Peripheral Blood Stem Cell Harvest Research Articles

Poor Mobilization-Associated Factors in Autologous Hematopoietic Stem Cell Harvest

Peripheral blood stem cell transplantation (PBSCT) is an important therapeutic measure for both hematologic and non-hematologic diseases. For PBSCT to be successful, sufficient CD34+ cells need to be mobilized and harvested. Although risk factors associated with poor mobilization in patients with hematologic diseases have been reported, studies of patients with non-hematologic diseases and those receiving plerixafor are rare. To identify factors associated with poor mobilization, data from autologous PBSC harvest (PBSCH) in 491 patients were retrospectively collected and analyzed. A multivariate analysis revealed that in patients with a hematologic disease, an age older than 60 years (odds ratio [OR] 1.655, 95% confidence interval [CI] 1.049–2.611, p = 0.008), the use of myelotoxic agents (OR 4.384, 95% CI 2.681–7.168, p < 0.001), and a low platelet count (OR 2.106, 95% CI 1.205–3.682, p = 0.009) were associated with poor mobilization. In patients with non-hematologic diseases, a history of radiation on the pelvis/spine was the sole associated factor (OR 12.200, 95% CI 1.934–76.956, p = 0.008). Among the group of patients who received plerixafor, poor mobilization was observed in 19 patients (19/134, 14.2%) and a difference in the mobilization regimen was noted among the good mobilization group. These results show that the risk factors for poor mobilization in patients with non-hematologic diseases and those receiving plerixafor differ from those in patients with hematologic diseases; as such, non-hematologic patients require special consideration to enable successful PBSCH.

Peripheral Blood Stem Cell Harvesting in Young Children Weighing Less Than 15 Kilograms

Autologous peripheral blood stem cell (PBSC) transplantation is crucial in pediatric cancer treatment, and tandem transplantation is beneficial in certain malignancies. Collecting PBSCs in small children with low body weight is challenging. We retrospectively analyzed data of pediatric cancer patients weighing <15 kg who underwent autologous PBSC harvesting in our hospital. Collections were performed in pediatric intensive care unit over 2 or 3 consecutive days, to harvest sufficient stem cells (goal ≥2 × 106 CD34+ cells/kg per apheresate). From April 2006 to August 2021, we performed 129 collections after 50 mobilizations in 40 patients, with a median age of 1.9 (range, 0.6-5.6) years and a body weight of 11.0 (range, 6.6-14.7) kg. The median CD34+ cells in each apheresate was 4.2 (range, 0.01-40.13) × 106/kg. 78% and 56% of mobilizations achieved sufficient cell dose for single or tandem transplantation, respectively, without additional aliquoting. The pre-apheresis hematopoietic precursor cell (HPC) count was highly correlated with the CD34+ cell yield in the apheresate (r = 0.555, P < 0.001). Granulocyte colony-stimulating factor alone was not effective for mobilization in children ≥2 years of age, even without radiation exposure. By combining the pre-apheresis HPC count ≥20/μL and the 3 significant host factors, including age <2 years, no radiation exposure and use of chemotherapy, the prediction rate of goal achievement was increased (AUC 0.787).

A case of allogeneic peripheral blood stem cell in a paroxysmal nocturnal hemoglobinuria patient from a COVID-positive donor: Managing the unpreventable

Abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease caused by clonal expansion of one or more hematopoietic stem cell lines due to a somatic mutation of the phosphatidylinositol glycan anchor gene. Peripheral blood stem cell (PBSC) harvest is a high-risk procedure and the major concern was regarding the development of COVID infection in the recipient. Herein, we describe an inevitable case of PBSC harvest in a PNH patient who was already started on myeloablation and where the donor became positive 1 day before the harvest. Considering the risk–benefit ratio and the need for elaborate arrangements, the initial plan for bone marrow harvesting was changed to PBSC, and hence, the harvest was performed in a COVID-designated unit. No features of graft versus host disease (GVHD) were observed in the patient. The patient was examined for signs and symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and there was no evidence of any infection after the procedure. The weekly analysis of the same was done for 1 month after PBSC and the SARS-CoV-2 status remained negative. The authors opine that PBSC from SARS-CoV-2 can be performed safely in some unpreventable situations.

Hematopoietic Progenitor Cell Counts of the Leukapheresis Product Determined Using Sysmex XN Analyzers Predict a Sufficient Number of CD34+ Stem Cells in a Peripheral Blood Stem Cell Harvest for Autologous Transplantation.

Objective Several institutions outsource CD34+ cell counting of leukapheresis products, limiting rapid measurements, as results are obtained the next day. This problem is compounded with plerixafor use, a stem cell-mobilizing drug that increases leukapheresis efficiency but requires administration the day before leukapheresis. Use of this drug for a second leukapheresis procedure before the first-day leukapheresis CD34+ count results are confirmed causes unnecessary leukapheresis and expensive plerixafor administration. We investigated whether or not measuring hematopoietic progenitor cells in leukapheresis products (AP-HPCs) using a Sysmex XN-series analyzer could resolve this problem. Methods We retrospectively compared the absolute AP-HPC value per body weight with the CD34+ (AP-CD34+) count in 96 first-day leukapheresis product samples obtained between September 2013 and January 2021. Comparisons were also conducted according to regimen: granulocyte colony-stimulating factor (G-CSF) monotherapy, chemotherapy plus G-CSF, or plerixafor mobilization. Results AP-CD34+ and AP-HPC counts correlated strongly (rs=0.846) overall and, in particular, under chemotherapy plus G-CSF (rs=0.92) but correlated mildly under G-CSF monotherapy (rs=0.655). AP-HPCs could not completely be dichotomized based on an AP-CD34+ threshold of 2×106/kg for any stimulation procedure. In most cases with AP-HPCs >6×106/kg, the AP-CD34+ count exceeded 2.0×106/kg, but in 5.7% of these cases, the AP-CD34+ count was <2.0×106/kg. A cut-off of AP-HPCs >4.843×106/kg yielded a sensitivity of 71% and specificity of 96% for predicting AP-CD34+≥2×106/kg. Conclusion AP-HPCs can identify cases in which sufficient stem cells have been collected.

