The Experts below are selected from a list of 3819 Experts worldwide ranked by ideXlab platform

Matthew M Hsieh - One of the best experts on this subject based on the ideXlab platform.

  • effect of high dose Plerixafor on cd34 cell mobilization in healthy stem cell donors results of a randomized crossover trial
    Haematologica, 2017
    Co-Authors: Jeremy Pantin, Matthew M Hsieh, Lisa Cook, Xin Tian, Elena Cho, Robert Reger, Hanh Khuu, Enkhtsetseg Purev, Theresa Donohuejerussi, Gary Calandra
    Abstract:

    Hematopoietic stem cells can be mobilized from healthy donors using single-agent Plerixafor without granulocyte colony-stimulating factor and, following allogeneic transplantation, can result in sustained donor-derived hematopoiesis. However, when a single dose of Plerixafor is administered at a conventional 240 μg/kg dose, approximately one-third of donors will fail to mobilize the minimally acceptable dose of CD34+ cells needed for allogeneic transplantation. We conducted an open-label, randomized trial to assess the safety and activity of high-dose (480 μg/kg) Plerixafor in CD34+ cell mobilization in healthy donors. Subjects were randomly assigned to receive either a high dose or a conventional dose (240 μg/kg) of Plerixafor, given as a single subcutaneous injection, in a two-sequence, two-period, crossover design. Each treatment period was separated by a 2-week minimum washout period. The primary endpoint was the peak CD34+ count in the blood, with secondary endpoints of CD34+ cell area under the curve (AUC), CD34+ count at 24 hours, and time to peak CD34+ following the administration of Plerixafor. We randomized 23 subjects to the two treatment sequences and 20 subjects received both doses of Plerixafor. Peak CD34+ count in the blood was significantly increased (mean 32.2 versus 27.8 cells/μL, P=0.0009) and CD34+ cell AUC over 24 hours was significantly increased (mean 553 versus 446 h cells/μL, P<0.0001) following the administration of the 480 μg/kg dose of Plerixafor compared with the 240 μg/kg dose. Remarkably, of seven subjects who mobilized poorly (peak CD34+ ≤20 cells/μL) after the 240 μg/kg dose of Plerixafor, six achieved higher peak CD34+ cell numbers and all achieved higher CD34+ AUC over 24 hours after the 480 μg/kg dose. No grade 3 or worse drug-related adverse events were observed. This study establishes that high-dose Plerixafor can be safely administered in healthy donors and mobilizes greater numbers of CD34+ cells than conventional-dose Plerixafor, which may improve CD34+ graft yields and reduce the number of apheresis procedures needed to collect sufficient stem cells for allogeneic transplantation. (ClinicalTrials.gov, identifier: NCT00322127).

  • effect of high dose Plerixafor on cd34 cell mobilization in healthy stem cell donors results of a randomized crossover trial
    Haematologica, 2017
    Co-Authors: Jeremy Pantin, Gary Calandra, Matthew M Hsieh, Lisa Cook, Xin Tian, Robert Reger, Hanh Khuu, Enkhtsetseg Purev, Theresa Donohuejerussi, Nancy L Geller
    Abstract:

    Hematopoietic stem cells can be mobilized from healthy donors using single-agent Plerixafor without granulocyte colony-stimulating factor and, following allogeneic transplantation, can result in sustained donor-derived hematopoiesis. However, when a single dose of Plerixafor is administered at a conventional 240 μg/kg dose, approximately one-third of donors will fail to mobilize the minimally acceptable dose of CD34+ cells needed for allogeneic transplantation. We conducted an open-label, randomized trial to assess the safety and activity of high-dose (480 μg/kg) Plerixafor in CD34+ cell mobilization in healthy donors. Subjects were randomly assigned to receive either a high dose or a conventional dose (240 μg/kg) of Plerixafor, given as a single subcutaneous injection, in a two-sequence, two-period, crossover design. Each treatment period was separated by a 2-week minimum washout period. The primary endpoint was the peak CD34+ count in the blood, with secondary endpoints of CD34+ cell area under the curve (AUC), CD34+ count at 24 hours, and time to peak CD34+ following the administration of Plerixafor. We randomized 23 subjects to the two treatment sequences and 20 subjects received both doses of Plerixafor. Peak CD34+ count in the blood was significantly increased (mean 32.2 versus 27.8 cells/μL, P =0.0009) and CD34+ cell AUC over 24 hours was significantly increased (mean 553 versus 446 h cells/μL, P <0.0001) following the administration of the 480 μg/kg dose of Plerixafor compared with the 240 μg/kg dose. Remarkably, of seven subjects who mobilized poorly (peak CD34+ ≤20 cells/μL) after the 240 μg/kg dose of Plerixafor, six achieved higher peak CD34+ cell numbers and all achieved higher CD34+ AUC over 24 hours after the 480 μg/kg dose. No grade 3 or worse drug-related adverse events were observed. This study establishes that high-dose Plerixafor can be safely administered in healthy donors and mobilizes greater numbers of CD34+ cells than conventional-dose Plerixafor, which may improve CD34+ graft yields and reduce the number of apheresis procedures needed to collect sufficient stem cells for allogeneic transplantation. ( [ClinicalTrials.gov][1], identifier: [NCT00322127][2] ) [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00322127&atom=%2Fhaematol%2F102%2F3%2F600.atom

  • High Dose Plerixafor Is Safe and Mobilizes Higher Numbers of CD34+ Cells Compared with Standard Dose Plerixafor
    Blood, 2012
    Co-Authors: Jeremy Pantin, Matthew M Hsieh, Aleah Smith, Lisa Cook, Xin Tian, Theresa Donohue, Elena Cho, Robert Reger, Thomas Trischman, Hanh Khuu
    Abstract:

