Daily Granulocyte Colony-stimulating Factor Research Articles

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<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.

Impact of the Addition of Daratumumab to the Standard Bortezomib-Thalidomide-Dexamethasone Regimen on Hematopoietic Stem Cell Mobilization and Collection, Post-Transplant Engraftment and Infectious Complications: A Case-Control Multicentre Real-Life Analysis

Background The pivotal clinical trial CASSIOPEIA established the quadruplet Daratumumab-Bortezomib-Thalidomide-Dexamethasone (Dara-VTD) as superior with regards to the standard Bortezomib-Thalidomide-Dexamethasone (VTD) regimen as induction therapy in newly diagnosed transplant-eligible (NDTE) multiple myeloma (MM) patients. As a matter of facts, Dara-VTD is currently the approved induction scheme in NDTE MM patients in Italy. Previous reports showed that adding Daratumumab in induction therapy patients yielded to a higher number of poor mobilizers, with a lower median number of collected hematopoietic stem cells (HSC). However, these reports included different types of induction therapies, merging patients on and off clinical trials, and real-life data focusing exclusively on Dara-VTD is lacking. We report our experience on the impact of Dara-VTD on HSC mobilization and collection, with a retrospective comparison with a cohort of patients treated with VTD and we also provided data concerning post-transplant engraftment and infectious complications. Methods From January 2022 to June 2023, 109 NDTE MM patients from 5 Haematology Institutions received Dara-VTD treatment induction according to the approved doses and schedule. The control group consisted of 116 age-matched patients treated with VTD in the years 2015-2016. Mobilizing therapy consisted of cyclophosphamide 1-3 gr/sqm followed by granulocyte colony-stimulating factor (G-CSF) 10 mcg/kg starting the 5th day thereafter, with HSC harvest planned on the 11th day. Patients received only G-CSF 10 mcg/kg if they were older than 70 years or had renal impairment (i.e., eGFR < 50 ml/min). Poor mobilizer was defined as having less than 20 CD34+/µL in peripheral blood on the 11th day after cyclophosphamide and G-CSF or on the 4th day of G-CSF alone administration. In that case, plerixafor was added at the standard dose of 0.24 mg/kg. Results In the Dara-VTD group, 96/109 patients received cyclophosphamide and G-CSF; among them, 3 patients had failed a previous G-CSF mobilizing therapy, even with the addition of plerixafor. Thirteen patients received G-CSF only. In the VTD group, all patients had received cyclophosphamide and G-CSF. Pre-harvest median number of CD34+/mL in the Dara-VTD group was 26 (range 0.8-279) vs 76 (range 20-294) in the VTD group and the incidence of poor mobilizing patients was 41.7% vs 5.9%, respectively (OR 0.3, 95% CI 0.16-0.54, P < 0.0001). Baseline disease characteristic did not have an impact on poor mobilizing events. On the contrary, patients who developed hematologic toxicity during induction turned out to be poor mobilizers (OR 3.5, 95% IC 1.36-9.59, p= 0.011). Plerixafor was used in 54/109 patients in the Dara-VTD group and in 16/116 patients of the VTD group. Two patients failed HSC mobilization both with G-CSF and cyclophosphamide and G-CSF. All patients that received G-CSF only resulted in poor mobilizers and required plerixafor before HSC harvest; therefore, cyclophosphamide showed to be superior with regards to G-CSF as mobilizing therapy (p= 0.011). The median number of collected HSC was significantly lower in the Dara-VTD group vs VTD group: 5.17 x 10^6/Kg (IQR 3.9-5.47) vs 8.7 x 10^6/kg (IQR 6.35-11.15), respectively (p < 0.0001). 33% of patients in Dara-VTD group collected at least 6 x 10^6 CD34+/Kg). Median time to neutrophils and platelets engraftment were different between the two groups (13 and 11 days, respectively, P < 0.0001), but we did not observe any difference in terms of infection incidence. Notably, post-transplant infections incidence in Dara-VTD group was 43%. Although the second transplant was planned for 36 patients treated with Dara-VTD, it was performed in 10 patients only, mainly because of insufficient HSC harvest. Conclusions Our experience with Dara-VTD confirms an increased number of poor mobilizers, a higher need for the use of plerixafor and a lower number of collected HSC. We observed a slightly lower engraftment in Dara-VTD group, probably because of a lower number of infused HSC. The lower number of collected HSC hampers the possibility of a double transplant.

Myeloid Derived Suppressor Cell Kinetics in Peripheral Blood Correlate with Efficacy and Toxicity of CAR T Cell Therapy in Relapsed or Refractory B Cell Lymphoma