Long-Term Cryopreservation of Peripheral Blood Stem Cell Harvest Using Low Concentration (4.35%) Dimethyl Sulfoxide with Methyl Cellulose and Uncontrolled Rate Freezing at -80 °C: An Effective Option in Resource-Limited Settings

Long-term cryopreservation of peripheral blood stem cells (PBSCs) is highly useful in the setting of tandem/multiple transplantations or treatment of relapse in the autologous hematopoietic stem cell transplantation (HSCT) setting. Even in allogeneic HSCT, donor lymphocyte infusions may be stored for months to years if excess stem cells are collected from donors. Cryopreservation is a delicate, complex, and costly procedure, and higher concentrations of dimethyl sulfoxide (DMSO), a commonly used cryoprotectant, can be toxic to cells and cause adverse effects in the recipient during infusions. In this study, we examined the effect of long-term cryopreservation using 4.35% DMSO (as final concentration) with methyl cellulose and uncontrolled rate freezing in a mechanical freezer (-80 °C) on the viability and colony-forming ability of CD34+ human PBSCs. For patients undergoing autologous HSCT, PBSCs were cryopreserved using DMSO (final concentration of 4.35%) with methyl cellulose. The post-thaw viability of PBSCs was determined using Trypan blue exclusion and flow cytometry-based 7-amino-actinomycin-D (FC-7AAD) methods. Concentrations of CD34+ stem cells and immune cell subsets in post-thaw PBSC harvest samples were assessed using multicolor flow cytometry, and the clonogenic potential of post-thaw stem cells was studied using a colony-forming unit (CFU) assay. CD34+ stem cell levels were correlated with the prestorage CD34 levels using the Pearson correlation test. The viability results in the Trypan blue dye exclusion method and the flow cytometry-based method were compared using Bland-Altman plots. We studied 26 PBSC harvest samples with a median cryopreservation duration of 6.6 years (range, 3.8 to 11.5 years). The median viability of post-thaw PBSCs was >80% using both methods, with a weak agreement between them (r=.03; P=.5). The median CD34+ stem cell count in the post-thaw samples was 9.13×106/kg (range, .44 to 26.27×106/kg). The CFU assay yielded a good proliferation and differentiation potential in post-thaw PBSCs, with a weak correlation between granulocyte macrophage CFU and CD34+ stem cell levels (r=.4; P=.05). Two samples that had been cryopreserved for >8 years showed low viability. Cryopreservation of PBSCs using 4.35% DMSO with methyl cellulose and uncontrolled freezing in a mechanical freezer at -80 °C allows the maintenance of long-term viability of PBSC for up to 8 years.

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

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

Efficacy and safety of plerixafor in pediatric cancer patients undergoing peripheral blood stem cell harvest for autologous hematopoietic stem cell transplant.

Plerixafor for peripheral blood hematopoietic stem cell (PB HSC) mobilization in children undergoing autologous hematopoietic stem cell transplantation is primarily used following failure of the initial mobilization attempt. Data on plerixafor use in pediatric patients are limited. This retrospective study conducted at a single tertiary care center in India, details the efficacy and safety of plerixafor for 10 children with relapsed/refractory solid tumors or lymphomas. High risk neuroblastomas (HR NB) underwent autologous HSCT as part of consolidation. Plerixafor was administered at a dose of 240 μg/kg body weight of the recipient, subcutaneously, approximately 11-12 h prior to harvest. Ten patients (eight males, two females), with a median age of 8 years (range 2-18 years), received plerixafor prior to PB HSC harvest. All patients were administered granulocyte colony stimulating factor (GCSF) before the administration of plerixafor. The median CD 34 count for all patients pre-plerixafor was 29/μL, nine patients exhibited higher CD 34 post plerixafor (median of 148/μL). In nine patients, the values of the CD 34 count and total leukocyte count (TLC) of the harvested product were available, and in all cases, we achieved a good yield. All patients in this study were heavily chemotherapy pre-treated, and the use of plerixafor resulted in a satisfactory yield of peripheral blood stem cells. No side effects were observed.

ATG in HLA-Matched, Peripheral Blood, Hematopoietic Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Secondary Analysis of a CIBMTR Database

