G-CSF plus plerixafor (Mozobil) to mobilize hematopoietic stem cells in patients with thrombocytopenia or leukopenia prior to auto-SCT

Micallef, Ivana N.; Jacobsen, Eric; Shaughnessy, Paul; Gandhi, Pritesh J.; Calandra, Gary B.; Rhee, Frits van; Uberti, Joseph P.

doi:10.1038/bmt.2012.125

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…However, at the last follow-up visit MM cells were no longer detectable in 7 of 10 patients (4 patients from the G-CSF alone and 3 patients from the G-CSF + plerixafor arm). AEs observed in the G-CSF + plerixafor arm of the study were consistent with the known safety profile of plerixafor, with no new safety concerns detected [7,18,19,[21][22][23]25,[29][30][31].…”

Section: Discussionsupporting

confidence: 78%

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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Section: Discussionsupporting

confidence: 78%

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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“…Neither of these strategies seems to make a lot of sense and, thus, the majority of programs have been left to decide how best to balance the pros of plerixafor (efficacy, predictability, and relative safety) with its cons (cost and relative inconvenience due to timing of administration). The recent deluge of manuscripts published following Food and Drug Administration approval of plerixafor focusing on its potential clinical benefits or cost effectiveness relative to chemotherapy based mobilization have facilitated the development of individual strategies, but in the end there is still some guesswork involved [3][4][5][6][7][8]. A publication by Nademanee et al [9] in this issue of Blood and Bone Marrow Transplantation should, hopefully, take some of that guesswork out of the equation.…”

Section: Toward a More Rational Policy For Autologous Hematopoietic Smentioning

confidence: 99%

Toward a More Rational Policy for Autologous Hematopoietic Stem Cell Mobilization

Devine

2012

Biology of Blood and Marrow Transplantation

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CXCL12-Abundant Reticular (CAR) Cells Direct Megakaryocyte Protrusions across the Bone Marrow Sinusoid Wall

Wagner

Mott

Upcin

et al. 2021

Cells

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Megakaryocytes (MKs) release platelets into the lumen of bone marrow (BM) sinusoids while remaining to reside within the BM. The morphogenetic events of this complex process are still not fully understood. We combined confocal laser scanning microscopy with transmission and serial block-face scanning electron microscopy followed by 3D-reconstruction on mouse BM tissue sections. These analyses revealed that MKs in close vicinity to BM sinusoid (BMS) wall first induce the lateral retraction of CXCL12-abundant reticular (CAR) cells (CAR), followed by basal lamina (BL) degradation enabling direct MK-sinusoidal endothelial cells (SECs) interaction. Subsequently, an endothelial engulfment starts that contains a large MK protrusion. Then, MK protrusions penetrate the SEC, transmigrate into the BMS lumen and form proplatelets that are in direct contact to the SEC surface. Furthermore, such processes are induced on several sites, as observed by 3D reconstructions. Our data demonstrate that MKs in interaction with CAR-cells actively induce BMS wall alterations, including CAR-cell retraction, BL degradation, and SEC engulfment containing a large MK protrusion. This results in SEC penetration enabling the migration of MK protrusion into the BMS lumen where proplatelets that are adherent to the luminal SEC surface are formed and contribute to platelet release into the blood circulation.

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G-CSF plus plerixafor (Mozobil) to mobilize hematopoietic stem cells in patients with thrombocytopenia or leukopenia prior to auto-SCT

Cited by 3 publications

References 9 publications

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

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

Toward a More Rational Policy for Autologous Hematopoietic Stem Cell Mobilization

CXCL12-Abundant Reticular (CAR) Cells Direct Megakaryocyte Protrusions across the Bone Marrow Sinusoid Wall

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