Daily G-CSF Research Articles

Complications and the impact of hematological parameters in donors involved in allogenic peripheral blood stem cell transplantation for hematological malignancies

Hematopoietic stem cell transplantation (HSCT) is a vital treatment option for many hematological malignancies, offering a more convenient alternative to bone marrow transplantation. In allogeneic HSCT, donors provide hematopoietic stem cells for transplantation into patients, necessitating careful consideration of the donor's health and hematological parameters to ensure successful engraftment and treatment outcomes. In a study involving 20 adult donors at Apeksha Hospital, Sri Lanka key hematological parameters, comorbidities, clinical histories, and medications were analyzed. Diabetes mellitus and hypertension were the most prevalent comorbidities among donors, while anemia, primarily linked to iron and vitamin B12 deficiencies, was common. Although baseline coagulation abnormalities were rare and no significant complications occurred during transplantation, early clinical issues such as pain and paresthesia correlated with abnormal peripheral blood smear findings. Notably, a 4-day single daily G-CSF dosing schedule was favored over a 5-day twice daily regimen due to fewer reported problems. While anemia and thrombocytopenia were infrequent, these findings underscore the critical importance of meticulous donor selection and vigilant monitoring throughout the transplantation process to optimize outcomes.

Impact of Daratumumab on Hematopoietic Stem Cell Mobilization with G-CSF and on-Demand Plerixafor in Newly-Diagnosed Multiple Myeloma Patients

Introduction Autologous stem cell transplantation (ASCT) is a standard of care for transplant eligible (TE) patients with newly diagnosed (ND) multiple myeloma (MM); therefore, an adequate hematopoietic stem cell (HSC) collection is crucial to allow patients to proceed to ASCT and ensure optimal hematologic recovery. A more frequent use of plerixafor (PLX) and lower HSC yields have been reported in patients treated with daratumumab, a backbone of induction therapy for NDMM patients. Chemotherapy-free mobilization with G-CSF and on-demand PLX is an effective mobilization strategy lacking chemotherapy-related toxicities. Here we present the results of a multicenter, retroprospective and prospective, observational study, aiming to compare the impact of daratumumab on HSC mobilization with G-CSF + on-demand PLX in patients with NDMM treated with bortezomib-thalidomide-dexamethasone (VTd) or VTd plus daratumumab (D-VTd). Methods NDMM patients undergoing a first HSC mobilization attempt with G-CSF (10 mcg/kg/day) were enrolled and observed up to 30 days after ASCT. According to its label, on-demand PLX was administered in patients with <20 CD34 + cells/µL after ≥ 4 days of G-CSF or in case <1×10 6 CD34 + cells/kg were collected on the first day of apheresis. The primary endpoint of the study was the rate of poor mobilizing patients (≤2x10 6 CD34 + cells/Kg collected or need for PLX to reach an adequate HSC harvest). Key secondary endpoints included: the rate of suboptimal (2 to 4 CD34 + cells/kg) and optimal (≥4 CD34 + cells/Kg) collection; the median number of apheresis required to obtain ≥2x10 6 CD34 + cells/Kg; the impact of daratumumab on HSC engraftment. Results A total of 190 NDMM patients (median age, 62 years) were enrolled in 2 Italian centres (IRCSS Istituto Clinico Humanitas and Città della Salute e della Scienza di Torino) and analyzed; of these, 70% (133/190) were treated with VTd and 30% (57/190) with D-VTd. The median number of induction cycles was 4 in both groups. Best response after the induction phase was at least very good partial response (VGPR) in 87/133 (65%) and 41/57 (72%) of patients treated with VTd or D-VTd, respectively (p=0.4). The median time from the end of induction to G-SCF administration was 24 days in the VTd group and 29 days in the D-VTd group (p=0.5). The rate of poor mobilizing patients was 31% (41/133) in the VTd group and 54% (31/57) in the D-VTd group (p=0.002), mainly due to a higher rate of PLX use in the D-VTd as compared to the VTd group (53% vs. 28%; p=0.001), while the rate of patients who failed HSC mobilization (≤2x10 6 CD34 + cells/kg collected) was similar in the two groups (2% vs. 3%; p=1). Despite a numerically higher median number of CD34 + cells collected in the VTd group (7.9) as compared to the D-VTd group (7.1; p=0.009), no difference in the rate of patients who collected 2-4 (5% vs. 5%; p=1) and ≥4 CD34 + cells/Kg (95% vs. 95%; p=1) was observed in the VTd and D-VTd groups, respectively. A higher median number of CD34 +/µL on the first day of count was observed in the VTd as compared to the D-VTd group (24.5 vs. 19, p=<0.001). Among patients who had <20 CD34 +/µL [32% (43/133) vs. 51% (29/57)] on the first day of count, a similar increase in the CD34 +/µL (48.5 vs. 55) was observed in the two groups after PLX administration. The median number of apheresis session needed to complete the harvestwas 1 fo the VTd group and 2 in the D-VTd group (p=0.1). Neutrophil and platelet recovery were achieved in 100% of patients with a median time to neutrophil recovery of 15 and 13 days in the VTd and D-VTd groups, respectively (p=<0.001) and a median time to platelet recovery of 16 and 14 days in the VTd and D-VTd groups, respectively (p=0.001). Conclusion G-CSF plus on-demand PLX for HSC mobilization demonstrated to be an effective strategy in NDMM patients treated with VTd with or without daratumumab, resulting in very low rates of mobilization failures irrespective of the use of daratumumab during induction. Despite a higher rate of patients requiring PLX for HSC collection and lower CD34 + yields, the incorporation of daratumumab as part of the induction treatment did not negatively impact the possibility to achieve an optimal HSC collection. Our results, along with the lack of chemotherapy-associated toxicity, support the use of a chemotherapy-free HSC mobilization with G-CSF and on-demand plerixafor also in patients receiving daratumumab upfront.