    Abstract 585 Introduction Plerixafor is a bicyclam compound that inhibits the binding of stromal cell derived factor-1 (SDF-1) to its cognate receptor CXCR4. This results in therapid release of CD34+ cells into circulation, which can then be collected by apheresis. Plerixafor is FDA approved at the 240 μg/kg dose to be used in conjunction with G-CSF to mobilize autografts for transplantation. Allogeneic grafts can also be mobilized using single agent Plerixafor without G-CSF, and following transplantation, result in sustained donor derived hematopoiesis. However, when the 240 μg/kg dose is used, 1/3 of donors fail to mobilize minimally acceptable doses of CD34+ cells. Recently, we demonstrated the safety of administration of a single dose of 480 μg/kg of subcutaneous (sc) Plerixafor in humans. We subsequently conducted a randomized cross-over trial comparing CD34+ mobilization in healthy subjects mobilized with a single dose of sc Plerixafor given at either a high dose (480 μg/kg) or a conventional dose (240 μg/kg). Methods Twenty normal healthy volunteers were randomized and received either a 240 or 480 μg/kg dose of sc Plerixafor followed by at least a 2 week wash out period then were administered the other dose of Plerixafor. Circulating numbers of leukocytes and CD34+ cells/μlwere measured at multiple time points for 24 hours following each Plerixafor injection and the CD34+ AUC over 24 hours was calculated for each subject at each dose level. Peripheral blood colony forming unit (CFU) assays were performed at baseline and 6 hours after Plerixafor dosing. Adverse events were graded using CTCAE version 3.A sample size of 20 subjects was determined to have over 90% power to detect an absolute CD34+ count difference of 10/μl using this crossover design and a two-sidedpaired t-test at the 0.05 level. Results Twenty-three subjects were enrolled and 20 completed administration of both doses. Peak circulating CD34+ cell numbers (median 31.5 vs 25, p=0.0009), circulating CD34+ cell numbers at 24hrs (median 15.5 vs 9, p Conclusion These preliminary data suggest high dose Plerixafor can be administered safely and may mobilize more CD34+ cells than standard dose Plerixafor. Furthermore, these data suggest mobilization following a single dose of Plerixafor and a single apheresis procedure would result in graft collections containing higher CD34+ cell numbers when allogeneic stem cell donors are mobilized with high-dose Plerixafor compared to standard-dose. Disclosures: Off Label Use: Plerixafor, a hematopoietic stem cell mobilizer, is indicated in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin9s lymphoma (NHL) and multiple myeloma (MM).

  • accelerated lymphocyte reconstitution and long term recovery after transplantation of lentiviral transduced rhesus cd34 cells mobilized by g csf and Plerixafor
    Experimental Hematology, 2011
    Co-Authors: Naoya Uchida, Aylin C Bonifacino, Allen E Krouse, Mark E Metzger, Gyorgy Csako, Agnes Leestroka, Ross M Fasano, Susan F Leitman, Joseph J Mattapallil, Matthew M Hsieh
    Abstract:

    Objective Granulocyte colony-stimulating factor (G-CSF) in combination with Plerixafor produces significant mobilization of CD34 + cells in rhesus macaques. We sought to evaluate whether these CD34 + cells can stably reconstitute blood cells with lentiviral gene marking. Materials and Methods We performed hematopoietic stem cell transplantation using G-CSF and Plerixafor-mobilized rhesus CD34 + cells transduced with a lentiviral vector, and these data were compared with those of G-CSF and stem cell factor mobilization. Results G-CSF and Plerixafor mobilization resulted in CD34 + cell yields that were twofold higher than yields with G-CSF and stem cell factor. CD123 (interleukin-3 receptor) expression was greater in G-CSF and Plerixafor-mobilized CD34 + cells when compared to G-CSF alone. Animals transplanted with G-CSF and Plerixafor-mobilized cells showed engraftment of all lineages, similar to animals who received G-CSF and stem cell factor−mobilized grafts. Lymphocyte engraftment was accelerated in animals receiving the G-CSF and Plerixafor-mobilized CD34 + cells. One animal in the G-CSF and Plerixafor group developed cold agglutinin-associated skin rash during the first 3 months of rapid lymphocyte recovery. One year after transplantation, all animals had 2% to 10% transgene expression in all blood cell lineages. Conclusions G-CSF and Plerixafor-mobilized CD34 + cells accelerate lymphocyte engraftment and contain hematopoietic stem cell capable of reconstituting multilineage blood cells. These findings indicate important differences to consider in Plerixafor-based hematopoietic stem cell mobilization protocols in rhesus macaques.

  • Long-Term Reconstitution of Transduced Rhesus CD34+ Cells Mobilized by G-CSF and Plerixafor.
    Blood, 2010
    Co-Authors: Naoya Uchida, Aylin C Bonifacino, Allen E Krouse, Mark E Metzger, Gyorgy Csako, Ross M Fasano, Susan F Leitman, Matthew M Hsieh, Sandra D. Price, Joseph J Mattapallil
    Abstract:

