Peripheral Blood Stem Cell Harvest Research Articles

Autologous peripheral blood stem cell harvest timing by absolute neutrophil count in children and young adult patients: Single-institute experience

BackgroundMyeloablative, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) improves outcome in some high-risk malignant solid tumors and lymphomas in children and young adults. MethodsWe performed 16 peripheral blood stem cell (PBSC) harvests in 12 children and 2 young adult patients with a high-risk malignant solid tumor or refractory/relapsed Hodgkin's lymphoma from August 2015 to December 2020. In our chemotherapy mobilization protocol, we used an absolute neutrophil count (ANC) of >1 × 109/L following the nadir after chemotherapy as the criterion for undertaking the apheresis. ResultsThe median CD34+ cell count per kg body weight of the 33 apheresis products was 4.92 × 106 cells/kg (range, 0.34–22.53 × 106 cells/kg). Thirteen of the 14 patients (93%) had successful PBSC collections that met their goals for PBSCT. Three patients did not receive PBSCT due to disease progression prior to transplantation. Prompt engraftment occurred in all the remaining 11 patients with 17 PBSCTs. ConclusionOur data suggest that ANC can be helpful as a surrogate parameter in clinical decision-making when the peripheral blood CD34+ count is unavailable.

Is an earlier strategy for harvesting peripheral blood stem cells in healthy allogeneic donors feasible?

IntroductionPeripheral blood stem cells (PBSC) mobilization with granulocyte colony stimulating factor (G-CSF) for healthy donors is generally performed at 5th day. However, earlier collection is sometimes feasible, raising the question of whether to initiate apheresis early to limit further G-CSF exposure, while considering the risk of mobilization failure. In the current study, we examined the factors predicting successful 4th day collection and developed a model that can be used practically. Patients and methodsThe study was carried out by obtaining the data of PBSC mobilizations performed between January 2009 and September 2022 in our transplantation center. ResultsA total of 141 healthy donors with a median donor age of 32 (18–64) were included. Adequate mobilization was achieved in 115 (81.6 %) patients. Median peripheral CD34 + cell count was 69.4/μL in the adequate mobilization group and 46/μL in the mobilization failure group (p < 0001). Multivariate analysis revealed that donor/recipient weight ratio and the 4th day peripheral CD34 + cell count≥ 50/μL were independent markers for 4th day collection success. A predictive model of our center including these parameters was available with 0.765 sensitivity and 0.968 specificity [(AUC):0.948 (95 % CI, 0.90–0.99), p < 0.001]. ConclusionThe result of the current study shows that peripheral 4th day collection can be performed in selected donors, taking into account peripheral CD34+ cell count and donor/recipient weight ratio. In addition, using these indicators, new predictive models can be created that may assist clinicians in daily practice.

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 kg

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 the 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 were 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 preapheresis hematopoietic progenitor 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 preapheresis 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 (area under the curve 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.

Usefulness of web-based application for health surveys before and after peripheral blood stem cell harvest from healthy donors

Health surveys to assess adverse events after peripheral blood stem cell harvest (PBSCH) have conventionally been conducted by phone, but phone calls are suboptimal for conducting frequent surveys. We developed a web-based application (donor app) that enables donors to inform healthcare professionals (HCPs) of their health status as an electronic patient-reported outcome (ePRO). In this prospective observational study, we compared the usefulness of this donor app to phone calls for conducting health surveys. App users reported ePRO daily, and patients called by HCPs reported their health status at least once a week when called. The observation period was from the first administration of granulocyte colony-stimulating factor to the first follow-up visit after PBSCH, excluding the hospitalization period. Each group consisted of eight donors with a median age of 32 years (range: 19-58). Nine (56.3%) were female. There were eight related donors in the phone call group and four in the donor app group. During the observation period, HCPs obtained health status reports more frequently from app users than from phone call recipients (mean proportion of days with reports made during the observation period, 27.0% vs 53.5%; p<0.05). Average time spent by the HCPs for one follow-up and total follow-ups were both significantly shorter when the donor app was used. There were no differences in donor burden or satisfaction with donation. Our study suggests that use of a donor app could provide more detailed health survey data without increasing the burden on donors and HCPs.

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

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

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