G-CSF Mobilized Apheresis As an Alternative Source of CAR T-Cells

Background Cellular therapies are traditionally manufactured from an apheresis product collected at 'steady state' i.e. without any cytokine administered prior. We sought to evaluate the feasibility of utilising the CD34-negative fraction of recombinant human granulocyte colony stimulating factor (rhG-CSF) mobilised apheresis products for the manufacture of CAR T-cells. The effect of rhG-CSF on CAR T-cell function is largely unknown. We conducted an extensive comparison of phenotypic and functional attributes of CAR T-cells manufactured after rhG-CSF exposure (mobCAR) to those manufactured from a steady state apheresis (ssCAR), in order to test the hypothesis that rhG-CSF mobilised CAR T-cells are functionally equivalent to steady state CAR T-cells. Methods Untransduced T-cells (UTD) and CAR T-cells targeting CD33 (CART33) were manufactured using paired steady state (ss) cells and cells collected after rhG-CSF treatment (mob). On a protocol approved by the institutional review board, 4 healthy volunteers had ss cells collected from peripheral blood and cryopreserved, and later underwent an apheresis collection after 4 days of G-CSF (10ug/kg/daily) to collect and cryopreserve mob cells. CART33 were then manufactured from thawed ss and mob cells in paired expansions. Cells were activated using CD3/CD28 beads, transduced with lentiviral vector and expanded using Ex-Vivo based cell culture media (fortified with IL-7/IL-15 and human serum), and cryopreserved when mean cell volume was less than 300fL. Extensive comparisons between ssCART33 and mobCART33 were completed, including analysis by flow cytometry, CyTOF, single cell RNA sequencing (scRNAseq) and metabolomics by mass spectrometry. In vitro assays of degranulation, cytokine production and killing were performed, and in vivo function was assessed using an immunodeficient murine model after engraftment with a CD33 expressing cell line. Results Paired effector T-cells were manufactured with lower fold expansion of mobCAR [4 vs. 7 population doublings, p<0.01] though a sufficient number of mob-CAR were able to be manufactured. Mean CAR expression was higher in ssCAR though this was not statistically significant [ssCAR 78.6% (55-79%) vs. 64.7% (59-71%), p>0.05], and no significant differences in CD4/CD8 ratio were observed. In vitro degranulation, cytokine production and tumour cytolysis were comparable between ssCAR and mobCAR. Functional equivalence was also seen between ssCAR and mobCAR in mouse xenografts of an acute myeloid leukemia (AML) model, with no differences in body weight, toxicity, or mouse survival observed (Figure 1). While significant inter-donor differences in T-cell subsets by CyTOF were observed, minimal differences were seen between the ss and mob products for a given donor, and integrated analysis of scRNASeq data showed a similar transcriptomic profile for ssCAR and mobCAR cells (Figure 2). Metabolomics analysis is ongoing. Conclusions and future directions We were able to successfully manufacture CAR T-cell products from G-CSF mobilized cryopreserved apheresis products, and found comparable in vivo anti-tumor efficacy and toxicity, with no significant differences in the G-CSF exposed product by multi-omic analyses. Successful completion of this work may support the use of cryopreserved G-CSF stimulated apheresis units for cell therapy applications. This may allow for an adjunct cell therapy to hematopoietic stem-cell transplant to be manufactured from the same mobilized collection, or provide a means by which previously cryopreserved mobilized units may be utilised, noting frequently lower cumulative chemotherapy exposure in historically cryopreserved T-cells. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Risk of Febrile Neutropenia in Very Elderly Patients Aged ≥80 Years Who Received R-CHOP Regimen: A Nationwide Analysis in Japan

Background: Despite the aging society, few studies have evaluated risk factors for febrile neutropenia (FN) in the very elderly. This may be due to the difficulty of conducting a prospective study in the presence of comorbidities and a limited number of patients. We retrospectively analyzed risk factors for FN in the first cycle of rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP) regimen in the very elderly aged ≥ 80 years using a nationwide inpatient database in Japan.Study Design and Methods: This study was a retrospective cohort study using the Diagnosis Procedure Combination database, a nationwide inpatient database in Japan. The database includes discharge abstracts and administrative claims data from >1200 acute-care hospitals and covers around 90% of all tertiary-care emergency hospitals in Japan. We identified patients aged ≥ 80 years old with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who received the first cycle of R-CHOP regimen between July 2007 and March 2017 from the database. The initial dose intensity (IDI, %) was calculated as the average ratio of the actual dose to the 100% dose of cyclophosphamide and doxorubicin. IDI less than 80% was defined as reduced IDI. Multivariable logistic regression analysis fitted with a generalized estimating equation accounting for within-hospital clustering was performed to identify factors associated with the occurrence of FN. P<0.05 was considered statistically significant.Results: We identified 1,819 patients aged ≥ 80 years old with DLBCL who were newly diagnosed and treated with R-CHOP. The median age was 83 years (interquartile range: 82-85). A total of 73 (4%) patients received antimicrobial prophylaxis, and 270 (15%) received primary prophylaxis with G-CSF. Reduced IDI of R-CHOP regimen was performed in 1,444 (79%) patients, including 697 patients with 60-80% of IDI and 747 patients with 40-60% of IDI. FN occurred in 115 of the 1,819 patients (6.3%) with a median of 10 days (interquartile range: 8-12) after the administration of cyclophosphamide. Antimicrobial prophylaxis, primary prophylaxis with daily G-CSF, and pegfilgrastim were not significantly associated with a lower occurrence of FN in the very elderly patients (odds ratio 0.69 [95% confidence interval 0.30-2.21], 1.39 [0.73-2.64], 1.43 [0.73-2.81], respectively). Reduced IDI was significantly associated with a lower occurrence of FN (40-60%: odds ratio 0.54 [0.32-0.92]). Advanced-stage lymphoma (>stage 2) and placement of central venous catheter was significantly associated with the occurrence of FN (odds ratio 1.59 [1.02-2.49], 3.19 [1.81-5.62], respectively).Conclusion: The present nationwide study showed that IDI was reduced in most of the very elderly patients with DLBCL in a real-world clinical practice. The proportion of the very elderly patients who developed FN tended to be lower than those in previous studies with younger patients, which may be explained by reduced IDI in the very elderly. Whereas, prevention strategies with G-CSF for FN may be less effective in the very elderly. DisclosuresMatsuda: Ono Pharmaceutical: Other: Lecture fee; Kyowa Kirin: Other: Lecture fee. Jo: Tsumura: Other: Lecture fee, Research Funding; AstraZeneca: Other: Lecture fee; Sanofi: Other: Lecture fee; Boehringer Ingelheim: Other: Lecture fee. Shimura: Eisai: Other: Lecture fee. Honda: Otsuka Pharmaceutical: Other: Lecture fee; Ono Pharmaceutical: Other: Lecture fee; Nippon Shinyaku: Other: Lecture fee; Jansen Pharmaceutical: Other: Lecture fee; Chugai Pharmaceutical: Other: Lecture fee; Takeda Pharmaceutical: Other: Lecture fee. Masamoto: MSD K.K.: Speakers Bureau; Eisai Co., Ltd.: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau; Takeda Pharmaceutical Company Limited.: Speakers Bureau; Chugai Pharmaceutical Company: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Speakers Bureau; Nippon Shinyaku Co., Ltd.: Speakers Bureau; AbbVie GK: Speakers Bureau; Janssen Pharmaceutical K.K.: Speakers Bureau; SymBio Pharmaceuticals: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Yasunaga: Pfizer: Consultancy, Other: Lecture fee; Novartis: Consultancy, Other: Lecture fee; Boehringer Ingelheim: Other: Lecture fee; Chugai Pharmaceutical: Other: Lecture fee; Tsumura: Other: Lecture fee. Kurokawa: MSD K.K.: Research Funding, Speakers Bureau; Eisai Co., Ltd.: Research Funding, Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Research Funding, Speakers Bureau; Takeda Pharmaceutical Company Limited.: Research Funding, Speakers Bureau; Chugai Pharmaceutical Company: Research Funding, Speakers Bureau; Daiichi Sankyo Company.: Research Funding, Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Research Funding, Speakers Bureau; AbbVie GK: Research Funding, Speakers Bureau; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding, Speakers Bureau; Nippon Shinyaku Co., Ltd.: Research Funding, Speakers Bureau; Astellas Pharma Inc.: Research Funding, Speakers Bureau; Teijin Limited: Research Funding, Speakers Bureau; Pfizer Japan Inc.: Research Funding, Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Research Funding, Speakers Bureau.

