of GVHD, hospitalization time, and transplant-related mortality (TRM) after ASCT. Materials and methods One hundred (71 males and 29 females) patients who did not receive G-CSF and 100 (58 males and 42 females) patients who received prophylactic G-CSF were included in the study. Results Age, diagnosis, the time between diagnosis and transplantation, preparation regimen, donor type, and the number of infused cluster of differentiation (CD) 34+ cells were not different in both groups (p>0.05). The frequency of female patients was higher in the group receiving G-CSF. Febrile neutropenia was more frequent in patients who did not receive G-CSF. Neutrophil engraftment and platelet engraftment were detected longer in patients not receiving G-CSF. The frequency of veno-occlusive disease (VOD) and hyperacute, chronic, and acute GVHD was not different in both groups (p>0.05). One hundred-day TRM and five-year overall survival (OS) were similar in the two groups (p>0.05). Conclusions Our study supports that G-CSF usage does not cause an increase in the frequency of GVHD and has a positive effect on the process by accelerating myeloid engraftment. In light of the data in our study, we can say that the use of G-CSF should be investigated in a randomized controlled clinical trial.
-
3.
Immunoglobulin and granulocyte-colony stimulating factor affecting infection and hematopoietic reconstruction in allogeneic hematopoietic stem cell transplantation
Ma, L., Liu, G., Chen, Y., Fu, J., Chen, J., Gong, Q.
Chinese medical journal. 2023
-
4.
[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.
-
5.
Impact of G-CSF administration post-allogeneic hematopoietic stem-cell transplantation on outcomes: a systematic review and meta-analysis
Gupta, A. K., Meena, J. P., Haldar, P., Tanwar, P., Seth, R.
American journal of blood research. 2021;11(5):544-563
Abstract
Granulocyte colony-stimulating factors (G-CSFs) have been used post hematopoietic stem cell transplant (HSCT) for earlier neutrophil engraftment. The use of G-CSFs, and their effect on other post-HSCT outcomes remains debatable. In this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane library, Google Scholar, and IndMed using a predefined search strategy. We included randomized controlled trials (RCTs) and non-randomized studies (NRSs) reporting data on G-CSF administration post-HSCT, published in the English language from their inception until Jan 31, 2021. The primary outcome of this systematic review and meta-analysis was to evaluate the time to neutrophil engraftment (NE). The secondary outcomes were probability of NE, time to platelet engraftment (PE), the incidence of graft-versus-host disease (GVHD), duration of hospital stay (HS), and overall survival (OS). The review is registered with PROSPERO (CRD42020206989). Fourteen studies were extracted (n=9850), of which five were RCTs, and nine were NRSs. As per Egger's test, publication bias was not present for any outcome. After meta-analysis, we found that the duration of NE favouring G-CSF arm from RCTs was -0.94 days (SMD) [(95% CI: -1.38, -0.51); I(2)=35%], and from NRSs -1.2 days (SMD) [(95% CI: -1.43, -0.96); I(2)=74%]. For the outcome of GVHD, the relative risks (RR) of incidence for chronic GVHD and overall GVHD were not significant for the RCTs, and these were 1.11 (RR) [(95% CI: 1.00, 1.22); I(2)=43%] and 1.10 (RR) [(95% CI: 1.03, 1.18); I(2)=48%], respectively for NRSs. There was no difference in the incidence of GVHD (acute or chronic) in both arms. No significant difference was found between the two arms for the outcomes of PE, HS, and OS. For NE, there was a marginal benefit of around one day with the use of G-CSF. The use of G-CSF did not alter time to PE, the incidence of GVHD, HS, and OS in both arms.
-
6.
The effect of granulocyte colony-stimulating factor dose and administration interval after allogeneic hematopoietic cell transplantation on early engraftment of neutrophil and platelet
Noorazar, L., Bonakchi, H., Sankanian, G., Parkhideh, S., Salimi, M., Hajifathali, A., Mirfakhraie, R., Roshandel, E.
