Granulocyte Colony-stimulating Factor Mobilization Research Articles

Psychological and physical side effects during G-CSF mobilization in related donors of allo-HCT.

The psychological side effects of granulocyte colony-stimulating factor mobilization in related donors of allogeneic hematopoietic cell transplantation (allo-HCT) and impacts of psychological/physical side effects on harvest outcomes remain largely unknown. We prospectively analyzed 349 consecutive related peripheral blood stem cell (PBSC) donors for allo-HCT at the First Affiliated Hospital, Zhejiang University, School of Medicine from March 2021 to August 2023. Higher baseline peripheral blood white blood cell counts (p = 0.046), monocyte counts (p < 0.001), platelet counts (p = 0.001), and hemoglobin (p < 0.001) had a positive correlation to CD34+ cell counts in the first leukapheresis, while female donors (male vs. female, p < 0.001) and older age (> 40 vs. < = 40, p = 0.003) were negatively related to CD34+ cell counts. Bone pain was the most observed physical side effect and was more frequent in female donors (p = 0.032). The incidence of fatigue was higher in female donors and older donors (female vs. male, p = 0.016; > 40 vs. < = 40, p = 0.015). Donor depression (pre vs. during mobilization, p < 0.001), anxiety (pre vs. during mobilization, p = 0.043) and insomnia (pre vs. during mobilization, p = 0.011) scores increased during the mobilization period. Donors with higher depression, anxiety and stress scores at admission were more likely to experience nausea. At 1 month after the last leukapheresis, the counts of white blood cell, neutrophil, monocyte and hemoglobin were significant lower than baseline counts, while the platelet counts recovered to baseline. The mobilization and harvest process can increase the depression, anxiety and insomnia scores. Poor psychological status of the donor can aggravate the occurrence of physical side effects.

Abstract LB066: Acute systemic beta-adrenergic receptor activation to improve graft composition and outcomes in hematopoietic stem cell transplantation

Abstract Background: Graft-versus-host disease (GvHD) and relapse persist as significant hurdles in achieving successful outcomes following allogeneic hematopoietic cell transplantation (alloHCT). The composition of the graft plays a substantial role in influencing transplant outcomes. Higher numbers of naïve CD4 and naïve CD8 T cells correlate with increased GvHD risk, conversely, elevated numbers of NK cells are associated with enhanced graft-versus-leukemia (GvL) effects. Acute systemic β-adrenergic receptor activation triggers the mobilization of favorable effector lymphocytes into the bloodstream, leading to a significant alteration in the composition of circulating immune cells. Aim: This study investigated whether infusion with the non-selective beta-agonist isoproterenol (ISO), following granulocyte colony-stimulating factor (G-CSF) mobilization, would enhance human peripheral blood hematopoietic cell (PBHC) grafts and improve transplant outcomes in NSG mice. Methods: Ten healthy volunteers received ISO infusion (50 ng/kg/min) for 20 minutes after 5 days of G-CSF. Blood samples were collected before and during the last 5 minutes of ISO infusion. Results: ISO infusion increased the total number of G-CSF-mobilized CD34 cells (28±13 cell/µl to 32±13 cells/µl) and significantly improved G-CSF-mobilized PBHC composition, increasing favorable graft cell subsets—NK cells (9.5% to 27.9%) and γδ T cells (5.0% to 7.5%)—and reducing unfavorable graft components—B cells (12.6% to 7.7%), naïve CD4 (18.1% to 11.2%), and naïve CD8 (8.9% to 5.8%) T cells (all p&amp;lt;0.05). NSG mice receiving G-CSF+ISO mobilized grafts exhibited lower GvHD (P=0.012) and extended survival (median survival: G-CSF alone = 45 days, G-CSF+ISO = 78 days) compared to mice receiving grafts mobilized by G-CSF alone. No difference in human CD45 engraftment was observed between the groups, with ~50% engraftment in both groups of mice. Upon challenge with the K562 chronic myeloid leukemia cell line, 42% of NSG-Tg(Hu-IL15) mice receiving G-CSF+ISO mobilized grafts were alive with low tumor burden at day 40, compared to 15% of mice receiving G-CSF mobilized grafts. In vitro, PBHC mobilized by G-CSF+ISO demonstrated an 8-fold increase in cytolysis against K562 compared to PBHC mobilized by G-CSF only (P=0.0002). Conclusion: ISO infusion post-G-CSF treatment favorably enhances graft composition, mitigates GvHD, prolongs survival, and augments GvL effects. Our findings suggest that acute systemic beta-adrenergic receptor activation could be a valuable strategy to enhance outcomes in alloHCT. Citation Format: Helena Batatinha, Grace M. Niemiro, Nicole Pena, Giovannah Hoskin, Preteesh Mylabathula, Forrest Baker, Tiffany Zuniga, Kyle Smith, Douglass Diak, Michael Seckeler, Emmanuel Katsanis, Richard Simpson. Acute systemic beta-adrenergic receptor activation to improve graft composition and outcomes in hematopoietic stem cell transplantation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB066.

Prolonged infusion time of cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) as a mobilization regimen may improve mobilization efficiency in newly diagnosed multiple myeloma patients: a single center experience

Objectives This study aimed to clarify the effectiveness and safety of two different infusion durations of cyclophosphamide (CTX) plus granulocyte colony-stimulating factor (G-CSF) for peripheral blood stem cell mobilization in patients with newly diagnosed multiple myeloma (NDMM). Methods One hundred and fifty-six consecutive NDMM patients receiving CTX plus G-CSF mobilization and autologous stem cell transplantation during the period of September 2008 to May 2020 were selected for retrospective analysis. According to differences in prolonged infusion time of CTX, they were divided into a 24-h group (24-h continuous infusion) and a control group (4-6 h of infusion). Mobilization and safety of infusion were analyzed. Flow cytometry was used to detect the peripheral blood CD34+ cell count. Multivariate analysis was performed to determine the factors influencing the number of CD34+ cells. Results The mean CD34+ cell counts collected in 24-h and control groups were 6.78 (interquartile range [IQR] 3.59-11.69) and 4.48 (IQR 2.39-6.30) ×106/kg, respectively (p < 0.001). Meanwhile, the target number of CD34+ cells/kg (defined as ≥4 × 106/kg) was collected from 51 (75%) of cases in 24-h group vs. 45 (51%) in the control group (p = 0.002). Multivariate analysis identified the independence of CTX infusion time as a factor influencing the target number of CD34+ cells/kg [odds ratio OR, 4.045; 95% CI: 1.630-10.038, p = 0.003]. The post-transplantation time to neutrophil engraftment was 10 (IQR 9-11) in 24-h group and 11 (IQR 10-12) in control group (p < 0.001). Finally, no statistical differences were identified between groups in terms of hematologic and non-hematologic toxicities. Conclusions For patients with NDMM, 24-h continuous infusion of CTX plus G-CSF contributes to improved mobilization efficiency and equivalent toxicity as a stem cell mobilization regimen.

