title: Oxaliplatin-mediated increase in spleen size as a biomarker for the development of hepatic sinusoidal injury.
abstract: OBJECTIVE
  Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury, with resultant sinusoidal damage and portal hypertension. We sought to explore the relationship between oxaliplatin induced hepatic sinusoidal injury, increases in spleen size, and the subsequent development of thrombocytopenia.
  
  
  METHODS
  We retrospectively assessed the relationship between chemotherapy exposure, changes in spleen size (determined by volumetric measurements), and platelet counts in 136 patients treated with adjuvant fluorouracil and oxaliplatin (FOLFOX) or fluoropyrimidine for stage II or III colorectal adenocarcinoma. Hepatic sinusoidal injury and changes in spleen size were graded in a separate population of 63 patients with metastatic colorectal cancer receiving fluoropyrimidine and oxaliplatin before liver resection.
  
  
  RESULTS
  Spleen size increased in 86% of patients treated with adjuvant FOLFOX (P < .001), with a > or = 50% increase in 24% of patients. Spleen size did not significantly increase in patients treated with adjuvant fluoropyrimidine. Increases in spleen size correlated with cumulative oxaliplatin dose (P = .003). Patients with splenic enlargement > or = 50% had higher rates of thrombocytopenia in the first year after completion of chemotherapy (27% v 5%; P = .003). In patients with hepatic metastases treated with preoperative fluoropyrimidine and oxaliplatin, increases in spleen size was a predictor of higher histologic grades of sinusoidal injury in both univariate (P = .03) and multivariate (P = .02) analyses.
  
  
  CONCLUSIONS
  Increases in spleen size correlate with increasing grade of hepatic sinusoidal injury and can serve as a simple method for identifying patients at risk for this toxicity. Oxaliplatin-induced increases in spleen size should be recognized as a potential etiology of persistent thrombocytopenia after oxaliplatin treatment.
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. moverman@mdanderson.org
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Overman
authors.forename: Dipen M
authors.initials: DM
authors.lastname: Maru
authors.forename: Chusilp
authors.initials: C
authors.lastname: Charnsangavej
authors.forename: Evelyn M
authors.initials: EM
authors.lastname: Loyer
authors.forename: Huamin
authors.initials: H
authors.lastname: Wang
authors.forename: Priyanka
authors.initials: P
authors.lastname: Pathak
authors.forename: Cathy
authors.initials: C
authors.lastname: Eng
authors.forename: Paulo M
authors.initials: PM
authors.lastname: Hoff
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Vauthey
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.forename: Scott
authors.initials: S
authors.lastname: Kopetz
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D000077150:Oxaliplatin; D010976:Platelet Count; D011379:Prognosis; D012004:Rectal Neoplasms / Q000097:blood / Q000188:drug therapy; D012189:Retrospective Studies; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013163:Splenomegaly / Q000139:chemically induced*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin