Plerixafor

High-dose melphalan plus autologous stem-cell transplantation (ASCT) is a standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM), and adequate hematopoietic stem-cell (HSC) collection is crucial to ensure hematologic recovery after ASCT. In this prospective, observational study we evaluated HSC mobilization with granulocyte colony-stimulating factor (G-CSF), cyclophosphamide, and 'on-demand' plerixafor (in patients with.

INTRODUCTION: Poor CD34 + cells mobilization in allogeneic donors could affect transplant outcome. In a subgroup of patient mobilization with granulocyte colony-stimulating factor (G-CSF) alone is unsatisfactory, and Plerixafor could be used to enhance CD34 + cells release from bone marrow niche. MATERIALS AND METHODS: We conducted a retrospective single-center, cohort study on healthy allogeneic donors both related and unrelated, treated by Udine Transfusion Center over the last 10 years (2012-2022)...

INTRODUCTION: In transplant-eligible, newly diagnosed multiple myeloma (NDMM) patients, autologous peripheral blood stem cell (PBSC) collection is usually pursued after induction therapy. While induction regimens are constantly refined regarding response, their impact on PBSC collection is not fully studied. The inclusion of the anti-CD38 antibody daratumumab into induction therapy significantly improved outcomes for patients with NDMM, e.g., as part of the daratumumab, bortezomib, thalidomide, and dexamethasone (Dara-VTD) protocol...

Ex vivo gene therapy (GT) is a promising treatment for inherited genetic diseases. An ideal transduction protocol should determine high gene marking in long-term self-renewing hematopoietic stem cells (HSCs), preserving their repopulation potential during in vitro manipulation. In the context of the improvement of a clinically applicable transduction protocol, we tested prostaglandin E2 (PGE2) as a transduction enhancer (TE). The addition of PGE2 shortly before transduction of human CD34+ cells determined a significant transduction increase in the in vitro cell progeny paralleled by a significant reduction of their clonogenic potential...

INTRODUCTION: High-dose chemotherapy (HDCT) followed by autologous blood stem-cell transplantation (ABSCT) remains the standard consolidation therapy for newly diagnosed eligible multiple myeloma (MM) patients. As a prerequisite, peripheral blood stem cells (PBSCs) must be mobilized and collected by leukapheresis (LP). Many factors can hamper PBSC mobilization/collection. Here, we provide a comprehensive multiparametric assessment of PBSC mobilization/collection outcome parameters in a large cohort...

BACKGROUND: Multiple myeloma is currently the leading indication for autologous hematopoietic cell transplantation (AHCT). A prerequisite for AHCT is mobilization and collection of adequate blood graft to support high-dose therapy. Current mobilization strategies include granulocyte colony-stimulating factor (G-CSF) alone or in combination with chemotherapy most commonly cyclophosphamide (CY). More recently, plerixafor has become into agenda especially in patients who mobilize poorly...

INTRODUCTION: Successful mobilization and collection of peripheral hematopoietic stem cells (HSCs) are necessary for lymphoma patients eligible for myeloablative chemotherapy with subsequent autologous stem cell transplantation (ASCT). Albeit G-CSF alone or combined with chemotherapy is well-established methods for HSC mobilization, up to 40% of the patients fail to mobilize (poor mobilizer, PM). Plerixafor (PLX) is commonly used in PM patients resulting in increased migration of HSCs into peripheral blood and thus improves the collection outcome...

BACKGOUND: Autologous stem cell transplantation (ASCT) is a standard treatment in transplant-eligible mantle cell lymphoma (MCL) patients after first-line chemoimmunotherapy. STUDY DESIGN AND METHODS: This prospective multicenter study evaluated the impact of CD34+ cell mobilization and graft cellular composition analyzed by flow cytometry on hematologic recovery and outcome in 42 MCL patients. RESULTS: During CD34+ cell mobilization, a higher blood CD34+ cell count (>30 × 106 /L) was associated with improved overall survival (median not reached [NR] vs...

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that responds poorly to single-drug immunotherapy with PD-L1 (CD274) inhibitors. Here, we prepared mesoporous nanomaterials Cu2 MoS4 (CMS)/PEG loaded with PD-L1 inhibitor BMS-1 and CXCR4 inhibitor Plerixafor to form the nanodrug CMS/PEG-B-P. In vitro experiments, CMS/PEG-B-P have a more substantial inhibitory effect on the expression of PD-L1 and CXCR4 as well as to promote the apoptosis of pancreatic cancer cells KPC and suppressed KPC cell proliferation were detected by flow cytometry, qPCR and Western blotting (WB)...

Autologous Stem Cell Transplant (ASCT) is increasingly used to treat hematological malignancies. A key requisite for ASCT is mobilization of hematopoietic stem cells into peripheral blood, where they are collected by apheresis and stored for later transplantation. However, success is often hindered by poor mobilization due to factors including prior treatments. The combination of G-CSF and GPC-100, a small molecule antagonist of CXCR4, showed potential in a multiple myeloma clinical trial for sufficient and rapid collection of CD34+ stem cells, compared to the historical results from the standards of care, G-CSF alone or G-CSF with plerixafor, also a CXCR4 antagonist...

