title: The impact of chemotherapy-associated neutrophil/ lymphocyte counts on prognosis of adjuvant chemotherapy in colorectal cancer.
abstract: BACKGROUND
  Leukocytes play an important role in cancer development. However, the impact of chemotherapy-associated neutropenia/lymphopenia on the prognosis of adjuvant chemotherapy is unknown. Here, we aimed to explore the impact of chemotherapy-associated neutrophil/lymphocyte counts on prognosis of adjuvant chemotherapy in colorectal cancer (CRC) and the risk factors for developing neutropenia/lymphopenia which showed impact on the prognosis of CRC receiving adjuvant chemotherapy.
  
  
  METHODS
  From February 2003 to January 2011, 243 stage II and III CRC patients receiving adjuvant chemotherapy were enrolled in this retrospective study. The associations between neutrophil/ lymphocyte counts and disease free survival (DFS)/overall survival (OS) of CRC, and the risk factors for neutropenia/lymphopenia were investigated.
  
  
  RESULTS
  No association of chemotherapy-associated neutrophil counts and CRC recurrence (AUC = 0.474, P = 0.534), death (AUC = 0.449, P = 0.249) was found by ROC analysis. However, the chemotherapy-associated lymphocyte counts could significantly affect CRC recurrence (AUC = 0.634, P = 0.001), or death(AUC = 0.607, P = 0.015), with a optimized cut-off of 0.66 × 10(9)/L for recurrence, and 0.91 × 10(9)/L for death, respectively. Kaplan-Meier method showed chemotherapy-associated lymphopenia <0.66 × 10(9)/L was associated with shorter DFS (P < 0.0001), and chemotherapy-associated lymphopenia <0.91 × 10(9)/L was associated with shorter OS (P = 0.003). Cox regression model showed chemotherapy-associated lymphopenia <0.66 × 10(9)/L was the independent prognostic factor for DFS (HR, 3.521; 95%CI = 1.703-7.282), and chemotherapy-associated lymphopenia <0.91 × 10(9)/L was the independent prognostic factor for OS (HR, 2.083; 95% CI = 1.103-3.936). Multivariate logistic regression showed the risk of developing chemotherapy-associated lymphopenia <0.66 × 10(9)/L was found in those with pretreatment CEA ≥10 ng ml(-1) (OR, 3.338; 95% CI = 1.523-7.315), and the risk of developing chemotherapy-associated lymphopenia <0.91 × 10(9)/L was found in those with age >60 years (OR, 2.872; 95% CI = 1.344-6.136).
  
  
  CONCLUSIONS
  Chemotherapy-associated lymphopenia <0.66 × 10(9)/L /0.91 × 10(9)/L has a significant impact on the prognosis of CRC receiving adjuvant chemotherapy. Pretreatment CEA ≥10 ng ml(-1) is the independent risk factor for developing lymphopenia <0.66 × 109/L, and age >60 years is the independent risk factor for developing lymphopenia <0.91 × 10(9)/L during adjuvant chemotherapy of CRC.
authors.affiliation: Department of Gastrointestinal Surgery, Lab of Surgery, the Second Affiliated Hospital of Guangzhou Medical University, 250 Chang-gang-dong Road, Guangzhou 510260Guangdong Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chu-Yuan
authors.forename: Peng
authors.initials: P
authors.lastname: Jing
authors.forename: Wei
authors.initials: W
authors.lastname: Yi-Sheng
authors.forename: Peng
authors.initials: P
authors.lastname: He-Ping
authors.forename: Yang
authors.initials: Y
authors.lastname: Hui
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chu-Xiong
authors.forename: Liang
authors.initials: L
authors.lastname: Guo-Jian
authors.forename: Wang
authors.initials: W
authors.lastname: Guo-Qiang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008214:Lymphocytes; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D009504:Neutrophils; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D055815:Young Adult
references.citation: Cancer Chemother Pharmacol. 2011 Nov;68(5):1305-13
references.pmid: 21448592
references.citation: Drugs. 2003;63(2):217-36
references.pmid: 12515569
references.citation: Lancet Oncol. 2008 Aug;9(8):730-56
references.pmid: 18639491
references.citation: Rev Med Interne. 2011 May;32(5):275-82
references.pmid: 21112131
references.citation: J Clin Oncol. 2005 Oct 20;23(30):7518-28
references.pmid: 16172461
references.citation: In Vivo. 2005 Nov-Dec;19(6):1077-80
references.pmid: 16277025
references.citation: J Clin Oncol. 1998 Feb;16(2):427-33
references.pmid: 9469325
references.citation: Eur J Cancer. 2009 Mar;45(5):866-73
references.pmid: 19136250
references.citation: N Engl J Med. 2003 Jul 17;349(3):247-57
references.pmid: 12867608
references.citation: Br J Cancer. 2010 Aug 10;103(4):482-5
references.pmid: 20664593
references.citation: Ai Zheng. 2008 Mar;27(3):225-30
references.pmid: 18334108
references.citation: BMC Cancer. 2010 Feb 21;10:50
references.pmid: 20170547
references.citation: BMC Cancer. 2010 Jan 12;10:12
references.pmid: 20067635
references.citation: PLoS One. 2006 Dec 27;1:e124
references.pmid: 17205128
references.citation: Blood. 2004 Feb 1;103(3):1050-8
references.pmid: 14525778
references.citation: Anticancer Res. 2007 Jan-Feb;27(1B):627-33
references.pmid: 17348452
references.citation: Cancer Res. 2009 Jul 1;69(13):5383-91
references.pmid: 19549917
references.citation: J Clin Oncol. 2007 Mar 1;25(7):767-72
references.pmid: 17228023
references.citation: J Hematol Oncol. 2011 Aug 15;4:34
references.pmid: 21843362
references.citation: Anticancer Drugs. 2004 Feb;15(2):137-43
references.pmid: 15075669
references.citation: Curr Med Chem. 2011;18(34):5172-3
references.pmid: 22172024
references.citation: Adv Drug Deliv Rev. 2009 May 20;61(5):375-80
references.pmid: 19100300
references.citation: Nutrition. 2010 Oct;26(10):1021-8
references.pmid: 20036516
references.citation: N Engl J Med. 2004 Jun 3;350(23):2343-51
references.pmid: 15175436
references.citation: Zhonghua Yi Xue Za Zhi. 2007 Jul 24;87(28):1950-3
references.pmid: 17923029
references.citation: Ann Oncol. 2006 Dec;17(12):1810-7
references.pmid: 16971666
references.citation: Cancer Immunol Immunother. 2012 Jan;61(1):79-88
references.pmid: 21847632
references.citation: Bone Marrow Transplant. 1999 Apr;23(8):783-8
references.pmid: 10231140
references.citation: J Bone Joint Surg Br. 2009 Jun;91(6):835-42
references.pmid: 19483243
references.citation: Blood. 2007 Mar 1;109(5):2086-8
references.pmid: 17053062
references.citation: J Clin Oncol. 2009 Jul 1;27(19):3109-16
references.pmid: 19451431
references.citation: Nat Rev Immunol. 2011 Jul 25;11(8):519-31
references.pmid: 21785456
references.citation: Nat Rev Cancer. 2006 Jan;6(1):24-37
references.pmid: 16397525
references.citation: BMC Cancer. 2011 Feb 10;11:64
references.pmid: 21306650
references.citation: J Clin Oncol. 2003 Jan 15;21(2):241-50
references.pmid: 12525515
references.citation: Int J Cancer. 2009 Sep 1;125(5):1092-101
references.pmid: 19391137