198P Complications associated with prolonged GCSF with dose-dense EC chemotherapy for early breast cancer patients

Primary granulocyte-colony stimulating factor (GSCF) prophylaxis with dose-dense chemotherapy for early stage breast cancer is routine practice to prevent febrile neutropenia (FN). Our current practice administers 7 days of GCSF, which reduces the FN risk but is associated with extra toxicity and costs. We reviewed the rates of FN, neutropenia, hospital admissions and GCSF-related toxicity in early stage breast cancer patients receiving 7 days of GCSF with dose-dense epirubicin and cyclophosphamide (EC).

A Value-Based Approach to Optimizing Peripheral Blood Progenitor Cell (PBPC) Mobilization and Collection for Autologus Hematopoietc Cell Transplantation (AHCT)

A Value-Based Approach to Optimizing Peripheral Blood Progenitor Cell (PBPC) Mobilization and Collection for Autologus Hematopoietc Cell Transplantation (AHCT)

Non-Myeloablative Transplant in Severe Sickle Cell Disease Is Safe & Effective. Single Center Experience from Saudi Arabia

Background:Sickle cell disease (SCD) is a severe monogenic disorder in the world with >300,000 newly born afflicted children per year. Prevalence of this disorder is high in sub-Saharan Africa, Mediterranean basin, Middle East and India. Patients with severe disease phenotype manifested with stroke or other complications may benefit from allogeneic hematopoietic stem cell transplant (SCT). Recent reports in pediatric patients using myeloablative regimen showed excellent outcomes but similar progress in adults has been hampered by higher rates of transplant related mortality (TRM) and infertility.Methods:We conducted a study of adult patients at our institution with SCD whom underwent a matched related SCT during the period of 2014-2017. Medical records of eligible patients were retrospectively reviewed and extracted. All patients received hydroxyurea (HU) at maximally tolerated doses with hyper-transfusion 2-3 months prior to SCT. Iron chelation was given for patients with ferritin > 1000 ug/L. The preperative regimen was non-myeloablative (NMA) consisting of alemtuzumab 1 mg/kg divided over 5 days (day -7 to -3) followed by Total Body Irradiation (TBI) 300 cGy on day -1. Stem cells were collected from peripheral blood via apheresis after 5 days of GCSF with target CD34 cells of 10×106/kg. Graft vs. host disease (GVHD) prophylaxis consisted of sirolimus starting from day -2 and continued for one year post SCT with dose modification based on chimerism. Event free survival (EFS) was defined from time to SCT to graft failure, development of GVHD or death from any cause. EFS and overall survival (OS) via time to end point analysis was computed using the Kaplan-Meir test.Results:A total of 18 adults patients were eligible and further analysed. Median age was 23.5 (14 - 39) years with 14 males and 4 females. All patients were on HU prior to SCT. Median ECOG performance status was 1 (0-1). Indications for transplant were recurrent vaso-occlusive crisis (VOC) refractory to standard therapy in 61%, stroke or other central nervous system (CNS) complication in 38%, recurrent avascular necrosis of joints in 38%, recurrent acute chest syndrome in 22% and severe disease requiring recurrent intensive care unit admission (ICU) in 17%. All donors were related siblings fully matched at 10/10 human leucocyte antigen (HLA) loci with median age of 23.6 years. A total of 11 (61%) of donors were sickle cell carriers with average Hgb S 33%. Stem cell mobilization was with 5 ug/kg GCSF in all donors and the average stem cell collected 11.6 x 106/kg. No significant complications resulted from GCSF use in donors with sickle cell trait.17 patients were conditioned with alemtuzumab / TBI regimen and GVHD prophylaxis with sirolmus. One patient who failed prior transplant received fludarabine, busulfan and thymoglobulin with GVHD prophylaxis as cyclosporine and methotrexate. Median duration of neutrophil engraftment was 20 days and platelet engraftment 2.6 days with half of patient's platelet nadir > 20. Average hemoglobin (Hb) pre- and post-SCT was 83 g/L and 142 g/L respectively. Average hemoglobin (Hb) S pre- and post-SCT was 77% and 13% respectively. Peri-SCT adverse events were 9 (50%) patients experienced neutropenic fever, 12 (67%) mucositis, 6 (33%) diarrhea. None of the patients developed acute or chronic GVHD. No SCD crises developed post SCT. One patient developed aplastic anemia while retaining 71% donor cell chimerism and underwent a second successful SCT from the same donor with fludarabine, cyclophosphamide and thymoglobulin. All patients have stable mixed chimerism resulting in full donor myeloid engraftment and normalization of blood count. With a median follow up of 9.1 months (2.3-32), all patients are alive and free of sickle cell crises. At last follow up, OS and EFS were 100% and 88.9%, respectively as shown in Figure 1.Conclusion:Herein, we report that SCT in adults with severe SCD using NMA regimen is safe, feasible and results in amelioration of disease severity. These excellent results are encouraging given the high prevalence and debilitating nature of SCD in our region. Follow up is on-going to assess the feasibility of sirolimus tapering and sustainability of donor chimerism status over time. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Combination of GROβ and AMD3100 Leads to Rapid and Robust Mobilization of Hematopoietic Stem Cells in Nonhuman Primates