G-CSF Induces MAIT Cells to Exert Anti-Intestinal Gvhd Effects Dependent on CXCR6 Mediated Chemotaxis

Background: Graft-versus-host disease (GVHD) is a major complication leading to transplantation failure and affecting overall survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Granulocyte colony-stimulating factor (G-CSF) can induce T-cell tolerance and altering graft cell components to enhance GVHD prevention in HSCT. MAIT cells are a group of innate immune T cells. It has unique biological properties, including mucosal tissue enrichment, activation of microbial riboflavin derivatives and tissue repair properties, which determine MAIT cells play an important role in mucosal immunity. Previous studies found that a high MAIT cell counts in G-CSF-induced grafts (G-grafts) is associated with a low incidence of gut acute GVHD (aGVHD). However, the effect of G-CSF mobilization on the phenotype, function and its regulatory mechanism in GVHD of MAIT cells has not been elucidated. Methods: MAIT cells in PB samples from four healthy donors before and after G-CSF treatment were isolated for Single-cell RNA sequencing (Figure A). Flow cytometry, In vitro experiment and NOD-SCID-IL-2Rg−/− mice (NSG mice) were performed to observe the phenotypic, functional changes and the dynamic distribution of G-CSF induced donor-derived MAIT cells in recipients. Results: A total of 80709 MAIT cells were divided into 14 clusters. Based on key type-associated marker genes and gene sets, MAIT0 (clusters 5 and 9), MAIT1 (cluster 7), MAIT2 (clusters 4 , 11), Cycling MAIT (clusters 12, 13), Activation (clusters 0, 8), ISG (cluster 10) and MAIT17 (clusters 1,2,3,6) cells were identified (Figure B,C). The subset frequencies and expression signatures of immunosuppression (MAIT2 and Cycling cells from cluster 12) and tissue repair (Activation and MAIT17) were both increased at both transcriptome (Figure D) and protein levels, suggesting that G-CSF enhanced the immune tolerance and tissue repair of MAIT cells. In vitro further confirmed that G-CSF-induced MAIT cells showed a stronger inhibition for T cell proliferation (Figure E). Besides, overexpressed genes related to immune regulation in G-CSF induced MAIT cells were strongly enriched in cluster 12 with high CSF3R (G-CSF receptor) expression (Figure F). The cluster 12 also showed the enrichment of IL-17 and TNF signaling pathway favoring tissue repair function, while downregulation of Graft-versus-host disease pathway upon G-CSF mobilization, indicating that G-CSF-CSF3R interaction is the potential mechanism by which G-CSF mediates the immune regulation of MAIT cells. Based on whether recipients develop gut aGVHD or not after allo-HSCT, the matched donor grafts after G-CSF mobilization were divided into two groups termed as post-G-CSF-no gut aGVHD (n=3) and post-G-CSF-gut aGVHD group (n=1), respectively. MAIT cells in post-G-CSF-no gut aGVHD group overexpressed CSF3R and its related target genes, immunosuppression and tissue repair signatures compared with post-G-CSF-gut aGVHD. Besides, MAIT cells from G-PB of recipients without gut aGVHD had a higher CD114 expression (encoded by CSF3R) compared with gut aGVHD (Figure G). These results suggest that the enhanced immunosuppression and tissue repair function of MAIT cells induced by G-CSF may exert anti-gut aGVHD effects. The NSG mice confirmed MAIT cells in G-PB to tissue chemotaxis especially gut tissues in the recipient. A higher frequency of MAIT cells was detected in gut tissues in the low GVHD score group (GVHD Score＜3) compared with the high GVHD score group on post-transplant day 14 (Figure H), suggesting recruited MAIT cells in gut tissues favor anti-gut aGVHD effect. Moreover, CXCR6 was the most differentially expressed chemotactic receptor gene between post-G-CSF-no gut aGVHD and post-G-CSF-gut aGVHD group (Figure I). At the protein level, the expression of CXCR6 were significantly upregulated upon G-CSF administration (Figure I), while that of CCR6 and CXCR6 was non-significant. These results suggest that CXCR6 is necessary for G-CSF induced MAIT cell recruitment to the gut tissue. Conclusions G-CSF-CSF3R interactions enhance immunosuppression and tissue repair functions of MAIT cells, while CXCR6 recruits these functional MAIT cells from PB to gut tissues to exert anti-gut aGVHD effect. Hence, CSF3R and CXCR6 expression in G-CSF mobilized MAIT cells is crucial to exert anti-gut aGVHD effect, and has the potential to become predictive markers of gut aGVHD.