w?>Peripheral blood stem cells (PBSC) are the preferred grafts for hematopoietic cell transplantation (HCT), according to the CIBMTR. Donor recovery is faster with PBSC harvest, but PBSC is associated with higher chronic graft-versus-host disease (GVHD) and poorer quality of life. Anti-T-cell globulin (ATG) is polyclonal IgG from rabbits or horses immunized with human thymocytes or a human T-cell line, which may reduce GVHD in HCT and improve outcomes. The objective of this study was to analyze the impact of ATG in HLA-matched related (MRD) and matched (HLA 8/8) unrelated donor (MUD) HCT. We used a freely available CIBMTR database published online for secondary analyses. The database included patients ≥ 40 years old who have undergone their first PBSC MRD or MUD HCT for acute myeloid leukemia or myelodysplastic syndrome with or without ATG between 2008 and 2017. Patients who received posttransplant cyclophosphamide or alemtuzumab were excluded. Overall survival was not different with ATG (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 1.00-1.19; P = .06) compared with no ATG. Relapse rate was higher with ATG (HR = 1.29; 95% CI, 1.17-1.43; P < .001) and non-relapse mortality was lower with ATG (HR = 0.84; 95% CI, 0.72-0.98; P = .03). Grades II-IV acute GVHD was significantly lower with ATG (HR = 0.77; 95% CI, 0.69-0.87; P < .001) but not grades III-IV acute GVHD (HR = 0.85; 95% CI, 0.69-1.04; P = .11). Both chronic GVHD (HR = 0.54; 95% CI, 0.48-0.60; P < .001) and moderate/severe chronic GVHD (HR = 0.45; 95% CI, 0.38-0.52; P < .001) were lower with ATG. There was an interaction between ATG and conditioning regimen for relapse rate and overall survival. Relapse rate was higher in those who received reduced-intensity (RIC) or non-myeloablative (NMA) conditioning regimens and ATG, compared with MAC ± ATG or RIC without ATG (interaction test, P = .003). Overall survival was also poorer with ATG and RIC or NMA conditioning regimens (interaction test, P = .03). Our results show that ATG can mitigate the more severe forms of chronic GVHD without impairing overall survival in HLA-matched HCT with PBSC grafts and myeloablative conditioning regimen. ATG should be standard in this population.© 2023 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Outcomes of poor peripheral blood stem cell mobilizers with multiple myeloma at the first mobilization: A multicenter retrospective study in Japan.

Autologous stem cell transplantation (ASCT) remains an important therapeutic strategy for multiple myeloma; however, a proportion of patients fail to mobilize a sufficient number of peripheral blood stem cells (PBSCs) to proceed to ASCT. In the present study, we aimed to clarify the characteristics and outcomes of poor mobilizers. Clinical data on poorly mobilized patients who underwent PBSC harvest for almost 10 years were retrospectively collected from 44 institutions in the Japanese Society of Myeloma (JSM). Poor mobilizers were defined as patients with less than 2 × 106/kg of CD34+ cells harvested at the first mobilization. The proportion of poor mobilization was 15.1%. A sufficient dataset including overall survival (OS) was evaluable in 258 poor mobilizers. Overall, 92 out of 258 (35.7%) poor mobilizers did not subsequently undergo ASCT, mainly due to an insufficient number of PBSCs. Median OS from apheresis was longer for poor mobilizers who underwent ASCT than for those who did not (86.0 vs. 61.9 mon., p = 0.02). OS from the diagnosis of poor mobilizers who underwent ASCT in our cohort was similar to those who underwent ASCT in the JSM database (3y OS rate, 86.8% vs. 85.9%). In this cohort, one‐third of poor mobilizers who did not undergo ASCT had relatively poor survival. In contrast, the OS improved in poor mobilizers who underwent ASCT. However, the OS of extremely poor mobilizers was short irrespective of ASCT.

Addition of bortezomib to high-dose cyclophosphamide therapy as a conditioning regimen for autologous peripheral blood stem cell harvest leads to an increased yield of hematopoietic stem cells.

Peripheral blood stem cell harvest (PBSCH) is a crucial procedure for autologous stem cell transplantation in patients with multiple myeloma. We herein report a retrospective study to verify the usefulness of bortezomib and high-dose cyclophosphamide therapy (Bor-HDCY) as a conditioning regimen for PBSCH. Thirty-three patients were evaluated. The median age at the first apheresis was 61 (interquartile range, 53-64) years old, and 18 (54.5%) patients were male. Bor-HDCY was performed in 15 patients, and HDCY was performed in 18. In the patients who underwent Bor-HDCY, the CD34+ cell count at the first apheresis was significantly higher than in the others (P<0.01), and the total CD34+ cell count also tended to be high (P=0.0933). In terms of apheresis days, two-thirds of the patients who underwent HDCY had two-day apheresis, whereas most who underwent Bor-HDCY had one-day apheresis. According to univariate analysis, Bor-HDCY (P<0.01), VRd (Bor, lenalidomide, and dexamethasone) as induction therapy (P=0.0529), and ≥VGPR before PBSCH (P=0.0767) were factors associated with a higher CD34+ cell count at first apheresis. Although multivariate analysis showed that there were no independently significant factors influencing the CD34+ cell count at the first apheresis, the stepwise selection method revealed that only the Bor-HDCY regimen remained in the final model (P<0.005). Bor-HDCY may be a useful conditioning regimen for increasing the CD34+ cell yield.

Plerixafor use in autologous hematopoietic stem cell mobilization: Experience from a single center in Southern India

BACKGROUND:Plerixafor is used for patients at risk of Stem cell mobilization failure based on clinical factors or low peripheral blood CD34 count. It is also added upfront to any mobilization irrespective of risk factor, but the cost-effectiveness of the approach is an issue. Data on plerixafor in different settings of autologous hematopoietic stem cell (HSC) collection from India are scant. We are hereby reporting the experience of failure/success of mobilization rate and few important significant variables (CD34+ dosage, failed collection) between plerixafor and granulocyte colony-stimulating factor alone groups among autologous hematopoietic stem cell transplantation (aHSCT) at our institute.METHODS:This was a record-based single-center study on patients who underwent aHSCT from January 2013 to June 2019 at a tertiary care hospital. Descriptive statistics were used for baseline characteristics, transplant-related factors, and peritransplant outcomes. All statistical analyses were performed at the 5% significance level.RESULTS:During the study duration, a total of 96 patients had undergone autologous hematopoietic stem cell collection (aHSCC), all by peripheral blood stem cell harvest, requiring 131 apheretic collections. Of the total 131 collections in 96 patients, plerixafor was used in 63 apheresis collections (48% of total pheresis) in 40 patients. Among the 40 patients who were administered plerixafor to augment the collection, 34 patients had upfront use of plerixafor. We did not observe any significant adverse event related to plerixafor use.CONCLUSION:A rational utilization of plerixafor can facilitate the process and logistics of aHSCC outcome.