Germline genetic variants alter the coding and enhancer sequences of GATA2, which encodes a master regulator of hematopoiesis. The conserved murine Gata2 enhancer (+9.5) promotes hematopoietic stem cell (HSC) genesis during embryogenesis. Heterozygosity for a single-nucleotide Ets motif variant in the human enhancer creates a bone marrow failure and acute myeloid leukemia predisposition termed GATA2 deficiency syndrome. The homozygous murine variant attenuates chemotherapy- and transplantation-induced hematopoietic regeneration, hematopoietic stem and progenitor cell (HSPC) response to inflammation, and HSPC mobilization with the therapeutic mobilizer G-CSF...

The success of the autologous stem cell transplantation is strictly related to an adequate hematopoietic stem cell mobilization and collection. The minimum threshold for a successful mobilization is currently defined as 2 × 106 /kg CD34+ cells. However, the optimal stem cell mobilization strategy is still controversial. The availability of plerixafor, a selective and reversible CXCR4 inhibitor, has been associated with an higher use of chemo-free protocols by many centres. In the near future, it is conceivable that artificial intelligence may became more accurate and comprehensive, possibly guiding clinicians in choosing the optimal mobilisation treatment for the various patients undergoing hematopoietic stem cell transplantation...

BACKGROUND: The incorporation of anti-CD38 monoclonal antibodies (mAb) in induction regimens of newly diagnosed transplant-eligible multiple myeloma (MM) patients has been established as a new standard. However, the optimal strategy of stem cell mobilization in this context is not yet clear. STUDY DESIGN AND METHODS: From May 2020 till September 2022, we retrospectively reviewed patients receiving anti-CD38 mAb-based induction therapy followed by stem cell mobilization either in a steady-state protocol (SSM) using 10 μg/kg granulocyte colony-stimulating factor (G-CSF) for 5 days or in a chemotherapy-based protocol (CM) using 1-4 g/m2 cyclophosphamide and G-CSF...

OBJECTIVE: To compare the efficacy of plerixafor (PXF) combined with granulocyte colony-stimulating factor (G-CSF) (PXF+G-CSF) and cyclophosphamide (Cy) combined with G-CSF (Cy+G-CSF) in the mobilization of peripheral blood stem cells (PBSCs) in patients with multiple myeloma (MM). METHODS: The clinical data of 41 MM patients who underwent PBSC mobilization using PXF+G-CSF (18 cases) or Cy+G-CSF (23 cases) in Shanxi Bethune Hospital from January 2019 to December 2021 were retrospectively analyzed, including the count of collected CD34+ cells, acquisition success rate, failure rate, and optimal rate...

To explore the optimal mobilization for multiple myeloma (MM) patients, we conducted a prospective trial comparing single-dose etoposide (375 mg/m2 for one day) plus G-CSF versus G-CSF alone, followed by risk-adapted plerixafor. After randomization, 27 patients in the etoposide group and 29 patients in the G-CSF alone group received mobilizations. Six (22.2%) patients in the etoposide group and 15 (51.7%) patients in the G-CSF alone group received plerixafor based on a peripheral blood CD34+ cell count of < 15/mm3 ( p = 0...

BACKGROUND: Multiple myeloma remains an incurable disease, with the majority of patients relapsing after autologous stem cell transplant (ASCT). After relapse, second transplant remains one of the therapeutic options, along with novel agents. METHODS: We reviewed the data of our patients who underwent ASCT for myeloma (N = 202) over the last two decades (2004-2019). Of these, 12 patients underwent a second transplant. RESULTS: Out of 12 patients, nine underwent second autologous stem cell transplant, whereas three received an allogeneic stem cell transplantation (Allo-SCT)...

Primary treatment of multiple myeloma (MM) often involves systemic induction therapy (SIT) followed by autologous stem cell transplantation (ASCT). Radiation therapy (RT) is sometimes used for palliation; however, many practitioners avoid RT out of concern that future peripheral blood progenitor cell (PBPC) collection required for ASCT may be compromised. In this study, we retrospectively examined the possible effect of RT on PBPC collection. We reviewed the charts of 732 patients with MM treated with RT at our institution from 1999 to 2017, including patients who received RT prior to PBPC collection for planned ASCT...

With the use of plerixafor in addition to growth factor for peripheral blood stem cell mobilization, the yield of autologous stem cell harvest has been higher while the length of apheresis days has become shorter. There is still debate whether higher cell collection efficacy in autologous stem cell transplant (ASCT) affect outcomes. In this retrospective study, we defined two groups of patients, group 1, super-mobilizers, with more than double the target cell dose collected (n = 15), while group 2 included all other patients (n = 75)...

In this review, we discuss recipient risk assessment for allo-HCT regarding comorbidities present at baseline to predict non relapse mortality. We further reviewed the incorporation of remission status and cytogenetic risk prior to allograft transplantation to predict relapse rates for hematologic malignancies. HCT-CI and DRI are tools available to physicians to assess the risk-benefit of allo-HCT in patients referred for transplantation. Next, we discuss our algorithm for donor selection and criteria for donor selection in case matched donors are not available...

Plerixafor increases stem cell mobilization by reversibly binding to the chemokine receptor CXCR4. In our study, we examined the results of mobilization with plerixafor and granulocyte colony-stimulating factor (G-CSF) and revealed their effects on autologous stem cell transplantation (ASCT) engraftment kinetics. The study included all cases of ASCT performed in the Adult Bone Marrow Transplantation Unit of xxx University between January 2014 and January 2022. It included a total of 300 patients. The total number of CD34 + cells collected was 7...