Diagnosis and management of hypersensitivity reactions related to common cancer chemotherapy agents.

OBJECTIVES: To review clinical hypersensitivity reactions related to common cancer chemotherapy agents and to discuss potential management strategies. DATA SOURCES: PubMed searches were performed for articles published from 1970 to 2008 regarding hypersensitivity to cancer chemotherapy and related agents using the keywords hypersensitivity, allergy, chemotherapy, platinums, taxanes, asparaginase, epipodophyllotoxins, and procarbazine. Retrieved articles were surveyed for additional citations. STUDY SELECTION: Articles were reviewed for relevance to the subject matter, and the most pertinent articles were included in this review. RESULTS: Hypersensitivity reactions are commonly associated with the use of certain cancer chemotherapy drugs, including platinums, taxanes, asparaginase, procarbazine, and epipodophyllotoxins. Platinum agents (cisplatin, carboplatin, oxaliplatin) are associated with IgE-mediated hypersensitivity reactions, and skin testing may be indicated. Taxane (paclitaxel, docetaxel)-related reactions are generally non-IgE mediated, and premedication with corticosteroids and antihistamines is usually effective. Asparaginase has a high rate of hypersensitivity reactions that are likely IgE mediated or related to complement activation. Skin testing has been recommended but has not been validated for asparaginase. Procarbazine reactions can be IgE mediated but are also associated with a type III reaction manifested by pulmonary toxicity and cutaneous reactions. Hypersensitivity reactions related to epipodophyllotoxins may involve both immunologic and nonimmunologic factors that may be avoided with a slow infusion and premedication. CONCLUSION: With the increasing use of cancer chemotherapy agents, hypersensitivity reactions are commonly encountered. Knowledge of the presentations of these reactions and management options give the treating physician the means to make an informed decision of how best to proceed.

Specific unresponsiveness to fully allogeneic kidney allografts in rats induced by procarbazine hydrochloride and antilymphocyte serum.

A short course of procarbazine hydrochloride (PCH; 50 mg/kg) and antilymphocyte serum (ALS; 5 ml/kg), administered to Lewis (LEW;RT1(1] rats in the first week following transplantation of Brown Norway (BN;RT1n) kidneys, substantially prolonged allograft survival and induced long-term survival in 62% of the grafts. The two agents acted synergistically, in that neither of them administered alone had much effect. Graft recipients did not produce detectable cytotoxic antibodies and antigen-reactive cells injected i.v. were not diverted to the liver, thus showing that neither antibodies nor immune complexes are likely to mediate the unresponsiveness. Spleen cells from graft-bearing recipients failed to cause graft-versus-host responses (GVHR) in both (LEW X BN)F1 and (LEW X DA)F1 hybrids, but they specifically suppressed the GVHR given by normal syngeneic cells to donor strain (BN) antigens. This suppression was specific because the response against third-party antigens (DA; RT1a) was unaffected. Adoptive transfer of spleen and thymus cells from PCH-ALS-treated LEW rats bearing healthy BN kidneys caused a profound prolongation of BN graft survival in sublethally irradiated LEW recipients. This transfer was specific and mediated by W3/13+ (T) lymphocytes. It is concluded that a limited regimen of PCH and ALS given in the first postoperative week incites the generation of specific suppressor T lymphocytes and that this form of immunosuppression, even without preoperative donor antigen, is an effective way of prolonging kidney allograft survival.