title: Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma.
abstract: High-dose cyclophosphamide (Cy) is frequently employed for peripheral blood mobilization of hematopoietic stem cells before high-dose chemotherapy with autologous stem cell transplantation (ASCT) in multiple myeloma (MM). The benefit of mobilization with Cy over filgrastim (granulocyte colony-stimulating factor; G-CSF) alone is unclear. Between 2000 and 2008, 167 patients with newly diagnosed MM underwent single ASCT after melphalan conditioning at our institution. Seventy-three patients were mobilized with G-CSF alone, and 94 patients with Cy plus G-CSF (Cy+G-CSF). We retrospectively analyzed Cy's impact on both toxicity and efficacy. Mobilization efficiency was augmented by Cy; a mean total of 12 versus 5.8 × 10(6) CD34+ cells/kg were collected from patients mobilized with Cy+G-CSF versus G-CSF, respectively, (P < 0.01), over a mean of 1.6 versus 2.2 days of peripheral blood apheresis (p = 0.001). Mobilization-related toxicity was also, however, augmented by Cy; 14% of Cy+G-CSF patients were hospitalized because of complications versus none receiving G-CSF (P < 0.0001). Toxicity, including death, related to ASCT was similar between cohorts. Regarding long-term outcomes, multivariate analysis revealed no difference for Cy+G-CSF versus G-CSF (hazard ratio 0.8 for event-free survival [95% confidence interval {CI} 0.57-1.25] and 0.96 for overall survival [95% CI 0.61-1.54]). In summary, we show that mobilization with Cy increases toxicity without positively impacting long-term outcomes in MM. Our findings place into question Cy's benefit as a routine component of stem cell mobilization regimens in MM. Randomized trials are needed to elucidate the risks and benefits of Cy more definitively.
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Sascha A
authors.identifier: http://orcid.org/0000-0003-2109-1573
authors.initials: SA
authors.lastname: Tuchman
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Wendi A
authors.initials: WA
authors.lastname: Bacon
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Huang
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Gwynn
authors.initials: G
authors.lastname: Long
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, North Carolina.
authors.forename: David
authors.initials: D
authors.lastname: Rizzieri
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Horwitz
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, North Carolina.
authors.forename: John P
authors.initials: JP
authors.lastname: Chute
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Keith
authors.initials: K
authors.lastname: Sullivan
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Ashley
authors.initials: A
authors.lastname: Morris Engemann
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Amanda
authors.initials: A
authors.lastname: Yopp
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Kelly
authors.initials: K
authors.lastname: Corbet
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Nelson
authors.initials: N
authors.lastname: Chao
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gasparetto
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001781:Blood Component Removal; D003520:Cyclophosphamide / Q000627:therapeutic use*; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D016016:Proportional Hazards Models; D012074:Remission Induction; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D008558:Melphalan
keywords: autologous; cyclophosphamide; mobilization; myeloma