Introduction. CAR T-cell therapy is potentially curative for patients with relapsed or refractory B-cell lymphoma (BCL). However, about 60% of patients fail CAR T-cell therapy. Immune-related adverse events (irAE) like cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) occur in an inflammatory state. Myeloid-derived suppressor cells (MDSCs) expand during acute inflammation as steady-state hematopoiesis switches to emergency myelopoiesis. We hypothesized that the acute inflammatory conditions created by CAR T-cell therapy may alter MDSC kinetics and investigated MDSC expansion in the context of CAR T-cell efficacy and toxicity in BCL. Methods. Patients with BCL receiving standard-of-care CAR T-cell therapy were enrolled in a prospective sample collection study. Blood samples were collected before lymphodepletion (baseline), prior to and at early intervals after CAR T-cell infusion. Viable white blood cell (WBC) and MDSC counts were evaluated by multicolor flow cytometry. Phenotypically, MDSCs were defined as immature myeloid cells (CD11b + CD33 + HLA-DR -/low IL-4R +) and divided into monocytic (M-MDSC, CD14 +) and polymorphonuclear (PMN-MDSC, CD15 +) subsets. Clinical response was assessed by Lugano criteria at 1, 3 and 6 months. Incidence and severity of CRS and ICANS were recorded. Cell counts were analyzed by descriptive statistics and reported as mean ± standard error or fold-change from baseline. Kinetics of MDSCs in blood and correlation with clinical outcomes were evaluated by Wilcoxon matched pair signed rank t-test and Mann Whitney U-test. Results. Forty-three BCL patients (41 large BCL, 2 mantle cell lymphoma) were enrolled in the study. Median age was 64 (range 27-83), 32.6% were female. Racial and ethnic minority groups represented 14% of enrolled subjects. One patient developed grade 5 ICANS and was not evaluable for response. Thirty-seven (86%) developed leukopenia and all received granulocyte colony stimulating factor (G-CSF) starting on day 5 post-CAR T infusion. WBC count fell sharply from baseline following lymphodepletion (7.7E +05±8.6E +04 baseline vs 2.9E +05±9.2E +04/mL, p<0.0001) and continued to decline 2-3 days post-CAR T infusion (baseline vs 1.4E +05±2.1E +04/mL, p<0.0001) before returning to baseline within 1 week post-CAR T (i.e. within 3 days of G-CSF). MDSCs followed similar kinetics early on but significantly increased from baseline levels by 1-week post-CAR T (3.4E +03±5.8E +02 baseline vs 8.5E +03±1.7E +02 /mL, p<0.0001). This effect was mainly driven by an exuberant expansion of M-MDSC observed in 33/43 patients (median 6.1-fold increase from baseline at 1 week, range 0.5-4301). Seven patients (16.3%) had progressive disease (PD) at 1 month, 6 (13.9%) additional patients progressed at 3 months and 4 (9.3%) more progressed at 6 months after CAR T-cell infusion. M-MDSC expansion 1-week post-CAR T was only observed in 3/7 refractory patients compared with 28/35 responding patients (Fisher's exact test, p=0.0635). Patients who progressed at 3 months had poorer M-MDSC retention compared to patients with sustained response (1.7E +02±6.1E +01 PD vs 1.4E +03±2.4E +01/mL at 2-week post-infusion, p<0.1). Similarly, patients who progressed at 6 months had lower M-MDSC compared with sustained responders (2.0E +02±8.1E +01 PD vs 4.5E +02±1.4E +02 ml at 1-month post-infusion, p<0.05). Thirteen patients (30.2%) developed > grade 2 CRS and had lower PMN-MDSC retention rate 2-3 days post-CAR-T compared with those with no/low-grade CRS (4.4E +02±2.6E +02 vs 1.4E +03±3.9E +02/mL, p<0.05). Similarly, patients who had ICANS > grade 2 (n=14, 32.5%) had lower PMN-MDSC early retention compared to those with no or low-grade ICANS (5.0E +02±2.5E +02 vs 1.5E +03±4.1E +02/mL, p<0.05). Further analyses are currently underway to bridge these findings with the kinetics of CAR T-cells and T-cell repertoire post-CAR T. Conclusions. The proinflammatory milieu after CAR-T and the use of G-CSF can lead to significant expansion of M-MDSCs. Rather than an impediment to CAR T therapy, M-MDSC expansion and retention are associated with favorable clinical response and PMN-MDSC with a lower risk of developing high grades CRS or ICANS. Whether MDSCs play a mechanistic role remains to be elucidated, but they may have a role as a biomarker in predicting outcomes after CAR T-cell therapy in BCL.

A prospective, multicenter study on hematopoietic stemcell mobilization with cyclophosphamide plus granulocyte colony-stimulating factor and 'on-demand' plerixafor in multiple myeloma patients treated with novel agents.

High-dose melphalan plus autologous stem cell transplantation (ASCT) is a standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM), and adequate hematopoietic stem cell (HSC) collection is crucial to ensure hematologic recovery after ASCT. In this prospective, observational study we evaluated HSC mobilization with granulocyte colony-stimulating factor (G-CSF), cyclophosphamide, and 'on-demand' plerixafor (in patients with <20×106 CD34+ cells/L after at least 4 days of G-CSF or failing to collect ≥1×106 CD34+ cells/kg after the first apheresis) in NDMM patients treated with novel agent-based induction therapy. The primary endpoint was the rate of poor mobilizers (patients collecting <2×106 CD34+ cells/kg or requiring plerixafor rescue to reach an adequate HSC harvest). Secondary endpoints included the rate of patients collecting ≥2×106 CD34+ cells/kg after plerixafor administration and the identification of factors predicting mobilization failure or plerixafor need. Overall, 301 patients (median age 60 years) were enrolled. Two hundred and eighty-seven of 301 (95%) and 274 of 301 (93%) patients collected ≥2×106 and ≥4×106 CD34+ cells/kg, respectively, with a median of 9.9×106 CD34+ cells/kg collected. Poor mobilizers were 48 of 301 (16%): 34 of 301 (11%) required plerixafor rescue, and 14 of 301 (5%) failed HSC collection regardless of plerixafor. Thirty-four of 38 (90%) patients receiving plerixafor collected ≥2×106 CD34+ cells/kg. Bone marrow plasmacytosis at diagnosis >60% (odds ratio [OR]=4.14), lenalidomide use (OR=4.45), and grade 3-4 hematologic toxicities during induction (OR=3.53) were independently associated with a higher risk of mobilization failure or plerixafor need. Cyclophosphamide plus G-CSF and 'on-demand' plerixafor is an effective strategy in NDMM patients treated with novel agents, resulting in a high rate of HSC collection and high HSC yield (clinicaltrials gov. identifier: NCT03406091).

