Peripheral Stem Cell Mobilization Research Articles

Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis

Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies. To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort. Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; information on the administered conditioning regimen and graft manipulation; and at least 1 follow-up visit or report after transplant. The last patient visit was on July 1, 2012. To avoid bias, all eligible patients were included in the analysis regardless of their duration of follow-up. Data analysis was conducted from September 1, 2014 to April 27, 2015. Demographic, disease-related, and treatment-related exposures were considered variables of interest, including age, disease subtype, baseline EDSS score, number of previous disease-modifying treatments, and intensity of the conditioning regimen. The primary outcomes were MS progression-free survival and overall survival. The probabilities of progression-free survival and overall survival were calculated using Kaplan-Meier survival curves and multivariable Cox proportional hazards regression analysis models. Valid data were obtained from 25 centers in 13 countries for 281 evaluable patients, with median follow-up of 6.6 years (range, 0.2-16 years). Seventy-eight percent (218 of 281) of patients had progressive forms of MS. The median EDSS score before mobilization of peripheral blood stem cells was 6.5 (range, 1.5-9). Eight deaths (2.8%; 95% CI, 1.0%-4.9%) were reported within 100 days of transplant and were considered transplant-related mortality. The 5-year probability of progression-free survival as assessed by the EDSS score was 46% (95% CI, 42%-54%), and overall survival was 93% (95% CI, 89%-96%) at 5 years. Factors associated with neurological progression after transplant were older age (hazard ratio [HR], 1.03; 95% CI, 1.00-1.05), progressive vs relapsing form of MS (HR, 2.33; 95% CI, 1.27-4.28), and more than 2 previous disease-modifying therapies (HR, 1.65; 95% CI, 1.10-2.47). Higher baseline EDSS score was associated with worse overall survival (HR, 2.03; 95% CI, 1.40-2.95). In this observational study of patients with MS treated with AHSCT, almost half of them remained free from neurological progression for 5 years after transplant. Younger age, relapsing form of MS, fewer prior immunotherapies, and lower baseline EDSS score were factors associated with better outcomes. The results support the rationale for further randomized clinical trials of AHSCT for the treatment of MS.

Clinical analysis of autologous peripheral blood hematopoietic stem cell mobilization regimen in 61 lymphoma patients

Clinical analysis of autologous peripheral blood hematopoietic stem cell mobilization regimen in 61 lymphoma patients

Mobilization of Peripheral Blood Stem Cells and Changes in the Concentration of Plasma Factors Influencing their Movement in Patients with Panic Disorder

In this paper we examined whether stem cells and factors responsible for their movement may serve as new biological markers of anxiety disorders. The study was carried out on a group of 30 patients diagnosed with panic disorder (examined before and after treatment), compared to 30 healthy individuals forming the control group. We examined the number of circulating HSCs (hematopoetic stem cells) (Lin−/CD45 +/CD34 +) and HSCs (Lin−/CD45 +/AC133 +), the number of circulating VSELs (very small embryonic-like stem cells) (Lin−/CD45−/CD34 +) and VSELs (Lin−/CD45−/AC133 +), as well as the concentration of complement components: C3a, C5a and C5b-9, SDF-1 (stromal derived factor) and S1P (sphingosine-1-phosphate). Significantly lower levels of HSCs (Lin−/CD45 +/AC133 +) have been demonstrated in the patient group compared to the control group both before and after treatment. The level of VSELs (Lin−/CD45−/CD133 +) was significantly lower in the patient group before treatment as compared to the patient group after treatment.The levels of factors responsible for stem cell movement were significantly lower in the patient group compared to the control group before and after treatment. It was concluded that the study of stem cells and factors associated with their movement can be useful in the diagnostics of panic disorder, as well as differentiating between psychotic and anxiety disorders.

