Pre-emptive plerixafor injection increases blood neutrophil, lymphocyte and monocyte counts in addition to CD34+ counts in patients with non-Hodgkin lymphoma mobilizing poorly with chemotherapy plus G-CSF: Potential implications for apheresis and graft composition

Varmavuo, Ville; Mäntymaa, Pentti; Kuittinen, Taru; Nousiainen, Tapio; Jantunen, Esa

doi:10.1016/j.transci.2012.03.011

Cited by 18 publications

(14 citation statements)

References 20 publications

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“…Several studies have shown the feasibility of a so-called justin-time approach, where plerixafor is added to G-CSF in only those patients who are likely to fail mobilization based on day 4 CD34 þ peripheral blood count. It is probable that such an approach may have lower costs; however, no published data are available [34,35]. In our current study, cost data of 2 mobilization methods employed are not available.…”

Section: Discussionmentioning

confidence: 81%

Plerixafor and Abbreviated-Course Granulocyte Colony–Stimulating Factor for Mobilizing Hematopoietic Progenitor Cells in Light Chain Amyloidosis

Dhakal

Strouse

D’Souza

et al. 2014

Biology of Blood and Marrow Transplantation

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Cytokine-based mobilization in light chain (AL) amyloidosis is frequently complicated by fluid overload, weight gain, cardiac arrhythmias, and peri-mobilization mortality. We analyzed hematopoietic progenitor cells (HPC) mobilization outcomes in 49 consecutive AL amyloidosis patients at our institution between 2004 and 2013 with granulocyte colony-stimulating factor (G) (10 μg/kg/day) (n = 25) versus an institutional protocol to limit G exposure using plerixafor (P) (.24 mg/kg s.c. starting day 3 of G 10 μg/kg) (n = 24). G+P strategy yielded higher total CD34(+) cells/kg (12.8 × 10(6) versus 6.3 × 10(6); P < .001) and CD34(+) cells/kg collected on day 1 (10.8 × 10(6) versus 4.9 × 10(6), P = .004) compared with the G cohort. More G+P patients collected ≥5 × 10(6) CD34(+) HPCs/kg (22 versus 16, P = .02) and ≥ 10 × 10(6) CD34(+) HPCs/kg (13 versus 5, P = .01). Four patients (16%) had mobilization failure with G; none with G+P. Peri-mobilization weight gain was lower with G+P strategy (median weight gain 1 versus 7 pounds, P = .009). Numbers of apheresis sessions (median, 1 versus 1, P = .52), number of hospitalization days (median, 1.1 versus 1.6, P = .52), transfusions, use of intravenous antibiotics, and cardiac arrhythmias were similar. In conclusion, our study demonstrates that upfront use of G+P as a mobilization strategy results in superior HPC collection, no mobilization failures, and less weight gain than G alone.

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Section: Discussionmentioning

confidence: 81%

Plerixafor and Abbreviated-Course Granulocyte Colony–Stimulating Factor for Mobilizing Hematopoietic Progenitor Cells in Light Chain Amyloidosis

Dhakal

Strouse

D’Souza

et al. 2014

Biology of Blood and Marrow Transplantation

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“…Many investigators [25][26][27][28][29] have shown the feasibility of a just-in-time approach, based on the day 4 CD34 þ cell level, to decide whether plerixafor should be added to an otherwise G-CSF-only mobilization to rescue patients likely to fail or have an inadequate mobilization yield. It is probable that such an approach may have a favorable cost profile; however, no convincing data, compared with an appropriately dosed chemotherapy mobilization, are available.…”

Section: Discussionmentioning

confidence: 99%

Comparable efficacy and lower cost of PBSC mobilization with intermediate-dose cyclophosphamide and G-CSF compared with plerixafor and G-CSF in patients with multiple myeloma treated with novel therapies