Comparison of different plerixafor-based strategies for adequate hematopoietic stem cell collection in poor mobilizers

Objectives: The main objective of the present study was to evaluate whether the use of plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) or subsequent use of isolated G-CSF and then plerixafor following disease-specific chemotherapy, and whether it would allow for adequate peripheral stem cell collection in patients. Methods: The retrospective study evaluated 54 patients with previous mobilization failure who were administered plerixafor in 2 centers. In patients without any side effects, CD 34+ cell counts, the percentage of patients who were found eligible for autologous transplantation, the engraftment kinetics of the patients who underwent transplantation, and their overall survival results were compared between the two groups where G-CSF was used with plerixafor, or where plerixafor was used after isolated G-CSF following chemotherapy. Results: The median age of the patients was 49 years (range: 17-70), and 64.8% (n = 35) were males. It was identified that 31 (57.4%) patients underwent mobilization treatment with isolated G-CSF and plerixafor, and 23 (42.6%) patients underwent mobilization treatment with chemotherapy plus G-CSF and plerixafor. In all patients, mean hemoglobin level (11.3 ± 1.5 g/dL vs. 9.3 ± 1.3 g/dL; p &amp;lt; 0.001) and median platelet level (129.2 ×103/µL vs. 58.4 ×103/µL) were found to be higher, while febrile neutropenia rate (3.3% vs. 60.9%), the percentage of replacement patients (6.7% vs. 65.2%), and median days of G-CSF (6 vs. 9) were found to be lower on the day of plerixafor administration in the isolated G-CSF and plerixafor group compared to the chemotherapy and G-CSF and plerixafor group. Conclusions: In conclusion, our study demonstrated that administration of plerixafor is generally safe and well-tolerated. Regardless of the underlying disease, it offers an effective alternative for patients with previous failed mobilization attempts using conventional regimens, and allows stem cell collection with fewer apheresis sessions.

Predicting Successful Hematopoietic Stem Cell Collection in Healthy Allogeneic Donors

Introduction: Collection of peripheral blood stem cells (PBSCs) from healthy donors is a well-established process. We aimed to identify factors predictive of successful CD34+ PBSC collection and established a formula capable of predicting CD34+ cell yield. Methods: We retrospectively evaluated 588 healthy adult donors (median age 29 years, range 18–69 years) at our institution from 2017 to 2022. The predicted minimal number of CD34+ cells was calculated as follows: (peripheral CD34+ cells/µL × adjusted collection efficiency of 30%) × total liters processed. This formula was further modified according to donor and recipient body weight (BW). Results: Median total collection was 8.0 × 106 CD34+ cells/kg BW (range 1.0–47.1 × 106 cells/kg BW) with 522 donors (89%) collecting ≥5.0 × 106 cells/kg of recipient BW. A second leukapheresis (LP) was performed in 49 donors. Need for two LPs was more common in female donors (OR 6.68, 95% CI, 2.62–17.05; p p = 0.003), donors with WBC count 9/L after 5 days of granulocyte-colony stimulating factor (G-CSF) stimulation (OR, 4.33; 95% CI, 1.59–11.83; p = 0.004), and a donor/recipient weight ratio p 6 CD34+ cells/kg of recipient BW) were peripheral blood (PB) CD34+ cell count >50/µL (OR 12.82, range 6.34–25.92, p p = 0.04), and a donor/recipient weight ratio >1 (OR 3.12, range 1.57–6.24, p = 0.001). WBC, platelets, hemoglobin, and age had no significant predictive value. Predicted versus observed number of CD34+ cells/kg BW collected demonstrated a very strong linear correlation (r = 0.925, 95% CI, 0.912–0.936, p Conclusions: Of the routinely monitored indicators in PBSC donors, CD34+ cell count in PB is the most important factor in predicting G-CSF-induced PBSC yields. Higher age, female sex, WBC 9/L, and a donor/recipient weight ratio

Haematopoietic Progenitor Cell Mobilisation Following Blinatumomab Therapy

Background: Our institution routinely performs autologous back-up haematopoietic progenitor cell (HPC) harvest prior to unrelated donor transplantation, particularly in the post-pandemic era, or in other circumstances if there is risk of graft failure. This practice is influenced by our relative geographical isolation and significant challenges in obtaining emergency allogeneic products. As the treatment landscape for paediatric acute lymphoblastic leukaemia (ALL) has expanded to incorporate immunotherapy, many patients proceeding to transplant receive the bispecific T-cell engager blinatumomab. Little is known about HPC mobilisation outcomes in patients following blinatumomab therapy. Here we report our experience with HPC mobilisation for autologous back-up harvest in paediatric patients with ALL treated with blinatumomab. Methods: We reviewed HPC mobilisation attempts in patients with ALL at The Children's Hospital at Westmead, Sydney, Australia from 1 January 2012 to 30 June 2022. Patients were analysed in two groups: those mobilised following blinatumomab and those mobilised following chemotherapy or from steady state. Patients were mobilised according to our institutional practice. Following chemotherapy or blinatumomab, granulocyte-colony stimulating factor (G-CSF) was given subcutaneously at a dose of 5 µg/kg/day after chemotherapy, or 10 µg/kg/day after blinatumomab or from steady state haematopoiesis. Records were assessed retrospectively for demographics, mobilisation strategy, G-CSF days, apheresis days, final HPC yield in CD34+ cells/kg, transplant characteristics, and outcomes. Successful mobilisation was defined as proceeding to apheresis and successful harvest at the patient level by achieving an HPC yield of at least 2 x 106 CD34+ cells/kg. Results: Over the 10.5 year (y) study period, 30 patients with ALL underwent 34 HPC mobilisation attempts for the purpose of autologous back-up HPC harvest prior to allogeneic transplant; 7 (23%) after blinatumomab and 23 (77%) after chemotherapy. Mobilisation and apheresis characteristics of the two groups are summarised in Table 1. There were no differences in age, weight, gender, disease status or prior exposure to radiotherapy between the blinatumomab and chemotherapy groups. Successful mobilisation was less likely in the blinatumomab group with 5/8 (63%) proceeding to apheresis vs 24/26 (92%) in the chemotherapy group, P=.037. In 29 successful mobilisations, the blinatumomab group had a lower median number of days of G-CSF (6 (range 5-7) vs 11 (3-24), P=.006), and greater utilisation of plerixafor (2/5 (40%) vs 0/24 (0%), P=.001). On day 1 of apheresis, the blinatumomab group had a lower median CD34+ count x 106/L (27 (20-32) vs 57 (13-636), P=.021) and a higher median white cell count x 109/L (37.4 (24.5-79) vs 15.6 (1.3-63.5), P=.015). Although the median total HPC yield of CD34+ cells x 106/kg was significantly lower in the blinatumomab group (2.2 (2-4.7) vs 5.6 (1.4-35.2), P=.033), there was no difference in the proportion of patients achieving the collection target of 2 x 106 CD34+ cells/kg (5/5 (100%) vs 21/23 (91%), P=.494). With a median follow up of 1.6y for the blinatumomab group and 7y for the chemotherapy group, there was no difference in 2y relapse-free (83% vs 57%, P=.310) or overall (83% vs 67%, P=.5903) survival between the groups. Of 28 patients who proceeded to transplant, 3 (11%) required autologous HPC reinfusion for secondary graft failure, 2/3 after 9/10 matched unrelated donor transplants without serotherapy, and all from the chemotherapy group. Neutrophil engraftment for these 3 patients occurred at a median of 13 days (range 11 - 14). One patient died 35 days after salvage reinfusion without achieving platelet engraftment. The 2 surviving patients achieved platelet engraftment at 18 and 29 days post reinfusion and remain alive in continuous complete remission more than 3y following HPC re-infusion. Conclusions: HPC mobilisation for autologous back-up harvest is feasible for ALL patients following blinatumomab. However, these patients are at risk of failed mobilisation and may benefit from pre-emptive strategies such as the use of plerixafor to optimise mobilisation success. Our relatively high rate of salvage reinfusion of autologous HPCs in ALL patients underlines the utility of universal back-up harvests for patients undergoing unrelated donor transplant. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