▪Introduction: Mobilized peripheral blood grafts are currently the predominant source of hematopoietic stem and progenitor cells (HSPC) for both autologous and allogeneic transplantation. The most common clinical hematopoietic stem cell mobilization protocol is five days of Filgrastim (G-CSF). This regimen requires daily injections, has been associated with bone pain and often results in unpredictably low yields. A rapid mobilization method that ideally only required a single treatment and had robust and predictable kinetics would be a significant improvement over the current standard of care. In mice, a unique CXCR2 agonist, GROβ, induces rapid mobilization of stem and progenitor cells 15 minutes after a single injection. When co-administered with plerixafor (AMD3100), an inhibitor of CXCR4, a synergistic increase in mobilization results, with a graft enriched in highly engraftable hematopoietic stem cells (Hoggatt et al., Blood 2016 128:368). Here, we present data demonstrating that combination treatment with GROβ and AMD3100 synergistically mobilizes CD34+ cells and colony forming units (CFU) in nonhuman primates (NHP).Methods: Cynomolgus macaques were injected with G-CSF (10 µg/kg/day, s.c. for four days), AMD3100 (1 mg/kg, s.c. once) or GROβ (various doses and routes) alone and in combination with AMD3100. Blood was collected at various times post treatment and analyzed by multicolor flow cytometry to quantitate HSPC numbers. Additional aliquots of mobilized blood were plated in methylcellulose and CFU were enumerated seven days later.Results: We tested the effect of GROβ alone or in combination with AMD3100 in Cynomolgus monkeys. As published previously, administration of G-CSF, AMD3100 or G-CSF+AMD3100 induced significant mobilization of hematopoietic stem and progenitor cells. In comparison, a single injection each of GROβ+AMD3100 yielded 4-fold more CD34+ cells compared to four days of G-CSF (p < 0.01). While the combination of G-CSF+AMD3100 mobilized significantly more CD34+ cells compared to GROβ+AMD3100 (p < 0.0001), the numbers of CD34+ CD90+ CD45RA- cells, representing the most primitive of hematopoietic stem and progenitor cells, were equivalent between treatment groups. Similarly, GROβ+AMD3100 treatment elicited 7-fold more CFU compared to animals treated with G-CSF (p < 0.01), 3.5-fold more CFU compared to AMD3100 (p < 0.01) and equivalent CFU compared to G-CSF+AMD3100. Importantly, the frequency of CFU among the CD34+ cells was significantly greater with GROβ+AMD3100 (1 in 4) compared to G-CSF (1 in 10) or G-CSF+AMD3100 (1 in 25). In contrast to the increased CD34+ numbers and CFU, white blood cell (WBC) and neutrophil counts were significantly lower with GROβ+AMD3100 compared to AMD3100 alone or G-CSF+AMD3100.Conclusions: We describe a rapid mobilization method that within four hours of a single treatment results in robust hematopoietic mobilization in nonhuman primates. The GROβ+AMD3100 regimen enriches for primitive CD34+ CD90+ CD45RA- stem and progenitor cells with increased colony forming capacity compared to CD34+ cells mobilized with G-CSF+AMD3100, suggesting a significant graft quality difference with the new regimen. The ability to rapidly mobilize primitive HSC with increased CFU frequency may allow effective single day mobilization of HPSCs for patients requiring a HSCT and be especially useful for HSC based gene therapy and gene editing protocols where HSPC grafts enriched for primitive HSC may reduce manufacturing costs and ensure durability of the gene modified HSC. The ability to achieve increased HSPC numbers without dramatically increasing WBC and neutrophils may be especially advantageous in patient populations where G-CSF mobilization is not well tolerated such as Sickle Cell Disease, or where G-CSF leads to increased disease activity such as in autologous transplant for Multiple Sclerosis. A single treatment that results in robust mobilization that is equivalent to G-CSF may allow for a one-day collection method of donor stem cells, and these findings in nonhuman primates support clinical exploration. DisclosuresFalahee:Magenta Therapeutics: Employment, Equity Ownership. Goncalves:Magenta Therapeutics: Employment, Equity Ownership. Hyzy:Magenta Therapeutics: Employment, Equity Ownership. Proctor:Magenta Therapeutics: Employment, Equity Ownership. Hoggatt:Magenta Therapeutics: Consultancy, Equity Ownership, Patents & Royalties. Morrow:Magenta Therapeutics: Employment, Equity Ownership. Cooke:Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties.

Low-Dose Plerixafor and Granulocyte Colony-Stimulating Factor for First-Line Autologous Peripheral Blood Stem Cell Mobilization in Lymphoma and Multiple Myeloma

Introduction: Approximately 10-30% of candidates to autologous hematopietic stem cell transplant (HSCT) are unable to collect an adequate yield of CD34+ cells/kg to support high-dose chemotherapy and autologous HSCT. Peripheral blood stem cell (PBSC) mobilization strategies vary considerably but the optimal methodology for mobilizing PBSC is not well defined. Plerixafor (Mozobil®) is approved for the mobilization of PBPC in combination with G-CSF at a dose of 0.24 mg/kg once daily for up to 4 consecutive days; however, it is an expensive drug and is expected to increase costs associated with PBSC harvest. Failure of peripheral blood (PB) mobilization and harvest is a critical issue for multiple myeloma (MM) and non hodgkin´s lymphoma (NHL) since the correlation between successful engraftment and the number of CD34+ cells infused is well established. We aim to investigate the safety and efficacy of the administration of low-dose plerixafor in mobilizing CD34+ cells plus G-CSF in MM and NHL.Methods: It is a preliminary report of a single-institution, open-label, phase II trial to test the feasibility and efficacy for mobilization of low-dose plerixafor added to daily G-CSF administration in adult patients with MM or NHL undergoing autologous HSCT. Institution ethic board approved the trial and all patients provided written informed consent. Consecutive patients in autologous transplant protocol with MM or NHL were included. The mobilization protocol consisted of G-CSF (10 μg/kg) subcutaneously daily for 4 days and plerixafor (0.12 mg/kg) administered subcutaneously 11 hours prior to initiation of apheresis. Stem cells collection was performed with a Cobe Spectra® or Spectra Optia® apheresis system. The planned target blood volume to be processed was 4-fold total blood volume calculated according to patients' weight and size. Peripheral blood CD34+ counts were analyzed using flow cytometry. Primary endpoint was the proportion of patients achieving at least 2 x 106 CD34+cells/kg in 1 apheresis harvest. Secondary end points included the rate of successful CD34+ cell mobilization, defined as a peak of CD34+ cells in PB >20 cells/mL. We measure PB CD34+ cells the day 4 and 5 after plerixafor administration. Toxicities and engraftment were documented.Results: Between april 2017 and july 2017, nine patients has been enrolled. Six with MM and 3 with NHL. The median PB CD34+ cell count for patients on day 4 before receiving plerixafor was 12.3/mL (range, 2.2-168.8) and 65.4/mL (range, 8.2-360.7) on day 5 after plerixafor (P=0.103). The median collection yield was 4.9 x 106 CD34+ cells/Kg (range, 1.4 - 24.5 million CD34+ cells/Kg). Plerixafor was well tolerated in most patients, only 2 referred moderate diarrhea. Eight of the 9 patients reached the target cell count (88.8%) with only 1 day of collection. Seven of nine patients had hematopoietic recovery with median neutrophil and platelet engraftment of 14 (range, 10-16) and 12 days (range, 10-16), respectively. Two patients are on day +1 and +5 and waiting for engraftment.Conclusions: Failure of PBSC mobilization is a critical issue for MM and NHL patients undergoing autologous HSCT. The combination of low-dose plerixafor with G- CSF in this study achieved 88% of successful yields, and appears to be an efficient and safe approach in first-line to improve the success of the yield. Aside of the costs related to plerixafor, this strategy can be counterweighed by reducing other resources as reducing number of apheresis and possibly reducing the impact on quality of life for patients. DisclosuresGomez-Almaguer:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol: Consultancy, Membership on an entity's Board of Directors or advisory committees.

