title: Low total lymphocyte count is associated with poor survival in patients with resected pancreatic adenocarcinoma receiving a GM-CSF secreting pancreatic tumor vaccine.
abstract: BACKGROUND
  Low total lymphocyte count (TLC) and lymphocyte-to-neutrophil ratio have been found to be poor prognostic indicators in several different tumor types at various stages. Although immune-based therapies are under rapid development, it is not known whether baseline complete blood counts, particularly lymphocytes, are associated with the clinical outcomes of patients receiving immunotherapies.
  
  
  METHODS
  We performed a retrospective analysis of complete blood count for 59 patients enrolled onto a phase II trial evaluating the integration of an adjuvant immunotherapy-irradiated granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting allogeneic pancreatic tumor vaccine (GVAX)-with standard chemoradiation.
  
  
  RESULTS
  After adjusting for nodal status, individuals with a TLC of <1,500 cells/mm(3) (10 patients) had significantly higher risk, both in terms of overall survival (OS) [adjusted hazard ratio 2.63, 95 % confidence interval (CI) 1.22-5.67, p = 0.013] and progression-free survival (adjusted hazard ratio 3.07, 95 % CI 1.03-6.93, p = 0.003), compared to those with a TLC of ≤ 1,500 cells/mm(3) (49 patients). Adjuvant chemoradiation significantly reduced lymphocyte counts from baseline values. Patients with suppression of their lymphocytes to <500 cells/mm(3) after chemoradiation also had shorter disease-free and OS.
  
  
  CONCLUSIONS
  Immunosuppressive conditions associated with surgical procedures and chemoradiation may affect the efficacy of immunotherapy.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Schueneman
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Sugar
authors.forename: Jennifer
authors.initials: J
authors.lastname: Uram
authors.forename: Elaine
authors.initials: E
authors.lastname: Bigelow
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Herman
authors.forename: Barish H
authors.initials: BH
authors.lastname: Edil
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Jaffee
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Laheru
mesh_terms: D000276:Adjuvants, Immunologic; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology / Q000401:mortality* / Q000628:therapy; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000401:mortality* / Q000628:therapy; D011379:Prognosis; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D000276:Adjuvants, Immunologic; D000964:Antimetabolites, Antineoplastic; D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005472:Fluorouracil
references.citation: Int J Biol Markers. 2004 Apr-Jun;19(2):135-40
references.pmid: 15255546
references.citation: N Engl J Med. 2012 Jun 28;366(26):2455-65
references.pmid: 22658128
references.citation: N Engl J Med. 2010 Aug 19;363(8):711-23
references.pmid: 20525992
references.citation: Nutrition. 1999 Oct;15(10):760-6
references.pmid: 10501289
references.citation: Clin Exp Immunol. 1977 May;28(2):315-25
references.pmid: 141353
references.citation: N Engl J Med. 2012 Jun 28;366(26):2443-54
references.pmid: 22658127
references.citation: Ann Surg. 2011 Feb;253(2):328-35
references.pmid: 21217520
references.citation: Curr Opin Urol. 2008 Mar;18(2):129-33
references.pmid: 18303531
references.citation: Surg Laparosc Endosc Percutan Tech. 2007 Aug;17(4):256-61
references.pmid: 17710044
references.citation: J Exp Med. 2004 Aug 2;200(3):297-306
references.pmid: 15289501
references.citation: HPB (Oxford). 2007;9(6):456-60
references.pmid: 18345294
references.citation: Clin Cancer Res. 2008 Mar 1;14(5):1455-63
references.pmid: 18316569
references.citation: J Gastrointest Surg. 2008 Apr;12(4):657-61
references.pmid: 18157582
references.citation: Crit Rev Oncol Hematol. 2008 Jul;67(1):27-38
references.pmid: 18356073
references.citation: J Clin Oncol. 2001 Jan 1;19(1):145-56
references.pmid: 11134207
references.citation: Surg Today. 2010 Sep;40(9):793-808
references.pmid: 20740341
references.citation: Am J Surg. 2010 Aug;200(2):197-203
references.pmid: 20122680
references.citation: J Thorac Cardiovasc Surg. 2009 Feb;137(2):425-8
references.pmid: 19185164
references.citation: World J Surg. 2012 Mar;36(3):617-22
references.pmid: 22223293
references.citation: World J Surg. 2011 Apr;35(4):868-72
references.pmid: 21312035
references.citation: Cancer Immunol Immunother. 2006 Jul;55(7):775-84
references.pmid: 16167144
references.citation: Br J Surg. 2011 Feb;98(2):268-74
references.pmid: 20960457
references.citation: Curr Opin Mol Ther. 2001 Feb;3(1):77-84
references.pmid: 11249735
references.citation: J Pediatr Hematol Oncol. 2007 Jan;29(1):48-52
references.pmid: 17230066
references.citation: N Engl J Med. 2010 Jul 29;363(5):411-22
references.pmid: 20818862
references.citation: JAMA. 2008 Mar 5;299(9):1019-26
references.pmid: 18319412
references.citation: Clin Cancer Res. 2011 Aug 15;17(16):5473-80
references.pmid: 21737504
references.citation: Cancer Invest. 2012 Oct;30(8):571-6
references.pmid: 22812722
references.citation: Cancer Immunol Immunother. 2003 Nov;52(11):680-5
references.pmid: 12955481