A Comparison of Efficacy Following Two Different Doses of Granulocyte Colony Stimulating Factor (G-CSF) Alone for Mobilization of Peripheral Blood Stem Cells in 221 Multiple Myeloma Patients

Introduction:Intensive chemotherapy followed by autologous stem cell transplantation (ASCT) is currently the treatment of choice in multiple myeloma (MM). Mobilization of hematopoietic stem cell blood (HSCs) can be achieved either by the combination of chemotherapy plus growth factors or by growth factors alone. However, there is no consensus concerning the dose of growth factor alone that should be administered, with ranges varying from 5 microgr to 16 microgr/kg body weight.In this context, we report our experience in mobilization of HSCs using growth factor alone at the dose between 15 microgr /kg and 10 microgr /kg in MM.Patients and methods:A total of 340 ASCT were performed in our center, from May 2009 until June the 31st 2016. These concerned 221 patients with MM. Patients were hospitalized at day -5 on which mobilization started with G-CSF alone (filgrastim) at the dose of 15 microgr /kg/daily subcutaneously for 5 days from May 2009 to October 2012 and at the dose of 10 microgr /kg from November 2012 to June 2016. The white blood cell count was assessed daily. Apheresis was performed at day -2 and day -1 using a Spectra Optia CMN device, and the CD34+ count was assessed by flow cytometry. A single leukapheresis was performed if the number of CD34+ cells was above 2.106/kg. Failure of mobilization was defined as a level of CD34+ less than 2.106/kg, after two leukapheresis.In our study patients were divided into two groups: Group1 (G-CSF=15 microgr /kg) and Group 2 (G-CSF=10 microgr /kg) and the number of CD34+ were divided into three groups: optimal (³5.0 x 106 CD34+ cells/kg), suboptimal (2.0Ð5.0 x 106 CD34+ cells/kg) and poor (<2.0 x 106 CD34+ cells/kg) mobilization. Intensification was done using melphalan 200 mg/m2 on day -1.Results:Patient's characteristics are shown in Table 1. No significant difference was observed between the 2 groups. In this study, we found no significant difference in terms of optimal (p= 0.73), sub-optimal (p= 0.19) or poor (p= 0.11) harvest of stem cells between the 2 groups (table 2). Among the poor mobilizators with G-CSF, only 4 of them had a level of CD34+ harvest less than 0.5 x 106/kg. These patients did not receive an ASCT. 1,3% (4) of all apheresis failed to achieve acceptable harvest level.Conclusion:Our study showed that the mobilization regimen with G-CSF alone at the doses of 10 microgr/kg have the same efficacy as the doses of 15 microgr/kg and is interesting alternative to chemotherapy and G-CSF in patients with MM because it can be administered as an outpatient and is not associated with the risk of febrile neutropenia. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Biosimilar Filgrastim in Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization and Post-Transplant Hematologic Recovery.

To date, two kinds of Granulocyte Colony-Stimulating Factors (G-CSF) have been approved for autologous peripheral blood hematopoietic stem cell (PBSCs) mobilization and posttransplant hematologic recovery after high-dose chemotherapy: filgrastim (originator and biosimilar) and lenograstim. Biosimilar filgrastim has been approved on the basis of comparable efficacy and safety in clinical studies where it has been used as chemotherapy-induced febrile neutropenia prophylaxis, but no specific pre-registration studies have been published in the transplant setting. Hence, there is still general skepticism about the role of biosimilar G-CSFs in this setting of patients. This review of biochemical, pre-clinical and clinical data suggests significant comparability of biosimilar filgrastim with both originator filgrastim and lenograstim in autologous PBSCs mobilization and post-autograft hematologic recovery.

Identifying Inherited and Acquired Genetic Factors Involved in Poor Stem Cell Mobilization and Donor-Derived Malignancy

Analysis of the clinical characteristics of hematopoietic stem cell transplant (HSCT) donors has proven beneficial for identifying cases of heritable hematopoietic disorders. This study examines poor peripheral blood hematopoietic stem cell mobilization after granulocyte colony–stimulating factor administration among 328 donors as a potential marker for suspected familial predisposition to myeloid malignancies. Here, we present data comparing the clinical characteristics of poor-mobilizing versus nonpoor-mobilizing donors and the results of panel-based sequencing of hematopoietic genes in poor-mobilizing donors. From this analysis, we identified a novel case of a donor-derived myelodysplastic syndrome in an HSCT recipient that is consistent with clonal evolution of TET2-mutated clonal hematopoiesis of indeterminate potential (CHIP) within the donor. This study demonstrates the potential risk of using hematopoietic stem cells from a donor with CHIP and raises the question of whether there should be increased screening measures to identify such donors.

Plerixafor is safe and efficacious for mobilization of peripheral blood stem cells in pediatric patients.

