Blood graft cellular composition and posttransplant outcomes in myeloma patients mobilized with or without low-dose cyclophosphamide: a randomized comparison

Transfusion. 2016 Jun;56(6):1394-401. doi: 10.1111/trf.13574. Epub 2016 Apr 4.

Abstract

Background: Autologous stem cell transplantation is a standard treatment in multiple myeloma (MM). Blood grafts are usually collected after mobilization with granulocyte-colony-stimulating factor (G-CSF) alone or in a combination with cyclophosphamide (CY). There is limited knowledge of the possible effects of different mobilization regimens on blood graft characteristics and posttransplant outcomes.

Study design and methods: Thirty-eight patients with MM were included in this study. The patients were randomly assigned at registration to mobilization with either low-dose CY plus G-CSF (Arm A) or G-CSF alone (Arm B) and received three cycles of lenalidomide, bortetzomib, and dexamethasone induction. Flow cytometry analysis of lymphocyte subsets in the blood grafts after cryopreservation was performed. Hematologic and immune recovery were evaluated up to 12 months posttransplant.

Results: The blood grafts in Arm A contained significantly more CD34+ cells but in Arm B there was a greater proportion of CD34+CD38- cells and higher numbers of T and B lymphocytes as well as natural killer (NK) cells. The engraftment was comparable but lymphocyte count at 15 days posttransplant was higher in Arm B (0.8 × 10(9) /L vs. 0.5 × 10(9) /L, p = 0.033). At 3 and 6 months posttransplant the total number of NK cells was also higher in G-CSF-mobilized patients. There was no difference in progression-free survival between the study arms.

Conclusion: CY plus G-GSF yields more CD34+ cells but seems to diminish lymphocyte and NK cell counts in the grafts and hampers immune recovery after transplantation. Thus G-CSF alone might be a preferred mobilization method due to more rapid immune recovery posttransplant.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD34 / analysis
  • Autografts / cytology*
  • Cyclophosphamide / pharmacology
  • Cyclophosphamide / therapeutic use*
  • Female
  • Graft Survival
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Hematopoietic Stem Cell Mobilization / methods*
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Killer Cells, Natural / cytology
  • Lymphocyte Count
  • Lymphocyte Subsets / cytology
  • Male
  • Middle Aged
  • Multiple Myeloma / therapy*
  • Transplantation, Autologous

Substances

  • Antigens, CD34
  • Granulocyte Colony-Stimulating Factor
  • Cyclophosphamide