Food, drug, insect sting allergy, and anaphylaxis
Hypersensitivity reactions to chemotherapy: Outcomes and safety of rapid desensitization in 413 cases

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Background

Hypersensitivity reactions (HSRs) to chemotherapeutic drugs, including mAbs, often require that the provoking medication be discontinued, thus raising a dilemma for the caregiver: further use could precipitate a severe, even fatal, allergic reaction on re-exposure, but alternative drugs might be poorly tolerated or much less effective compared with the preferred agent.

Objective

We have developed a standardized rapid desensitization protocol for achieving temporary tolerization to drug allergens. In this study we evaluate the safety and efficacy of this protocol.

Methods

Ninety-eight patients who had HSRs in response to treatment with carboplatin, cisplatin, oxaliplatin, paclitaxel, liposomal doxorubicin, doxorubicin, or rituximab received rapid desensitization to these agents. A standardized 12-step protocol was used, with treatment given intravenously or intraperitoneally. Initial desensitizations occurred in the medical intensive care unit, whereas most subsequent infusions took place in an outpatient setting. Safety and efficacy of the protocol were assessed by review of treatment records.

Results

Of the 413 desensitizations performed, 94% induced mild or no reactions. No life-threatening HSRs or deaths occurred during the procedure, and all patients received their full target dose. Most reactions occurred during the first desensitization. Reactions were most commonly reported at the last step of the protocol. Desensitizations through the intravenous and intraperitoneal routes were equally effective.

Conclusions

Our standardized 12-step protocol for rapid drug desensitization is safe and effective and has been adopted as the standard of care at our institutions in treating patients with HSRs to chemotherapeutic drugs, including mAbs.

Section snippets

Patients

This collaboration between investigators at Dana Farber Cancer Institute (DFCI) and Brigham and Women's Hospital (BWH; Allergy and Medical Intensive Care divisions) was approved by the Human Research Committee (institutional review board protocol no. 2007-P-000050/1). Between January 1, 2005, and October 31, 2006, patients with known HSRs to chemotherapy were referred to the allergy service for rapid desensitization.

The inclusion criteria were (1) age greater than 18 years, (2) ability to

Patient characteristics

Over 22 months, 98 patients with HSRs to chemotherapy, including rituximab, received rapid desensitization. Patients' ages ranged from 30 to 78 years (mean, 55 years). Ninety-seven patients were being treated for a malignancy (1 male and 96 female patients), and 1 patient was being treated for polymyositis. The most common malignancies were ovarian, breast, and peritoneal (Table III). Twenty-five patients were treated for primary cancers, and 72 were treated for recurrent cancers. Three

Discussion

We present the results of the first large-scale series of desensitizations carried out in 98 patients by using the standardized protocol developed at our institutions. Over the course of 22 months, 413 rapid desensitizations to various chemotherapeutic agents, including rituximab, were performed, in which no deaths occurred; moreover, all patients received their full target dose, demonstrating the efficacy of the procedure. In our hands the protocol has been uniformly successful in permitting

References (24)

  • L.H. Sehn et al.

    Rapid infusion rituximab in combination with corticosteroid-containing chemotherapy or as maintenance therapy is well tolerated and can safely be delivered in the community setting

    Blood

    (2007)
  • M. Markman et al.

    Clinical features of hypersensitivity reactions to carboplatin

    J Clin Oncol

    (1999)
  • Cited by (467)

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    Supported by the Ovations for the Cure Desensitization Program.

    Disclosure of potential conflict of interest: D. E. Sloane has received honoraria from Genentech. F. I. Hsu has served as a coinvestigator for Dyax Corporation and has received a research grant from the American Academy of Allergy, Asthma & Immunology. N. A. Barrett has served as a coinvestigator for the National Institutes of Health and has served as a primary investigator for the American Academy of Allergy, Asthma & Immunology and Altana. D. I. Hong and T. M. Laidlaw have received training grant salary from the National Institutes of Health. S. N. Nallamshetty has received training grant salary from the National Institutes of Health and research grants from the American Academy of Allergy, Asthma & Immunology and GlaxoSmithKline. S. M. Campos has served as a research consultant for Genentech and has received research support from Genentech, Novartis, and Ortho-Biotechnology. The rest of the authors have declared that they have no conflict of interest.

    These authors contributed equally to this work.

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