Granulocyte colony-stimulating factor (G-CSF) dose-dependent efficacy in peripheral blood stem cell mobilization in patients who had failed initial mobilization with chemotherapy and G-CSF

Lie, Albert K. W.; Hui, Chi-Hung; Rawling, T.; Dyson, P. G.; Thorp, D.; Benic, J.; Rawling, C. M.; Toogood, Ian; Horvath, Noemi; Simmons, Paul J.; To, LB

doi:10.1038/sj.bmt.1701463

Cited by 48 publications

(26 citation statements)

References 10 publications

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“…In a previous report we described that doubling the dose of filgrastim led to successful mobilization in six of 10 patients who had failed a prior mobilization with filgrastimplus-chemotherapy or filgrastim-only. 13 Further, patients enrolled in this filgrastim dose escalation program continued to show a 50% success rate (data not shown). While a comparison between these two options is still to be performed, rHuSCF may enhance mobilization using nonfilgrastim-dependent pathways and may be useful even in patients who fail mobilization with filgrastim.…”

Section: Discussionmentioning

confidence: 97%

“…12 While it is not ethical to repeat mobilization procedures in patients who have sufficient stem cells for transplantation, repeat mobilization studies may be done in patients who fail to mobilize sufficient cells for transplantation. 13 This design would avoid the confounding effect of interpatient differences and tests rHuSCF's efficacy by comparing the mobilization yield with and without rHuSCF in the same patient. Using a prior mobilization in the same patient as a historical control should provide a powerful way to study the efficacy of mobilization regimens.…”

Section: Discussionmentioning

confidence: 99%

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Successful mobilization of peripheral blood stem cells after addition of ancestim (stem cell factor) in patients who had failed a prior mobilization with filgrastim (granulocyte colony-stimulating factor) alone or with chemotherapy plus filgrastim

Bashford

Durrant

et al. 2003

Bone Marrow Transplant

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Summary:This study assessed the ability of recombinant human stem cell factor (rHuSCF) to mobilize stem cells in 44 patients who had failed a prior mobilization (CD34 + yield 0.5-1.9 Â 10 6 /kg BW) with filgrastim-alone or chemotherapyplus-filgrastim. The same mobilization regimen was used with the addition of rHuSCF. In the filgrastim-alone group (n ¼ 13), rHuSCF 20 lg/kg was started 3 days before filgrastim and continued for the duration of filgrastim. In the chemotherapy-plus-filgrastim group (n ¼ 31), rHuSCF 20 lg/kg/day plus filgrastim 5-10 lg/ kg/day were administered concurrently. Leukaphereses were continued to a maximum of four procedures or a target of X3 Â 10 6 CD34 + cells/kg. In both groups, CD34 + yield ( Â 10 6 /kg BW) of the study mobilization was higher than that of the prior mobilization (median: 2.42 vs 0.84 P ¼ 0.002 and 1.64 vs 0.99 P ¼ o0.001, respectively). In all 54 and 45% of patients in the filgrastim-alone group and chemotherapy-plus-filgrastim group, respectively, reached the threshold yield of 2 Â 10 6 / kg. The probability of a successful mobilization was the same in those with a CD34+ yield of 0.5-0.75 Â 10 6 /kg BW in the prior mobilization as in those with 0.76-1.99 Â 10 6 /kg BW. Downmodulation of c-kit expression and a lower percentage of Thy-1 positivity in the mobilized CD34 + cells were noted in the successful mobilizers compared with those in the poor mobilizers. This study shows that rhuSCF is effective in approximately half the patients who had failed a prior mobilization and allows them to proceed to transplant. It also points to the likely role of the SCF/c-kit ligand pair in mobilization.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Successful mobilization of peripheral blood stem cells after addition of ancestim (stem cell factor) in patients who had failed a prior mobilization with filgrastim (granulocyte colony-stimulating factor) alone or with chemotherapy plus filgrastim

Bashford

Durrant

et al. 2003

Bone Marrow Transplant

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“…Approaches to failed mobilization after conventional regimens include increased doses of G-CSF 120 or combination with SCF. 39,40,121,122 However, the success rate is often still Ͻ 50%.…”