Chemotherapy followed by filgrastim is the most common strategy used to mobilize autologous peripheral blood stem cells (PBSCs) for high-dose chemotherapy and autologous stem cell transplantation. Unfortunately, this method does not always lead to adequate PBSC collection in heavily treated patients with relapsed malignancies or if multiple transplants are required. Plerixafor, a hematopoietic stem cell mobilizer that inhibits the CXCR4 chemokine receptor and blocks binding of its cognate ligand, stromal cell-derived factor-1α (SDF-1α), has been shown to be safe and efficacious in the mobilization of autologous PBSC in adults. Despite its use in adults, little evidence exists to support its use in children. We report a retrospective review of 16 consecutive pediatric patients receiving plerixafor as part of their mobilization regimen at Cincinnati Children's Hospital Medical Center. All patients but one were given 0.24 mg/kg dose of plerixafor and the median number of plerixafor doses received was two (range, one to four doses). One patient received higher doses of plerixafor. An adequate number of CD34+ cells were obtained in 14 of 16 patients (87.5%). The median number of CD34+ cells collected for patients who reached collection goal was 6 × 10(6) CD34+ cells/kg (range, 1.6 × 10(6) -12.4 × 10(6) /kg). No acute adverse events were noted to be attributable to plerixafor administration. Our findings suggest that plerixafor use in children is safe and efficacious for the mobilization of autologous PBSCs in subjects with relapsed malignancies or requiring stem cells for multiple transplants.

Efficient Stem Cell Collection after Modified Cisplatin-Based Mobilization Chemotherapy in Patients with Diffuse Large B Cell Lymphoma

In patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL), R-DHAP (rituximab, dexamethasone, cytarabine, and cisplatin) is a commonly used regimen for salvage therapy and for mobilization of peripheral blood stem cells (PBSCs). At our center, a modified R-DHAP regimen with administration of 25 mg/m2 cisplatin as a 3-hour infusion over 4 consecutive days, instead of a single infusion of 100 mg/m2 over 24 hours, has been established. The aim of this study was to analyze the efficiency of this modified R-DHAP regimen plus G-CSF as a mobilization strategy. We retrospectively analyzed clinical characteristics, PBSC collection and autologous stem cell transplantation parameters, and hematologic reconstitution data for 65 patients with relapsed or refractory DLBCL who underwent PBSC collection after mobilization with the modified R-DHAP protocol at our institution between 2002 and 2013. Data were evaluated for the overall cohort and with regard to the number of R-DHAP cycles received before PBSC collection. PBSC collection was performed after the first R-DHAP course in 32 patients (49%), after the second course in 30 patients (46%), and after the third course in 3 patients (5%). Sixty-three patients (97%) achieved the collection goal of ≥2.0 × 106 CD34+ cells/kg body weight. A significantly higher median CD34+ cell collection yield was achieved when cells were collected after the first R-DHAP course compared with after the second course (P < .01). A peripheral blood leukocyte increase of ≥1.0 × 109/L and a platelet increase of ≥20 × 109/L were observed by 11 days after ASCT. In our cohort, the modified R-DHAP regimen proved safe and feasible, showed an overall response rate (complete response, complete response unconfirmed, and partial response) of 66%, and allowed efficient mobilization of CD34+ cells for PBSC collection.

Analysis of Factors Influencing Peripheral Blood Stem Cell Collection of 151 Lymphoma Cases

To analyze the influential factors related to mobilization and collection of stem cells so as to improve the collection efficiency of autologous peripheral stem cell transplantation in lymphoma patients. The peripheral blood stem cell collection data of 151 cases of lymphoma in our hospital was analyzed retrospectively. The relationship between the harvested CD34(+) stem cells and some factors, such as age, sex, height, weight, histological type, staging, mobilization programs, collecting days, blood transfusion, time and duration of chemotherapy, was analyzed. The single factor analysis showed that sex, height, weight, histological type, staging, mobilization program, collecting days, blood transfusion were not significantly associated with CD34(+) stem cells collection, respectively. Age (r = -0.248, P = 0.002), duration of sick and cycles of chemotherapy were significantly associated with CD34(+) cell collection. At the age older than 50 years, the collected CD34(+) cell number decreased significantly; and at the age older than 60 years, the CD34(+) cell number was greatly reduced; CD34(+) cells non-significantly correlated with peripheral blood WBC (r = 0.053, P = 0.527), but significantly with the percentage of mononuclear cells (r = 0.260, P = 0.002) and the absolute value of mononuclear cells (r = 0.338, P = 0.00003) . The patients less than 60 years old, fewer chemotherapy cycles, shorter duration time or PB mononuclear cells between (2-6) × 10(9)/L may contribute to the better mobilization and collection of peripheral blood stem cells.

