Activation of peripheral-blood granulocytes is strongly correlated with patient outcome after immunotherapy with anti-GD2 monoclonal antibody and granulocyte-macrophage colony-stimulating factor Journal Article


Authors: Cheung, I. Y.; Hsu, K.; Cheung, N. K. V.
Article Title: Activation of peripheral-blood granulocytes is strongly correlated with patient outcome after immunotherapy with anti-GD2 monoclonal antibody and granulocyte-macrophage colony-stimulating factor
Abstract: Purpose: Adjuvant therapy using anti-GD2 monoclonal antibody and granulocyte-macrophage colonystimulating factor (GM-CSF) has shown treatment success for patients with high-risk neuroblastoma (NB). Although there is ample evidence on how the antibody targets NB, in vivo contribution by GM-CSF remains unclear. This report investigates granulocyte activation and its correlation with treatment outcome. Patients and Methods: Patients enrolled onto NCT00072358 received multiple treatment cycles, each consisting of anti-GD2 antibody 3F8 plus subcutaneous (SC) GM-CSF. Peripheral-blood (PB) samples from 151 patients were collected on day 0 and day 4 of cycle 1. PB from a subgroup of 35 patients had intravenous (IV) instead of SC GM-CSF during cycle 4. Samples were analyzed by flow cytometry for CD11a, CD63, CD87, and CD11b and its activation epitope CBRM1/5. Results: Comparing cycle 1 day 4 PB samples with day 0 PB samples, five of five activation marker-positive granulocytes were significantly higher. The change in frequency and mean fluorescence intensity of CBRM1/5-positive granulocytes correlated with progression-free survival (PFS; P=.024 and P=.008, respectively). A multivariable analysis identified increasing CBRM1/5-positive granulocytes and missing killer immunoglobulin-like receptor ligand as positive independent prognostic factors for PFS, whereas second-line cyclophosphamide- based therapy before protocol entry negatively influenced outcome. Thirty-five patients who received SC GM-CSF at cycle 1 and IV GM-CSF at cycle 4 had significantly less CBRM1/5 activation after IV GM-CSF. In contrast, 63 patients who received SC GM-CSF at both cycles had comparable CBRM1/5 activation. Conclusion: GM-CSF-induced granulocyte activation in vivo is associated with improved patient outcome. This activation was more apparent when GM-CSF was given by the SC route instead of IV route. © 2011 by American Society of Clinical Oncology.
Keywords: adult; child; preschool child; school child; treatment outcome; unclassified drug; major clinical study; clinical trial; flow cytometry; antigen expression; multiple cycle treatment; cyclophosphamide; cell population; monoclonal antibody; drug mechanism; neuroblastoma; blood sampling; cd11b antigen; epitope; killer cell immunoglobulin like receptor; isotretinoin; cell activation; leukocyte; recombinant granulocyte macrophage colony stimulating factor; granulocyte; monoclonal antibody 3f8; urokinase receptor; lymphocyte function associated antigen 1; cbrm1 epitope; cd63 antigen
Journal Title: Journal of Clinical Oncology
Volume: 30
Issue: 4
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2012-02-01
Start Page: 426
End Page: 432
Language: English
DOI: 10.1200/jco.2011.37.6236
PROVIDER: scopus
PMCID: PMC3269968
PUBMED: 22203761
DOI/URL:
Notes: --- - "Export Date: 1 March 2012" - "CODEN: JCOND" - "Source: Scopus"
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MSK Authors
  1. Nai-Kong Cheung
    430 Cheung
  2. Katharine C Hsu
    131 Hsu
  3. Irene Y Cheung
    72 Cheung