G-CSFR Is a Checkpoint of Natural Killer Cells Against Tumor

G-CSFR is a cell surface receptor that can activate cell proliferation and differentiation after binding to granulocyte colony stimulating factor(G-CSF). However, in natural killer (NK) cells, the biological role of G-CSFR has not been fully elucidated. Here we show that granulocyte colony-stimulating factor receptor, that is encoded by the CSF3R gene, is a novel and potent checkpoint in both human and mouse NK cells fighting against tumors. Previous studies have shown that NK cells under resting state with low expression of G-CSFR, but highly expressed in peripheral blood and bone marrow NK cells after G-CSF mobilization. We therefore used G-CSFR blocking agent in vitro to evaluate the effect of G-CSFR on human NK cells proliferation and cytotoxicity capacity. The results showed that G-CSFR agonist significantly down-regulated the proliferation and cytotoxicity of NK cells in vitro and this is independent of G-CSF stimulation. Since NK92 and YT cell lines highly express G-CSFR, we then knocked down G-CSFR in NK92 and YT cells. The results showed that the low expression of G-CSFR enhanced the expression of CD107a in vitro, indicating G-CSFR may be an inhibitory signaling in NK cells. To the further evaluate the specific role of G-CSFR in NK cells and we therefore constructed NK-specific CSF3R deficiency mice (CSF3R △NK/NK; CSF3Rfl/flNCR1cre, thecre group) and the control group ( CSF3Rfl/fl ( CSF3RWT/WT mice, the flox group). We then evaluated the phenotype, differentiation and functional state of NK cells between the two group. NK-specific CSF3R deficiency increased mature NK subsets in mice, and these CSF3R-deficient NK cells exhibited enhanced activation, cytotoxicity and proliferation, which is in accordance with the role in human NK cells. After constructing four tumor-bearing models, namely MC38 (colon tumor), LLC (lung tumor), MLL-AF8(acute myeloid leukemia), B16-F10(melanoma), we found that CSF3R specific depletion in NK cells reduced the tumor burden, prolonged the survival and reduced tumor metastasis in CSF3R△NK/NK mice (Figure 1A-D), indicating CSF3R depletion in NK cells promotes increased ability against tumors. To further evaluate the molecular mechanism of G-CSFR regulation of NK cell function, single cell RNA sequencing on bone marrow cells from both CSF3R△NK/NK mice and CSF3RWT/WT mice and NK cells were extracted for further subpopulation analysis. UMAP analysis revealed the clustering of bone marrow NK cells from both genotypes into ten subsets and on the basis of the key gene expression of NK cell effector molecules, transcriptional factors, maturation markers, and proliferation marker, we identified NK cell maturation program as mBM5+mBM8, mBM2+mBM3+ mBM6 and mBM0, by which immature NK cells should go through to gain optimal effector function, according to this model, CSF3R△NK/NK mice contained more NK cells belonging to the terminally mature mBM0 than CSF3RWT/WT mice. “Cell Killing” and “leukocyte mediated cytotoxicity” pathway was enriched in CSF3R△NK/NK mice, indicating enhanced activation state of NK cells. In conclusion, our results uncover a potent checkpoint in NK cells protecting against tumors, suggesting a promising approach of targeting G-CSFR for NK cell-based immunotherapies.

Outcomes of Patients Treated at First Transplant Center in Dubai, UAE

Introduction: Autologous stem cell transplant (ASCT) is a well-known treatment modality for decades with curative potential in the field of hematological malignancies such as lymphoma (Relapsed Hodgkin's Lymphoma) and multiple myeloma (MM), but access in the Middle East, specifically in the metropolitan city of Dubai, United Arab Emirates (UAE) has been limited. This is despite the fact that UAE is a high-income country according to the Gross national income (GNI) and has a population of approximately 9.5 million. In 2021, we developed the first and only ASCT unit in Dubai, United Arab Emirates (UAE). This was a milestone achievement to offer ASCT to residents. This service was available since approval by Dubai Health Authority (DHA) in September 2021 and capacity for 2 ASCT at a time. The unit comprises 2 positive pressure isolation rooms, with in-house apheresis, stem cell storage facilities. This is the first report of the safety and efficacy outcomes of patients (pts) who were transplanted to date at our center. Despite the modest volume, this data will serve as a resource for policymakers, healthcare professionals and is important for the ASCT community as we advance care of ASCT recipients in regions with previously limited access. Methods: This is a single-center retrospective study performed at American Hospital Dubai, UAE. We identified and included pts who received ASCT for lymphoma and MM between September 2021-June 2023. Per institutional protocols, mobilization was done with granulocyte colony-stimulating factor (GCSF). The stem cells were collected via Optia®spectra apharesis system. MM pts collected for 2 ASCT while those with relapsed HL collected for 1 ASCT. Conditioning chemotherapy administration was outpatient for melphalan (for MM) and inpatient for rHL with BEAM. Monitoring was per institutional standards. Descriptive analysis is reported. Results: There have been 17 ASCTs performed with at least one month follow-up. The most common indication was MM (9) followed by Relapsed lymphoma (8) and 1 case of multiply relapsed Ewing's Sarcoma. (Table 1) Mobilization:100% pts received granulocyte colony-stimulating factor (GCSF) mobilization with one patient required plerixafor in addition. The median days of collection was 1 (Range 1-2 days). All pts collected successfully. Neutropenic Events: Almost all patients (95%) had expected neutropenic fever by day +8.Median time to onset of Grade 4 neutropenia (absolute neutrophil count &amp;lt;500) was 6 days (3-8); Median time to onset of neutropenic fever was 7 days (3-10). Causative organisms were identified in 2 (11%) (Both bacterial infections). Antibiotic of choice was meropenem. ICU Admissions: Only one (6%) patient was admitted in ICU for neutropenic typhilitis on Day +3. That pt spent 20 days in ICU and total of 45 days in hospital with recovery to baseline. Resource Utilization: ASCT for MM was 100% outpatient chemotherapy and cell infusions. The patients were admitted on Day 6 post-transplant for neutropenic care, except 1 patient who presented at the emergency department with febrile neutropenia and diarrhea on day +3. The patients planned for ASCT for rHL were admitted for conditioning chemotherapy, stem cell infusion and neutropenic care until count recovery. Median duration of hospital stay was 17 days (8-45 days). The median days of GCSF post-cell infusion per patient was 8 days (6-15). Efficacy Outcomes: Of the 9 MM pts, all achieved complete response (CR). With a median follow up of 21 months, 100% continued to be on maintenance. For the rHL cohort, response rate was 100%, all CR, and continue to have ongoing responses. The patient with relapsed refractory Ewing's sarcoma has progression-free survival (PFS) of 5 months after ASCT. Overall survival (OS) was 100% for all diseases post-transplant. Conclusion: Our study describes promising outcomes of pts treated at our center, which is the first and only center offering ASCT in Dubai, UAE. This demonstrates that with available infrastructure and expertise, ASCT programs in countries similar to UAE are feasible and increase access to this therapy. Continued efforts at monitoring outcomes, education of the local population, and outreach partnerships with colleagues are essential to increase access to patients in the region.

