title: Oxaliplatin Immune-Induced Syndrome Occurs With Cumulative Administration and Rechallenge: Single Institution Series and Systematic Review Study.
abstract: Oxaliplatin immune-induced syndrome (OIIS) is an uncommon, potentially life-threatening, side effect associated with oxaliplatin-based chemotherapy. The present study reports 5 original cases of OIIS and systematically reviewed the available published cases. We retrospectively analyzed the clinical archives of the Niguarda Cancer Center from 2009 to 2015 and conducted a search for OIIS using the PubMed database, followed by deeper investigation of the references of the recorded studies. We pooled our series with other reported cases for systematic review in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement using only English language as the selection criterion. A total of 61 OIIS cases were analyzed, the largest series reported to date. Of the 61 patients, 56 (91.8%) had received oxaliplatin for metastatic colorectal cancer. In 32 of the 61 patients (52.5%), OIIS was associated with grade 4 thrombocytopenia and in 4 (6.6%) with grade 4 anemia. OIIS was fatal in 4 patients. In 49 patients, oxaliplatin-induced immune system activation was tested using the Coombs test or by detection of antiplatelet antibodies and was positive in 87.7% of the patients. The average number of oxaliplatin cycles until the onset of OIIS was 16.7, and the number was significantly lower when oxaliplatin was administered as a rechallenge after a period of vacancy of treatment with this agent (4.6 cycles as rechallenge vs. 13.6 as first-time exposure; P < .00001). OIIS is triggered by cumulative administration of oxaliplatin, characteristically with a threefold earlier onset when the drug is administered as a rechallenge. Prompt identification of OIIS can be expected to reduce the risk of iatrogenic morbidity and mortality.
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Bencardino
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Mauri
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Amatu
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Tosi
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Bonazzina
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Palmeri
authors.affiliation: Nephrology, Dialysis, and Transplant Unit, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Querques
authors.affiliation: Nephrology, Dialysis, and Transplant Unit, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Ravera
authors.affiliation: Immunohematolgy and Transfusion Medicine Department, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Menegotto
authors.affiliation: Immunohematolgy and Transfusion Medicine Department, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Boiani
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy. Electronic address: andrea.sartorebianchi@ospedaleniguarda.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sartore-Bianchi
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy; Dipartimento di Oncologia e Emato-Oncologia, Università degli Studi di Milano, Milan, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Siena
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects*; D000077150:Oxaliplatin; D013577:Syndrome
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin
keywords: Chemotherapy; Hemolysis; Rechallenge; Thrombocytopenia; Timing