Successful carboplatin desensitization in patients with proven carboplatin allergy

Abstract

We present the first all‐atom model for the structure of a T = 3 virus, pariacoto virus (PaV), which is a nonenveloped, icosahedral RNA virus and a member of the Nodaviridae family. The model is an extension of the crystal structure, which reveals about 88% of the protein structure but only about 35% of the RNA structure. New modeling methods, combining coarse‐grained and all‐atom approaches, were required for developing the model. Evaluation of alternative models confirms our earlier observation that the polycationic N‐ and C‐terminal tails of the capsid proteins must penetrate deeply into the core of the virus, where they stabilize the structure by neutralizing a substantial fraction of the RNA charge. This leads us to propose a model for the assembly of small icosahedral RNA viruses: nonspecific binding of the protein tails to the RNA leads to a collapse of the complex, in a fashion reminiscent of DNA condensation. The globular protein domains are excluded from the condensed phase but are tethered to it, so they accumulate in a shell around the condensed phase, where their concentration is high enough to trigger oligomerization and formation of the mature virus. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 530–538, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

The Contribution of the Basophil Activation Test to the Diagnosis of Hypersensitivity Reactions to Oxaliplatin

“…Regarding the immune mechanism underlying hypersensitivity reactions to platins, the IgE-mediated mechanism is considered predominant; it is sustained by the sudden onset of symptoms during or shortly after infusion of the drug and previous sensitization due to multiple exposures until the onset of the reaction [5]. This hypothesis is supported by positive results of skin prick and intradermal tests found in previous reports, with an estimated sensitivity of between 66 and 100% for carboplatin [9][10][11] and 26 and 100% for oxaliplatin [12,13]. The main disadvantages of this diagnostic method are, fundamentally, the potential to induce irritant local skin reactions (pruritus, pain, erythema, and/or local cutaneous necrosis) and the possibility of contamination by health professionals.…”

Management of Hypersensitivity to Platinum- and Taxane-Based Chemotherapy: cepo Review and Clinical Recommendations

“…Other multi-step desensitization protocols of 4-13 steps have been suggested 40,[69][70][71] . Most patients completed them with few or no hypersensitivity symptoms.…”

Carboplatin hypersensitivity in children with glial tumors: a report of two cases

“…The exact underlying mechanism in the carboplatin hypersensitivity and delayed type reactions are not known. However, IgE-medicated immediate type hypersensitivity is thought to be involved 9, 10 . Repeated doses of the drug increases the risk of hypersensitivity with highest risk reported at 8th course of carboplatin 11,12 .…”

“…Various desensitization protocols have been reported 10,15,16 . Confino-Cohen et al 10 used different diluted concentrations of carboplatin and started with the lowest diution with premedication including antiemetic and dexamethasone. Success rate was reported to be 95% with desensitization.…”