Level of Unique T-Cell Clonotypes Are Associated with Clonal Hematopoiesis and Survival in Patients with Lymphoma Intended for Autologous Stem Cell Transplant

The advent of novel immunotherapy (CAR-T cell therapy, bispecific CD20×CD3 antibodies) have highlighted the importance of T-cells in the treatment of lymphoma. However, overall T-cell characteristics have not been properly examined in patients receiving conventional chemotherapy. Next-generation sequencing (NGS) of the T-cell receptor (TCR) has enabled the possibility of identifying hundred thousands of unique T-cell clones in a single patient sample. Here we analyzed the impact of systemic TCR diversity and T-cell clonotypes in patients with Non-Hodgkin lymphoma (NHL) and Hodgkin-lymphoma (HL) receiving high-dose chemotherapy with stem cell support (HDT/ASCT).Autologous peripheral blood stem cell harvest samples from patients with lymphoma (predominantly B-cell NHL) were collected as part of a national population-based study (Husby et al. - Leukemia 2020). We performed high-throughput RNA-based sequencing of the V, D and J segment of the TCR β-chain to identify unique clonal rearrangements.To ensure supreme quality for TCR repertoire calculations, samples with less than 100.000 aligned reads to the TCR β chain were omitted from further analysis. By using the MiXCR bioinformatic pipeline we analyzed the number of unique clonotypes and TCR repertoire diversity, as calculated by the Simpson index. T-cell clonotype and diversity were for categorical analyses split in two groups by the median, respectively.A total of 96 patients with lymphoma who were intended for HDT/ASCT were included and analyzed for TCR characteristics. In brief, median age was 56 years, 64% were male and major subtypes were diffuse large B-cell lymphoma (37%), follicular lymphoma (24%), Hodgkin lymphoma (16%), and mantle cell lymphoma (14%). Median follow-up time was 6.7 years. Number of unique T-cell clonotypes was not associated with age (Fig. 1A), but low levels were highly associated with inferior survival (Fig. 1B, p=0.008), especially in the first year of follow-up. In contrast, elderly patients had a trend toward lower TCR diversity (Fig. 1C, p=0.08), but this did not impact overall survival (Fig. 1D).Low T-cell clonotype levels was also significantly associated with presence of clonal hematopoiesis (Fig. 1E, p=0.033). No association with clonal hematopoiesis was found with regard to TCR diversity (Fig. 1F). Furthermore, we investigated TCR repertoire in relation to subsequent severe infections (defined as sepsis, pneumonia, or invasive fungal infection). Number of unique T-cell clonotypes did not have an impact (Fig. 1F), but remarkably patients with a high T-cell diversity had significant increased incidence of severe infections in the first 500 days after sampling (Fig. 1G, p=0.029). This implies that patients who have a high T-cell diversity before high-dose chemotherapy, are more capable of mounting an immune response against infectious pathogens.These findings should be validated in larger homogenous cohorts. However, they imply the importance of inherent immune characteristics in patients with lymphoma. Although the immune response is exceedingly complex, we have identified systemic T-cell characteristics that associate with several important clinical variables. Assessment of systemic immunological parameters in patients with aggressive lymphoma may in the future inform on choice of optimal personalized therapy. [Display omitted] DisclosuresEl-Galaly: ROCHE Ltd: Ended employment in the past 24 months; Abbvie: Other: Speakers fee. Larsen: Odense University Hospital, Denmark: Current Employment; Celgene: Consultancy; BMS: Consultancy; Novartis: Consultancy; Gilead: Consultancy.

Peripheral blood stem cell mobilization with pegylated granulocyte colony stimulating factor in children.

Background and AimWe report here our experience of using pegylated granulocyte colony stimulating factor (peg‐GCSF) for peripheral blood stem cell (PBSC) mobilization in children.Methods and resultsA total of nine children suffering from high‐risk/relapsed solid tumors were mobilized with chemotherapy and peg‐GCSF (100 microgram/kg single dose). Mean age was 7.7 years (range 2–15 years).The mean time from peg‐GCSF administration to PBSC harvest was 9.7 days. Adequate stem cells (median dose 26.9 million/kg) could be harvested in all children by a single apheresis procedure. No major adverse events observed.ConclusionIt is feasible and safe to mobilize PBSC with peg‐GCSF in children with cancer.

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.

Gene Therapy for Beta Thalassemia: Preliminary Results from the PHASE I/II Tiget-Bthal Trial of Autologous Hematopoietic Stem Cells Genetically Modified with GLOBE Lentiviral Vector