    Abstract 1449 Granulocyte colony-stimulating factor (G-CSF) in combination with Plerixafor (AMD3100) produces significant mobilization of peripheral blood stem cells in the rhesus macaque model. The CD34+ cell population mobilized possesses a unique gene expression profile, suggesting a different proportion of progenitor/stem cells. To evaluate whether these CD34+ cells can stably reconstitute blood cells, we performed hematopoietic stem cell transplantation using G-CSF and Plerixafor-mobilized rhesus CD34+ cells that were transduced with chimeric HIV1-based lentiviral vector including the SIV-capsid (χHIV vector). In our experiments, G-CSF and Plerixafor mobilization (N=3) yielded a 2-fold higher CD34+ cell number, compared to that observed for G-CSF and stem cell factor (SCF) combination (N=5) (8.6 ± 1.8 × 10 7 vs. 3.6 ± 0.5 × 10 7 , p in vitro bulk CD34+ cells and lymphocytes at one month, three months, and six months post-transplantation. At one and three months after transplantation, data from G-CSF and Plerixafor mobilization showed higher ratio of %EGFP in lymphocytes to that of in vitro CD34+ cells when compared to that of G-CSF and SCF mobilization. At six months after transplantation the ratios were similar. These results again suggest that G-CSF and Plerixafor-mobilized CD34+ cells might include a larger proportion of early lymphoid progenitor cells when compared to G-CSF and SCF mobilization. In summary, G-CSF and Plerixafor mobilization increased CD34+ cell numbers. G-CSF and Plerixafor-mobilized CD34+ cells contained an increased number of lymphoid progenitor cells and a hematopoietic stem cell population that was capable of reconstituting blood cells as demonstrated by earlier lymphoid recovery and stable multilineage transgene expression in vivo , respectively. Our findings should impact the development of new clinical mobilization protocols. Disclosures: No relevant conflicts of interest to declare.

John F Dipersio - One of the best experts on this subject based on the ideXlab platform.

  • phase 1 clinical study of mgta 145 in combination with Plerixafor shows rapid single day mobilization and collection of cd34 hscs without g csf
    Biology of Blood and Marrow Transplantation, 2020
    Co-Authors: John F Dipersio, Steven M Devine, Jonathan Hoggatt, David T Scadden, Haley Howell, Veit Schmelmer, Jason Neale, Anthony E Boitano, Michael P Cooke, Kevin A Goncalves
    Abstract:

    Background G-CSF mobilization of hematopoietic stem cells (HSCs) requires 4-7 days of injections that provide unreliable collections. G-CSF is associated with significant side effects and potential for fatal complications in some patient populations (e.g. sickle cell disease, multiple sclerosis). MGTA-145 is an analog of the chemokine GROβ that activates CXCR2 and with Plerixafor rapidly mobilizes HSCs in mice and non-human primates. The combination promises to be a same-day mobilization regimen that does not require G-CSF. Methods This phase 1 study consisted of four parts in healthy volunteers- Part A: single-agent doses of MGTA-145 (or placebo); Part B: MGTA-145 or placebo given immediately or 2 hours after Plerixafor; Part C: MGTA-145 or placebo given 2 hours after Plerixafor on 2 consecutive days; Part D: MGTA-145 given 2 hours after Plerixafor, at the start of apheresis cell collection. Results MGTA-145 monotherapy was well tolerated with no significant adverse events (AEs). Grade 1, transient lower back pain that dissipated within minutes was reported. The combination of MGTA-145 with Plerixafor was well tolerated, with some subjects experiencing grade 1/2 gastrointestinal AEs commonly observed with Plerixafor and one grade 2 back pain with MGTA-145 at 0.075 mg/kg that resolved within minutes. Monotherapy of MGTA-145 led to an immediate mobilization of CD34+ cells within minutes that peaked within 1-hour post MGTA-145 and yielded a median peak of 11 CD34+ cells/µL (7-fold increase vs baseline) at the optimal single-agent dose of 0.03 mg/kg. White blood cells and neutrophils followed a similar pattern. Importantly, markers of neutrophil activation were relatively unchanged (≤2-fold vs baseline). MGTA-145 combined with Plerixafor increased CD34+ cell mobilization, whether given simultaneously or 2h after Plerixafor (Fig. 1A, 0.03 mg/kg dose shown). Mobilization was highly enriched for CD34+CD90+CD45RA- HSCs, which tracked closely with the total CD34 count (Fig. 1B). Mobilization efficacy was assessed by achievement of thresholds of peak peripheral blood CD34+ cells/µL: ≥20 was achieved in 12/14 (86%) subjects, and a median of 40 was achieved with staggered dosing. This regimen has advanced to Part D where mobilization and CD34+ cell collection by apheresis will be performed. Results of Parts A-D and apheresis graft analysis will be presented. Conclusions CD34+ cell mobilization with Plerixafor + MGTA-145 was immediate and superior to Plerixafor alone. MGTA-145 monotherapy is safe, well tolerated, and induced rapid mobilization of significant numbers of HSCs. These data suggest that the combination can enable the collection of sufficient HSCs for transplant in a single day. Further clinical development as a first line mobilization product is warranted in hematologic malignancies, autoimmune diseases, and gene therapy.

  • phase i ii study of intravenous Plerixafor added to a mobilization regimen of granulocyte colony stimulating factor in lymphoma patients undergoing autologous stem cell collection
    Biology of Blood and Marrow Transplantation, 2017
    Co-Authors: Amanda F Cashen, Michael P Rettig, Feng Gao, A Smith, Camille N Abboud, Keith Stockerlgoldstein, Ravi Vij, Peter Westervelt, John F Dipersio
    Abstract:

    Plerixafor, given subcutaneously with granulocyte colony-stimulating factor (G-CSF), improves autologous stem cell collection in patients with lymphoma and multiple myeloma. Intravenous (i.v.) administration of Plerixafor allows administration of Plerixafor on the same day as pheresis and it may improve stem cell collection. The primary objectives of this phase I/II study were to determine the maximum tolerated dose of i.v. Plerixafor and the efficacy of i.v. Plerixafor + G-CSF to mobilize ≥ 2 × 106 CD34+ cells/kg from patients with lymphoma. In phase I, 25 patients were treated with G-CSF + i.v. Plerixafor at escalating doses; in phase II, 36 patients were treated with G-CSF + Plerixafor .40 mg/kg. The treatment was well tolerated. Fifty-nine of 61 patients (98%) met the collection goal and 47 of 61 patients (77%) collected ≥ 5.0 × 106 CD34+ cells/kg in a median of 2 pheresis days. Analysis of CD34+ hematopoietic stem and progenitor cells (HSPCs) revealed that G-CSF-mobilized grafts were enriched with CD34+CD45RA-CD123+/- primitive HSPCs whereas Plerixafor preferentially mobilized CD34+CD45RA+CD123++ plasmacytoid dendritic cell precursors. In conclusion, i.v. Plerixafor is well tolerated and effective when added to G-CSF for the mobilization of stem cells from patients with lymphoma, with mobilization kinetics and stem cell collections that compare favorably with subcutaneous dosing.