A Phase II Study Evaluating the Safety and Efficacy of Sunitinib Malate in Combination With Weekly Paclitaxel Followed by Doxorubicin and Daily Oral Cyclophosphamide Plus G-CSF as Neoadjuvant Chemotherapy for Locally Advanced or Inflammatory Breast Cancer

IntroductionNeoadjuvant chemotherapy is standard treatment for locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). We hypothesized that adding sunitinib, a tyrosine kinase inhibitor with antitumor and antiangiogenic activity, to an anthracycline and taxane regimen would improve pathologic complete response (pCR) rates to a prespecified endpoint of 45% in patients with HER2-negative LABC or IBC. MethodsWe conducted a multicenter, phase II trial of neoadjuvant sunitinib with paclitaxel (S+T) followed by doxorubicin and cyclophosphamide plus G-CSF for patients with HER2-negative LABC or IBC. Patients received sunitinib 25 mg PO daily with paclitaxel 80 mg/m2 IV weekly ×12 followed by doxorubicin 24 mg/m2 IV weekly + cyclophosphamide 60 mg/m2 PO daily with G-CSF support. Response was evaluated using pCR in the breast and the CPS + EG score (clinical-pathologic scoring + estrogen receptor [ER] and grade). ResultsSeventy patients enrolled, and 66 were evaluable for efficacy. Eighteen patients (27%) had pCR in the breast (10 had ER+ disease and 8 had triple-negative disease). When defining response as pCR and/or CPS + EG score ≤2, 31 (47%) were responders. In pateints with ER positive disease, 23 (64%) were responders. The most common toxicities were cytopenias and fatigue. ConclusionsNeoadjuvant S+T followed by AC+G-CSF was safe and tolerable in LABC and IBC. The study did not meet the prespecified endpoint for pCR; however, 47% were responders using pCR and/or CPS + EG score ≤2. ER positive patients had the highest response rate (64%). The addition of sunitinib to neoadjuvant chemotherapy may provide promising incremental benefit for patients with ER positive LABC.

A phase (Ph) 1b/2 study of ribociclib (R) in combination with docetaxel (D) plus prednisone (P) in metastatic castration-resistant prostate cancer (mCRPC).

5043 Background: The survival benefit of D in mCRPC is modest. CDK4/6 inhibitors such as R have shown synergistic activity with taxanes in pre-clinical cancer models. We sought to determine the safety and efficacy of R + D + P in mCRPC patients (pts). Methods: This was a Ph 1b/2 multicenter, open-label single arm trial of mCRPC pts with progression (PD) on ≥ 1 prior androgen receptor signaling inhibitor (ARSi) who had not previously received D for mCRPC (NCT02494921). Pts were treated with escalating doses of R in combination with D + P for 6-9 cycles, followed by single agent maintenance R until radiographic or clinical PD. The Ph 2 primary endpoint was 6-month (mo) radiographic progression-free survival (rPFS) rate by PCWG2 criteria, with a target rate of 55% and null hypothesis of 35%. Ph 2 pts underwent baseline circulating tumor cell (CTC) enumeration and genome sequencing (Epic Sciences). Cox proportional hazard model and log-rank test were used to test for associations between rPFS and CTC burden and copy number (CN) variants, respectively. Results: 43 pts were enrolled from 11/2015 to 6/2019. Median age was 68 (range 55-84). 20.9% of pts had visceral metastases. 33 (77%) had PD on prior abiraterone, 27 (63%) on enzalutamide, and 17 (40%) on both. In Ph 1b, 19 pts were enrolled. In the first cohort (D 75 mg/m2 day [d] 1, R 200 mg/d d2-14 of every 21d cycle), 2 pts experienced DLTs (febrile neutropenia [FN] and grade 4 neutropenia). With an alternative dosing schema of D 60 mg/m2 on d1, and R daily on d1-4 and 8-15 of cycle, with daily G-CSF support on d5-7, the MTD was not reached and D 60 mg/m2 + R 400 mg/d was chosen as the recommended Ph 2 dose (RP2D). In total, 30 pts were treated at RP2D; median number of D cycles was 8.5 and 60% went on to receive maintenance R. The Ph 2 primary endpoint was met with a 6-mo rPFS rate of 65% (95% CI 50-85%). Median rPFS was 8.0 mos (95% CI 4.1-10.0). PSA response rate (RR) defined as ≥50% reduction was 27.6% (95% CI 12.7-47.2%) and objective RR was 30.8% (95% CI 9.1-61.4%). Among pts treated at RP2D, the most common grade ≥3 treatment-related adverse events were neutropenia (n= 11, 36.7%), lymphocytopenia (n=3, 10%); no cases of FN were observed. Baseline CTC burden was associated with an increased risk of radiographic PD or death (HR 1.038, 95% CI 1.001-1.074, p = 0.038). Pts harboring CTCs without MYC (4/11 pts) or CDK6 CN gain (7/11 pts) had prolonged rPFS compared to those with gene amplification (median rPFS 10.76 vs 4.11 mos, p = 0.03, and 7.01 vs 1.92 mos, p = 0.053, respectively). Conclusions: The combination of R + D was well tolerated and showed promising activity in mCRPC pts who had progressed on an ARSi. The Ph 2 study met its primary endpoint, with an encouraging 6-mo rPFS rate of 65%. Lack of MYC or CDK6 amplification on CTC sequencing was associated with longer rPFS. Funding: Novartis Pharmaceuticals, PCF YIA. Managed by the PCCTC. Clinical trial information: NCT02494921.

Old is bad? The effect of age on peripheral stem cell mobilization and transplantation outcomes

IntroductionAllogeneic stem cell transplantation (Allo-SCT) is a well-established treatment option for hematological malignancies. With the introduction of reduced-intensity conditioning regimens (RIC) and better supportive measures the elderly are able to receive Allo-SCT. A considerable number of patients are elderly, and often their HLA matched sibling donor is elderly, moreover. Here, we aim to explore the effect of donors’ age on stem cell harvesting, engraftment duration after Allo-SCT, and product quality. MethodSixty-one healthy allogeneic stem cell donors aged 50 years and older who underwent stem cell mobilization at our center between 2009–2019 were enrolled for the study. All donors received 4–5 days of G-CSF, mostly filgrastim or lenograstim and their biosimilar equivalents were given subcutaneously as a total dose of 10 mcg/kg/day. Groups were separated into three groups as aged 50–54 group A, 55–59 group B, aged 60 and older group C. ResultsPre-apheresis peripheral blood CD34+ count was similar all groups (p = 0.2). One day apheresis was sufficient for 72.7 % of group A, 27.3 % for group B and 47.1 % for group C (p = 0.02). Total harvested CD34+ cells were comparable among groups (p = 0.5). ConclusionAdequate stem cell harvest in older donors is feasible. Older donors may require more than one apheresis procedure and generally procedure was well tolerated. When assessing donors, age should represent less significance.