Gene therapy for transfusion dependent beta-thalassemia is based on the autologous transplantation of hematopoietic stem cells (HSCs) engineered by lentiviral vectors expressing a transcriptionally regulated human beta-globin gene.Gene therapy (GT) could represent an alternative to HSCT with the following potential advantages: use of autologous stem cells, tailored conditioning with no need for immune suppression post GT, no risk of GVHD or rejection.Our contribution to this field was devoted to the clinical development of a gene therapy protocol based on the high-titer vector GLOBE, a 3rd generation self-inactivating lentiviral vector encoding for the human beta globin gene. Transfusion dependent beta thalassemia patients (any genotype) undergo peripheral blood stem cell harvest following mobilization with the lenograstim and plerixafor. After transduction of immune-selected autologous CD34+ cells and successful release of the frozen drug substance, patient undergo a conditioning regimen based on myeloablative treosulfan and thiotepa favoring efficient engraftment of corrected cells with reduced extra-medullary toxicity (TIGET-BTHAL; EudraCT number 2014‐004860‐39). The route of administration of gene modified HSCs is intraosseous in the posterior-superior iliac crests with the aim of enhancing engraftment and minimizing first-pass intravenous filter. Three days after gene therapy, previously collected unstimulated autologous peripheral blood leucocytes (1-10 x107 CD3+/kg) are reinfused intravenously to favor immune-reconstitution. After 2 years follow-up, patients will be followed up for a further six years in a long-term follow-up study. On the basis of extensive efficacy and safety preclinical studies the clinical trial TIGET-BTHAL was approved and started in 2015 at Scientific Institute San Raffaele, Milan, Italy. The clinical study foresees treatment of 10 patients: 3 adults (group 1) followed by 3 patients aged 8-17 years (group 2) and 4 patients aged 3-7 years (group 3), with a staggered enrolment strategy based on evaluation of safety and preliminary efficacy in adult patients by an independent data safety monitoring board (DSMB) before inclusion of pediatric subjects. In March 2016 the DSMB approved enrolment of group 2 patients and, in September 2016, of group 3 patients. As of August 2017, seven patients (3 adults aged 31-35 years and 4 pediatric patients aged 6-13 years) with different genotypes (β0/β0, β+/β+ and β0/β+) have been treated with GLOBE-transduced CD34+ cells at a dose of 16x106-19.5x106 cells/kg and a vector copy number (VCN)/cell ranging from 0.7 to 1.5. Median follow-up is 13 months (range 8-22). The procedure was well tolerated by all patients, with no product-related adverse events, no evidence of replication competent lentivirus nor of abnormal clonal proliferation on regular peripheral blood and bone marrow analyses. Grade 3-4 adverse events or serious adverse events were principally of infectious origin as expected after a myeloablative autograft. Median time to neutrophil engraftment was 19 days (range 17-25) and to platelet engraftment 15 days (range 10-21). Multilineage engraftment of gene-marked cells was observed in peripheral blood and bone marrow, with a median of 0.58 (range 0.37-1.55) vector copy number/cell in GlyA+ bone marrow erythroid cells at 6 months post GT.Polyclonal vector integrations profiles have been detected in the first 3 patients tested. The three adult patients had a reduction of transfusion requirement but are still transfusion dependent at the last follow-up (22, 18 and 16 months respectively). Among the 4 pediatric patients, 3 have discontinued transfusion shortly after gene therapy and are transfusion independent at the last follow-up (13, 10 and 8 months respectively). One pediatric patient is still receiving regular blood transfusions. A correlation was observed between level of engraftment of gene-marked cells in peripheral blood and bone marrow and transfusion requirement. Preliminary data suggest that the applied clinical protocol for gene therapy with GLOBE LV is well tolerated and leads to significantly reduced transfusion requirement. Follow up analysis are ongoing and updated clinical outcome will be presented. DisclosuresMarktel:GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding. Naldini:San Raffaele Institute: Employment, Patents & Royalties; Telethon Foundation: Consultancy, Patents & Royalties; Bioverativ: Research Funding; Editas: Research Funding; Genenta Sciences: Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Magenta: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Oncorus: Membership on an entity's Board of Directors or advisory committees; Sangamo Biosciences: Membership on an entity's Board of Directors or advisory committees. Cappellini:Sanofi-Genzyme: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria; Vifor: Honoraria; Novartis: Speakers Bureau. Ciceri:GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding. Aiuti:GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding. Ferrari:GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding.

An Open-Label Phase I/II Study of Carfilzomib, Bendamustine and Dexamethasone (CBD) in Newly Diagnosed Multiple Myeloma Patients

