Plerixafor plus pegfilgrastim is a safe, effective mobilization regimen for poor or adequate mobilizers of hematopoietic stem and progenitor cells: a phase I clinical trial

Herbert, Kirsten; Demosthenous, Lisa Catherine; Wiesner, Glen; Westerman, David; Came, Neil; Ritchie, David; Harrison, Simon J.; Seymour, John F.; Prince, H. Miles

doi:10.1038/bmt.2014.112

Cited by 11 publications

(7 citation statements)

References 28 publications

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“… 76 Combining plerixafor with pegfilgrastim or with mobilizing chemotherapy seems safe and effective in PMs, but these results require confirmative data. 77 The main disadvantage of plerixafor is its cost, requiring the development of algorithms for the use of plerixafor in autologous HSPC mobilization. 78 …”

Section: Pb Hspc Harvesting: Mobilization and Apheresis Techniquesmentioning

confidence: 99%

Hematopoietic stem and progenitor cell harvesting: technical advances and clinical utility

Héquet¹

2015

JBM

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Hematopoietic stem and progenitor cell (HSPC) transplantations require prior harvesting of allogeneic or autologous HSPCs. HSPCs are usually present in bone marrow (BM) during the entire life, in cord blood (CB) at birth, or in peripheral blood (PB) under particular circumstances. HSPCs were first harvested in BM and later in CB and PB, as studies showed interesting features of such grafts. All harvesting methods were in use throughout the years, except BM harvesting for HSPC autologous transplantation, which was replaced by PB harvesting. BM, CB, and PB harvesting methods have been developed, and materials and devices technically improved to increase the number of HSPCs harvested. In parallel, knowing the features of the donors or patients associated with successful numbers of HSPCs allows the adaptation of appropriate harvesting methods. Moreover, it is important to ensure the safety of donors or patients while harvesting. This review describes the methods used for harvesting based on recent studies or developments around these methods, and more particularly, the means developed to increase the numbers of HSPCs harvested in each method. It also explains briefly the influence of technical improvements in HSPC harvesting on potential changes in HSPC graft composition.

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Section: Pb Hspc Harvesting: Mobilization and Apheresis Techniquesmentioning

confidence: 99%

Hematopoietic stem and progenitor cell harvesting: technical advances and clinical utility

Héquet¹

2015

JBM

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“…The effect of G-CSF plus plerixafor on tumor cell contamination of peripheral blood and apheresis product has been investigated in several studies [6,7,27,28]. One study of 12 patients (10 patients with lymphoma and 2 patients with myeloma) treated with plerixafor + G-CSF for stem cell mobilization showed no detectable tumor cells were present in the peripheral blood or apheresis product [6]. This finding was supported by the findings from another study that showed the absence of tumor cell mobilization after treatment with G-CSF and plerixafor in myeloma patients known to be poor mobilizers [7].…”

Section: Discussionmentioning

confidence: 99%

“…Concerns have been raised that agents that mobilize cells using the CXCR-4/CXCL12 interaction may theoretically also mobilize tumor cells [5,6]. The likelihood of tumor cell mobilization in peripheral blood and apheresis product at the same time of CD34 + cell mobilization continues to be controversial [7].…”

Section: Introductionmentioning

confidence: 99%

A Pilot, Exploratory, Randomized, Phase II Safety Study Evaluating Tumor Cell Mobilization and Apheresis Product Contamination in Patients Treated with Granulocyte Colony-Stimulating Factor Alone or Plus Plerixafor

Nahi

Celanovic

Liu

et al. 2019

Biology of Blood and Marrow Transplantation

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Because of the potential risk of tumor cell mobilization with granulocyte colony-stimulating factor (G-CSF), it is crucial to evaluate any potential effect of plerixafor treatment in the presence of G-CSF on multiple myeloma (MM) cell mobilization. This was an open-label, multicenter, randomized, exploratory, safety study (NCT01753453) that investigated the extent of MM cell mobilization after treatment with G-CSF + plerixafor in patients who were deemed poor mobilizers of hematopoietic stem cells. The primary efficacy outcome was the number of MM cells in peripheral blood and apheresis product after G-CSF + plerixafor treatment versus G-CSF alone. Key secondary efficacy outcomes included overall survival and disease status up to 2years after the first G-CSF dose. Twenty patients were randomized and received at least 1 dose of study treatment. There were no patients with MM cells in peripheral blood up to day 8 G-CSF administration in either treatment group. Up to day 8 no patient in the G-CSF + plerixafor arm and only 1 patient in the G-CSF arm mobilized at least 4.5 × 10 MM cells in the apheresis product. Nine of 10 patients from each treatment arm proceeded to transplantation. MM cells were detected in 5 patients from each treatment arm before and after transplantation. Adverse events observed in the G-CSF + plerixafor arm were consistent with the known safety profile of plerixafor. No MM cells were detected in peripheral blood of either treatment group up to day 8 of mobilization. Only 1 patient in the G-CSF alone group mobilized at least 4.5 × 10 MM tumor cells in apheresis product up to day 8. However, 50% of patients in both treatment arms had detectable amounts of MM cells in their peripheral blood pre- and post-transplantation. There were no new safety concerns with plerixafor.

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“…Even though the effect on HIV was quite disappointing, its ability to block the hematopoietic stem cell homing mechanism was noteworthy. Today, plerixafor is administered as a safe and efficient stem cell mobilizer during autologous or allogeneic stem cell collection [ 65 ].…”

Section: Strategies To Overcome Viral Reboundmentioning

confidence: 99%

CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape

Hütter

Bodor

Ledger

et al. 2015

Viruses

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Allogeneic transplantation with CCR5-delta 32 (CCR5-d32) homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a wider population. There are two cellular ways to do this. The first one is to use a CCR5 negative cell source e.g., hematopoietic stem cells (HSC) to copy the initial finding. However, a recent case of a second allogeneic transplantation with CCR5-d32 homozygous stem cells suffered from viral escape of CXCR4 quasi-species. The second way is to knock down CCR5 expression by gene therapy. Currently, there are five promising techniques, three of which are presently being tested clinically. These techniques include zinc finger nucleases (ZFN), clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9), transcription activator-like effectors nuclease (TALEN), short hairpin RNA (shRNA), and a ribozyme. While there are multiple gene therapy strategies being tested, in this review we reflect on our current knowledge of inhibition of CCR5 specifically and whether this approach allows for consequent viral escape.

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Plerixafor plus pegfilgrastim is a safe, effective mobilization regimen for poor or adequate mobilizers of hematopoietic stem and progenitor cells: a phase I clinical trial

Cited by 11 publications

References 28 publications

Hematopoietic stem and progenitor cell harvesting: technical advances and clinical utility

Hematopoietic stem and progenitor cell harvesting: technical advances and clinical utility

A Pilot, Exploratory, Randomized, Phase II Safety Study Evaluating Tumor Cell Mobilization and Apheresis Product Contamination in Patients Treated with Granulocyte Colony-Stimulating Factor Alone or Plus Plerixafor

CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape

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