Ancestim (recombinant human stem cell factor, SCF) in association with filgrastim does not enhance chemotherapy and/or growth factor-induced peripheral blood progenitor cell (PBPC) mobilization in patients with a prior insufficient PBPC collection

Silva, M G da; Pimentel, Pedro; Carvalhais, Alzira; Barbosa, I.L.; Machado, Alex Martins; Campilho, Fernando; Sousa, Susana R.; Miranda, Nuno; Costa, Fernando Leal da; Campos, António; Vaz, Carlos Pinho; Antas, J; Passos‐Coelho, José Luís

doi:10.1038/sj.bmt.1704602

Cited by 16 publications

(5 citation statements)

References 24 publications

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“…Our results contrast with those reported by Da Silva et al, 28 who failed to demonstrate an increased mobilization efficacy using an rHuSCF-based regimen in those who had previously failed a G-CSF-based regimen. In contrast to our study, the study by Da Silva et al contained fewer patients and included patients with solid tumours.…”

Section: Discussioncontrasting

confidence: 57%

Successful mobilization of peripheral blood stem cells using recombinant human stem cell factor in heavily pretreated patients who have failed a previous attempt with a granulocyte colony-stimulating factor-based regimen

Dawson

Schwarer

Muirhead

et al. 2005

Bone Marrow Transplant

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Summary:To assess the efficacy of recombinant human stem cell factor (rHuSCF), 48 patients who had failed to mobilize 42.0 Â 10 6 CD34 þ cells/kg with granulocyte colonystimulating factor (G-CSF) (10 lg/kg twice daily) with, or without, concomitant chemotherapy (G-CSF-based regimen), were remobilized with the addition of rHuSCF (20 lg/kg/day). In all, 18/48 (38%) achieved a total of 42.0 Â 10 6 CD34 þ cells/kg with the second rHuSCFbased mobilisation alone and 29/48 (60%) achieved a cumulative total of 42.0 Â 10 6 CD34 þ cells/kg following remobilization. Inclusion of chemotherapy in the mobilization regimen resulted in a higher yield of CD34 þ cells/ kg for both the initial G-CSF-based and subsequent rHuSCF-based regimens (0.90 vs 0.54, Po0.01 and 2.36 vs 1.34, Po0.01, respectively). The total peripheral blood stem cells PBSC collected from the G-CSF-based regimen, performance status, baseline platelet count and albumin were significantly associated with successful remobilization. Patients with multiple myeloma were also more likely to successfully remobilize. There was no threshold of total collected from the failed G-CSF-based regimen below which successful remobilization with the rHuSCF-based regimen was not possible. We therefore propose a predictive model [PBSC expected ¼ 0.6 þ (G-CSF-based total collection) þ 2 (rHuSCF-based day 1 collection)] to calculate the cumulative total of PBSC expected following a maximum of five leukaphereses. This algorithm may permit the early identification of patients who are unlikely to achieve sufficient PBSC for transplantation and allow physicians to direct the resources involved in PBSC collection in a more appropriate and economical manner.

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Section: Discussioncontrasting

confidence: 57%

Successful mobilization of peripheral blood stem cells using recombinant human stem cell factor in heavily pretreated patients who have failed a previous attempt with a granulocyte colony-stimulating factor-based regimen

Dawson

Schwarer

Muirhead

et al. 2005

Bone Marrow Transplant

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“…However, because of the clear risk of toxicity related to the mast cell-activation properties of SCF (Costa et al, 1996), some subjects were excluded from clinical trials of SCF plus G-CSF either because they had a history of allergic disorders or because of adverse effects upon treatment with SCF that probably were related to effects of SCF on mast cells, which were observed even when such subjects had been pre-treated with pharmacological agents to counteract the effects of mast cell activation (Moskowitz et al, 1997). Moreover, da Silva et al reported dose-limiting mast cell-related toxicities of SCF when it was administered in amounts beyond 20 μg/kg/day, which severely impeded the adequate evaluation of the full clinical potential of SCF as an agent to enhance the development and/or mobilization of hematopoietic progenitor cells alone or in combination with G-CSF (da Silva et al, 2004). A human analog of S4-3a would likely be free from these restrictions given its narrowed pleiotropy and selectivity for hematopoietic progenitor cells.…”

Section: Dicussionmentioning

confidence: 99%

Decoupling the Functional Pleiotropy of Stem Cell Factor by Tuning c-Kit Signaling

Chhabra

Starkl

et al. 2017

Cell

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SUMMARY Most secreted growth factors and cytokines are functionally pleiotropic because their receptors are expressed on diverse cell types. While important for normal mammalian physiology, pleiotropy limits the efficacy of cytokines and growth factors as therapeutics. Stem cell factor (SCF) is a growth factor that acts through the c-Kit receptor tyrosine kinase to elicit hematopoietic progenitor expansion, but can be toxic when administered in vivo because it concurrently activates mast cells. We engineered a mechanism-based SCF partial agonist that impaired c-Kit dimerization, truncating downstream signaling amplitude. This SCF variant elicited biased activation of hematopoietic progenitors over mast cells in vitro and in vivo. Mouse models of SCF-mediated anaphylaxis, radioprotection, and hematopoietic expansion revealed that this SCF partial agonist retained therapeutic efficacy while exhibiting virtually no anaphylactic off-target effects. The approach of biasing cell activation by tuning signaling thresholds and outputs has applications to many dimeric receptor-ligand systems.

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“…We thank Dr Mijovic and colleagues for their thoughtful comments on our paper. 1 They report their experience with ancestim mobilization of PBPC in a population of 'poor mobilizers' similar to the population included in our study. In their series, seven of the 31 patients (22.5%) were able to have X2.5 Â 10 6 CD34 þ cells/kg collected in the second mobilization attempt with ancestim.…”

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confidence: 87%

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Silva¹,

Passos‐Coelho²

2005

Bone Marrow Transplant

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Ancestim (recombinant human stem cell factor, SCF) in association with filgrastim does not enhance chemotherapy and/or growth factor-induced peripheral blood progenitor cell (PBPC) mobilization in patients with a prior insufficient PBPC collection

Cited by 16 publications

References 24 publications

Successful mobilization of peripheral blood stem cells using recombinant human stem cell factor in heavily pretreated patients who have failed a previous attempt with a granulocyte colony-stimulating factor-based regimen

Successful mobilization of peripheral blood stem cells using recombinant human stem cell factor in heavily pretreated patients who have failed a previous attempt with a granulocyte colony-stimulating factor-based regimen

Decoupling the Functional Pleiotropy of Stem Cell Factor by Tuning c-Kit Signaling

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