  • diabetes limits stem cell mobilization following g csf but not Plerixafor
    Diabetes, 2015
    Co-Authors: Gian Paolo Fadini, John F Dipersio, Mark A Fiala, Roberta Cappellari, Marianna Danna, Soo Park, Nicol Poncina, Lisa Menegazzo, Mattia Albiero, Keith Stockerlgoldstein
    Abstract:

    Previous studies suggest that diabetes impairs hematopoietic stem cell (HSC) mobilization in response to granulocyte colony-stimulating factor (G-CSF). In this study, we tested whether the CXCR4 antagonist Plerixafor, differently from G-CSF, is effective in mobilizing HSCs in patients with diabetes. In a prospective study, individuals with and without diabetes (n = 10/group) were administered Plerixafor to compare CD34+ HSC mobilization; Plerixafor was equally able to mobilize CD34+ HSCs in the two groups, whereas in historical data, G-CSF was less effective in patients with diabetes. In a retrospective autologous transplantation study conducted on 706 patients, diabetes was associated with poorer mobilization in patients who received G-CSF with/without chemotherapy, whereas it was not in patients who received G-CSF plus Plerixafor. Similarly in an allogeneic transplantation study (n = 335), diabetes was associated with poorer mobilization in patients who received G-CSF. Patients with diabetes who received G-CSF without Plerixafor had a lower probability of reaching >50/μL CD34+ HSCs, independent from confounding variables. In conclusion, diabetes negatively impacted HSC mobilization after G-CSF with or without chemotherapy but had no effect on mobilization induced by G-CSF with Plerixafor. This finding has major implications for the care of patients with diabetes undergoing stem cell mobilization and transplantation and for the vascular regenerative potential of bone marrow stem cells.

  • safety and efficacy of upfront Plerixafor g csf versus placebo g csf for mobilization of cd34 hematopoietic progenitor cells in patients 60 and 60 years of age with non hodgkin s lymphoma or multiple myeloma
    American Journal of Hematology, 2013
    Co-Authors: Ivana N Micallef, Edward A. Stadtmauer, Auayporn Nademanee, Richard T Maziarz, Patrick J Stiff, Brian J Bolwell, Angela M Partisano, Sachin Marulkar, John F Dipersio
    Abstract:

    The efficacy and safety of Plerixafor + G-CSF in enhancing hematopoietic stem cell mobilization and collection has been demonstrated in two phase III studies involving patients with NHL or MM. In these pivotal studies, Plerixafor + G-CSF significantly increased the proportion of patients achieving target stem cell yields, compared to placebo + G-CSF. In this analysis, we compare the efficacy and safety of Plerixafor + G-CSF versus placebo + G-CSF in patients enrolled in the two phase III studies, stratified by age: ≥60 years of age and <60 years of age. The proportion of older patients who achieved target stem cell yields was significantly higher in the Plerixafor group than in placebo group (NHL: 50.9 vs. 25.4%, P < 0.001; MM: 69.6 vs. 23.7%, P < 0.001). In this older cohort, the median times to neutrophil and to platelet engraftment following autologous stem cell transplant were comparable between the Plerixafor and placebo groups. Similar efficacy findings were observed in the younger age group. The most common adverse events (all grades) reported among older patients in the Plerixafor group included diarrhea (41.3%), nausea (38.9%), fatigue (30.2%), and injection-site reaction (29.4%). The frequency of adverse events was similar between the older and the younger age groups. Taken together, our subanalysis demonstrate that Plerixafor + G-CSF can be safely and effectively used in adult patients of all ages, including those ≥60 years, to support optimal stem cell mobilization for autologous stem cell transplantation.

  • Plerixafor plus granulocyte colony stimulating factor versus placebo plus granulocyte colony stimulating factor for mobilization of cd34 hematopoietic stem cells in patients with multiple myeloma and low peripheral blood cd34 cell count results of a
    Biology of Blood and Marrow Transplantation, 2012
    Co-Authors: Auayporn Nademanee, John F Dipersio, Edward A. Stadtmauer, Richard T Maziarz, Gary J Bridger, Ivana N Micallef, Patrick J Stiff, Frank J Hsu, Brian J Bolwell
    Abstract:

