title: Lymphopenia and its association with survival in patients with locally advanced cervical cancer.
abstract: OBJECTIVE
  To evaluate the association between lymphopenia and survival in women with cervical cancer treated with primary chemoradiation.
  
  
  METHODS
  A single institution, retrospective analysis of patients with stage IB2-IVA cervical cancer who received upfront chemoradiation from 1998 to 2013 was performed. Complete blood counts from pre-treatment to 36 months post-treatment were analyzed. Lymphopenia and known prognostic factors were evaluated for an association with progression-free (PFS) and overall survival (OS).
  
  
  RESULTS
  Seventy-one patients met study criteria for whom 47 (66%) had a documented total lymphocyte count (TLC) two months after initiating chemoradiation. FIGO stage distribution was 6% Stage I, 46% Stage II, 45% Stage III and 3% Stage IV. Pre-treatment TLC was abnormal (<1000 cells/mm3) in 15% of patients. The mean reduction in TLC was 70% two months after initiating chemoradiation. Severe post-treatment lymphopenia (TLC <500 cells/mm3) was observed in 53% of patients; they experienced inferior median OS (21.2 vs. 45.0 months, P=0.03) and similar 25th percentile PFS (6.3 vs. 7.7 months, P=0.06) compared to patients without severe lymphopenia. Multivariate analysis demonstrated pre-treatment TLC ≥1000 cells/mm3 and post-treatment TLC >500 cells/mm3 had a 77% (HR: 0.23; 95% CI 0.05-1.03; P=0.053) and 58% decrease in hazards of death (HR: 0.42; 95%CI 0.12-1.46; P=0.17) respectively.
  
  
  CONCLUSIONS
  More than half of cervical cancer patients treated with chemoradiation experienced severe and prolonged lymphopenia. Although statistical significance was not reached, the findings suggest that pre- and post-treatment lymphopenia may be associated with decreased survival. Further research is warranted, given that lymphopenia could be a reversible prognostic factor.
authors.affiliation: Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, Johns Hopkins Hospital School of Public Health, Baltimore, MD, USA.
authors.forename: Titilope
authors.initials: T
authors.lastname: Oduyebo
authors.affiliation: Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Lauren P
authors.initials: LP
authors.lastname: Cobb
authors.affiliation: Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Cholakian
authors.affiliation: Department of Epidemiology, Johns Hopkins Hospital School of Public Health, Baltimore, MD, USA.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Kong
authors.affiliation: Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Amanda N
authors.initials: AN
authors.lastname: Fader
authors.affiliation: Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Levinson
authors.affiliation: Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Tanner
authors.affiliation: Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Stone
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Piotrowski
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Grossman
authors.affiliation: Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Kara Long
authors.initials: KL
authors.lastname: Roche
mesh_terms: D000328:Adult; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008231:Lymphopenia / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D002583:Uterine Cervical Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*
keywords: Cervical cancer; Chemoradiation; Lymphopenia