Comparison of 140mg/m2 vs 200mg/m2 Dose of Melphalan in Myeloma Autograft - a Single Centre Experience from Chennai, India

Introduction: - Melphalan at a dose of 200mg/m2 is considered the standard autograft dose in patients with multiple myeloma without significant co-morbidity. This drug was formulated in the early years before the era of novel agent induction and maintenance. Considering the deeper remission of novel agents and prevailing refractory gram-negative sepsis in most Indian setups, we compared 140mg/m2 (MEL140)vs. 200mg/m2(MEL200) of Melphalan in Indian myeloma patients who achieved a complete remission before transplant without having any significant co-morbidity. Methods and results: - We analysed myeloma autograft patients from September 2014 to August 2017. 42 patients received MEL200, and 43 patients received MEL140. Diabetes on oral medications was randomised equally on both sides. The median age of patients in MEL200 was 52 years, and MEL140 was 53.6 years. There were 60% and 55% of males in MEL200 vs. MEL140, respectively. ISS-III patients was 48% and 49% in MEL200 vs. MEL140, respectively. The standard induction regimen was three to four cycles of RvD chemotherapy. Around 16% of patients in the MEL140 group had a creatinine clearance between 30-50ml/min. The mobilisation regimen followed was five days of GCSF based mobilisation. The stem cell cut-off was kept to a minimum of 2 x 106/CD34+ve cells/kg body weight. Overall, 12% of patients in both groups needed a second-day stem cell collection. Three-year overall survival, progression-free survival, the incidence of relapse, rate of refractory sepsis, the time difference in hematopoietic recovery, and secondary cancers were compared between two groups. In outcome analysis, there was no transplant-related mortality in both groups. The mean day of engraftment was around Day +9 in MEL140 vs. Day +11 in MEL200. The rate of Gram-Negative Bacilli sepsis was around 14% in MEL140 vs. 27% in Mel200 (p 0.02). These findings were reflected in the use of high-end antibiotics like Colistin and Fosfomycin in such patients. There was a delay in engraftment, which may have been confounded by sepsis. The median progression-free survival was 26.1 months in MEL200and 27.2 months in the MEL140 group. The cumulative incidence of relapse at three years was not significantly different between the Mel200 (33.3%) and Mel140 (34.9%) groups. The adjusted HR for relapse was 0.98. Subgroup analysis suggests that in overall survival, progression-free survival, and cumulative incidence of relapse, there was no significant advantage associated with Melphalan 200 mg/m2. Age, renal status, proteasome inhibitor treatment, gender, or Karnofsky score did not interact with overall/progression-free survival or relapse rate in the two melphalan dose groups. One patient in the MEL200 group developed -5q deletion Myelodysplastic syndrome after five years of transplant. Discussion: This study was conducted taking into account the changing scenario in myeloma induction and maintenance to novel agents and increasing rate of resistant gram-negative sepsis in Indian febrile neutropenic patients. As we can achieve a deeper remission before transplant, we formulated to compare lower dose melphalan to prevent a stormy post-transplant course and prevent patients succumbing to sepsis. This may not be an issue in western countries where gram-negative sepsis rates are lower. The biggest worry for us is not compromising the myeloma outcome due to lower doses of Melphalan in fit patients who achieve complete remission. This study concluded that there is not much of a difference in overall survival, Progression-free survival, and cumulative incidence of relapse at three years among MEL200 vs. MEL140. Conclusion: - We conclude that Melphalan autograft at a dose 140mg/m2 can achieve comparable responses to 200mg/m2 in Indian myeloma patients who are taken to transplant post complete remission. We need a more prominent multicentric study and a longer follow-up to recommend MEL140 as a standard of care in Indian settings.

Abstract P5-14-09: Prospective cohort study of febrile neutropenia in breast cancer patients with neoadjuvant and adjuvant chemotherapy: CSPOR-BC FN Study

Abstract Background: Febrile neutropenia (FN) is one of the greatest concerns when maintaining chemotherapy dosage for early breast cancer patients. However, the incidence proportion of FN remains unclear because of the empirical prescription of oral antibiotics, the use of G-CSF, and the absence of body temperature examination and hematology test. Therefore, we performed a prospective cohort study of FN in breast cancer patients receiving adjuvant or neoadjuvant chemotherapy. Methods: Breast cancer patients were prospectively enrolled from August 2015 to July 2017. The regimens included 4 cycles of FEC (epirubicin 100 mg/m²), E(A)C (epirubicin 90 mg/m² or doxorubicin 60 mg/m²), and TC (docetaxel 75 mg/m²). Considering the current practice of empirically prescribing oral antibiotics without hematology tests, we followed 2 groups and surveyed FN using 2 different definitions: true FN (T-FN): ≥ 37.5°C and grade 4 neutropenia by a hematologic test with a visit to the hospital (visiting group), and surrogate FN (S-FN): ≥ 37.5°C and oral antibiotic intake without a mandatory visit to the hospital (non-visiting group). The primary objective was to investigate the FN incidence of each regimen during the first 4 cycles. The overall incidence proportion of FN was calculated as (patients with T-FN or S-FN) / (total patients). The proportion of T-FN or S-FN in each group was also examined. In the secondary analysis, the risk factors of FN and the safety of FN management in the non-visiting group were investigated. Multiple logistic regression analysis was performed to assess the risk factors. As we assumed that FN occurs in 20% of the patients by these regimens, the planned sample size based on the confidence intervals was 1000. This trial was registered as UMIN 000017857. Results: A total of 1005 female patients with Stage I to III breast cancer were enrolled. Of these patients, 25 were excluded because of incomplete treatments or other regimens administered. There were 477 patients in the visiting group and 503 patients in the non-visiting group. The numbers of patients in each regimen were 338 in FEC, 335 in E(A)C, and 307 in TC. The overall incidence proportions of FN were 22.5%, 27.5%, and 33.9% in FEC, E(A)C, and TC, respectively. The incidence proportions of T-FN were 27.7%, 22.4%, and 36.6%; those of S-FN were 17.3%, 32.4%, and 31.5%. Pegfilgrastim (PEG-G) was used in the 1st cycle more frequently in the non-visiting group than in the visiting group: in FEC, E(A)C, and TC, 39.0%, 11.8%, and 52.1% in the non-visiting group; 4.71%, 1.82%, and 14.1% in the visiting group, respectively. The risk factors of FN were regimen (TC: OR: 2.67, 95%CI: 1.36-5.26), age (&amp;gt; 65 OR: 2.24, 95%CI: 1.34-3.75), neutrophil count at registration (/1000/μl: OR: 0.8, 95%CI: 0.67-0.95), pre-/post-operation (pre-: OR: 0.51, 95%CI: 0.29-0.88), and PEG-G (OR: 0.04, 95%CI: 0.01-0.34). There were no significant differences in the frequency of grade 3 adverse events, hospitalization, intake of oral antibiotics, and relative dose intensity between the visiting group and the non-visiting group. Therapeutic daily G-CSF was more frequently used in the visiting group than in the non-visiting group. Conclusions: FN occurred at a rate higher than 20% in these 3 regimens, most frequently in TC. Neutrophil count at registration was found to be one of the risk factors of FN. The current practice of prescribing antibiotics without hematologic tests is acceptable for FN management because the outcomes were not significantly different between the visiting group and the non-visiting group. Citation Format: Takashi Ishikawa, Kentaro Sakamaki, Kazutaka Narui, Hideki Nishimura, Takafumi Sangai, Kentaro Tamaki, Yoshie Hasegawa, Ken-ichi Watanabe, Nobuyasu Suganuma, Shintaro Michishita, Sadatoshi Sugae, Tomohiko Aiharya, Koichiro Tsugawa, Hiroshi Kaise, Hirofumi Mukai. Prospective cohort study of febrile neutropenia in breast cancer patients with neoadjuvant and adjuvant chemotherapy: CSPOR-BC FN Study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-09.

