Life-threatening carboplatin hypersensitivity during conditioning for autologous PBSC transplantation: successful rechallenge after desensitization

Abstract

Summary:Carboplatin hypersensitivity has rarely been reported in patients receiving repeated cycles of therapy, but has not been reported in transplant settings. We report a case of carboplatin hypersensitivity during conditioning for autologous PBSC transplantation. The patient suddenly developed chest tightness, hemoptysis, hypoxia and hypotension, resulting in a transient myocardial ischemia. The pathophysiologic mechanism for the event seemed to be non-immune-mediated direct histamine release given the lack of prior exposure to platinum. Contrary to advice not to continue further treatment with carboplatin by some authors, we successfully desensitized the patient and subsequently gave more carboplatin as a part of conditioning. Awareness of carboplatin as one of the causes of hypersensitivity may help avoid further problems either by substitution or desensitization, along with premedications. Keywords: carboplatin; hypersensitivity; conditioning; PBSC transplantation; desensitization Carboplatin, a second-generation, platinum-containing chemotherapeutic agent, is increasingly used in transplant conditioning regimens for a variety of solid tumors. Although type I hypersensitivity has been reported in 1% to 20% of patients who receive cisplatin, there are few reports of similar reactions in patients receiving repeated cycles of carboplatin therapy.1,2 To our knowledge, there have been no reported cases of life-threatening carboplatin hypersensitivity in the transplant setting.We report a case of carboplatin hypersensitivity who presented with hemoptysis and hypoxia resulting in transient myocardial ischemia during conditioning for autologous PBSC transplantation. Most of the patients reported who have had allergic reactions to carboplatin were unable to tolerate further treatment with it despite heavy premedication with steroids and antihistaminics. however, carboplatin was re-introduced successfully as a conditioning regimen after a course of desensitization. Case reportAn 8-year-old girl was admitted for autologous PBSC transplantation. One year earlier she had developed fever and jaundice, and was diagnosed to have a sarcoma botryoides arising in the bile duct. The tumor was stage III and only a partial resection was possible at that time. Chemotherapy consisting of vincristine, actinomycin-D and ifosfamide (VAI) along with radiotherapy had effected a good response on the second-look operation. A total of six leukaphereses were performed by CS3000+ after two mobilization cycles employing VAI plus G-CSF. The planned conditioning regimen was: carboplatin 800 mg/m 2 once daily i.v. on days Ϫ6 and Ϫ5, etoposide 200 mg/m 2 twice daily i.v. on days Ϫ6 to Ϫ4 (total six doses), and melphalan 180 mg/m 2 i.v. on day Ϫ2. The first morning dose of etoposide was administered uneventfully. Carboplatin was dissolved in 500 ml of D 5 . saline solution. Five minutes after starting the infusion when a total of about 10 mg of carboplatin had been administered, she suddenly developed tachypnea, chest tightness, cyanosis, vomit...

Evaluation of Basophil CD203c as a Predictor of Carboplatin-Related Hypersensitivity Reaction in Patients with Gynecologic Cancer

“…Carboplatinrelated hypersensitivity reactions are thought to be mediated by IgE, 26,27) although other studies suggested platinum salts can release histamine from basophils and mast cells without an immune-mediated mechanism (pharmacological effect of platinum). 28,29) In conclusion, the results of this study suggest that the basophil activation test based on the induction of CD203c expression seems a promising simple test for the prediction of carboplatin-related HR, particularly prediction of severe anaphylaxis.…”

Drug Desensitization in Oncology: Chemotherapy Agents and Monoclonal Antibodies

“…Patients treated with multiple courses of carboplatin experience increased incidence of hypersensitivity reactions, which are uncommon during the initial courses. The incidence of reactions increases to 27% in patients receiving more than seven cycles of carboplatin [9,22] . Symptoms of hypersensitivity reactions vary from cutaneous reactions such as flushing and urticaria to life-threatening respiratory and cardiovascular compromise, including bronchospasm, chest pain, and hypotension, with more than 50% of patients developing at least moderately severe symptoms [9] .…”

Safety and efficacy of repeated monthly carboplatin desensitization

“…1 Carboplatin hypersensitivity is often heralded by a sudden reaction after multiple uneventful courses; less commonly, platinum-naive patients have also reacted immediately with the first infusion. 2 Each separate exposure to carboplatin has been postulated to lower the threshold for development of overt hypersensitivity, which poses a problem because of the frequent need to administer carboplatin repeatedly. Available data suggest that reactions to carboplatin usually recur with the subsequent rechallenge.…”