Tbo-Filgrastim: A Review in Neutropenic Conditions.

Tbo-filgrastim (filgrastim XM02; Biograstim(®), Ratiograstim(®), Tevagrastim(®)) is approved in the EU as a biosimilar of filgrastim (Neupogen(®)) for use in all indications for which reference filgrastim is approved, including chemotherapy-induced neutropenia, neutropenia in patients undergoing myeloablative therapy followed by bone marrow transplantation, mobilization of peripheral blood stem cells (PBSCs), severe chronic neutropenia, and neutropenia in HIV infection. Tbo-filgrastim (Granix(®)) is also approved as a biologic in the USA for neutropenia associated with chemotherapy. Tbo-filgrastim has demonstrated bioequivalence to reference filgrastim in terms of its pharmacokinetic and pharmacodynamic profiles. In phase III trials, tbo-filgrastim was equivalent to reference filgrastim in ameliorating severe neutropenia in patients receiving chemotherapy for breast cancer, lung cancer, or non-Hodgkin lymphoma. In addition, the efficacy of tbo-filgrastim for PBSC mobilization in the allogeneic and autologous settings has been demonstrated in several small studies. Tbo-filgrastim was generally well tolerated, with a similar safety profile to that of reference filgrastim. Most adverse events were of mild or moderate severity. Biosimilars such as tbo-filgrastim have the potential to reduce healthcare costs compared with those of reference filgrastim; this may provide patients with more cost-effective treatment options. Current evidence indicates that tbo-filgrastim is a useful alternative to reference filgrastim in patients requiring filgrastim therapy for various neutropenic conditions.

Evaluation of the efficacy and safety of original filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) in CD34+ peripheral hematopoietic stem cell mobilization procedures for allogeneic hematopoietic stem cell transplant donors

Objectives and AimIn this study, we aimed to compare the potency of different G-CSF agents including original filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) on CD34+ cell mobilization in patients that underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). Patients and MethodsThe data of 243 donors for alloHSCT recipients diagnosed with mostly acute leukemia and myelodsyplastic syndromes (MDS) were analyzed, retrospectively. Data for stem cell mobilization have been recorded from patients' files. Donors who received Filgrastim (Neupogen®, Group I), biosimilar Filgrastim (Leucostim®, Group II) and Lenograstim (Granocyte®, Group III) were analyzed for total CD34+ cell count at the end of mobilization procedures. ResultsA total of 243 donors and patients for alloHSCT were analyzed retrospectively. The diagnosis of the patients were; acute myeloid leukemia (AML) (110 patients, 45.2%), acute lymphoid leukemia (ALL) (61 patients, 25.1%), aplastic anemia (AA) (38 patients, 15.6%), lymphomas (14 patients, 5.7%) and others (20 patients, 8.4%). The median number of total collected PB CD34+ cells (×106/kg) was 7.12 (min–max: 5.38–7.90) in the Neupogen® group, 7.27 (min–max: 6.79–7.55) in the Leucostim® group and 7.15 (min–max: 5.34–7.58) in the Granocyte® group. There was no statistically significant difference among groups in terms of total collected PB CD34+ cells (p = 0.919). The median doses of G-CSF agents (µg/kg/day) in PBSC collection in Neupogen® group was; 11.00 (10.00–12.00) in Leucostim® group10.35 (min–max: 10.00–11.10) and in Granocyte® group11.00 (min–max: 10.00–11.00). There was no statistical significance among groups (p = 0.215). ConclusionBiosimilar filgrastim (Leucostim®) was found comparable to original Filgrastim (Neupogen®) and Lenograstim (Granocyte®) for PBSC mobilization in donors of the patients that underwent alloHSCT.

The effect of age on peripheral stem cell mobilization in healthy donors, single center experience.

