G-CSF use post peripheral blood stem cell transplant is associated with faster neutrophil engraftment, shorter hospital stay and increased incidence of chronic GVHD
Leukemia & lymphoma. 2020;:1-8
The use of G-CSF post allogeneic transplant has become a common practice to accelerate neutrophil engraftment. There is some controversy in its use. To further evaluate the effectiveness, we compared outcomes in patients who underwent PBSCT, either with or without the planned use of G-CSF post SCT. Among consecutive 162 patients from October 2012 to October 2014, 65 patients received G-CSF post-PBSCT, and 97 did not. More patients in G-CSF group received MAC (78% vs. 55%). Patients who received G-CSF had earlier neutrophil engraftment (median days 11 vs. 14) and shorter post-transplant hospital stay (median days 16 vs. 20, p?=?0.001). G-CSF use was associated with a higher rate of extensive chronic GVHD (44.3% vs.61.5%, p?=?0.027). G-CSF cost the equivalent of 0.25 hospital days but shortened the initial transplant admission by 4?days. Early cost-benefit may be later offset by the economic burden of chronic GVHD and associated complications.
Flat-dose granulocyte colony-stimulating factor evaluation after autologous hematopoietic stem cell transplant in multiple myeloma patients: Does one dose fit all?
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2020;:1078155220968611
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.
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
PloS one. 2020;15(11):e0241778
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.
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.
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
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020;:Jco1903277
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.
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.
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.
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.
"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.