P932: ON-DEMAND PLERIXAFOR WITH CYCLOPHOSPHAMIDE AND G-CSF FOR HEMATOPOIETIC STEM-CELL MOBILIZATION IN MULTIPLE MYELOMA PATIENTS: FINAL RESULTS OF THE MOZOBL06877 STUDY

Background: High-dose melphalan and autologous stem-cell transplant (ASCT) are pillars for the upfront treatment of ASCT-eligible newly diagnosed multiple myeloma (ND)MM patients (pts) or as salvage strategy at relapse. Failure to collect an adequate number of hematopoietic stem cells (HSC) to receive ASCT (<2×106 CD34+ cells/kg) occurs in 5%-15% of MM pts undergoing HSC mobilization with granulocyte colony-stimulating factor (G-CSF) or G-CSF+cyclophosphamide (G-CSF/CY). Aims: We report the final results of the observational MOZOBL06877 study (NCT03406091; partially supported by Sanofi investigation funds) to prospectively assess the performance of HSC mobilization with G-CSF/CY plus on-demand CXCR4 inhibitor plerixafor (PLX) in NDMM pts treated with novel agents. Methods: NDMM pts undergoing HSC mobilization with CY (2-4 g/m2) and G-CSF (5-10 mcg/kg/day) were enrolled and observed up to 30 days after mobilization. According to its label, “on-demand” PLX was administered in pts with <20 CD34+ cells/ul after ≥4 days of G-CSF or in case <1×106 CD34+ cells/kg were collected on the first apheresis day. Pts gave written informed consent. The primary endpoint was the poor mobilizer rate, defined as the rate of pts collecting <2×106 CD34+ cells/kg or requiring PLX. Secondary endpoints were the identification of predictive factors for PLX use and safety during mobilization. Results: 301 NDMM pts were enrolled and analyzed; 72% received induction with bortezomib-thalidomide-dexamethasone, 9% a lenalidomide (Len)-based and 3% a daratumumab (Dara)-based regimen. Overall, 48 pts (16%) were poor mobilizers: 14 (5%) failed to yield ≥2×106/Kg CD34+, while 34 (11%) required rescue with PLX. Among pts yielding <2×106/Kg CD34+ cells, 4 received PLX, while 10 did not. Among pts who successfully collected ≥2×106/Kg CD34+ (n=287, 95%), 34 (12%) required PLX: 23 (68%) due to a CD34+/uL count ≤20 after ≥4 days of G-CSF and 11 (32%) to a collection <1×106/Kg after the first apheresis day. In pts mobilized with PLX, median number of CD34+×106/L cells increased from 17.5 (IQR 10.8-25.6) before PLX to 58.3 (IQR 34.2-100.2) after PLX. Median number of CD34+/Kg collected in pts who did not require PLX was 10.2×106 (IQR 8.3-13.2). In pts who required PLX, a median of 6.5×106 CD34+/Kg (IQR 4.6-9.6) was collected. An adequate HSC yield for ≥2 ASCTs (≥4×106/Kg) was obtained in 96% and 85% of pts not receiving or receiving PLX, respectively. Median number of apheresis days was 1 (IQR 1-2) in pts not requiring PLX and 2 (IQR 1-2) in pts requiring PLX. In a multivariate analysis (Table), factors predicting PLX use were advanced disease stage (R-ISS 3 vs 1-2, OR 5.5, P=0.01), bone marrow (BM) plasma cell (PC) infiltration at diagnosis (PC>60% vs ≤60%, OR 4.2, P<0.001), pre-mobilization absolute neutrophil count (ANC, < vs >2500/mmc, OR 2.8, P=0.01), and the use of Len-based (Yes vs No, OR 3.4, P=0.02) or Dara-based induction regimens (Yes vs No, OR 5.3; P=0.04). Grade 3 infections occurred in 3 pts (1%), with no grade 4-5 reported. Image:Summary/Conclusion: Among NDMM pts treated with novel-agent-based induction and undergoing HSC mobilization with CY/GCSF, “on-demand” PLX in case of low CD34+ cell count or insufficient HSC yield was a safe and effective rescue strategy, reducing mobilization failure from 16% to 5%. Predictive factors for PLX use were advanced disease stage, high BM plasmacytosis, low ANC values before mobilization and the use of Len/Dara during induction. Preemptive PLX in pts with ≥1 risk factors should be investigated to further reduce the risk of mobilization failure.