Peripheral stem cell transplantation is used as a life-saving therapeutic option in hematological malignancies. As previously established, most hematological malignancies are seen in the elderly population. Therefore, possible HLA-identical sibling donors of elderly patients are generally of an advanced age. In this study, we aimed to evaluate the effect of old age on stem cell mobilization and quality in older adult healthy sibling donors. Between 2006 and 2014, we evaluated 38 healthy donors aged ≥55 years. The granulocyte-colony stimulating factor (G-CSF) analogs were used at a dose of 5 µg/kg/day and administered subcutaneously twice a day for five days. CD34+ cells were estimated in the peripheral blood before collection of the apheresis product. The National Marrow Donor Program selects healthy unrelated donors if they are younger than 60 years. Therefore, we compared the product quality in donors over the age of 60 to that in donors aged 60 years or less. We collected sufficient products from all the donors with one to three apheresis procedures. No serious complication was detected in all donors. Reaching the target CD34+ cell count in one day were detected in 83% of younger and 79% of older donors (P = NS). Collected CD34+ cells x10e6/recipient body weight (kg) was same and 5.1 in the groups (P = NS). There were no correlation between the donor age and these parameters. Healthy donor apheresis in older adults can be performed effectively and possible donors should be evaluated regardless of their age. J. Clin. Apheresis 32:16-20, 2017. © 2016 Wiley Periodicals, Inc.

Mobilization of autologous and allogeneic peripheral blood stem cells for transplantation in haematological malignancies using biosimilar G-CSF.

Biosimilars of the granulocyte colony stimulating factor (G-CSF) filgrastim were approved by the European Medicines Agency (EMA) for registered indications of the originator G-CSF, including prevention and treatment of neutropenia, as well as mobilization of peripheral blood stem cells in 2008. Nevertheless, there is still an ongoing debate regarding the quality, efficacy and safety of biosimilar G-CSF. This article is a meta-analysis of clinical studies on the use of biosimilar G-CSF for mobilization and transplantation of haematopoietic stem cells as available in public databases. All data sets were weighted for the number of patients and parameters and then subjected to statistical meta-analysis employing the Mann-Whitney U-test followed by the Hodges-Lehmann estimator to assess differences between biosimilar and originator G-SCF. A total of 1892 individuals, mostly with haematological malignancies but also including 351 healthy donors have been successfully mobilized for autologous or allogeneic stem cell transplantation using biosimilar G-CSF (Zarzio(TM) : 1239 individuals; Ratiograstim(TM) /Tevagrastim(TM) : 653 individuals). A total of 740 patients with multiple myeloma, 491 with non-Hodgkin's lymphoma (NHL), 150 with Hodgkin's lymphoma (HL) and other diseases are included in this meta-analysis, as well as 161 siblings and 190 volunteer unrelated donors. For biosimilar and originator G-CSF, bioequivalence was observed for the yield of CD34+ stem cells as well as for the engraftment of the transplants. Biosimilar G-CSF has equivalent effects and safety as originator G-CSF.

The Effect of the Use of Chemotherapy and Growth Factor on the Success of Stem Cell Product and Mobilization at Autologous Peripheral Stem Cell Mobilization for the Elder Multiple Myeloma Patients

The Effect of the Use of Chemotherapy and Growth Factor on the Success of Stem Cell Product and Mobilization at Autologous Peripheral Stem Cell Mobilization for the Elder Multiple Myeloma Patients

Does bendamustine impact the mobilization of peripheral blood stem cells? A multicenter retrospective study of 23 cases

Bendamustine is used in the treatment of different relapsing or refractory subtypes of lymphoma. Its impact on the yield of peripheral blood stem cells is not well known. Twenty three patients who received bendamustine followed immediately or after another chemotherapy by stem cell mobilization (SCM) were included. The patients were divided into two groups: group 1 (n=17), in whom SCM was performed immediately after bendamustine chemotherapy, and group 2 (n=6), in whom SCM was performed after another cycle of chemotherapy. The success rate of mobilization after Bendamustine+/−plerixafor was 36% (eight cytapheresis succeeded for a total number of 22 cytapheresis); and 75% after other approaches (chemotherapy based or steady state) used for patients who received bendamustine previously. Although bendamustine used alone was not an effective drug to mobilize stem cells, this agent does not seem to have detrimental effects on subsequent SCM.

Inter-tissue coexpression network analysis reveals DPP4 as an important gene in heart to blood communication.

