Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma

J Clin Apher. 2015 Jun;30(3):176-82. doi: 10.1002/jca.21360. Epub 2014 Oct 8.

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.

Keywords: autologous; cyclophosphamide; mobilization; myeloma.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD34 / metabolism
  • Antineoplastic Agents / therapeutic use
  • Blood Component Removal
  • Cyclophosphamide / therapeutic use*
  • Databases, Factual
  • Disease-Free Survival
  • Female
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Hematopoietic Stem Cell Mobilization / methods*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Male
  • Melphalan / therapeutic use
  • Middle Aged
  • Multiple Myeloma / therapy*
  • Proportional Hazards Models
  • Remission Induction
  • Retrospective Studies
  • Transplantation Conditioning / methods
  • Treatment Outcome

Substances

  • Antigens, CD34
  • Antineoplastic Agents
  • Granulocyte Colony-Stimulating Factor
  • Cyclophosphamide
  • Melphalan