Constructing a Machine Learning-Based Rating Model to Predict the Outcome of GCSF Mobilization of Hematopoietic Stem Cells in Peripheral Blood

Objective Peripheral blood stem cells serve as the primary source of hematopoietic stem cells for both autologous and allogeneic stem cell transplantation. Granulocyte colony-stimulating factor (G-CSF) stands as the most commonly employed mobilizing agent in clinical practice. While the majority of donors receiving G-CSF mobilization demonstrate high mobilization efficiency, there remains a subset of donors who fail to yield a sufficient quantity of hematopoietic stem cells. Inefficient mobilization not only leads to wastage of valuable resources but also significantly impacts transplant outcomes for recipients. Therefore, addressing the challenges associated with predicting mobilization outcomes, optimizing donor selection strategies, and further enhancing mobilization approaches is of paramount importance. Methods In this study, we conducted a retrospective analysis of mobilization data from 1008 donors who underwent hematopoietic stem cell mobilization using G-CSF at the Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, over the past 5 years. We meticulously examined the correlation between mobilization outcomes (quantified by the quantity of collected CD34+ cells) and various factors, including mobilizing agent usage, demographic data, complete blood count, and blood biochemistry. Furthermore, we harnessed the power of machine learning algorithms, such as linear regression, decision tree, and AdaBoost, to develop a robust scoring model capable of predicting mobilization outcomes. The primary objective of this model is to furnish a predictive tool for assessing mobilization outcomes with accuracy and precision. Results (1) Prior to receiving G-CSF, several factors exhibited a significant positive correlation with the quantity of CD34+ cells in the collection: donor's body weight (R=0.37, p&amp;lt;0.001), peripheral blood leukocytes (R=0.24, p&amp;lt;0.001), hemoglobin (R=0.23, p&amp;lt;0.001), monocytes (R=0.22, p&amp;lt;0.001), lymphocytes (R=0.18, p&amp;lt;0.001), platelets (R=0.18, p&amp;lt;0.001), red blood cells (R=0.12, p&amp;lt;0.001), neutrophils (R=0.15, p&amp;lt;0.001), hematocrit (R=0.21, p&amp;lt;0.001), mean corpuscular-hemoglobin concentration (R=0.15, p&amp;lt;0.001), low-density lipoprotein (R=0.11, p&amp;lt;0.01), albumin (R=0.09, p&amp;lt;0.05), ferritin (R=0.19, p&amp;lt;0.001), triglycerides (R=0.17, p&amp;lt;0.001), creatinine (R=0.17, p&amp;lt;0.001), and uric acid (R=0.29, p&amp;lt;0.001). (2) Age exhibited a significant negative correlation with the quantity of collected CD34+ cells in the collection (R=-0.11, p&amp;lt;0.001). (3) When the total dose of G-CSF administration was fixed, mobilization with twice-daily dosing yielded superior results compared to once-daily dosing (collected CD34+ cell count: 1268/μl vs. 1044/μl, p&amp;lt;0.001). (4) The ratio of G-CSF dosage to body weight demonstrated a significant negative correlation with the quantity of CD34+ cells (R=-0.09, p&amp;lt;0.01). Mobilization with a ratio of 6-7 μg/kg/day showed better results compared to a ratio of 7-12 μg/kg/day (p=0.07). (5) A scoring model was developed using machine learning methods to predict the mobilization outcomes of donors. Validation on the test dataset exhibited a high predictive ability of the model (AUC&amp;gt;0.7). Conclusion This study provides valuable insights for selecting hematopoietic stem cell donors and serves as a reference for future strategies aimed at improving mobilization outcomes. The identified factors, such as donor weight, peripheral blood parameters, G-CSF dosing regimen, and the ratio of dosage to body weight, can be considered when selecting donors and optimizing mobilization protocols. By incorporating machine learning techniques, a scoring model was developed, demonstrating a high predictive ability that can assist in forecasting mobilization outcomes for potential donors. These findings contribute to the optimization of donor selection and mobilization strategies.

Study on the Impact of G-CSF Mobilization on the Level of MDSCs in Donor Peripheral Blood and Its Correlation with Patient Prognosis

Introduction:MDSCs are a newly discovered and heterogeneous population of immature bone marrow cells with immunosuppressive characteristics, capable of inhibiting innate and adaptive immune responses. Granulocyte colony-stimulating factor (G-CSF) is a member of the hematopoietic growth factor cytokine family responsible for the proliferation, maturation, differentiation, and survival of neutrophil lineage. In many hospitals in China, allo-HSCT procedures often involve administering G-CSF continuously for 5 days to healthy donors before collecting the graft, to mobilize white blood cells. This study discusses the impact of G-CSF mobilization on the absolute values and functions of total immunosuppressive myeloid-derived suppressor cells (MDSCs) and their subsets, M-MDSCs and P-MDSCs, in the peripheral blood of healthy donors. Furthermore, it explores the effects of transferring MDSCs from the graft to the patient's body on their prognosis and immune reconstitution. Method：From August 2022 to December 2022, a total of 72 donors and 72 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) were selected as the subjects at Lu Daopei Hospital in Beijing. Among the donors, there were 47 males and 25 females, with a median age of 34 years (19, 48). Among the patients, there were 33 males and 39 females, with a median age of 34 years (23, 45). The patients were diagnosed as acute leukemia or MDS in CR status and further categorized into infection group, graft-versus-host disease (GVHD) group, and no-event group based on post-transplantation outcomes. Peripheral blood samples were collected from the donors before and on the 5th day after mobilization, as well as from the graft and the patients. Flow cytometry was employed to determine the absolute counts of MDSCs and their subsets. Result 1. The absolute count of total MDSCs in the donor's peripheral blood before mobilization was 3/μl (2, 8), accounting for 0.1% (0.0, 0.2) of PBMCs, significantly lower than the absolute count of total MDSCs in the donor's peripheral blood after G-CSF mobilization, which was 2283/μl (1091, 5288), accounting for 6.4% (3.2, 9.5) of PBMCs, P&amp;lt;0.01. In the infection group, the absolute count and percentage of total MDSCs, P-MDSCs, and LOX1+P-MDSCs in the donor's peripheral blood after mobilization were higher than those in the donor's peripheral blood corresponding to the no-event group, and significantly higher than those in the donor's peripheral blood corresponding to the GVHD group. P&amp;lt;0.05. Similarly, the absolute count and percentage of total MDSCs, P-MDSCs, and LOX1+P-MDSCs in the correspondingdonor's peripheral blood inthe infection group after mobilization were higher than those in the donor's peripheral blood corresponding to the no-event group, and significantly higher than those in the donor's peripheral blood corresponding to the GVHD group., P&amp;lt;0.05. The absolute count and percentage of M-MDSCs in the infection group were higher than the no-event group and GVHD group, but the differences among the three did not reach statistical significance. Patients who developed infections after transplantation received a higher absolute count of total MDSCs from the graft compared to the no-event group, and significantly higher than the GVHD group, P&amp;lt;0.05. The mortality rate in the infection group was 30% (8/26), in the GVHD group was 14% (3/21), and in the no-event group was 0% (0/25). The ROC curve area under the curve (AUC) for the absolute count of total MDSCs per kilogram of body weight from the donor in the GVHD group was 0.669, with a cutoff of 1.7×107/kg, while in the infection group, the AUC was 0.661, with a cutoff of 4.3×107/kg. Conclusion: G-CSF can induce an increase in the content and enhancement of function of MDSCs in the donor's peripheral blood Maintaining a balance of MDSCs helps ensure immune homeostasis after transplantation.