BackgroundCarfilzomib is an irreversible epoxyketone proteasome inhibitor which has demonstrated superior disease control and PFS for myeloma compared to bortezomib. Bendamustine is a bifunctional alkylating agent with demonstrated activity in relapsed/refractory myeloma. We hypothesized that the combination of carfilzomib and bendamustine may result in additive and synergistic effects, without excessive toxicity. In this phase I/II study, we investigate the safety and efficacy of carfilzomib, bendamustine and dexamethasone (CBD) for newly diagnosed myeloma.ObjectivesThe primary objective is to determine the maximum tolerated dose (MTD) of carfilzomib in combination with bendamustine and dexamethasone. Secondary endpoints include overall response rate (ORR), duration of response (DOR), progression free survival (PFS), overall survival (OS), and assessment of stem cell collection.MethodsPatients with newly diagnosed myeloma were enrolled. Carfilzomib was administered intravenously on days 1, 2, 8, 9, 15, 16 of a 28-day cycle. Bendamustine was given intravenously on days 1 and 2. Dexamethasone was administered orally or intravenously on days of carfilzomib and on day 22 of each cycle. The dose escalation portion of the study used an Up-and-Down dose escalation scheme (Storer's schema D), with one patient per dose level run in. Transplant eligible patients received 4 cycles of treatment and then underwent peripheral blood stem cell harvest (SCH) after mobilization with granulocyte-stimulating factor +/- plerixafor. They then received an additional 4 cycles and underwent stem cell transplant (SCT) after 8 total cycles of CBD. Transplant ineligible patients also received 8 total cycles of treatment. Both groups then received maintenance therapy with carfilzomib 36 mg/m2 on days 1, 2, 15, 16 of each 28-day cycle for up to 2 years. Adverse events were assessed according to CTCAE V4 and responses were assessed using IMWG criteria.ResultsAt 38 months into the study, 15 patients have been treated, amongst which 14 were evaluable for response. Median age was 65 (range: 51-74); 10/15 (67%) were male; 6 (40%) were Hispanic, 6 Caucasian, 2 (13%) Asian and 1 (7%) African American. Four patients were allocated to lower level doses and 11 patients thus far have been given the maximum planned dose - carfilzomib 56 mg/m2, bendamustine 90 mg/m2, dexamethasone 20 mg. No dose-limiting toxicities have been noted and the most common adverse events (AEs) are shown in Table 1. Hematologic AEs were most common, occurring in 9 (64%) patients, and Grade 3 or 4 events occurring in 7 (50%). Other notable AEs included Grade 1 or 2 fever (50%), Grade 1 or 2 headache (43%) and thromboembolic events (29%). There were no deaths. No congestive heart failure or arrhythmias were noted. 11 patients underwent stem cell collection, with data available for 10. Median total stem cell yield, in million CD34/kg, was 6.85 (range 5.44-13.83). Median day 1 stem cell yield was 4.43 (range 1.28-13.83). 5 patients received plerixafor. 5 patients had 2 days of collection and 1 had a third.ResponseThe ORR was 14/14 (100%). 10 (71%) had a complete response (CR) / very good partial response (VGPR): 1 (7%) MRD-negative CR by flow, 1 stringent CR, 2 (14%) CR / near CR, 6 (43%) VGPR. 4 (29%) had partial response (PR). 3 of the 6 patients with VGPR and all 4 patients with PR are still on induction therapy and anticipated to have deeper responses. 3 of 4 patients with ISS stage III disease had CR with one being MRD-negative by flow. By time of SCH (after 4 cycles), 1/11 (9%) had attained CR, 7 (64%) VGPR and 3 (27%) PR. To date, 4 patients underwent SCT, and all have attained CR with 1 being MRD-negative by flow. Amongst other patients who underwent SCH, 3 were deemed ineligible for SCT, 1 declined, and 4 are eligible. Median time to best response was 3 months (range 1-11) amongst patients whose response has plateaued, and median time to CR was 4 months (range 1-11). Median follow-up was 8.8 months (range 2-37.3). To date, only 1 patient has progressed, at 18 months after start of therapy, and median PFS has not been reached. No patients have died.ConclusionsCurrent preliminary evidence suggests that CBD is a potent induction regimen. CBD does not appear to impact stem cell collection, and toxicities were acceptable, although increased attention to thromboembolic events is warranted. Further evaluation of this regimen at our maximum dose level is planned. [Display omitted] DisclosuresLentzsch:Caelum Biosciences: Other: leadership position and stock; BMS: Consultancy; Amgen: Consultancy.

Phase 1 Study of Elotuzumab and Peripheral Blood Mononuclear Cell Reconstitution in Combination with Autologous Stem Cell Transplantation and Lenalidomide Maintenance for Multiple Myeloma

Introduction: Elotuzumab is a humanized IgG kappa monoclonal antibody against SLAMF7 that is approved in combination with lenalidomide and dexamethasone for relapsed myeloma. This agent promotes antibody-dependent, cell-mediated cytotoxicity (ADCC) and activation of natural killer (NK) cells to kill tumor cells through ligation of the target. We hypothesized that the addition of elotuzumab and autologous peripheral blood mononuclear cell (PBMC) infusion (to provide NK cells post-transplant) to standard-of-care autologous hematopoietic stem cell transplantation (ASCT) and lenalidomide maintenance for consolidation therapy in myeloma patients will be safe and feasible. This strategy may target residual disease and promote adaptive anti-myeloma immunity, resulting in long-term maintenance of a minimal disease state.Methods. The primary objective of this Phase 1b, open-label, trial is to assess the safety and efficacy of elotuzumab and autologous PBMC in conjunction with high-dose melphalan and autologous CD34+ stem cell transplantation followed by elotuzumab and lenalidomide maintenance. The secondary objectives are to assess myeloma disease status and progression-free survival (PFS) after one year of treatment. Subjects must have achieved a partial response or better by IMWG criteria with induction chemotherapy, be eligible for ASCT by institutional standards, and meet inclusion/exclusion criteria. Fifteen subjects are planned. Subjects undergo standard peripheral blood stem cell mobilization and harvest, and steady-state leukopheresis for PBMC collection. Subjects receive standard melphalan conditioning (day -1) and autologous stem cell rescue (day 0). Autologous PBMC are reinfused on day +3 and cycle 1 of elotuzumab 20 mg/kg IV is given on day +4. Subjects receive subsequent cycles of elotuzumab every 28 days up to cycle 12. Lenalidomide maintenance at 10 mg orally daily days 1-21 of every 28-day cycle begins with cycle 4 of elotuzumab, and may continue off study beyond cycle 12 at the investigator's discretion. Bone marrow aspirates and peripheral blood are collected for correlative studies at screening, cycle 2, cycle 4, and at the end of study after cycle 12. For the primary endpoint analysis, the safety population includes all subjects who received at least one dose of study treatment. The evaluable population constitutes all subjects who received at least four of the first five planned doses of elotuzumab.Results: The study completed accrual of the planned 15 subjects, all of whom are included in the safety population and are evaluable. Demographic and staging data reflect the general patient population at our institution. Subjects received 1-2 lines of induction therapy. The majority of adverse events, including infusion reactions attributable to elotuzumab, were grade 2 or lower. Grade 3 or higher hematologic AEs, including anemia, neutropenia, lymphopenia, thrombocytopenia, and non-hematologic AEs including nausea, vomiting, and dehydration, were attributable to the ASCT procedure. One subject demonstrated a delay in hematopoietic reconstitution, which resulted in hospitalization greater than the expected 21 days. Only one subject experienced neutropenic fever during the ASCT admission. One episode of grade 3 hypertension was attributed to elotuzumab infusion and resolved with supportive care. No AEs were attributed to PBMC administration. Two subjects came off study before completion; one for personal choice (VGPR at time of study withdrawal) and one for early progression.Thirteen subjects completed the study protocol. At one-year post-ASCT, subjects were re-staged and the results are as follows: 1 PR, 6 VGPR, and 7 sCR. ORR was 93% (14/15) and one-year PFS was 93% (14/15). Eleven of 13 subjects who completed the study protocol continued on lenalidomide maintenance. Two subjects (one VGPR and one PR) elected to pursue further consolidation with combination chemotherapy. Correlative studies including tumor microenvironment immunophenotyping, MRD assessment, and T cell receptor sequencing will be presented.Conclusions: Elotuzumab and PBMC administration with standard ASCT and lenalidomide maintenance for consolidation therapy of multiple myeloma is safe and feasible. One-year disease status, PFS data, and safety profile suggest this protocol compares favorably to standard ASCT consolidation and merits further investigation for efficacy. DisclosuresChari:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Bristol-Myers Squibb: Consultancy, Other: Research funding (to AC's institution); travel; Array BioPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Pharmacyclics: Research Funding; Acetylon Pharmaceuticals: Other: Research funding (to AC's institution); Biotest: Other: Research funding (to AC's institution); Onyx: Research Funding; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Gnjatic:GlaxoSmithKline: Patents & Royalties; Boehringer Ingelheim Corporation: Membership on an entity's Board of Directors or advisory committees. Jagannath:MMRF: Speakers Bureau; Bristol-Meyers Squibb: Consultancy; Novartis: Consultancy; Merck: Consultancy; Celgene: Consultancy; Medicom: Speakers Bureau. Cho:Agenus, Inc.: Research Funding; Bristol Myers-Squibb: Other: advisory board, Research Funding; Genentech: Other: advisory board, Research Funding; Ludwig Institute for Cancer Research: Research Funding; Multiple Myeloma Research Foundation: Research Funding.