A prospective cohort study to evaluate the incidence of febrile neutropenia in patients receiving pegfilgrastim on-body injector versus other options for prophylaxis of febrile neutropenia: breast cancer subgroup analysis

BackgroundBreast cancer chemotherapy often carries a high risk of febrile neutropenia (FN); guidelines recommend prophylaxis with granulocyte colony-stimulating factor (G-CSF), such as pegfilgrastim. Neulasta® Onpro® on-body injector (OBI) is a delivery device administering pegfilgrastim approximately 27 h after application.MethodsThis prospective study examined patients with breast cancer who received chemotherapy with a high risk of FN, receiving OBI (“OBI”) or other options (other G-CSF or none; “other”). The primary endpoint was FN incidence; secondary endpoints included chemotherapy delivery, adherence (G-CSF in all cycles), compliance (G-CSF day after chemotherapy), and FN incidence in patients receiving curative or palliative treatment.ResultsA total of 1776 patients with breast cancer were enrolled (OBI, n = 1196; other, n = 580). Across all cycles, FN incidence was lower for OBI (4.4% [95% CI, 3.3–5.6%]) than other (7.4% [5.3–9.6%]). For curative treatment, the FN incidence across all cycles was lower for OBI (4.6% [3.4–5.8%]) than for other (7.1% [5.0–9.3%]). For palliative treatment (OBI, n = 33; other, n = 20), 3 patients (15%) in the other and none in the OBI group had FN. After adjusting for baseline covariates, FN incidence remained lower for OBI (4.6% [3.5–6.1%]) versus other (7.8% [5.7–10.5%]). Adherence was higher for OBI (93.8%) than for other G-CSF (69.8%), as was compliance (90.5 and 53.2%, respectively). Chemotherapy dose delays/reductions were similar for OBI (4.7%/32.3%, respectively) and other (4.7%/30.0%) groups.ConclusionPegfilgrastim OBI was associated with a lower FN incidence in patients with breast cancer compared to other options for FN prophylaxis.Trial registrationwww.clinicaltrials.gov, NCT02178475, registered 30 June, 2014

Factors for the optimal selection of granulocyte colony-stimulating factor preparations and predictors for R-CHOP dose reductions/delays among patients with non-Hodgkin B-cell lymphoma (STOP FN in NHL 2 subanalysis)

BackgroundA classification tree was used to analyze background factors for granulocyte colony-stimulating factor (G-CSF) preparation selection for febrile neutropenia (FN) prophylaxis in Japanese patients with non-Hodgkin B-cell lymphoma receiving the first R-CHOP cycle.MethodsThis was a subanalysis of the retrospective observational study STOP FN in NHL 2 (UMIN000029534). Patient characteristics, changes in neutrophil count, incidence and severity of neutropenia, and risk factors for dose reduction/delay of R-CHOP were assessed by G-CSF formulation.ResultsAmong 234 patients in cycle 1, 25.6% received no G-CSF preparation, 52.1% received daily G-CSF, and 22.2% received pegfilgrastim. Pegfilgrastim use was most frequent among patients aged ≥ 80 years, while that of daily G-CSF was most frequent in patients with lymphocyte count (LC) < 1000 cells/μL. Changes in neutrophil count were more marked with pegfilgrastim compared with daily G-CSF and no G-CSF. Relevant factors for G-CSF preparation selection in the first R-CHOP cycle were age ≥ 80 years and LC < 1000 cells/μL; for chemotherapy dose reduction were FN onset in cycle 1 and female sex; and for dose delay was hemoglobin (< 12 g/dL). After cycle 2 and onward, pegfilgrastim use increased markedly (72.6%) compared with cycle 1 (22.2%), with significantly greater proportions continuing pegfilgrastim use and switching from daily G-CSF.ConclusionRelevant factors for G-CSF preparation selection were age ≥ 80 years and LC < 1000 cells/μL. The use of pegfilgrastim increased markedly after cycle 2. These results may be useful for selecting appropriate G-CSF preparations in the first R-CHOP cycle.Trial registrationUMIN000029534; registered on 13 October 2017, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033733.

Cost saving, patient centered algorithm for progenitor cell mobilization for autologous hematopoietic cell transplantation.

Administration of plerixafor with granulocyte-colony stimulating factor (G-CSF) mobilizes CD34+ cells much more effectively than G-CSF alone, but cost generally limits plerixafor use to patients at high risk of insufficient CD34+ cell collection based on low peripheral blood (PB) CD34+ counts following 4 days of G-CSF. We analyzed costs associated with administering plerixafor to patients with higher day 4 CD34+ cell counts to decrease apheresis days and explored the use of a fixed split dose of plerixafor instead of weight-based dosing. We analyzed 235 patients with plasma cell disorders or non-Hodgkin's lymphoma who underwent progenitor cell mobilization and autologous hematopoietic cell transplantation (AHCT) between March 2014 and December 2017. Two hundred ten (89%) received G-CSF plus Plerixafor and 25 (11%) received G-CSF alone. Overall, 180 patients (77%) collected in 1 day, 53 (22%) in 2 days and 2 (1%) in 3 days. Based on our data, we present a probabilistic algorithm to identify patients likely to require more than one day of collection using G-CSF alone. CD34+ cell yield, ANC and platelet recovery were not significantly different between fixed and standard dose plerixafor. Plerixafor enabled collection in 1 day and with estimated savings of $5000, compared to patients who did not receive plerixafor and required collection for three days. While collection and processing costs and patient populations vary among institutions, our results suggest re-evaluation of current algorithms.