Journal of clinical laboratory analysis. 2021;35(12):e24060
-
-
Free full text
-
Abstract
BACKGROUND Hematopoietic stem cell transplantation (HSCT) is one of the treatments for hematologic malignancies. Numerous factors affect the HSCT outcome. The purpose of this study was to investigate the effect of post-HSCT administration of granulocyte colony-stimulating factor (post-G-CSF) on early neutrophil and platelet engraftment in allogeneic HSCT (allo-HSCT). MATERIAL & METHODS The study was performed on 76 patients diagnosed with AML and ALL. All patients underwent allo-HSCT at Taleghani stem cell transplantation center, Tehran, Iran, from February 2016 to December 2018. Chemotherapy regimens based on patients' conditions were selected between myeloablative and reduced-intensity regimens. RESULTS Statistical analysis revealed that the number of administered G-CSF units after HSCT was a time-dependent variable. Statistical analysis before day +11 reported that patients who received G-CSF <14 units had three times better early neutrophil engraftment than those with G-CSF ≥14 (CI 95%, AHR = 3.03, p:0.002). CD3+ cells count <318.5 × 10(6) /kg was associated with fast platelet engraftment (CI 95%, AHR 2.28, p:0.01). CONCLUSION In this study, post-G-CSF stimulation was associated with early engraftment in a time- and dose-dependent manner. Administration of G-CSF beyond 14 units resulted in adverse effects on neutrophil early engraftment. It also appeared that with a reduction in CD3+ cell counts, the likelihood of GVHD decreases, and platelet engraftment occurs earlier. Further investigations in the future are required to determine the factors affecting the process of early engraftment.
-
7.
Effect of rhG-CSF Combined With Decitabine Prophylaxis on Relapse of Patients With High-Risk MRD-Negative AML After HSCT: An Open-Label, Multicenter, Randomized Controlled Trial
Gao, L., Zhang, Y., Wang, S., Kong, P., Su, Y., Hu, J., Jiang, M., Bai, H., Lang, T., Wang, J., et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020;:Jco1903277
-
-
Free full text
-
Abstract
PURPOSE Relapse is a major cause of treatment failure after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) for high-risk acute myeloid leukemia (HR-AML). The aim of this study was to explore the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) combined with minimal-dose decitabine (Dec) on the prevention of HR-AML relapse after allo-HSCT. PATIENTS AND METHODS We conducted a phase II, open-label, multicenter, randomized controlled trial. Two hundred four patients with HR-AML who had received allo-HSCT 60-100 days before randomization and who were minimal residual disease negative were randomly assigned 1:1 to either rhG-CSF combined with minimal-dose Dec (G-Dec group: 100 µg/m(2) of rhG-CSF on days 0-5 and 5 mg/m(2) of Dec on days 1-5) or no intervention (non-G-Dec group). The primary outcome was relapse after transplantation, and the secondary outcomes were chronic graft-versus-host disease (cGVHD), safety of the treatment, and survival. RESULTS The estimated 2-year cumulative incidence of relapse in the G-Dec group was 15.0% (95% CI, 8.0% to 22.1%), compared with 38.3% (95% CI, 28.8% to 47.9%) in the non-G-Dec group (P < .01), with a hazard ratio (HR) of 0.32 (95% CI, 0.18 to 0.57; P < .01). There was no statistically significant difference between the G-Dec and non-G-Dec groups in the 2-year cumulative incidence of cGVHD without relapse (23.0% [95% CI, 14.7% to 31.3%] and 21.7% [95% CI, 13.6% to 29.7%], respectively; P = .82), with an HR of 1.07 (95% CI, 0.60 to 1.92; P = .81). After rhG-CSF combined with minimal-dose Dec maintenance, increasing numbers of natural killer, CD8+ T, and regulatory T cells were observed. CONCLUSION Our findings suggest that rhG-CSF combined with minimal-dose Dec maintenance after allo-HSCT can reduce the incidence of relapse, accompanied by changes in the number of lymphocyte subtypes.
-
8.
The effect of G-CSF use on hospital length of stay after an allogeneic hematopoietic cell transplantation: a retrospective multicenter cohort study
George, G., Martin, A. S., Chhabra, S., Eapen, M.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
Granulocyte colony stimulating factor (G-CSF) is administered after allogeneic hematopoietic cell transplantation (HCT) to aid with neutrophil recovery. We compared the effect of empiric G-CSF administration on duration of index inpatient hospitalization stay after HCT for patients aged =18 years with hematologic malignancy. G-CSF was considered empiric if administered between day -3 to day +6 in relation to infusion of the graft. We studied 3562 transplants (N=1487 HLA-matched sibling and N=2075 HLA-matched unrelated donor) between 2007 to 2016. Three hundred and thirteen (21%) recipients of HLA-matched sibling and 417 (20%) recipients of HLA-matched unrelated donor HCT received empiric G-CSF. The effect of G-CSF on index hospitalization stay was examined in general linear models (GLM) with adjustment for other patient, disease and transplant characteristics and acute graft-versus-host disease and infection post-transplant. Length of index hospitalization by treatment group did not differ for HLA-matched sibling HCT but was shorter with G-CSF (15 vs. 19 days, p<0.001) for HLA-matched unrelated donor HCT. GLM models confirmed shorter hospitalization with use of G-CSF for HLA-matched unrelated donor HCT (p=0.01). G-CSF was not associated with early survival for either donor type. There is no benefit or disadvantage of giving G-CSF to promote neutrophil recovery.
-
9.
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.
-
10.
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.