HSCT may lower leukemia risk in ELANE neutropenia: a before-after study from the French Severe Congenital Neutropenia Registry.

ELANE neutropenia is associated with myelodysplasia and acute leukemia (MDS–AL), and severe infections. Because the MDS–AL risk has also been shown to be associated with exposure to GCSF, since 2005, in France, patients receiving high daily GCSF doses (>15 μg/kg/day) are eligible for HSCT, in addition to classic indications (MDS–AL or GCSF refractoriness). We analyzed the effect of this policy. Among 144 prospectively followed ELANE-neutropenia patients enrolled in the French Severe Congenital Neutropenia Registry, we defined two groups according to period: “before 2005” for those born before 2005 and followed until 31/12/2004 (1588 person-years); and “after 2005” comprised of those born after 2005 or born before 2005 but followed after 2005 until 31/03/2019 (1327 person-years). Sixteen of our cohort patients underwent HSCT (14 long-term survivors) and six developed MDS–ALs. Six leukemic transformations occurred in the before-2005 group and none after 2005 (respective frequencies 3.8 × 10–3 vs. 0; P < 0.01), while four HSCTs were done before 2005 and 12 since 2005 (respective HSCT rates increased 2.5 × 10–3 vs. 9 × 10–3; P < 0.01). Our results support early HSCT for patients with ELANE mutations who received high GCSF doses, as it might lower the risk of leukemic transformation.

The Impact of Different Mobilization Strategies in the Setting of Multiple Myeloma

INTRODUCTION Multiple myeloma (MM) is considered an incurable disease. Despite the introduction of novel agents allowed deeper response, high-dose chemotherapy and autologous stem cell transplantation (ASCT) remain the standard of care for patients (pts) in good clinical conditions. The most used strategies to mobilize stem cells from bone marrow (BM) into peripheral blood are high-dose cyclophosphamide (HD-CTX) plus G-CSF and G-CSF plus plerixafor (G-CSF+P). The goal of this retrospective study is to investigate whether the two different mobilization strategies have an impact on the clearance of monoclonal PCs in the apheresis products and on pts' outcome. PATIENTS AND METHODS We analyzed 62 pts (median age 61, range 41-75, 37 males and 25 women) diagnosed with MM and treated with ASCT between Mar 2014 and Mar 2018 at our Hematology Division (Pisa, Italy). All pts received induction therapy with at least 4 cycles of bortezomib, thalidomide and dexamethasone (VTD). 9/62 pts obtained a less than partial response (PR) and received lenalidomide-based regimens. After induction, 8 (12,9%) pts achieved complete remission (CR), 26 (41,9%) were in PR, 28 (45,2%) obtained a very good partial response (VGPR). 43/62 fit pts received HD-CTX (2-3 g/sqm) on day 1 followed by G-CSF (30 MU/day) started on day 4 until day 7, increased to 60 MU/day from day 8 until the end of apheresis. In 19/62 pts, after 4 days of G-CSF (60 MU/day) administration and not sufficient mobilization, we added plerixafor (0,24 mg/kgbw) for up to 4 consecutive days. In 43/62 pts we collected apheresis samples (10μl) analyzed through flow citometry to enumerate clonal residual PCs. The panel used to asses clonality included: CD138 Per-Cp, CD38 APC, CD19 PE-Cy7, CD45 APC-Cy7, cytoplasmic immunoglobulin K chain and L chain. RESULTS At the end of the peripheral blood stem cell (PBSC) collection, pts treated with HD-CTX presented a higher CD34+ absolute count (p=0.0489) and achieved the threshold of 5x106 CD34+ cells/kgbw in a significantly (p=0.006) higher percentage. We found a nearly significant (p=0.0517) lower count of CD34+ PBSCs in pts who received lenalidomide-based regimens before the mobilization. Performing flow citometry on apheresis samples, we observed that the number of the harvested clonal PCs showed a significant correlation (p=0.0115) with the occurrence of post-ASCT relapse. ROC curve analysis investigating the predictive effect of the number of pathological PCs on disease relapse showed an area under the curve of 0,6978 (95% CI 0.5392-0.8564; p=0.0267). Neither BM residual PCs detectable on BM biopsies performed before apheresis (r=-0.1323; p=0.609) nor the type of mobilization scheme (p=0.707) had an impact on the proportion of clonal PCs in the graft. Additionally, we did not observe any statistically significant difference in progression free- (PFS) (p=0.8276) and overall survival (OS) (p=0.2475) between the HD-CTX and G-CSF+P groups. DISCUSSION PBSC mobilization has a succession rate &gt; 85%. Despite the use of HD-CTX to increase PBSC yields and decrease tumor burden, there is not clear evidence of a superior mobilization strategy. Additionally, HD-CTX has a not negligible toxicity and approximately 10% of the pts require hospitalization. Conversely, G-CSF+P is a safe and effective approach also in poor mobilizers. In our study, we observed a significative difference in the apheresis yields (p=0.0489) and in the percentage of pts who achieved the threshold of 5x106 CD34+ cells/kgbw (p=0.006) in favor of HD-CTX. Additionally, the detection of harvested residual clonal PCs could be a promising strategy to recognise pts more likely to relapse after ASCT. Nonetheless, we failed to demonstrate a superior effect of HD-CTX in the clearance of harvested clonal PCs, in agreement with the absence of a different pts' outcome amongst the two mobilization strategies. In conclusion, the choice between the two regimens is challenging and requires careful consideration of multiple factors. Overall, young fit pts, especially in the high-risk setting, should be treated with all appropriate modalities including chemiomobilization followed by double-ASCT. Conversely, in pts candidate to a single-ASCT it is reasonable to use G-CSF+P, since HD-CTX does not improve PFS and OS and add toxicity. The absence of an in-vivo purging effect on apheresis products of chemiomobilization further strengthens a chemotherapy-free mobilization. Disclosures Galimberti: Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau.