Section: Strategies To Improve the Likelihood Of Success In Poor Mobimentioning

confidence: 99%

How I treat patients who mobilize hematopoietic stem cells poorly

Levesque

Herbert

2011

Blood

218

235

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Transplantation with 2-5 ؋ 10 6 mobilized CD34 ؉ cells/kg body weight lowers transplantation costs and mortality. Mobilization is most commonly performed with recombinant human G-CSF with or without chemotherapy, but a proportion of patients/donors fail to mobilize sufficient cells. BM disease, prior treatment, and age are factors influencing mobilization, but genetics also contributes. Mobilization may fail because of the changes affecting the HSC/progenitor cell/BM niche integrity and chemotaxis. Poor mobilization affects patient outcome and increases resource use. Until recently increasing G-CSF dose and adding SCF have been used in poor mobilizers with limited success. However, plerixafor through its rapid direct blockage of the CXCR4/CXCL12 chemotaxis pathway and synergy with G-CSF and chemotherapy has become a new and important agent for mobilization. Its efficacy in upfront and failed mobilizers is well established.To maximize HSC harvest in poor mobilizers the clinician needs to optimize current mobilization protocols and to integrate novel agents such as plerixafor. These include when to mobilize in relation to chemotherapy, how to schedule and perform apheresis, how to identify IntroductionHematopoietic stem cell transplantation (HSCT) has revolutionized the curative approach to a number of malignancies and BM failure syndromes by providing hematopoietic and immune rescue after high-dose cytoreductive therapy and, in allogeneic transplantations, graft-versus-tumor effect. [1][2][3][4] The term "mobilization" was first used to describe a 4-fold increase of circulating myeloid progenitors (granulocyte macrophage CFU [CFU-GM]) after the administration of endotoxin to healthy volunteers in 1977. 5 High levels of CFU-GM after recovery from myelosuppressive chemotherapy in humans was first described in 1976. 6 However, it was not until the 1980s that the use of chemotherapy-mobilized HSCs for transplantation was established. [7][8][9] Subsequently, a single high-dose cyclophosphamide was developed as a generic mobilizer. 10 Prof Metcalf led the study that showed the potential of G-CSF in mobilization. 11 Subsequently, 2 Australian centers in Melbourne and Adelaide showed for the first time the use of G-CSF-mobilized HSCs for transplantation, 12 and reports of combined G-CSF and chemotherapy mobilization soon followed. 13 Now, virtually all autologous and three-quarters of allogeneic transplantations are performed with mobilized HSCs (CIBMTR reports). 14,15 The cell dose effect of HSCT describes a threshold of HSCs that, when transplanted, is associated with rapid and sustained blood count recovery. 16 The benefits of rapid recovery are reduced hospitalization, blood product usage, and infections. 12,17 The minimum threshold for autologous transplantation is currently defined as 2 ϫ 10 6 CD34 ϩ cells/kg body weight (BW). 18 Many centers use a minimum of 3 ϫ 10 6 CD34 ϩ cells/kg BW for myeloablative and nonmyeloablative allogeneic and matched unrelated transplantations. Furthermore, Ͼ 5 ϫ 10 6 CD3...

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“…35,36 However, remobilization with dose escalation of G-CSF alone has resulted in more favourable outcomes. 37,38 A randomized control trial of remobilization, comparing dose escalation of G-CSF alone with an rHuSCF-based regimen needs to be conducted. This will allow the evaluation of the merits of rHuSCF with respect to cost and efficacy in heavily pre-treated patients and also permit the validation of the predictive model proposed in this study.…”

Section: Discussionmentioning

confidence: 99%

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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Granulocyte colony-stimulating factor (G-CSF) dose-dependent efficacy in peripheral blood stem cell mobilization in patients who had failed initial mobilization with chemotherapy and G-CSF

Cited by 48 publications

References 10 publications

Successful mobilization of peripheral blood stem cells after addition of ancestim (stem cell factor) in patients who had failed a prior mobilization with filgrastim (granulocyte colony-stimulating factor) alone or with chemotherapy plus filgrastim

Successful mobilization of peripheral blood stem cells after addition of ancestim (stem cell factor) in patients who had failed a prior mobilization with filgrastim (granulocyte colony-stimulating factor) alone or with chemotherapy plus filgrastim

How I treat patients who mobilize hematopoietic stem cells poorly

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

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