    Preapheresis peripheral blood (PB) CD34 + cell count is a strong predictor of hematopoietic stem cell (HSC) mobilization and is routinely used to optimize the timing, cost, and success of HSC collection in patients with multiple myeloma. However, a uniform PB CD34 + cell count that predicts mobilization failure has not been defined, resulting in the development of institute-specific algorithms for mobilization, particularly regarding the decision of when to use the novel stem cell mobilization agent Plerixafor. In this post hoc analysis, we evaluated the mobilization efficacy of Plerixafor plus granulocyte colony-stimulating factor (G-CSF) versus placebo plus G-CSF in patients with multiple myeloma, stratified by preapheresis PB CD34 + cell count: + cell count, the total yield of CD34 + cells from apheresis was significantly higher in the Plerixafor group than in the placebo group, and significantly more patients in the Plerixafor group collected the minimum (≥2 × 10 6 cells/kg) and optimum (≥6 × 10 6 cells/kg) stem cell yields on each day of apheresis. As a corollary, the greater stem cell collection in Plerixafor-treated patients resulted in the need for significantly fewer days of apheresis to reach minimum and optimum cell doses across all cell count groups. For all CD34 + cell count groups, the proportion of patients proceeding to transplantation and the median time to platelet and neutrophil engraftment were similar in the Plerixafor and placebo groups. Our findings demonstrate that in patients with multiple myeloma who might be predicted to fail mobilization based on low PB CD34 + cell count, the addition of Plerixafor to G-CSF allows for collection of the minimal and optimal cell doses in a greater proportion of patients compared with G-CSF alone. In addition, Plerixafor plus G-CSF significantly improves the likelihood of optimal HSC collection in patients with higher preapheresis PB CD34 + cell counts (≥20 cells/μL) compared with placebo plus G-CSF. Collectively, this analysis of predicted poor mobilizers validates the superiority of Plerixafor plus G-CSF compared with G-CSF alone, which had been demonstrated previously in the overall patient population.

Esa Jantunen - One of the best experts on this subject based on the ideXlab platform.

  • Plerixafor injection: a hematopoietic stem cell mobilizer in non-Hodgkin lymphoma and multiple myeloma.
    Expert review of hematology, 2016
    Co-Authors: Esa Jantunen, Ville Varmavuo, Jaakko Valtola
    Abstract:

    ABSTRACTIntroduction: A combination of granulocyte colony-stimulating factor (G-CSF) and chemotherapy or G-CSF alone are the most common mobilization regimens for autotransplantations. Plerixafor is used for mobilization of CD34+ cells with G-CSF in non-Hodgkin lymphoma (NHL) and myeloma (MM) patients.Areas covered: The available phase II and III data on Plerixafor has been reviewed. The efficacy of Plerixafor in the mobilization of CD34+ cells in predicted poor mobilizers as well as in patients who had failed a mobilization has been evaluated. The pre-emptive use of Plerixafor as well as studies on cost-effectiveness are covered. Also effects in the composition of the collected grafts along with the data on long-term outcome of Plerixafor-mobilized patients is discussed.Expert commentary: Plerixafor combined with G-CSF mobilizes CD34+ cells more efficiently than G-CSF alone in patients with NHL or MM. In phase III studies, engraftment after high-dose therapy has been comparable to G-CSF mobilized patient...

  • Plerixafor for mobilization of blood stem cells in autologous transplantation: an update
    Expert opinion on biological therapy, 2014
    Co-Authors: Esa Jantunen, Ville Varmavuo
    Abstract:

    Introduction: About 99% of all autologous transplants are now performed with blood stem cells. G-CSF alone or combined with chemotherapy have been used to mobilize CD34+ cells. Plerixafor is a novel drug used for mobilization purposes. Areas covered: We have evaluated recent data in regard to Plerixafor use in predicted or proven poor mobilizers. In addition, we have looked for preemptive strategies to optimize the use of this expensive drug. Also cost-efficacy issues and effects of Plerixafor on graft composition and post-transplant outcomes will be discussed. Expert opinion: Plerixafor added to G-CSF is superior than G-CSF alone for mobilization of CD34+ cells. This combination is also efficient in patients who have failed a previous mobilization attempt with other methods or in patients with risk factors for poor mobilization. Addition of Plerixafor to G-CSF or chemotherapy plus G-CSF mobilization in patients who appear to mobilize poorly is under active investigation and algorithms for a preemptive us...

  • Blood graft composition after Plerixafor injection in patients with NHL
    European journal of haematology, 2012
    Co-Authors: Ville Varmavuo, Taru Kuittinen, Pentti Mantymaa, Tapio Nousiainen, Piia Valonen, Esa Jantunen
    Abstract:

    Background Plerixafor is used to mobilize CD34+ hematopoietic stem cells from bone marrow to circulation. Limited data are available in regard to graft cellular content collected after Plerixafor. Objectives The aim of this study was to assess effects of Plerixafor added to chemomobilization on graft CD34+ cell subclasses, lymphocyte subsets, engraftment, and post-transplant course in non-Hodgkin lymphoma (NHL) patients. Methods Thirty-four patients with NHL were included. All patients received chemotherapy plus G-CSF to mobilize stem cells. Nineteen patients received Plerixafor pre-emptively owing to poor mobilization or poor collection yields. The rest of the patients constituted the control group. Flow cytometric analyzes were performed from cryopreserved graft samples. Also, data on post-transplant engraftment and outcome were collected. Results The proportion of primitive stem cells (CD34+ CD133+ CD38−) was significantly higher after the Plerixafor injection when compared to the first collection in the control group. The amount of T cells (CD3+), helper (CD3+ CD4+) T subsets, and suppressor (CD3+ CD8+) T subsets in the graft was all significantly higher in the Plerixafor group. Also, the amount of NK cells (CD3− CD16/56+) was higher. Engraftment after high-dose therapy was comparable between the groups, but leukocyte and platelet count at 6 months were higher in patients receiving Plerixafor-mobilized grafts. Conclusion Plerixafor, when used pre-emptively in addition to chemomobilization, seems to mobilize more primitive CD34+ stem cells, T lymphocytes, and NK cells. Whether these differences are associated with immune reconstitution, long-term engraftment, or patient outcomes needs to be evaluated in larger patient groups with longer follow-up.