A research on the influence of G-CSF mobilization on donor's peripheral blood MDSCs and its relationship with patient prognosis

ObjectiveTo discuss the effects of mobilization of healthy donors with granulocyte colony-stimulating factor (G-CSF) on the absolute values and functions of myeloid-derived suppressor cells (MDSCs) and subpopulations of M-MDSCs and P-MDSCs in their peripheral blood. In addition, this study also aims to investigate the impacts of the adoptively transferred MDSCs from the grafts to the patients on their prognosis and immune reconstitution. MethodsThe selection of 72 donors and 72 patients were conducted for allogeneic hematopoietic stem cell transplantation (allo-HSCT) from August 2022 to December 2022 at Lu Daopei Hospital in Beijing, China. Statistical calculations were performed by Wilcoxon signed-rank test, Kruskal Wallis test, χ2 test, Kaplan Meier test, and log-rank test to analyze the data. Results & ConclusionG-CSF induced significant amplification of MDSCs in the peripheral blood of donors in percentage and absolute values. Whether the level of P-MDSCs in patients conducted for the adoptive transfer of P - MDSCs is higher than 3.7× 107/kg or lower than 1.4× 107/kg leads to a poor prognosis of the patients. Ensuring a balanced state of MDSCs is crucial for effective immunotherapy. Transferring a high level of MDSCs from the graft to the patient's body is advantageous for the development of MDSCs while simultaneously inhibiting the proliferation of lymphocyte subgroups.

Comparison of Plerixafor or Cyclophosphamide Combined with G-CSF in Mobilization of Peripheral Blood Stem Cells in Multiple Myeloma

To compare the efficacy of plerixafor (PXF) combined with granulocyte colony-stimulating factor (G-CSF) (PXF+G-CSF) and cyclophosphamide (Cy) combined with G-CSF (Cy+G-CSF) in the mobilization of peripheral blood stem cells (PBSCs) in patients with multiple myeloma (MM). The clinical data of 41 MM patients who underwent PBSC mobilization using PXF+G-CSF (18 cases) or Cy+G-CSF (23 cases) in Shanxi Bethune Hospital from January 2019 to December 2021 were retrospectively analyzed, including the count of collected CD34+ cells, acquisition success rate, failure rate, and optimal rate. The correlation of sex, age, disease type, DS staging, ISS staging, number of chemotherapy cycle, disease status before mobilization, and mobilization regimen with the collection results was analyzed, and the adverse reactions, length of hospital stay, and hospitalization costs were compared between the two mobilization regimens. The 41 patients underwent 97 mobilization collections, and the median number of CD34+ cells collected was 6.09 (0-34.07)×106/kg. The acquisition success rate, optimal rate, and failure rate was 90.2%, 56.1%, and 9.8%, respectively. Univariate analysis showed that sex, age, disease type, and disease stage had no significant correlation with the number of CD34+ cells collected and acquisition success rate (P >0.05), but the patients with better disease remission than partial remission before mobilization were more likely to obtain higher CD34+ cell count (P <0.05). The PXF+G-CSF group had a larger number of CD34+ cells and higher acquisition success rate in the first collection than Cy+G-CSF group (both P <0.05), and had lower infection risk and shorter length of hospital stay during mobilization (both P <0.05), but the economic burden increased (P <0.05). PXF+G-CSF used for PBSC mobilization in MM patients has high first acquisition success rate, large number of CD34+ cells, less number of collection times, and short length of hospital stay, but the economic cost is heavy.

A comparison of peripheral blood stem cell collection outcomes for multiple myeloma; mobilization matters in the era of IMiD induction.

Collection of peripheral blood stem cells (PBSCs) for autologous stem cell transplant (ASCT) requires mobilization from the bone marrow. There is variation in mobilization choice; during the COVID-19 pandemic BSBMT&CT guidelines recommended using granulocyte-colony stimulating factor (G-CSF) alone to minimize the use of chemotherapy. We report on the impact of mobilization regimen on stem cell collection, and whether IMiD-containing induction therapy impacts on mobilization and consequently transplant engraftment times for 83 patients undergoing ASCT at Leeds Teaching Hospitals. Cyclophosphamide plus G-CSF (cyclo-G) mobilization yielded more CD34+ cells (8.94vs. 4.88 ×106/kg, p=<0.0001) over fewer days (1.6vs. 2.4 days, p=0.007), and required fewer doses of salvage Plerixafor than G-CSF only (13.6%vs. 35%, p=0.0407). IMiD-containing induction impaired all of these factors. CD34+ doses>8×106/kg were more frequent with Cyclo-G (62%vs. 11%, p=0.0001), including for those receiving IMiD 1st line induction (50%vs. 13.3%, p=0.0381). Note that 92.6% of those receiving IMiD-free inductions were mobilized with Cyclo-G. The novel agents used in modern induction regimens (e.g Daratumumab) have been shown to impair yields, increasing the importance of optimizing mobilization regimens in the first instance. Furthermore, as cellular therapies become established in the management of multiple myeloma emerging data highlights the potential benefits of stem cell top up in the management of the haematological toxicities of these therapies. Our findings support re-adoption of Cyclo-G as the gold standard for mobilization to optimize PBSC harvesting and ensure sufficient cells for subsequent ASCTs.

Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial

Autologous hematopoietic stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). However, many individuals are unable to collect optimal CD34+ hematopoietic stem and progenitor cell (HSPC) numbers with granulocyte colony-stimulating factor (G-CSF) mobilization. Motixafortide is a novel cyclic-peptide CXCR4 inhibitor with extended in vivo activity. The GENESIS trial was a prospective, phase 3, double-blind, placebo-controlled, multicenter study with the objective of assessing the superiority of motixafortide + G-CSF over placebo + G-CSF to mobilize HSPCs for ASCT in MM. The primary endpoint was the proportion of patients collecting ≥6 × 106 CD34+ cells kg–1 within two apheresis procedures; the secondary endpoint was to achieve this goal in one apheresis. A total of 122 adult patients with MM undergoing ASCT were enrolled at 18 sites across five countries and randomized (2:1) to motixafortide + G-CSF or placebo + G-CSF for HSPC mobilization. Motixafortide + G-CSF enabled 92.5% to successfully meet the primary endpoint versus 26.2% with placebo + G-CSF (odds ratio (OR) 53.3, 95% confidence interval (CI) 14.12–201.33, P < 0.0001). Motixafortide + G-CSF also enabled 88.8% to meet the secondary endpoint versus 9.5% with placebo + G-CSF (OR 118.0, 95% CI 25.36–549.35, P < 0.0001). Motixafortide + G-CSF was safe and well tolerated, with the most common treatment-emergent adverse events observed being transient, grade 1/2 injection site reactions (pain, 50%; erythema, 27.5%; pruritis, 21.3%). In conclusion, motixafortide + G-CSF mobilized significantly greater CD34+ HSPC numbers within two apheresis procedures versus placebo + G-CSF while preferentially mobilizing increased numbers of immunophenotypically and transcriptionally primitive HSPCs. Trial Registration: ClinicalTrials.gov, NCT03246529

Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.

Cyclophosphamıde–Etoposıde + G-csf Compared to G-csf alone in Perıpheral Blood Stem Cell Mobılızatıon for Multıple Myeloma

Background: Multiple myeloma (MM) is the leading indication of autologous hematopoietic stem cell transplantation (AHSCT). There are different regimens used for peripheral blood stem cell mobilization in MM. A minimum of 2 × 106 CD34 + cells/kg are needed for engraftment. This study that present a comparison of the mobilization outcomes Cyclophosphamide-Etoposide (Cy-Et) + granulocyte-colony stimulating factor (G-CSF) group and G-CSF alone group. Patients and methods: This study has been performed in a retrospective manner. 110 patients with diagnosed MM who underwent stem cell mobilization at Memorial Sisli Hospital between the years of 2013 and 2018 were evaluated. We retrieved data on patient demographics, disease status at mobilization, treatment characteristics, stem cell mobilization, collection and post AHSCT outcomes. For mobilization, 70 patients received cyclophosphamide 1250 mg/m2 for 2 day, etoposide 100 mg/m2 for 3 day and G-CSF 10 mcg/kg/day from day 4 onwards and 40 patients received G-CSF alone. Results: In 98 of 110 patients (89.1%) first mobilization trial was successful. Four patients in the Cy-Et group (5,7%) and eight patients in the G-CSF alone group (20%) were mobilized three times (p=0.001). The number of CD34 in peripheral blood was significantly higher in Cy-Et group (94±14) than G-CSF alone group (54±7) (p=0.04) on the stem cell mobilization time. Stem cell collection was higher in the Cy-Et group (13.8 × 106 CD34 + cells/kg) compared to the G-CSF alone group (8.8× 106 CD34 + cells/kg) (p =0.001). The median time to neutrophil engraftment was 11 and 13 days in Cy-Et group and G-CSF alone group respectively (p=0.014). The median time to platelet engraftment was 15 and 17 days in Cy-Et group and G-CSF alone group respectively (p=0.006). Median 360 ml stem cells in Cy-Et group and 470 ml stem cells in G-CSF alone group were collected and this difference was statistically significant (P=0.001). Conclusion: In conclusion, this study was demonstrated that Cy-Et + G-CSF mobilization provides a higher peripheral CD 34 count, less apheresis sessions, less volume, more stem cell mobilization, earlier neutrophils and platelet engraftment for patients with MM and eligible for AHSCT. Today, Cy-Et + G-CSF mobilization is a really useful method than G-CSF alone.

Exploring the Effects of G-CSF Mobilization on the Immune Function of Mucosal-Associated Invariant T Cell Subsets By Single-Cell RNA-Seq

Background: Mucosal-associated invariant T cells (MAITs) are a group of mucosal-enriched unconventional T cells that can exert a variety of immune functions including pro-inflammatory, cytotoxic and immunomodulatory effects, whereas with the characteristics of innate immune cells. A few studies including our previous work have confirmed the relationship between MAITs and gut acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). In addition, we further proved that specific gut microbiota can promote MAIT17 subset activation, and MAITs has a direct immunosuppressive effect on T cells in vitro, which may potentially explain our results that higher number of MAITs in granulocyte colony-stimulating factor (G-CSF) mobilized grafts is associated with lower incidence of gut aGVHD. G-CSF has been widely used to mobilize hematopoietic stem/progenitor cells before HSCT. It also plays an important immunomodulatory role in inducing immune tolerance by regulating both innate and adaptive immune cells, especially T cells. Therefore, we used single-cell RNA sequencing to further explore the different effects of G-CSF mobilization on the immune function of each subset of MAITs. Methods & Cases: We isolated MAITs from the peripheral blood (PB) of 4 healthy donors pre- and post-G-CSF mobilization by flow cytometry pre-transplantation. 8 samples were performed by single-cell RNA-seq (Figure 1A). One of these recipients who received these 4 healthy donor grafts developed gut aGVHD after transplantation. Through single-cell bioinformatics analysis, we compared the sequencing data from pre- and post-G-CSF-mobilized MAITs of doners, and from G-CSF-mobilized donors in the group of recipients with or without gut aGVHD after transplantation. Results: By performing UMAP cluster analysis on these 8 samples, according to the expression of key cell type-associated marker genes of each cluster, MAITs were annotated into 14 subsets (Figure 1A and 1B). Among these subsets, Cluster 1(CD8_effector_EOMES), 4(CD4_effector_CCR6), 5(CD4_immature_CCR7), 6(CD8_effector_RORC), 12(CD4_immunomodulatory) increased significantly after G-CSF mobilization (Figure 1C). By comparing the bioinformatical data of MAITs of pre- and post-G-CSF mobilization, the results showed that molecular markers responsible for MAIT cell hyporesponsiveness were upregulated, including potential direct or indirect modulation mediated by the IL-4/IL-13 signaling pathway (FOS, JUNB, DDIT4, NFKBIA, MT2A, VIM, etc.) (Figure 1D) or ligand receptor (G-CSF-CSF3R) interactions (Figure 1E). Besides, a specific subset of MAITs defined as Cluster 12-CD4_immunomodulatory MAITs (Figure 1A) was found that played the most important role in immune regulation after G-CSF stimulation, which specifically expressed G-CSF receptor CSF3R. Furthermore, IL-17 signaling pathway was up-regulated and GVHD pathway was down-regulated in Cluster 12 post-G-CSF mobilization (Figure 1F), which suggested the Cluster 12 is an important subset of MAITs anti-GVHD. Compared to the sequencing data of donors in the group of recipients with gut aGVHD after G-CSF mobilization (post-G-CSF-gut aGVHD), we also observed the higher expression of immunosuppressive genes (JUN, DUSP2, JUNB, VIM, etc.) of doner MAITs in group without gut aGVHD after mobilization (post-G-CSF-no gut aGVHD). In addition, in the post-G-CSF-no gut aGVHD group, the expression of SOCS3, STAT3, CCR6 (Figure 1G) and other key markers that may potentially explain the anti-GVHD effect of MAITs was upregulated, as well as the ability of tissue repair and gut-directed migration of MAITs was upregulated (Figure 1H), while its cytotoxic effector functions were not significantly affected. Conclusions: Our results indicated that G-CSF mobilization can enhance the immunosuppressive effect of MAITs. Cluster 12 (CD4_immunomodulatory) is an important immunoregulatory and anti-GVHD subset of MAITs, contributing to the differentiation of MAITs towards MAIT17. The upregulation of markers such as SOCS3, CCR6, STAT3 that involved in CSF3R-JAK-STAT pathway, as well as markers related to mucosal tissue repair may partially explain the protective effect from gut aGVHD of G-CSF mobilized MAITs. These results also enlighten us that gut aGVHD might be prevented by effectively expanding the specific immunosuppressive subset of MAIT cells in the future. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Increased serum pro-B-type natriuretic peptide in hematopoietic progenitor cell donors stimulated with G-CSF.

Hematopoietic stem cells (HPCs) donors mobilized by granulocyte-colony-stimulating factor (G-CSF) can develop various signs and symptoms. proBNP (pro-B-type natriuretic peptide) is a serum marker of heart failure. A donor who developed severe adverse reactions after G-CSF mobilization was found to have high serum proBNP levels. We followed additional donors who received identical mobilization regimen to investigate the prevalence of this phenomenon. Eighteen healthy donors underwent a mobilization regimen of 10μg/Kg G-CSF daily for 5 days prior to allogeneic HPC collection using Spectra Optia between January 2016 and February 2017 were included in this study. Serum proBNP levels were measured before and after G-CSF stimulation and immediately after apheresis. Apheresis collection parameters and other laboratory results were also reviewed. The majority of donors (86.7%) had post-G-CSF elevation of serum proBNP. Seven of those had elevated proBNP above upper normal range (124 pg/ml). The subgroup of donors with normal proBNP is younger (median age of 37 vs 42 years), with majority being male (90.9% vs 28.6%) and with smaller processed blood volume (2.2 vs 3 × total blood volume). This case series demonstrates an increase of serum proBNP can be common in HPC donors stimulated with 5 days of 10 mcg/kg G-CSF. This is an adverse reaction that has not been described before. The temporary elevation of proBNP in these donors is not associated with ventricular dysfunction of the heart. The risk factors for marked elevation of proBNP post-G-CSF should be further investigated.

Superior physical and mental health of healthy volunteers before and five\xa0years after mobilized stem cell donation

BackgroundSafety, tolerability and efficacy of granulocyte colony-stimulating factor (G-CSF) for mobilization of hematopoietic stem and progenitor cells (HSPCs) from healthy donors have been conclusively demonstrated. This explicitly includes, albeit for smaller cohorts and shorter observation periods, biosimilar G-CSFs. HSPC donation is non-remunerated, its sole reward being “warm glow”, hence harm to donors must be avoided with maximal certitude. To ascertain, therefore, long-term physical and mental health effects of HSPC donation, a cohort of G-CSF mobilized donors was followed longitudinally.MethodsWe enrolled 245 healthy volunteers in this bi-centric long-term surveillance study. 244 healthy volunteers began mobilization with twice-daily Sandoz biosimilar filgrastim and 242 underwent apheresis after G-CSF mobilization. Physical and mental health were followed up over a period of 5-years using the validated SF-12 health questionnaire.ResultsBaseline physical and mental health of HSPC donors was markedly better than in a healthy reference population matched for ethnicity, sex and age. Physical, but not mental health was sharply diminished at the time of apheresis, likely due to side effects of biosimilar G-CSF, however had returned to pre-apheresis values by the next follow-up appointment after 6 months. Physical and mental health slightly deteriorated over time with kinetics reflecting the known effects of aging. Hence, superior physical and mental health compared to the general healthy non-donor population was maintained over time.ConclusionsHSPC donors are of better overall physical and mental health than the average healthy non-donor. Superior well-being is maintained over time, supporting the favorable risk–benefit assessment of volunteer HSPC donation.Trial registration National Clinical Trial NCT01766934

320 - Safety and Efficacy of High Dose Granulocyte Colony Stimulating Factor Mobilization in Familial Haploidentical Adult Donors with Sickle Cell Trait Followed By CD34+ Cell Enrichment and Mononuclear Cell Add-Back Prior to Haploidentical Allogeneic Transplantation in High-Risk Sickle Cell Disease Recipients

320 - Safety and Efficacy of High Dose Granulocyte Colony Stimulating Factor Mobilization in Familial Haploidentical Adult Donors with Sickle Cell Trait Followed By CD34+ Cell Enrichment and Mononuclear Cell Add-Back Prior to Haploidentical Allogeneic Transplantation in High-Risk Sickle Cell Disease Recipients