Intracoronary autologous bone marrow mononuclear cells for the compassionate treatment of advanced heart failure

Abstract Background Intracoronary delivery of autologous bone marrow-derived mononuclear cells (BMCs) has been shown to be beneficial in the treatment of patients with ischaemic (IHD) and non-ischaemic dilated cardiomyopathy (DCM). Given the results of phase II clinical trials in this population, our centre initiated the only programme to offer intracoronary BMCs to patients with advanced heart failure due to IHD or DCM in the UK. Clinical data and outcomes in these patients were maintained as part of a registry, the results of which are reported herein. Purpose To report outcomes of the first 20 patients with DCM treated at the compassionate stem cell unit. Methods A total of 45 patients with advanced heart failure (left ventricular ejection fraction (LVEF) at referral of ≤45%, New York Heart Association (NYHA) classification ≥2 and no secondary cause for the cardiomyopathy) despite optimal medical therapy (OMT) were accepted into the programme and received treatment with intracoronary BMCs, manufactured and supplied as Advanced Therapy Medicinal Products, with adjunctive granulocyte colony stimulating factor (G-CSF). All patients received 5 days of G-CSF followed by bone marrow aspiration and IC infusion of cells (∼10ml of BMCs) on Day 6. LVEF was assessed by cardiac CT. Results Of the 20 patients with DCM, 80% were male with a mean age of 64.6±10.6 years (range 45–81 years old). Baseline LVEF was 36.1%±10.6. Baseline NYHA class distributions were 70% NYHA class II (n=14), NYHA class III 25% (n=5), and NYHA class IV – 5% (n=1). All procedures were performed successfully with no procedural complications (100% radial). One year after treatment, 71.4% of people improved by 1 or more NYHA classes with 28.6% noting no change (1 year NYHA classes I (60%), II (27%) and III (13%)). No patients felt worse. A mean increase of 3.4% (±9.6%) was seen in LVEF at 1 year compared to baseline with a corresponding mean reduction in NT-pro-BNP of 18.9% (mean 1012pmol/l vs 1250pmol/l). In terms of clinical events, at 1 year all treated patients were alive, with no reported MACE events and no admissions for heart failure. Conclusion IC autologous BMC injections are a novel therapy for patients with advanced HF despite OMT. These data indicate this therapy is safe and results in significant improvement in symptoms of heart failure. An improvement in the LVEF is seen at levels which support initial findings of phase II clinical trials. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Heart Cell Foundation; Barts Heart Centre, St Bartholomew's Hospital

'CARMEN': is less, more? Lessons from trials in human immunodeficiency virus-Burkitt lymphoma (HIV-BL).

'CARMEN': is less, more? Lessons from trials in human immunodeficiency virus-Burkitt lymphoma (HIV-BL).

Weighty choices: selecting optimal G-CSF doses for stem cell mobilization to optimize yield

AbstractThere are limited data on the effect of donor body mass index (BMI) on peripheral blood stem cell (PBSC) mobilization response to granulocyte colony-stimulating factor (G-CSF), especially in unrelated donors. Obesity has been associated with persistent leukocytosis, elevated circulating progenitor cells, and enhanced stem cell mobilization. Therefore, we hypothesized that adequate collection of CD34+ cells may be achieved with lower doses (per kilogram of body weight) of G-CSF in donors with higher BMI compared with donors with lower BMI. Using the Center for International Blood and Marrow Transplant Research database, we evaluated the impact of donor BMI on G-CSF–mobilized PBSC yield in healthy unrelated donors. We examined 20 884 PBSC donations collected at National Marrow Donor Program centers between 2006 and 2016. We found significantly higher collection yields in obese and severely obese donors compared with normal and overweight donors. An increase in average daily G-CSF dose was associated with an increase in stem cell yield in donors with normal or overweight BMI. In contrast, an increase in average daily G-CSF dose beyond 780 μg per day in obese and 900 μg per day in severely obese donors did not increase cell yield. Pain and toxicities were assessed at baseline, during G-CSF administration, and postcollection. Obesity was associated with higher levels of self-reported donation-related pain and toxicities in the pericollection and early postdonation recovery periods. This study suggests a maximum effective G-CSF dose for PBSC mobilization in obese and severely obese donors, beyond which higher doses of G-CSF add no increased yield.

Multiple Cycles of Granulocyte Colony-Stimulating Factor Increase Survival Times of Patients With Decompensated Cirrhosis in a Randomized Trial

There is controversy regarding the inclusion of granulocyte colony stimulating factor (G-CSF) in the treatment of decompensated cirrhosis. Previous studies tested only a single cycle of G-CSF administration or were underpowered to detect changes in survival time. We performed an adequately powered study to determine whether multiple cycles of G-CSF increased the survival of patients 1 year after the start of therapy. We conducted an open-label trial of 100 patients with decompensated cirrhosis without acute-on-chronic liver failure at a tertiary center from July 2016 through June 2018. The patients were assigned randomly to a group given 5 days of G-CSF every 3 months, with standard medical therapy, in 4 cycles (group A, n=50), or standard medical therapy alone (group B, n=50). The primary outcome was survival for 12 months after treatment began. Secondary outcomes were an increase in the number of CD34+ cells at day 6 compared with day 0, along with reductions in Child-Turcotte-Pugh and model for end-stage liver disease scores, increased control of ascites, reduced decompensation and episodes of infection, fewer hospitalizations, lower liver stiffness measurements, increased quality of life and nutrition, fulfilment of liver transplant criteria, and fewer adverse events at 12 months after the start of treatment. Groups A and B were comparable at baseline. Survival at 12 months after initiation of treatment was significantly higher in group A (74%) than in group B (42%) (P<.001). Blood samples from patients in group A had significantly more CD34+ cells on day 6 than on day0 (P<.001); there was no significant change in group B. Compared with patients in group B, patients in group A had significant reductions in Child-Turcotte-Pugh and model for end-stage liver disease scores, increased ascites control, fewer infections and hospitalizations, lower liver stiffness measurements, an increased quality of life, and a lower number fulfilled the liver transplant criteria (P<.05). There was no improvement in nutrition in either group compared with baseline. G-CSF was safe and well tolerated. Administration of multiple cycles of G-CSF increases the numbers of hematopoietic stem cells and survival of patients with decompensated cirrhosis receiving standard medical treatment. The addition of G-CSF to medical treatment might provide a bridge to liver transplantation for these patients. ClincialTrials.gov no: NCT03415698.

Role of Granulocyte-colony Stimulating Factor in the Protection of Cerebral Vascular Endothelium, White Matter, and Cognition.