Feasibility and Kinetics of CD34+ Hematopoietic Cells Mobilization By Low-Dose Pegfilgrastim in Lymphoma Patients

▪Introduction: Hematopoietic stem cell rescue with autologous peripheral blood stem cells (PBSC) following high-dose chemotherapy has been used for the treatment of lymphoma and myeloma. Granulocyte colony-stimulating factor (G-CSF) is used for PBSC mobilization but data on PBSC mobilization by pegfilgrastim is limited. Recent studies showed successful PBSC harvest by single dose of pegfilgrastim given at 6mg or 12mg within 4 days after chemotherapy in patients with malignant lymphoma. However, administration of pegfilgrastim early after chemotherapy administration induces overshoot of neutrophils, which may result in rapid plasma clearance of G-CSF due to internalization of the G-CSF/G-CSF receptor complexes via endocytosis in neutrophils. Previous studies demonstrated that day 7 injection of pegfilgrastim in the course of chemotherapy mitigated the neutrophil overshoot compared to day 4 injection of pegfilgrastim. We hypothesized that day 7 administration of lower dose 3.6mg pegfilgrastim could avoid neutrophil overshoot and efficiently mobilize PBSCs. Here we show the kinetics of CD34+ PBSC mobilization after 3.6mg pegfilgrastim given on day 7 in the course of chemotherapy.Patients and Methods: Between February 2016 and May 2017, twenty patients with malignant lymphoma enrolled in this study (14 DLBCL, 2 AITL, 2 ALCL, 1 ATLL, 1 FL). Median age was 54 (range 30-65). Eight patients had clinical stage III-IV. Median number of prior chemotherapy was 0 (range 0-2). All patients received cytotoxic chemotherapy (13 CHOP, 2 DeVIC, 2 ESHAP, 1 DHAP, 1 EPOCH, 1 HD-AraC) on day 1 and 3.6mg of pegfilgrastim was administered subcutaneously on day 7. Peripheral blood CD34+ cell counts were analyzed from day 11 to 14 after chemotherapy by flowcytometric analysis using single platform method based on ISHAGE guideline. The primary objective is to clarify the kinetics of peripheral blood CD34+ cells without harvesting intervention. CD34+ values on each time point is statistically tested using one-sample t-test. To visualize the primary result, bar graph with mean and its confidence interval on each day is represented with the reference line (Figure). The secondary objectives are to search peak point of CD34+ cell counts after each chemotherapy regimen and the feasibility of pegfilgrastim administration on day 7. Successful mobilization was defined as to achieve more than 10×106/L peripheral blood CD34+ cells on any time points between day 11 and 14. All patients were assessed for toxicity according to the National Cancer Institute Common Toxicity Criteria, version 4.0. This study was approved by the institutional review board and conducted in accordance with the Declaration of Helsinki.Results: Successful mobilization was achieved in 19 of the 20 patients (95%). Mean number (SD) of WBC (×109/L) on each day between day 11 and day 14 was 5.4 (3.7), 11.4 (9.1), 14.2 (9.1) and 13.9 (7.4), respectively. Mean number (SD) of CD34+ cells (×106/L) on each day between day 11 and day 14 was 20.3 (22.5), 38.0 (35.7), 40.3 (39.8), and 40.1 (53.5), respectively. The 98.75% confidence interval [CI] of CD34+ cells (×106/L) on each day between day 11 and day 14 was [6.39-34.22], [16.16-60.25], [15.77-64.97] and [7.09-73.16], respectively (Figure). The number of CD34+ cells on day 12 or 13 showed significantly higher than 10×106/L CD34+ cell (P = 0.0022 and 0.0030, respectively) (Figure). We then compared the peak of CD34+ cells in a peripheral blood in each chemotherapy regimens. The peak day of CD34+ cell in patients who received CHOP regimen was day 13 (mean 54.3 ×106/L, range 15.8-151.0×106/L) . However, in 4 of 5 patients who received platinum containing regimen, CD34+ cells failed to reach the peak before day 14 because of prolonged myelosuppression. The number of prior chemotherapy regimen (0 vs 1-2) was not associated with the kinetics of CD34+ cells (p = 0.35). No infectious events including febrile neutropenia were observed. Pain and LDH elevation (Grade 1-2) were the main adverse events related to pegfilgrastim administration. We had not detected any severe adverse events.Conclusion: Our data indicated that 3.6mg pegfilgrastim on day 7 can efficiently mobilize CD34+ cells to peripheral blood without any severe adverse events. [Display omitted] DisclosuresTeshima:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Research Funding; Kyowa-Hakko Kirin: Research Funding; Pfeizer: Research Funding; Chugai: Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