  • efficacy of pre emptively used Plerixafor in patients mobilizing poorly after chemomobilization a single centre experience
    European Journal of Haematology, 2011
    Co-Authors: Esa Jantunen, Taru Kuittinen, Eija Mahlamaki, Marja Pyorala, Pentti Mantymaa, T Nousiainen
    Abstract:

    A significant proportion of patients with lymphoid malignancies are hard-to-mobilize with a combination of chemotherapy plus granulocyte colony-stimulating factor (G-CSF) (chemomobilization). Plerixafor is a novel drug used to improve mobilization of blood stem cells. However, it has been studied mainly in association with G-CSF mobilization. We evaluated the efficacy of 'pre-emptive' use of Plerixafor after chemomobilization in patients who seem to mobilize poorly. During a 15 month period, altogether 63 patients with lymphoid malignancies were admitted to our department for blood stem cell collection. Sixteen patients (25%) received Plerixafor after the first mobilization due to the low blood (B) CD34(+) cell counts (n = 12) or poor yield of the first collection (n = 4). The median number of Plerixafor injections was 1 (1-3). The median B-CD34(+) count after the first Plerixafor dose was 39 × 10(6) /L (<1-81) with the median increase of fivefold. Stem cell aphaereses were performed in 14/16 patients (88%) receiving Plerixafor and a median of 2.9 × 10(6) /kg (1.6-6.1) CD34(+) cells were collected with a median of one aphaeresis (1-3). Altogether 13/16 patients mobilized with a combination of chemomobilization and Plerixafor received high-dose therapy with stem cell support and all engrafted. Pre-emptive use of Plerixafor after chemomobilization is efficient and safe and should be considered in poor mobilizers to avoid collection failure. In patients with low but rising B-CD34(+) counts, the use of Plerixafor might be delayed as late mobilization may occur. Further studies are needed to optimize patient selection and timing of Plerixafor.

  • Efficacy of pre-emptively used Plerixafor in patients mobilizing poorly after chemomobilization: a single centre experience.
    European journal of haematology, 2011
    Co-Authors: Esa Jantunen, Taru Kuittinen, Eija Mahlamaki, Marja Pyorala, Pentti Mantymaa, Tapio Nousiainen
    Abstract:

    A significant proportion of patients with lymphoid malignancies are hard-to-mobilize with a combination of chemotherapy plus granulocyte colony-stimulating factor (G-CSF) (chemomobilization). Plerixafor is a novel drug used to improve mobilization of blood stem cells. However, it has been studied mainly in association with G-CSF mobilization. We evaluated the efficacy of 'pre-emptive' use of Plerixafor after chemomobilization in patients who seem to mobilize poorly. During a 15 month period, altogether 63 patients with lymphoid malignancies were admitted to our department for blood stem cell collection. Sixteen patients (25%) received Plerixafor after the first mobilization due to the low blood (B) CD34(+) cell counts (n = 12) or poor yield of the first collection (n = 4). The median number of Plerixafor injections was 1 (1-3). The median B-CD34(+) count after the first Plerixafor dose was 39 × 10(6) /L (

Auayporn Nademanee - One of the best experts on this subject based on the ideXlab platform.

  • Plerixafor plus granulocyte colony stimulating factor for patients with non hodgkin lymphoma and multiple myeloma long term follow up report
    Biology of Blood and Marrow Transplantation, 2018
    Co-Authors: Ivana N Micallef, Edward A. Stadtmauer, Auayporn Nademanee, Richard T Maziarz, Patrick J Stiff, Mitchell E Horwitz, Jonathan L Kaufman, John M Mccarty, Rita Vargo, Peter D Cheverton
    Abstract:

    Abstract The purpose of this report is to analyze long-term clinical outcomes of patients exposed to Plerixafor plus granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization. This was a study of patients with non-Hodgkin lymphoma (NHL; n = 167) and multiple myeloma (MM; n = 163) who were enrolled in the long-term follow-up of 2 pivotal phase III studies (NCT00741325 and NCT00741780) of 240 µg/kg Plerixafor plus 10 µg/kg G-CSF, or placebo plus 10 µg/kg G-CSF to mobilize and collect CD34+ cells for autologous hematopoietic stem cell transplantation. Overall survival (OS) and progression-free survival (PFS) were evaluated over a 5-year period following the first dose of Plerixafor or placebo. The probability of OS was not significantly different in patients with NHL or MM treated with Plerixafor or placebo (NHL: 64%; 95% confidence interval [CI], 56% to 71% versus 56%; 95% CI, 44% to 67%, respectively; MM: 64%; 95% CI, 54% to 72% versus 64%; 95% CI, 53% to 73%, respectively). In addition, there was no statistically significant difference in the probability of PFS over 5 years between treatment groups in patients with NHL (50%; 95% CI, 44% to 67% for Plerixafor versus 43%; 95% CI, 31% to 54% for placebo) or those with MM (17%; 95% CI, 10% to 24% for Plerixafor versus 30%; 95% CI, 21% to 40% for placebo). In this long-term follow-up study, the addition of Plerixafor to G-CSF for stem cell mobilization did not affect 5-year survival in patients with NHL or patients with MM.

