The effect of G-CSF use on hospital length of stay after an allogeneic hematopoietic cell transplantation: a retrospective multicenter cohort study
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
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.
The use of granulocyte colony stimulating factor after autologous hematopoietic stem cell transplantation
Bratislavske lekarske listy. 2019;120(9):668-672
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).
A comparative effectiveness study of lipegfilgrastim in multiple myeloma patients after high dose melphalan and autologous stem cell transplant
Annals of hematology. 2019
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 /L) was 5 days in both LIP and FIL groups, whereas the median number of days to reach ANC ≥ 0.5 x 10 /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  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.
G-CSF administration prior to donor lymphocyte apheresis promotes anti-leukaemic effects in allogeneic HCT patients
British journal of haematology. 2019
Donor lymphocyte infusion (DLI) is an effective method to establish full donor chimerism or to prevent and treat relapse after allogeneic haematopoietic cell transplantation (allo-HCT). Usually, DLIs are collected from naive donors as steady-state lymphocytes. When donor lymphocytes are collected during stem cell apheresis, donors are pre-treated with granulocyte colony-stimulating factor (G-CSF). However, the impact of G-CSF stimulation and the resulting composition of DLIs on beneficial anti-leukaemic responses and survival remain elusive. Therefore, we performed a retrospective analysis to evaluate the role of G-CSF-DLIs: 44 patients received either steady-state DLIs or G-CSF-DLIs to prevent and treat relapse or establish full donor chimerism after allo-HCT. The G-CSF-DLI patient cohort showed an improved conversion to full donor chimerism and a lower cumulative incidence of relapse or disease progression without a significantly increased cumulative incidence of graft-versus-host disease (GVHD). CD34(+) cells, monocytic myeloid-derived suppressor cells and monocytes as well as donor age and the subsequent occurrence of chronic GVHD were identified as risk factors that significantly improve overall survival after DLI administration. In conclusion, our data suggest that administration of G-CSF-DLIs results in graft-versus-leukaemia effects without exacerbating GVHD, therefore, improving survival after DLIs.
Autologous Stem Cell Transplantation for Multiple Myeloma: Growth Factor Matters
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
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.
A comparison of the effect of xinruibai versus filgrastim on hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation
Italian journal of pediatrics. 2018;44(1):63
BACKGROUND To compare the effect of xinruibai (Pegfilgrastim) and filgrastim injections on white blood cell and platelet (PLT) recovery, adverse events, post-operative complications, and cost effectiveness after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS Children who underwent allo-HSCT at our hospital from January 2014 to May 2017 due to thalassemia major, aplastic anemia, leukemia, and mucopolysaccharidosis were included. Among the children, 53 received xinruibai injections and 33 received filgrastim injections. RESULTS There were no significant differences in the average time to neutrophil and platelet recovery, the incidence of post-operative complications after allo-HSCT, the number of red blood cell and PLT infusions, or the incidence of adverse events related to the injection between two groups (P > 0.05). The pain score was 3.06 (SD 0.41) for the xinruibai group and 25.18 (SD 6.22) for the filgrastim group, indicating significant differences between the two groups (P < 0.001). No difference was found in the hospitalization cost. The cost of the granulocyte-colony stimulating factor (G-CSF) was 257.11 +/- 61.87 Euro in the xinruibai group and 214.79 +/- 0.00 Euro in the filgrastim group, showing significant difference (P < 0.001). CONCLUSIONS Xinruibai injection was more convenient, simple, effective, and safer than filgrastim.
Granulocyte colony-stimulating factor utilization postautologous hematopoietic stem cell transplant in multiple myeloma patients: Does one size fit all?
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2018;:1078155218781888
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.
Impact on acute myeloid leukemia relapse in granulocyte colony-stimulating factor application: a meta-analysis
Hematology (Amsterdam, Netherlands). 2018;:1-9
OBJECTIVES This meta-analysis evaluated the impact of granulocyte colony-stimulating factor (G-CSF) added to chemotherapy on treatment outcomes including survival and disease recurrence in patients with acute myeloid leukemia (AML). METHODS Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 19 September 2016 using search terms. Studies that investigated patients with AML who underwent stem-cell transplantation were included. RESULTS The overall analysis revealed a significant improvement in overall survival (OS) (P = .019) and disease-free survival (DFS) (P = .002) for patients receiving G-CSF with chemotherapy. Among patients without prior AML treatment, there was a significant improvement in DFS (P = .014) and reduction in incidence of relapse (P = .015) for those who received G-CSF. However, subgroup analyses found no significant difference between G-CSF (+) and G-CSF (-) treatments in rates of OS (P = .104) and complete remission (CR) (P = .572) for patients without prior AML treatment. Among patients with relapsed/refractory AML, there was no significant difference found between G-CSF (+) and G-CSF (-) groups for OS (P = .225), DFS (P = .209), and CR (P = .208). DISCUSSION Treatment with chemotherapy plus G-CSF appears to provide better survival and treatment responses compared with chemotherapy alone, particularly for patients with previously untreated AML. ABBREVIATIONS AML, acute myeloid leukemia; CI, confidence interval; CR, complete remission; DFS, disease-free survival; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte macrophage colony-stimulating factor; HR, hazard ratio; MDS, myelodysplastic syndrome; OR, odds ratio; OS, overall survival; RCTs, randomized control trials; RR, relative risk.