The Impact of Single Dose Plerixaforas an Adjunct to G-CSF Based Peripheral Blood Stem Cell Mobilisation on the Graft Composition and Outcome for T Replete Haploidentical PBSC Transplantation with Post Transplantation Cyclophosphamide: A Pilot Study

▪Introduction : We conducted a prospective study on T cell and NK cell subset composition of the graftand the transplant outcome with single dose of subcutaneous Plerixafor(Px) to GCSF based mobilisation in T-replete Haploidentical Peripheral blood Stem cell transplantation with post-transplantation cyclophosphamide (PTCy) in 25 donors (G+Px group). This was compared with 26 donors who received G-CSF alone for mobilisation (G group).Material and Methods : With the aim to collect 10 x 106/kg CD34 cells in a single apheresis, donors with peripheral CD 34 count less than 50 cells /µl in the peripheral blood on day 4 of mobilization were administered Injection Plerixafor at the dose of 0.12mcg/kg at 12 midnight in addition to routine GCSF. This was followed by PBSC harvest starting 11 hours later at 11 A.M on the next day. The rest were continued G-CSF only as per protocol.Results: CD 34 cell count[G+Px-136(range, 52-351)vs G-139 (range,72-240) cells/µl ] in the peripheral blood on day 5 as well as that in the graft [G+Px- 2.7(range 1.1-6.0) VsG-2.3(range 0.5-5.3) X106 /ml, p=0.05] comparable between the two groups, despite a significantly lower peripheral CD34 cell count on day 4 in the pleraxifor group (G+Px-33(range, 6-47) vs G-81(58-168) cells/µl, p=0.0001). The total nucleated cell count was higher in the G- group[ 3.4(range 1.7-5.0) vs 3.1(range 1.15-4.73) X108/ml, p=0.05 ]. Despite the lower trend of CD4+ T cells[ 2.3(range 0.3-6.8) Vs 2.7(range 0.53-6.8) X107/ml, p=0.09 ]in the G-CSF group, mobilisation of Tregs was similar(7.1% vs 6.9% in G+Px group,p=0.1). There were no differences noted in the absolute number of NK cells [G+Px-5.3(range 0.8-11.6) vs 5.7.(range 1.7-12.9) X106/ml, p=0.9 ], or the CD56+16+/16- subsets. The time to engraftment was similar in both groups. The incidences of acute and chronic GVHD, non-relapse mortality and relapse were also similar.Conclusion: Addition of single dose pleraxifor to G-CSF mobilisation improves CD34 recovery and does not significantly alter the T and NK cell composition of the graft, including Tregs. No adverse impact was noted on engraftment, GVHD, NRM and relapse. Our study demonstrates that pleraxifor can be safely used as an adjunct to G-CSF to boost CD34 mobilisation without impacting conventional or regulatory T cells and NK cells in the graft. The preliminary data suggests no adverse impact on transplant outcomes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Usefulness of hematopoietic progenitor cell monitoring to predict autologous peripheral blood stem cell harvest timing: A single-center retrospective study

IntroductionIn autologous peripheral blood stem cell harvest (APBSCH), CD34-positive cells have been measured to assess the numbers of hematopoietic stem cells, but measurement requires specialized equipment. Recently, there was a report that peripheral blood hematopoietic progenitor cells (HPCs) are useful indicators of the presence of hematopoietic stem cells. We examined the usefulness of HPC monitoring to predict APBSCH timing. MethodsWe retrospectively analyzed the relationship between HPC and collected CD34-positive cells in 84 consecutive patients who underwent APBSCH. ResultsAccording to the receiver operating characteristics curve for the collection of ≥2 × 106 CD34-positive cells/kg, the HPC cut-off value on the day before collection was 21/μL, while that on the day of collection was 41/μL. No significant factors were found in the univariate analysis except for the HPC count on the day before collection (p < 0.001) and the day of collection (p < 0.001). According to the multivariate analysis, the HPC count on the day before collection (p < 0.001) and the day of collection (p < 0.001) were also factors that strongly influenced the quantity of CD34-positive cells collected. ConclusionOur results suggest that the HPC count on not only the day of collection but also the day before collection is a good indicator for appropriate APBSCH timing.