BackgroundInter-tissue molecular interactions are critical to the function and behavior of biological systems in multicellular organisms, but systematic studies of interactions between tissues are lacking. Also, existing studies of inter-tissue interactions are based on direct gene expression correlations, which can’t distinguish correlations due to common genetic architectures versus biochemical or molecular signal exchange between tissues.MethodsWe developed a novel strategy to study inter-tissue interaction by removing effects of genetic regulation of gene expression (genetic decorrelation). We applied our method to the comprehensive atlas of gene expression across nine human tissues in the Genotype-Tissue Expression (GTEx) project to generate novel genetically decorrelated inter-tissue networks. From this we derived modules of genes important in inter-tissue interactions that are likely driven by biological signal exchange instead of their common genetic basis. Importantly we highlighted communication between tissues and elucidated gene activities in one tissue inducing gene expression changes in others.ResultsWe reveal global unidirectional inter-tissue coordination of specific biological pathways such as protein synthesis. Using our data, we highlighted a clinically relevant example whereby heart expression of DPP4 was coordinated with a gene expression signature characteristic for whole blood proliferation, potentially impacting peripheral stem cell mobilization. We also showed that expression of the poorly characterized FOCAD in heart correlated with protein biosynthetic processes in the lung.ConclusionsIn summary, this is the first resource of human multi-tissue networks enabling the investigation of molecular inter-tissue interactions. With the networks in hand, we may systematically design combination therapies that simultaneously target multiple tissues or pinpoint potential side effects of a drug in other tissues.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0268-1) contains supplementary material, which is available to authorized users.

Pegylated granulocyte colony stimulating factor versus non-pegylated granulocyte colony stimulating factor for peripheral stem cell mobilization

This is the protocol for a review and there is no abstract. The objectives are as follows: To compare the efficacy and safety of pegylated G-CSF with non-pegylated G-CSF for peripheral blood stem cell mobilization. © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

DHAP plus filgrastim as an effective peripheral stem cell mobilization regimen for autologous stem-cell transplantation in patients with relapsed/refractory lymphoma: A single center experience

This study aimed to evaluate the efficiency of DHAP regimen plus filgrastim for mobilization of stem cells in patients with recurrent and/or refractory lymphoma. Thirty-four patients who took DHAP as salvage therapy prior to autologous stem cell transplantation were included. After chemotherapies, 2 cycles of DHAP plus filgrastim were administered to the patients. Stem cells from 32 patients (94%) were collected on median 11th day (8–12), and the median collected CD34+ cell dose was 9.7 × 106/kg (range 3.8–41.6). DHAP plus filgrastim was found to be an effective chemotherapy regimen in mobilizing CD34+ stem cells into the peripheral.

Outcome Comparison of Lymphoma and Myeloma Patients after Autologous Stem Cell Transplantation (ASCT) with Peripheral Blood Stem Cell Mobilization Between Plerixafor (P) Mobilized in Poor Mobilizer Patients and Non-Plerixafor Mobilized Patients

Background: P is used in combination with G-CSF to improve the mobilization of peripheral blood hematopoietic stem cells in poor mobilizers. Limited data are available in regard to effects of P on post-transplant outcomes in comparison with non-P chemomobilized patients.Methods: In this retrospective study, we compare the engraftment and the outcomes of 34 patients mobilized with P + G-CSF or just-in-time rescue P in combination with chemotherapy and G-CSF to 143 patients (control group) mobilized with G-CSF with or without chemotherapy in lymphoma and myeloma patients who underwent ASCT between February 2012 and April 2014 at the University of Maryland Greenebaum Cancer Center. Post-transplantation outcomes including infections, hematologic recovery, relapse, progression and survival were recorded.Results: The median number of collected of CD34+ cells/Kg was 5.9 x 10(6) in the P group and 12.3 x 10(6) in the control group (p=0.0002). Median time to neutrophil engraftment (>0.5 × 10(9) /L) was comparable between the 2 groups: 12 days for the P group and 11 for the control group (p=0.28). There was a trend toward a shorter time to platelet engraftment (>20 × 10(9) /L) in the control (12 days) compared to the P group (14 days) (p=0.056). Progression-free survival at 1 year after (ASCT) was 88.2% in the P group and 81.8% in the control group. There was no difference in the overall survival of both groups (p=0.62)Conclusions: Short and long-term engraftment and outcomes after ASCT seem to be comparable in lymphoma and myeloma patients receiving plerixafor compared to chemomobilized patients without plerixafor. This observation support the use of plerixafor + G-CSF or just-in-time rescue P in patients who mobilize poorly without P. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Pilot Study of Peripheral Blood Hematopoietic Stem Cells Mobilization with the Combination of Bortezomib and G-CSF in Multiple Myeloma and Non-Hodgkin's Lymphoma Patients.