"Filgrastim following HLA-identical allogeneic bone marrow transplantation: long-term outcomes of a randomized trial"
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Human recombinant G-CSF reduces the duration of neutropenia following HLA-identical allogeneic bone marrow transplantation. However, its use remains controversial due to the risk of increasing the incidence of acute graft-versus-host disease (aGvHD) and slower platelet recovery. To clarify these risks, we conducted a prospective randomised placebo-controlled trial of filgrastim 5 mcg/kg/day IV from day 7 post-transplant until neutrophil recovery in 145 consecutive adults undergoing HLA-identical allogeneic bone marrow transplantation, with cyclosporine and methotrexate as GvHD prophylaxis. The primary endpoint was the incidence of aGvHD; haematological recovery, non-relapse mortality and post-transplant complications were secondary endpoints. Filgrastim had no significant effect on the incidence of aGvHD, platelet recovery, platelet transfusion requirements, chronic GvHD or survival. Filgrastim accelerated granulocyte recovery significantly (with absolute neutrophil counts>0.5x10(9)/L achieved after a median of 16 days versus 23 days for placebo, p <10(-4)), and reduced both early non-relapse mortality (2.9% versus 10.5%; p=0.042) and the duration of IV antibiotic therapy (18 versus 26 days, p=0.001) and hospitalisation (27 versus 34 days, p=0.017). In conclusion, in this setting, filgrastim reduced significantly the duration of neutropenia, IV antibiotic therapy, hospitalization and early non-relapse mortality, without increasing the risk of acute and chronic GvHD, relapse or delaying platelet recovery.
Impact of recommended weight-based dosing of granulocyte-colony stimulating factors in acute leukemia and stem cell transplant patients
Supportive Care in Cancer. 2017;25(6):1853-1858
PURPOSE Febrile neutropenia (FN) is a major risk factor for infection-related morbidity and mortality. The National Comprehensive Cancer Network recommends the prophylactic use of granulocyte-colony stimulating factors (G-CSF), dosed at 5 mcg/kg and rounded to the nearest vial size. A previous medication use evaluation conducted within a multi-hospital healthcare system demonstrated that only 67% of patients were started on appropriate weight-based dosing. The purpose of this study was to evaluate the effect of appropriate weight-based G-CSF dosing in patients on clinical outcomes. METHODS A retrospective chart review of patients with acute leukemia or stem cell transplant recipients who received G-CSF from May 2009 to September 2015 was conducted. Patient admissions were reviewed in regards to neutropenia length, incidence of FN, length of stay, and final disposition (alive or deceased). Admissions were divided into one of three weight-based dosing groups of under 5 mcg/kg, recommended 5 mcg/kg within a 10% range, and over 5 mcg/kg which were named under, recommended, and over, respectively. RESULTS Ninety-four admissions were included. Average age of this patient population was 58 years old, and the majority of patients were male (53%) and Caucasian (55%). Majority of patients had been diagnosed with acute myeloid leukemia (91%). Data showed average duration of neutropenia was around 10 days regardless if the patient received under 5 mcg/kg, the recommended 5 mcg/kg or over 5 mcg/kg G-CSF (10.1 +/- 6.7 days, 8.9 +/- 9.2 days, 10.1 +/- 9.1 days, respectively). Length of stay was similar for patients regardless of initial G-CSF dose (29.6 +/- 16.0 days, 29.1 +/- 18.4 days, and 24.5 +/- 17.0, respectively). However, the incidence of FN was significantly greater for those who received under 5 mcg/kg of G-CSF (87% for under, 68% for recommended, and 54% for over). CONCLUSIONS In this retrospective analysis, variations from the recommended 5 mcg/kg G-CSF dose did not significantly impact length of neutropenia, length of stay, nor mortality. However, patients who received under the 5 mcg/kg of G-CSF dose may be at a greater risk of FN.