  • Efficacy of just-in-time Plerixafor rescue for Hodgkin's lymphoma patients with poor peripheral blood stem cell mobilization.
    Transfusion, 2014
    Co-Authors: Shan Yuan, Joycelynne Palmer, Auayporn Nademanee, Sepideh Shayani, Mark Kaniewski, Shirong Wang
    Abstract:

    Background Plerixafor is a Food and Drug Administration–approved agent for improving peripheral blood stem cell (PBSC) mobilization in filgrastim (granulocyte–colony-stimulating factor [G-CSF])-stimulated patients with multiple myeloma and non-Hodgkin's lymphoma. Limited information is available on its use in Hodgkin's lymphoma (HL) patients. We describe our experience with Plerixafor as an immediate rescue agent in HL patients with poor PBSC mobilization. Study Design and Methods We retrospectively reviewed the collection data of 27 consecutive HL patients at our center in whom Plerixafor was added to rescue a failing PBSC collection after G-CSF and chemotherapy (26) or G-CSF alone (1). Plerixafor was added in 11 patients due to peripheral blood (PB) CD34+ counts that persisted below the threshold (>10 × 106/L) to initiate collection (median, 1.47 × 106; range 0 × 106-6.28 × 106/L) and in 16 patients due to low collection yields, who had a median yield of 0.33 × 106 (0.14 × 106-0.65 × 106) CD34+ cells/kg on the last collection before Plerixafor administration. Results After a median of 2 (range, 2-4) collections with Plerixafor, the patients collected a median of 1.82 × 106 (0.52 × 106-11.14 × 106) CD34+ cells/kg. The addition of Plerixafor enabled 20 patients (74.1%) to reach the 2.0 × 106 CD34+ cells/kg minimum required for autologous stem cell transplantation (ASCT) during the same collection cycle. Subsequent remobilization in three patients with Plerixafor enabled all three to reach this goal. Conclusion Plerixafor can be used in HL patients with poor mobilization as a rescue agent and boosts mobilization sufficiently in most patients in the same collection attempt, thus not only permitting ASCT, but also avoiding remobilization and the associated costs, treatment delays, and patient inconvenience.

  • safety and efficacy of upfront Plerixafor g csf versus placebo g csf for mobilization of cd34 hematopoietic progenitor cells in patients 60 and 60 years of age with non hodgkin s lymphoma or multiple myeloma
    American Journal of Hematology, 2013
    Co-Authors: Ivana N Micallef, Edward A. Stadtmauer, Auayporn Nademanee, Richard T Maziarz, Patrick J Stiff, Brian J Bolwell, Angela M Partisano, Sachin Marulkar, John F Dipersio
    Abstract:

    The efficacy and safety of Plerixafor + G-CSF in enhancing hematopoietic stem cell mobilization and collection has been demonstrated in two phase III studies involving patients with NHL or MM. In these pivotal studies, Plerixafor + G-CSF significantly increased the proportion of patients achieving target stem cell yields, compared to placebo + G-CSF. In this analysis, we compare the efficacy and safety of Plerixafor + G-CSF versus placebo + G-CSF in patients enrolled in the two phase III studies, stratified by age: ≥60 years of age and <60 years of age. The proportion of older patients who achieved target stem cell yields was significantly higher in the Plerixafor group than in placebo group (NHL: 50.9 vs. 25.4%, P < 0.001; MM: 69.6 vs. 23.7%, P < 0.001). In this older cohort, the median times to neutrophil and to platelet engraftment following autologous stem cell transplant were comparable between the Plerixafor and placebo groups. Similar efficacy findings were observed in the younger age group. The most common adverse events (all grades) reported among older patients in the Plerixafor group included diarrhea (41.3%), nausea (38.9%), fatigue (30.2%), and injection-site reaction (29.4%). The frequency of adverse events was similar between the older and the younger age groups. Taken together, our subanalysis demonstrate that Plerixafor + G-CSF can be safely and effectively used in adult patients of all ages, including those ≥60 years, to support optimal stem cell mobilization for autologous stem cell transplantation.

  • Second time a charm? Remobilization of peripheral blood stem cells with Plerixafor in patients who previously mobilized poorly despite using Plerixafor as a salvage agent
    Transfusion, 2013
    Co-Authors: Shan Yuan, Amrita Krishnan, Auayporn Nademanee, Neil Kogut, Sepideh Shayani, Shirong Wang
    Abstract:

    Background Plerixafor is a recently introduced agent used to improve peripheral blood stem cell (PBSC) mobilization in patients with hematologic malignancies. However, some patients still cannot mobilize adequately even with Plerixafor. Study Design and Methods We retrospectively reviewed the PBSC collections of 18 consecutive lymphoma and multiple myeloma patients, who had previously mobilized poorly despite the use of Plerixafor and received Plerixafor again during remobilization. Results During the first mobilization attempt, all 18 recombinant granulocyte–colony-stimulating factor (G-CSF; two) or G-CSF plus chemotherapy–mobilized patients (16) had poor response to Plerixafor, with peripheral blood (PB) CD34+ counts ranging from 0 to 7.48 × 106/L after the first dose. They collected only 0.15 × 106 to 1.63 × 106 (median, 0.40 × 106) CD34+ cells/kg after one to four collections. The median average daily yield was 0.24 × 106 CD34+ cells/kg. Remobilization began 1 to 4 weeks later with G-CSF, Plerixafor, and with (three) or without (15) cyclophosphamide. The PB CD34+ cell counts after the first dose of Plerixafor were 3.04 × 106 to 127.54 × 106/L (median, 14.58 × 106/L). After one to four doses of Plerixafor, each patient collected an additional 0.39 × 106 to 14.02 × 106 (median, 1.89 × 106) CD34+ cells/kg, and the median daily average was 0.78 × 106 CD34+ cells/kg. Cumulatively, after two rounds of collections, 15 collected more than 2.0 × 106 CD34+ cells/kg. Thirteen have proceeded to autologous stem cell transplantation (ASCT) and successfully engrafted. Conclusion In patients who had responded poorly to the use of Plerixafor as a mobilization salvage agent, response to remobilization with Plerixafor for the second time was variable, but most (83.3%) patients were able to collect enough PBSCs to proceed to ASCT.