Background: Bortezomib has become an integral part of front-line therapy of multiple myeloma in a large majority of patients. There are preliminary reports which show that addition of bortezomib can augment the peripheral blood CD34 count during stem cell mobilization. In this single center prospective trial we added bortezomib to G-CSF to evaluate the effects of bortezomib on peripheral CD34 counts and collection.Methods: Patients aged 18-70 years with diagnosis of multiple myeloma (MM) or non-hodgkin's lymphoma (NHL) who were eligible for autologous stem cell transplantation (ASCT) and had received no more than three prior chemotherapeutic regimens were eligible for the study. Patients were enrolled in two groups. Group A (N=3) received G-CSF 16mcg/kg for 5 days and proceeded to stem cell collection on D5 and then received bortezomib 1.3mg/m2 on D5 after stem cell collection and G-CSF 16mcg/kg on D6, 7, 8 and repeat stem cell collection on D6, 7, 8 till the goal was achieved. Group B (N=17) received G-CSF 16mg/kg on D1-5 and received bortezomib 1.3mg/m2 on D4 and proceeded to stem cell collection on D5. If the patient was not able to collect the predefined goal CD34, G-CSF was continued on D 6, 7, 8 and a second dose of bortezomib 1.3mg/m2 was given on D7. Mobilization procedure was stopped once the predefined goal CD34 collection (4 x 106/kg for MM and 2 x 106/kg for NHL) had been collected.Primary objectives of the study was to determine if addition of bortezomib to G-CSF will result in an increase in PBSCs by > 2-fold and to achieve median neutrophil engraftment 12 days post ASCT. Secondary objectiveswere to evaluate the collected product for co-mobilization of lymphoma or myeloma cells and to determine if the use of bortezomib increases the mobilization of immune-stimulatory Dendritic cell (DC) -1 subsets.Results: A total of 23 patients were enrolled and 20 were evaluable for the results. Only one patient with NHL was enrolled and rest had MM. Median age of pts was 57 years, M/F 8/12, median number of previous chemotherapy regimens was 1 (range 1-3).The median peripheral blood CD34 count pre and post bortezomib in all patients were 28.8 x 106/kg and 37 x 106/kg respectively. All three patients in group A had drop in peripheral blood CD34 counts on D6 post bortezomib as they had undergone stem cell collection on day 5. In part B (N=17), 15 patients had increase in peripheral blood CD 34+ve cell counts with 4 patients achieved doubling while 11 pts had less than doubling of peripheral blood CD34 count after receiving bortezomib. Two patients had minimal drop in the peripheral blood CD34 counts post bortezomib. Median number of CD34 cells collected in15 patients (part B) were 5.06 x 106 CD34 cells/kg (range 4-15.1). 18 patients proceeded to ASCT and median time to neutrophil engraftment (ANC ≥500/cumm) post transplant was 12 days (range 11-16) and platelet engraftment (Plt count ≥ 20,000/cumm) was 18 days (range 15-27). There was no significant change in DC1/DC2 ratio in both groups following treatment with bortezomib and G-CSF (Figure 1).In group A all three patients collected goal CD34 count on day 5 and 2/3 patients collected >4 x106 CD34 cells/kg on D6 post bortezomib and1/3 patients collected 2.6 x 106 on D6 post bortezomib. In group B (n=17), 2 patients were unable to collect because of low CD34 counts on D4 and D5, 11 pts collected the goal in one day (D 5) and 4 pts required two days of apheresis (D 5 and 6). None of the patients received D7 bortezomib.Conclusion: Use of bortezomib during autologous stem cell collection was safe and well tolerated. Majority of patients had increase in peripheral blood CD34 counts post bortezomib administration on D4. Future trials should explore bortezomib as an alternate strategy to chemo-mobilization in combination with growth factors. [Display omitted] [Display omitted] DisclosuresOff Label Use: Bortezomib for stem cell mobilization. Lum:Karyopharm Therapeutics Inc: Equity Ownership; Transtarget.Inc: Equity Ownership. Deol:Bristol meyer squibb: Research Funding. Abidi:celgene: Speakers Bureau; Millenium: Research Funding.