Age Matters: Younger Unrelated PBSC Donors Experience Less G-CSF-Related Symptoms and Have a Faster Emotional Recovery Than Older Donors

Introduction Young adults are more likely to be selected as unrelated stem cell donors because younger donor age has been associated with improved overall survival for recipients. Younger donors are also less likely to have co-morbidities leading to cancellation at the donor medical. Due to this, donor recruitment policies target the young adult population, and in 2012 the Anthony Nolan Bone Marrow Registry lowered the recruitment age for donors from 18 to 16 years. Previously published studies of unrelated donor recovery and experience have not included donors under 18, and have included relatively low proportions of young adult donors. The aim of this study was to compare donor availability, stem cell yield, and recovery across donor age groups. Methods All sequential first peripheral blood stem cell (PBSC) donations to adult patients from unrelated donors at the Anthony Nolan Registry between May 2015 and September 2017 were analysed (n=879). The primary outcome was achievement of optimal collection yield (CD34+ ≥4x106 cells per kg patient weight) following 4 or 5 days of G-CSF (depending on whether 1 or 2-day collection were required). The secondary outcomes were turnaround time from verification typing stage to donation (to assess donor availability), and the incidence of complications post-donation (skeletal pain, general symptoms and emotional state) as well as self-reported recovery. Donors were grouped in age-based equal quartiles (17-22.9, 23-25.9, 26-30.9 and 31-60 year-old). Groups were compared using the chi-squared test, or chi-squared trend test for categorical variables, and the Kruskal-Wallis test for continuous variables. Follow-up data was collected prospectively via online questionnaires post-donation at day 2, day 7, day 30 and 1 year. Results Results by age group are presented in Table 1. There were no differences in the proportion of donors achieving the optimal CD34+ count (p=0.44) between the different age groups, regardless of the number of collection days required. Furthermore, no differences were found in the turnaround time from the verification typing stage to stem cell collection between younger and older donors (p=0.54). During G-CSF administration, older donors were more likely to suffer from bony pain (p=0.005) and general symptoms (such as anorexia, tiredness or night sweats) compared to younger donors (p=0.001). Two days post-collection, a higher number of younger donors reported emotional (p=0.001) and physical recovery (p=0.024) compared to older donors. Also older donors experienced more general symptoms after donation (p=0.036), and tiredness was particularly more prevalent among older donors at this time point (p=0.006). There was a trend in older donors reporting more bony pain than younger donors (p=0.062). One week after donation, there was a higher physical recovery rate in younger donors (p=0.015). Longer-term recovery did not differ by age. Conclusions Younger donors proceed to donation as quickly as older donors, and are equally effective in achieving the stem cell yield. Younger donors report fewer complications and experience a faster physical and emotional recovery following PBSC donation. In addition, G-CSF has a favourable side effect profile on this population. These results support recruitment of unrelated donors from 16 years of age and suggest that our current registry pathway for support of these donors is adequate. Follow-up is fundamental to address medical or psychological issues, and manage them accordingly, mainly within the first week post-donation and particularly in older donors. Disclosures No relevant conflicts of interest to declare.

P010 - The optimal timing and duration of daily G-CSF for primary prophylaxis after adjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy in breast cancer patients

P010 - The optimal timing and duration of daily G-CSF for primary prophylaxis after adjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy in breast cancer patients

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

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

Weighty Choices: Selecting Optimal G-CSF Doses for Stem Cell Mobilization to Optimize Yield

Introduction. There is little information on the effect of donor body mass index (BMI) on mobilization response to Filgrastim (G-CSF), especially in the unrelated donor setting. Obesity has been associated with chronic low-grade inflammation due to chronic activation of the innate immune system. Obesity-induced pro-inflammatory cytokines can interfere with bone marrow SDF1/CXCR4 axis and promote mobilization of progenitor cells leading to persistent leukocytosis and an increase in number of circulating progenitor cells. Given a higher number of circulatory progenitor cells in obese individuals compared to non-obese, a reduced G-CSF dose in obese donors may elicit adequate response, thus reducing the adverse events associated with peripheral blood stem cell (PBSC) collection. The aim of this study is to evaluate the impact of donor BMI on G-CSF mobilized peripheral blood progenitor cell yield in healthy donors. This study also examines whether there is a G-CSF dose threshold above which there is a significant increase in skeletal pain and other acute toxicities from mobilization without an appreciable increase in progenitor cell yield.Methods. The primary outcome was examination of CD34+ per liter of blood processed (x106/L) on Day 5 of G-CSF administration as a measure of collection yield. The secondary outcomes were the incidence of skeletal pain and highest toxicity level across selected body symptoms (fatigue, nausea, anorexia, insomnia, dizziness) at 24 hours after first G-CSF dose, day 1 to 5 of G-CSF administration, 2 days and 1-week post collection. The population studied was domestic unrelated G-CSF mobilized PBSC donors reported to the NMDP/CIBMTR between 2006 and 2016. G-CSF dosing was based on the NMDP weight-based dosing schema rounded to the nearest vial content. Donors were divided into normal, overweight, obese, and morbidly obese categories based on BMI. Multivariate analysis of collection yields between cohorts were done using linear regression analysis. Stepwise variable selection was used to add variables to the model: BMI group and G-CSF dose was forced into the final model as the variables of interest. Pain and acute toxicities at each time point were described using frequencies and compared between groups using chi-squared test or Fisher's exact test after adjusting for donor and baseline characteristics.Results. Examination of 20, 884 PBSC donors mobilized by G-CSF revealed a significant increase in collection yield in obese and morbidly obese compared to normal and overweight donors. Median CD34+ per liter of blood processed (x106/L) on Day 5 of G-CSF was 29.6, 36.4, 40.8 and 42.9 in normal, overweight, obese and morbidly obese donors, respectively (p<0.001). Based on the subgroup analyses evaluating impact of average daily dose of G-CSF on the collection yield for each BMI group, an increase in average daily G-CSF dose was associated with an increase in stem cell yield in normal and overweight BMI donors. In contrast, an increase in the average daily G-CSF dose beyond 780 mcg per day in obese and 900 mcg per day in morbidly obese did not increase the yield (Table 1).Figure 1 shows the time course and degree of toxicities in different BMI categories. Obese and morbidly obese were more likely to experience grade 2-4 pain and toxicities compared with normal or overweight in both the peri-collection and early post-donation recovery period but by one week after donation most toxicities abated and there was no difference. Donors with a higher BMI were more likely to experience grade 2 to 4 skeletal pain 24 hours post first G-CSF dose, 2 days post donation and at day 1 to 5 G-CSF administration. In addition, donors with higher BMI were more likely to have grade 2-4 toxicities (fatigue, anorexia, insomnia) at day 1 to 5 of G-CSF and 2 days after collection. However, within each BMI group, incremental increase in G-CSF dose was not associated with greater pain or other toxicities.Conclusions. Our data indicates a correlation between average daily G-CSF dose and CD34+ cell yield in normal and overweight donors. However, in obese and morbidly obese donors, there was no benefit in CD34+ yield with increasing average daily G-CSF dose above 780 mcg and 900 mcg respectively. Therefore, there appears to be a maximum effective G-CSF dose for mobilization in obese and morbidly obese donors where higher doses of G-CSF add no additional benefit and may result in additional complications. [Display omitted] DisclosuresPulsipher:Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Honoraria; Adaptive Biotech: Consultancy, Research Funding; CSL Behring: Consultancy.