Awan

Kochuparambil

Falconer

et al. 2013

Bone Marrow Transplant

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Studies comparing the efficacy and cost of stem cell mobilization with intermediate-dose CY (ID-CY) and G-CSF against plerixafor and G-CSF, specifically in multiple myeloma (MM) patients treated in the novel therapy era, are not available. Eighty-eight consecutive patients undergoing mobilization with ID-CY (3-4 g/m 2 ) and G-CSF (n ¼ 55) were compared with patients receiving plerixafor and G-CSF (n ¼ 33). Compared with plerixafor, ID-CY use was associated with higher median peak peripheral blood CD34 þ cell count (68 vs 160 cells/mL, Po0.001), and CD34 þ cell yield on day 1 of collection (6.9 Â 10 6 vs 11.7 Â 10 6 cells/kg, Po0.001). Total CD34 þ cell yield was significantly higher in the ID-CY patients (median collection 16.6 Â 10 6 vs 11.6 Â 10 6 cells/kg; Po0.001). ID-CY use was associated with significantly more frequent episodes of febrile neutropenia (16.3% vs 0%; P ¼ 0.02), intravenous antibiotic use (16.3% vs 3%; P ¼ 0.03) and hospitalizations (P ¼ 0.02). The average total cost of mobilization in the plerixafor group was significantly higher compared with the ID-CY group ($28 980 vs $22 504.8; P ¼ 0.001). Our data indicate robust stem cell mobilization in MM patients treated with novel agents, with G-CSF and either ID-CY or plerixafor. When compared with plerixafor, ID-CY-containing mobilization was associated with significantly lower average total mobilization costs.

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“…In a model of pancreatic ductal carcinoma, a CXCR4 antagonist improved response to anti-PD1 treatment, which was correlated with increases in the numbers of both effector T and T Reg cells 55 (see Supplementary information S1 (table)). Plerixafor (Mozobil; AnorMED/Genzyme), a CXCR4 antagonist, is an approved immunostimulant used to mobilize haematopoietic stem cells in patients with cancer, and pharmacodynamic studies in nonHodgkin lymphoma evince that neutrophil, lymphocyte and monocyte populations all increase following its systemic administration 145 . Other CXCR4 inhibitors currently being evaluated in cancer clinical trials include TG-0054 (also known as burixafor), MSX-122, CTCE-9908, POL6326 (REF.…”

Section: Chemokinesmentioning

confidence: 99%

Big opportunities for small molecules in immuno-oncology

Adams

Smothers

Srinivasan

et al. 2015

Nat Rev Drug Discov

387

303

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The regulatory approval of ipilimumab (Yervoy) in 2011 ushered in a new era of cancer immunotherapies with durable clinical effects. Most of these breakthrough medicines are monoclonal antibodies that block protein-protein interactions between T cell checkpoint receptors and their cognate ligands. In addition, genetically engineered autologous T cell therapies have also recently demonstrated significant clinical responses in haematological cancers. Conspicuously missing from this class of therapies are traditional small-molecule drugs, which have previously served as the backbone of targeted cancer therapies. Modulating the immune system through a small-molecule approach offers several unique advantages that are complementary to, and potentially synergistic with, biologic modalities. This Review highlights immuno-oncology pathways and mechanisms that can be best or solely targeted by small-molecule medicines. Agents aimed at these mechanisms--modulation of the immune response, trafficking to the tumour microenvironment and cellular infiltration--are poised to significantly extend the scope of immuno-oncology applications and enhance the opportunities for combination with tumour-targeted agents and biologic immunotherapies.

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Pre-emptive plerixafor injection increases blood neutrophil, lymphocyte and monocyte counts in addition to CD34+ counts in patients with non-Hodgkin lymphoma mobilizing poorly with chemotherapy plus G-CSF: Potential implications for apheresis and graft composition

Cited by 18 publications

References 20 publications

Plerixafor and Abbreviated-Course Granulocyte Colony–Stimulating Factor for Mobilizing Hematopoietic Progenitor Cells in Light Chain Amyloidosis

Plerixafor and Abbreviated-Course Granulocyte Colony–Stimulating Factor for Mobilizing Hematopoietic Progenitor Cells in Light Chain Amyloidosis

Comparable efficacy and lower cost of PBSC mobilization with intermediate-dose cyclophosphamide and G-CSF compared with plerixafor and G-CSF in patients with multiple myeloma treated with novel therapies

Big opportunities for small molecules in immuno-oncology

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