  • Plerixafor plus granulocyte colony stimulating factor versus placebo plus granulocyte colony stimulating factor for mobilization of cd34 hematopoietic stem cells in patients with multiple myeloma and low peripheral blood cd34 cell count results of a
    Biology of Blood and Marrow Transplantation, 2012
    Co-Authors: Auayporn Nademanee, John F Dipersio, Edward A. Stadtmauer, Richard T Maziarz, Gary J Bridger, Ivana N Micallef, Patrick J Stiff, Frank J Hsu, Brian J Bolwell
    Abstract:

    Preapheresis peripheral blood (PB) CD34 + cell count is a strong predictor of hematopoietic stem cell (HSC) mobilization and is routinely used to optimize the timing, cost, and success of HSC collection in patients with multiple myeloma. However, a uniform PB CD34 + cell count that predicts mobilization failure has not been defined, resulting in the development of institute-specific algorithms for mobilization, particularly regarding the decision of when to use the novel stem cell mobilization agent Plerixafor. In this post hoc analysis, we evaluated the mobilization efficacy of Plerixafor plus granulocyte colony-stimulating factor (G-CSF) versus placebo plus G-CSF in patients with multiple myeloma, stratified by preapheresis PB CD34 + cell count: + cell count, the total yield of CD34 + cells from apheresis was significantly higher in the Plerixafor group than in the placebo group, and significantly more patients in the Plerixafor group collected the minimum (≥2 × 10 6 cells/kg) and optimum (≥6 × 10 6 cells/kg) stem cell yields on each day of apheresis. As a corollary, the greater stem cell collection in Plerixafor-treated patients resulted in the need for significantly fewer days of apheresis to reach minimum and optimum cell doses across all cell count groups. For all CD34 + cell count groups, the proportion of patients proceeding to transplantation and the median time to platelet and neutrophil engraftment were similar in the Plerixafor and placebo groups. Our findings demonstrate that in patients with multiple myeloma who might be predicted to fail mobilization based on low PB CD34 + cell count, the addition of Plerixafor to G-CSF allows for collection of the minimal and optimal cell doses in a greater proportion of patients compared with G-CSF alone. In addition, Plerixafor plus G-CSF significantly improves the likelihood of optimal HSC collection in patients with higher preapheresis PB CD34 + cell counts (≥20 cells/μL) compared with placebo plus G-CSF. Collectively, this analysis of predicted poor mobilizers validates the superiority of Plerixafor plus G-CSF compared with G-CSF alone, which had been demonstrated previously in the overall patient population.

Abraham S. Kanate - One of the best experts on this subject based on the ideXlab platform.

  • Hematopoietic progenitor cell mobilization with “just-in-time” Plerixafor approach is a cost-effective alternative to routine Plerixafor use
    Cytotherapy, 2015
    Co-Authors: Lauren Veltri, Aaron Cumpston, Alexandra Shillingburg, Sijin Wen, Jin Luo, Sonia Leadmon, Kathy Watkins, Michael Craig, Mehdi Hamadani, Abraham S. Kanate
    Abstract:

    Abstract Background aims Hematopoietic cell mobilization with granulocyte-colony stimulating factor (G-CSF) and Plerixafor results in superior CD34+ cell yield compared with G-CSF alone in patients with myeloma and lymphoma. However, Plerixafor-based approaches may be associated with high costs. Several institutions use a "just-in-time" Plerixafor approach, in which Plerixafor is only administered to patients likely to fail mobilization with G-CSF alone. Whether such an approach is cost-effective is unknown. Methods We evaluated 136 patients with myeloma or lymphoma who underwent mobilization with 2 approaches of Plerixafor utilization. Between January 2010 and October 2012, 76 patients uniformly received mobilization with G-CSF and Plerixafor. Between November 2012 and June 2014, 60 patients were mobilized with Plerixafor administered only to those patients likely to fail mobilization with G-CSF alone. Results The routine Plerixafor group had a higher median peak peripheral blood CD34+ cell count (62 versus 29 cells/μL, P 6 CD34+ cells/kg versus 2.1 × 10 6 CD34+ cells/kg, P  = 0.001). The median total CD34+ collection was higher with routine Plerixafor use (5.8 × 10 6 CD34+ cells/kg versus 4.5 × 10 6 CD34+ cells/kg, P  = 0.007). In the "just-in-time" group, 40% (n = 24) completed adequate collection without Plerixafor. There was no difference in mobilization failure rates. The mean Plerixafor doses used was lower with "just-in-time" approach (1.3 versus 2.1, P  = 0.0002). The mean estimated cost in the routine Plerixafor group was higher (USD 27,513 versus USD 23,597, P  = 0.01). Discussion Our analysis demonstrates that mobilization with a just-in-time Plerixafor approach is a safe, effective, and cost-efficient strategy for HPC collection.

  • Impact of body mass index (BMI) on Plerixafor efficacy during hematopoietic progenitor cell (HPC) mobilization.
    Journal of Clinical Oncology, 2014
    Co-Authors: Rebecca M. Gonzalez, Alexandra Shillingburg, Sijin Wen, Sonia Leadmon, Michael Craig, Mehdi Hamadani, Abraham S. Kanate, Michael Newton, Aaron Cumpston
    Abstract:

    7047 Background: Plerixafor in combination with G-CSF is commonly used to mobilize HPC for autologous transplantation. The effect of BMI on Plerixafor mobilization efficacy is controversial, with conflicting results from previous studies. Methods: One hundred and fourteen patients received G-CSF (10mcg/kg TBW) daily, with Plerixafor (0.24mg/kg TBW) added on the evening of day 4 of G-CSF, to mobilize and collect HPCs from 12/2009-12/2013. The first 83 patients before 11/2012 received upfront Plerixafor/GCSF mobilization, and the remaining patients received a “just in time” approach, with Plerixafor added if peripheral CD34 count was