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Hematopoietic Cell Collection

Bendamustine, etoposide and dexamethasone to mobilize peripheral blood hematopoietic stem cells for autologous transplantation in patients with multiple myeloma

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Abstract

Chemotherapeutic agents without cross-resistance to prior therapies may enhance PBSC collection and improve patient outcomes by exacting a more potent direct antitumor effect before autologous stem cell transplant. Bendamustine has broad clinical activity in transplantable lymphoid malignancies, but concern remains over the potential adverse impact of this combined alkylator–nucleoside analog on stem cell mobilization. We performed a prospective, nonrandomized phase II study including 34 patients with multiple myeloma (MM) (n=34; International Staging System (ISS) stages I (35%), II (29%) and III (24%); not scored (13%)) to evaluate bendamustine’s efficacy and safety as a stem cell mobilizing agent. Patients received bendamustine (120 mg/m2 IV days 1, 2), etoposide (200 mg/m2 IV days 1–3) and dexamethasone (40 mg PO days 1– 4) (bendamustine, etoposide and dexamethasone (BED)) followed by filgrastim (10 μg/kg/day SC; through collection). All patients (100%) successfully yielded stem cells (median of 21.60 × 106/kg of body weight; range 9.24–55.5 × 106/kg), and 88% required a single apheresis. Six nonhematologic serious adverse events were observed in 6 patients including: neutropenic fever (1, grade 3), bone pain (1, grade 3) and renal insufficiency (1, grade 1). In conclusion, BED safely and effectively mobilizes hematopoietic stem cells.

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Acknowledgements

This study was supported by Teva Pharmaceutical Industries, NCI K08 CA151682 (to DJG), NCI P01CA44991, NCI R01CA076287, NCI R01 CA138720, 1K24CA184039, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Cancer Center Support Grant P30 CA015704 and philanthropic gifts from Frank and Betty Vandermeer. AKG is a Scholar in Clinical Research for the Leukemia and Lymphoma Society.

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Correspondence to D J Green.

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Research funding was provided by Teva Pharmaceuticals for this investigator-initiated research study. The funding was used to support the salaries of research study staff. Bendamustine was provided to patients by Teva Pharmaceuticals at no cost. Teva Pharmaceuticals played no role in the study design, the collection and analysis of the data the decision to publish this work or the writing of this manuscript. Drs Green, Gopal and Budde have received research support from Teva Pharmaceuticals. Dr Pagel has received compensation as a consultant to Teva Pharmaceuticals. The authors have no personal financial interests in Teva Pharmaceuticals and declare no other conflict of interest.

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Green, D., Bensinger, W., Holmberg, L. et al. Bendamustine, etoposide and dexamethasone to mobilize peripheral blood hematopoietic stem cells for autologous transplantation in patients with multiple myeloma. Bone Marrow Transplant 51, 1330–1336 (2016). https://doi.org/10.1038/bmt.2016.123

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