Type II hypersensitivity reactions after oxaliplatin rechallenge can be life threatening

Int Immunopharmacol. 2019 Sep;74:105728. doi: 10.1016/j.intimp.2019.105728. Epub 2019 Jul 6.


Background: Rechallenge with oxaliplatin is common in the treatment of colorectal cancer and increases the risk of a detrimental oxaliplatin-induced immune reaction. Allergic reactions to oxaliplatin may be partially avoided by desensitization protocols involving immune suppressive drugs, slow administration and gradually increasing chemotherapeutic doses. However, non-IgE-mediated immunopathologic reactions to oxaliplatin remain challenging and may be potentially life-threatening.

Case presentation: Here we report two potentially fatal cases of type II hypersensitivity to oxaliplatin in metastatic colorectal cancer patients. Both patients manifested with severe thrombocytopenia, intravascular haemolysis, and acute kidney injury 4-6 h after oxaliplatin administration in a rechallenge setting. Serology revealed that the reactive entity for immune haemolysis was an IgG oxaliplatin-induced antibody. The course of anti-cancer treatment and severe adverse event after oxaliplatin rechallenge including diagnostic dilemma and the results of detailed routine clinical chemistry and hematology testing are described. Extended immunohaematology/serology testing revealed that the oxaliplatin-induced IgG antibody was present in the circulation prior to the onset of hypersensitivity, persisted for months and elicited cross-reactivity with other platinum agents.

Conclusion: Development of type II hypersensitivity reaction manifesting as a sudden onset of severe thrombocytopenia and immune haemolysis must be considered in patients treated with oxaliplatin, especially those on long-term therapy or when rechallenged. Step-wise diagnosis involves clinical presentation, detection of haemolysis in patient's blood and/or urine, evaluation of platelet count, and direct anti-globulin Coombs test.

Keywords: Acute kidney injury; Chemotherapy rechallenge; Immune haemolytic anemia; Oxaliplatin; Type II hypersensitivity reaction.

Publication types

  • Case Reports

MeSH terms

  • Acute Kidney Injury
  • Adenocarcinoma / complications
  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / drug therapy
  • Adrenal Cortex Hormones / therapeutic use
  • Aged
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Desensitization, Immunologic
  • Drug Hypersensitivity / diagnosis*
  • Drug Hypersensitivity / drug therapy
  • Drug Hypersensitivity / etiology
  • Drug-Related Side Effects and Adverse Reactions / diagnosis*
  • Drug-Related Side Effects and Adverse Reactions / drug therapy
  • Drug-Related Side Effects and Adverse Reactions / etiology
  • Female
  • Hemolysis
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Oxaliplatin / adverse effects*
  • Oxaliplatin / therapeutic use
  • Rectal Neoplasms / complications
  • Rectal Neoplasms / diagnosis*
  • Rectal Neoplasms / drug therapy
  • Thrombocytopenia


  • Adrenal Cortex Hormones
  • Antineoplastic Agents
  • Oxaliplatin