Granulocyte-colony stimulating factor (G-CSF) has protective effects on many neurological diseases. The effects of G-CSF on vascular endothelium and White Matter (WM) injury in Cerebral Small Vessel Disease (CSVD) were explored in this study via a model of spontaneously hypertensive rat (SHR) in order to elucidate the mechanism of G-CSF in Vascular Cognitive Impairment (VCI). 24-week-old male SHRs were randomly divided into the treatment group and model group, with the same age Wistar rats as the control group. The novel object recognition test (NORT) and Morris water maze were conducted after 7 days of G-CSF(50ug/kg) or normal saline treatment to examine their non-spatial and spatial cognitive functions. After that, a transmission electron microscope (TEM) and FLB staining were used to observe the vascular endothelial cell and WM damage. Furthermore, the expression of VEGF, MMP-9, Caspase-3, TUNEL and BrdULaminin in the cortical area was detected by immunostaining methods. Our results showed that G-CSF promoted the expression of VEGF and BrdU+-Laminin+ endothelial cells, but down-regulated the level of MMP-9, thus significantly repaired the cerebral vascular endothelial cells and perivascular structure in SHR. The WM damage, the expression of caspase-3 and the apoptosis rate decreased after G-CSF treatment. Ultimately, G-CSF improved the non-spatial cognitive function in SHR rather than the spatial cognitive function. Therefore, our findings indicated that G-CSF might facilitate the improvement of non-spatial cognitive function in CSVD by repairing endothelial cells and alleviating WM damage.

Recombinant human granulocyte colony-stimulating factor alleviates liver fibrosis in bile duct-ligated mice

Introduction: Biliary atresia (BA) is the leading cause of liver fibrosis and failure in neonates with surgical jaundice, leading to poor outcome. Clinical and animal studies showing that granulocyte colony-stimulating factor (GCSF) treatment could improve liver fibrosis and cirrhosis suggest that GCSF may be offered as a low-cost intervention to improve the course of BA. This study aims to test the hypothesis that 10 µg/kg/day x 5 days of GCSF could improve liver function, reduce molecular pro-fibrotic markers and decrease liver fibrosis in a mouse model of bile duct ligation (BDL).&#x0D; Methods: Balb/c mice underwent Sham surgery, or BDL for seven days followed by subcutaneous GCSF administration at 10 µg/kg/day for five consecutive days. Twelve days post-operation, blood samples were taken from the facial vein for leukocyte/neutrophil count and for measurement of serum enzymatic activities. The median lobe of the liver was acquired for total RNA and protein extraction. Moreover, the median liver lobe was used for hematoxylin-eosin staining, sirius red staining, and for visualization by immunohistochemistry (IHC).&#x0D; Results: Twelve days post-operation, GCSF-treated bile duct-ligated (BDL) mice had a higher survival rate than that of placebo-treated mice (hazard ratio=1.88, p=0.084). The GCSF-treated mice had diminished liver serum transaminase activities (AST: 228.92 ± 222.67 vs. 313.46 ± 164.80 IU/L; ALP: 573.24 ± 177.89 IU/L vs. 471.75 ± 117.92 IU/L). GCSF treatment also reduced fibrosis with down-regulation of expression of pro-fibrotic markers including TGF-β1 (-2.61-fold mRNA), α-SMA (-2.46-fold mRNA; -1.88-fold protein, p&lt;0.001) and collagen (-3.28-fold mRNA; -1.79-fold collagen deposit, p=0.0055). Moreover, GCSF treatment led to an improvement of histological grade and a reduction of extension of ductular structures caused by cholestasis (-1.77-fold CK7-positive bile ducts, p&lt;0.0001; -2.33-fold CK7 positivity, p&lt;0.0001).&#x0D; Conclusion: Administration of GCSF (10 μg/kg/day) for five consecutive days improved the pathological condition of BDL mice. In this study, the positive effect of GCSF could be eventually surpassed due to end-stage liver disease caused from BDL in the mouse model. Further experiments are required to elucidate the effects and mechanisms of GCSF on bile obstruction.&#x0D;

Feasibility and cost analysis of day 4 granulocyte colony-stimulating factor mobilized peripheral blood progenitor cell collection from HLA-matched sibling donors

BackgroundGuidelines recommend treatment with 4–5 days of granulocyte colony-stimulating factor (G-CSF) for optimal donor peripheral blood progenitor cell (PBPC) mobilization followed by day 5 collection. Given that some autologous transplant recipients achieve adequate collection by day 4 and the possibility that some allogeneic donors may maximally mobilize PBPC before day 5, a feasibility study was performed evaluating day 4 allogeneic PBPC collection. MethodsHLA-matched sibling donors underwent collection on day 4 of G-CSF for peripheral blood (PB) CD34+ counts ≥0.04 × 106/mL, otherwise they underwent collection on day 5. Those with inadequate collected CD34+ cells/kg recipient weight underwent repeat collection over 2 days. Transplant and PBPC characteristics and cost analysis were compared with a historical cohort collected on day 5 per our prior institutional algorithm. ResultsOf the 101 patient/donor pairs, 50 (49.5%) had adequate PBPC collection on day 4, with a median PB CD34+ cell count of 0.06 × 106/mL. Day 4 donors were more likely to develop bone pain and require analgesics. Median collected CD34+ count was significantly greater, whereas total nucleated, mononuclear and CD3+ cell counts were significantly lower, at time of transplant infusion for day 4 versus other collection cohorts. There were no significant differences in engraftment or graft-versus-host disease. Cost analysis revealed 6.7% direct cost savings for day 4 versus historical day 5 collection. DiscussionDay 4 PB CD34+ threshold of ≥0.04 × 106/mL identified donors with high likelihood of adequate PBPC collection. Day 4 may be the optimal day of collection for healthy donors, without adverse effect on recipient transplant outcomes and with expected cost savings.

