title: A randomized study comparing chemotherapy followed by G-CSF alone or in combination with GM-CSF for mobilization of peripheral blood stem cells in patients with non-Hodgkin's lymphomas.
abstract: OBJECTIVE
  Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) are the two most commonly used cytokines for mobilization of stem cells in patients undergoing high dose chemotherapy with stem cell support. Both cytokines increase the peripheral blood white blood cell count and the stem cell count but there are other differences in the stem cell products mobilized by G-CSF versus those mobilized with GM-CSF. Generally higher numbers of dendritic cells are mobilized with GM-CSF than by G-CSF. The primary objective of this randomized study was to evaluate the safety and efficacy of chemotherapy plus G-CSF versus chemotherapy plus G-CSF and GM-CSF in patients with B-cell non-Hodgkin's lymphoma (NHL) who were undergoing chemo-mobilization. Secondary objectives were to determine the expression of various dendritic cell subsets in the two groups and to determine the incidence of disease progression or relapse at 12 months.
  
  
  METHODS
  We prospectively evaluated 84 patients with relapsed NHL who were candidates for high dose therapy (HDT). All patients underwent chemo-mobilization using ifosfamide, etoposide, and rituximab. All patients were randomized in an adaptive manner to receive either G-CSF or G-CSF plus GM-CSF (G+GM) starting 24 hours after completion of chemotherapy and continuing until completion of apheresis. The stem cell yield/kg, the number of apheresis procedures needed in the two groups, and the toxicity were recorded. We also enumerated dendritic cell subsets, myeloid DCs (mDC) and plasmacytoid DCs (pDC), in apheresis products and in peripheral blood (PB) samples collected pre-chemotherapy. The data were expressed as a percentage of peripheral blood mononuclear cells.
  
  
  RESULTS
  A total of 84 patients were treated. Forty-three patients received G-CSF and 41 received G+GM. Both regimens were well tolerated. The median CD34+ cell dose collected was similar in the two groups. A total of 54 (G-CSF N = 25 and G+GM N = 29) paired samples from baseline and post-apheresis were available for analysis of dendritic cell subsets. There was no significant difference in the percentages of mDC subsets between baseline and post-apheresis collected with G-CSF or G+GM mobilization. However, there was a significant increase in the percentage of pDC subsets in the G-CSF alone when compared to the G+GM arm (P = 0.002). Furthermore, the ratio of mDC and pDC was significantly lower after mobilization with G-CSF versus G+GM (P = 0.029).
  
  
  CONCLUSIONS
  Addition of GM-CSF to G-CSF to the mobilization regimen resulted in lower percentages of pDC in the apheresis products when compared to those with G-CSF alone. This shifts the mDC/pDC ratio in the apheresis grafts in favor of mDC in the combination arm. However, these differences did not seem to impact the clinical outcomes in the two groups. (ClinicalTrials.gov Identifier: NCT00499343).
authors.affiliation: Stem Cell Transplantation and Cellular Therapy.
authors.forename: Chitra
authors.initials: C
authors.lastname: Hosing
authors.forename: Mark F
authors.initials: MF
authors.lastname: Munsell
authors.forename: James M
authors.initials: JM
authors.lastname: Reuben
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authors.lastname: Popat
authors.forename: Bang-Ning
authors.initials: BN
authors.lastname: Lee
authors.forename: Hui
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authors.lastname: Gao
authors.forename: Martin
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authors.lastname: Körbling
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.forename: Partow
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authors.lastname: Alousi
authors.forename: Marcos
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authors.lastname: De Lima
authors.forename: John
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authors.lastname: McMannis
authors.forename: Muzaffar
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authors.lastname: Qazilbash
authors.forename: Paolo
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authors.lastname: Anderlini
authors.forename: Sergio
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authors.lastname: Giralt
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.forename: Issa
authors.initials: I
authors.lastname: Khouri