Addition of Plerixafor Overcomes Poor Mobilization in Autologous and Allogeneic Stem Cell Grafts and Leads to Efficient and Sustained Engraftment

▪Poor hematopoietic stem cell (HSC) mobilization upon granulocyte-colony stimulating factor (G-CSF) remains a significant problem for autologous and allogeneic hematopoietic cell transplantation (HCT). In up to 20% of patients, no sufficient autografts can be collected. The chemokine receptor CXCR4 plays a pivotal role in the homing of HSCs to the bone marrow. CXCR4 inhibition by the bicyclam derivative plerixafor can lead to improved HSC yields. We here evaluated the effects of plerixafor supported HSC apheresis in order to enable otherwise impossible HCT and with regard to graft quality and transplantation outcomes in both the autologous and allogeneic setting.Data retrospectively obtained from all 2,257 leukaphereses between 2014 and 2017 (588 for autologous and 1,669 for allogeneic transplantation) were analyzed. 48 individuals (31 male and 17 female, median age 52 years, range 31-72 years) were identified who received plerixafor due to insufficient HSC mobilization upon G-CSF stimulation. 44 patients (non-hodgkin lymphoma n=19, multiple myeloma n=19, systemic sclerosis n=3, Ewing sarcoma n=2, germinal cell cancer n=1) collected HSC for autologous, 4 HLA-identical siblings for allogeneic transplantation representing a low rate of poor mobilizers of 7% (44/588) and 0.2% (4/1669) autologous and allogeneic donors, respectively.A median of 1 dose plerixafor (range, 1-3 doses) was applied. Aphereses after addition of plerixafor were performed at a median of 2 days (range, 1-651 days) after insufficient attempts (median CD34+ cells 13/µl; range, 0-46/µl). 4 patients received a second mobilization chemotherapy before plerixafor application. 2 donors received plerixafor despite collection of >3.0x106 HSC per kilogram recipient body weight (kg BW) to enable in vitro graft manipulation or more than one HCT.Patients collecting HSC for autologous HCT received a median of 7 therapy cycles (range, 3-25 cycles) before HSC mobilization. Allogeneic donors tended to be older (median age of 54 years; range, 49-69 years).HSC mobilization was improved in 38/44 patients and 4/4 allogeneic donors. Before and after plerixafor application, median CD34+ cell counts were 0.6x106 (0.1-4.1 x106) cells/kg BW in 51 aphereses (range, 1-3 per patient) and 2.0x106 (range, 0.1-23.3 x106) cells/kg BW in 94 aphereses (range, 1-4 per patient), respectively (p<0.0001).Autologous HCT was performed in 32/44 patients. In the remaining, no HCT was performed due to further insufficient HSC mobilization despite plerixafor application (n=6), death due to progressive disease (n=3) or due to infection (n=1) before HCT. Two recent patients did not undergo autologous HCT, yet. All patients received G-CSF during autologous HCT. Median neutrophil (>500/µl) and platelet (>20,000/µl) engraftment was reached on day 12 (range, days 9-21) and 14 (range, days 10-23), respectively. No primary or secondary graft failure or poor graft function (PGF) was observed.The collected allogeneic grafts were applied to the patients in all 4 cases. Allogeneic HCT patients did not receive G-CSF. Median neutrophil and platelet engraftment was noted on days 13 (range, days 11-20) and 15 (range, days 11-23), respectively. Again, neither primary or secondary graft failure nor PGF was noted.Median overall survival after HCT for patients receiving autologous and allogeneic grafts was 31 (range, 1-72) and 7 (range, 5-53) months, respectively.For both autologous and allogeneic grafts, addition of plerixafor improved HSC yields in most poor mobilizers and therefore enabled for an otherwise impossible HCT including in vitro manipulation of allogeneic grafts and repetitive HCT. Of note, using G-CSF and plerixafor mobilization resulted in insufficient cell counts in only 0.3% of donors (6/2,257; for patients 6/588: 1%; for allogeneic donors 0/1,669: 0%) allowing HCT for almost every patient. Of note, poor mobilizers overall appeared to be seldom. Since plerixafor application was successful in most patients, these data might also help to reduce G-CSF application especially to patients who should not suffer from additional pulmonal toxicity (e.g. in systemic sclerosis). Hematopoietic engraftment after HCT of plerixafor mobilized grafts was rapid and sustained without observation of graft failure or PGF. The time to engraftment was comparable to G-CSF mobilized grafts showing that the quality of plerixafor mobilized grafts is to be estimated equal. DisclosuresBethge:Miltenyi Biotech GmbH: Consultancy, Honoraria, Research Funding; Neovii GmbH: Honoraria, Research Funding.

Chemotherapy-based versus chemotherapy-free stem cell mobilization (\xb1 plerixafor) in multiple myeloma patients: an Italian cost-effectiveness analysis

Given the availability and efficacy of the mobilizing agent plerixafor in augmenting hematopoietic progenitor cell mobilization with granulocyte colony-stimulating factor (G-CSF), there is a strong case for comparing the cost-effectiveness of mobilization with G-CSF + cyclophosphamide versus G-CSF alone. This study investigated the cost and effectiveness (i.e., successful 4 million-CD34+ collection) of G-CSF alone versus high-dose cyclophosphamide (4 g/m2) + G-CSF mobilization (± on-demand plerixafor) in patients with multiple myeloma (MM) eligible for autograft in Italy. A decision tree-supported cost-effectiveness analysis (CEA) model in MM patients was developed from the societal perspective. The CEA model compared G-CSF alone with cyclophosphamide 4 g/m2 + G-CSF (± on-demand plerixafor) and was populated with demographic, healthcare and non-healthcare resource utilization data collected from a questionnaire administered to six Italian oncohematologists. Costs were expressed in Euro (€) 2019. The CEA model showed that G-CSF alone was strongly dominant versus cyclophosphamide + G-CSF ( ± on-demand plerixafor), with incremental savings of €1198.59 and an incremental probability of a successful 4 million-CD34+ apheresis (+0.052). Sensitivity analyses confirmed the robustness of the base-case results. In conclusion, chemotherapy-free mobilization (± on-demand plerixafor) is a “good value for money” option for MM patients eligible for autograft.