A Phase I Study of the Safety and Feasibility of Bortezomib in Combination With G-CSF for Stem Cell Mobilization in Patients With Multiple Myeloma

BackgroundWe previously reported that administration of bortezomib (BTZ) after 4 days of granulocyte colony-stimulating factor (G-CSF) significantly augments mobilization in mice. We hypothesized that administration of BTZ at peak G-CSF mobilization in patients with multiple myeloma (MM) would be safe, augment mobilization, and have an in vivo purging effect on circulating myeloma cells. Patients and MethodsThis was a phase I study using 3 dose levels of BTZ. G-CSF was administered for 5 days. On the evening of the fourth day, a single dose of BTZ was administered. Peripheral blood was drawn 1 to 2 hours before and 15 to 18 hours after BTZ administration (before day 5 G-CSF administration) to analyze the mobilization effect of BTZ. Standard apheresis was then performed starting on day 5. After mobilization, patients underwent autologous stem cell transplantation (ASCT) per institutional guidelines. ResultsTen patients were enrolled. There were no dose-limiting toxicities. Median peripheral blood CD34+ cells at day 4 before BTZ administration was 16 per microliter and 15 hours later was 32 per microliter suggesting that administration of BTZ at peak G-CSF mobilization augments the mobilization effect of G-CSF. The effect of BTZ on circulating MM cells was unclear. All patients had successful engraftment after ASCT. ConclusionAdministration of 1 dose of BTZ at peak G-CSF mobilization was safe and well tolerated, enhanced stem cell mobilization, and did not affect graft viability. The mobilization effect of BTZ at peak G-CSF mobilization shown in this phase I study needs to be confirmed in a larger randomized trial.

Feasibility and Cost Analysis of Day 4 Granulocyte Colony-Stimulating Factor Mobilized Peripheral Blood Progenitor Cell Collection from HLA-Matched Sibling Donors

Introduction: Published guidelines recommend mobilization of allogeneic peripheral blood progenitor cells (PBPC) with 4-5 days of granulocyte colony-stimulating factor (G-CSF) followed by PBPC collection on day 5. Given that some autologous transplant patients are adequately mobilized by day 4, and concern that a subset of allogeneic donors may be maximally mobilized before day 5 of G-CSF administration, we performed a feasibility study evaluating day 4 allogeneic PBPC collection.Methods: This single-center prospective study included adult patients with malignant diseases who received a first allogeneic hematopoietic stem cell transplant (HCT) at our center between 7/1/2013 - 6/30/2017. HLA-matched sibling donors received 10 μg/kg of G-CSF subcutaneously prior to PBPC collection. Donors were collected on day 4 of G-CSF if peripheral blood (PB) CD34+ counts were ≥0.04x106/ml. Donors with day 4 PB CD34+ counts <0.04x106/ml were collected on day 5, and those with inadequate collected CD34+ cells/kg recipient weight underwent repeat collection over two days. Patient and donor characteristics, PBPC product composition, transplant outcomes, and cost analysis of the PBPC collection procedure were compared to a historical cohort of donors collected on day 5 according to our prior algorithm.Results: One hundred and one patients/donors were eligible for inclusion on study, and 75 were included in the historical cohort. Of the 101 donors on study, 50 (49.5%) had adequate PBPC collection on day 4 of G-CSF, 26 (25.7%) were collected on day 5, and 25 (24.8%) required two-day collections on days 4 and 5. The median day 4 donor PB CD34+ cell count was 0.06 (range 0.03-0.13) x 106/ml among donors collecting on day 4, 0.03 (range 0.007-0.09) x 106/ml for donors collecting on day 5, and 0.019 (range 0.004-0.04) x 106/ml for donors collecting over two-days (p<0.001).The most common reported donor symptoms were bone pain, myalgia/malaise, headache, and circumoral tingling/electrolyte abnormalities. Compared to the historical cohort, donors with PBPC collection on day 4 were significantly more likely to develop bone pain, require narcotics, and take over-the-counter (OTC) medications, day 5 donors were significantly more likely to develop bone pain and take OTC medications, and two-day donors were significantly more likely to develop bone pain and circumoral tingling/electrolyte abnormalities.The median collected PBPC CD34+ cell count (7.25 x 106/kg recipient weight) and infused PBPC product CD34+ cell count (5.67 x 106/kg recipient weight) were significantly greater in products collected on day 4, compared to products collected on other days. In comparison, the infused PBPC product total nucleated cell (TNC) count (7.13 x 108/kg recipient weight), mononuclear cell (MNC) count (5.84 x 108/kg recipient weight), and CD3+ cell count (2.14 x 108/kg recipient weight) were significantly lower in products collected on day 4 compared to other collection cohorts (p<0.001, p<0.001, and p=0.002, respectively for day 5, two-day, and historical cohort).There were no significant differences in time to neutrophil or platelet engraftment, or in the incidence of acute or chronic graft-versus-host-disease, based on day of collection. There was a non-significant trend towards improved 1-year survival among patients transplanted with PBPC collected on day 4 (p=0.077). Cost analysis revealed a 6.7% savings in direct costs per collection procedure for the day 4 collection method versus historical cohort.Conclusions: Using a day 4 PB CD34+ threshold of ≥0.04x106/ml identifies donors with a high likelihood of adequate PBPC collection. While differences in PBPC product composition and donor symptoms were seen based on day of collection, we found no evidence of adverse post-HCT outcomes associated with day 4 PBPC collection. Day 4 may be the optimal day of stem cell collection for a population of healthy donors without adverse effect on transplant outcomes, and with an anticipated cost savings. Ongoing analyses include resource utilization review, matched cohort analysis of day 4 versus 5 collection and correlation with transplant outcomes, more detailed PBPC production composition analysis among the collection cohorts, and longer post-HCT follow-up and association with outcomes based on day of PBPC collection. These findings merit further analysis in larger HCT cohorts. [Display omitted] DisclosuresCook:Syros Pharmaceuticals: Consultancy. Maziarz:Incyte: Consultancy, Honoraria; Kite Therapeutics: Honoraria; Novartis Pharmaceuticals Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Athersys, Inc.: Patents & Royalties; Juno Therapeutics: Consultancy, Honoraria.