Standard Desensitization Protocol Research Articles

Pre-transplant crossmatch-negative donor-specific anti-HLA antibody predicts acute antibody-mediated rejection but not long-term outcomes in kidney transplantation: an analysis of the Korean Organ Transplantation Registry.

Pre-transplant donor-specific anti-human leukocyte antigen antibody (HLA-DSA) is a recognized risk factor for acute antibody-mediated rejection (ABMR) and allograft failure. However, the clinical relevance of pre-transplant crossmatch (XM)-negative HLA-DSA remains unclear. We investigated the effect of XM-negative HLA-DSA on post-transplant clinical outcomes using data from the Korean Organ Transplantation Registry (KOTRY). This study included 2019 living donor kidney transplant recipients from 40 transplant centers in South Korea: 237 with HLA-DSA and 1782 without HLA-DSA. ABMR developed more frequently in patients with HLA-DSA than in those without (5.5% vs. 1.5%, p<0.0001). Multivariable analysis identified HLA-DSA as a significant risk factor for ABMR (odds ratio = 3.912, 95% confidence interval = 1.831-8.360; p<0.0001). Furthermore, the presence of multiple HLA-DSAs, carrying both class I and II HLA-DSAs, or having strong HLA-DSA were associated with an increased incidence of ABMR. However, HLA-DSA did not affect long-term clinical outcomes, such as allograft function and allograft survival, patient survival, and infection-free survival. Pre-transplant XM-negative HLA-DSA increased the risk of ABMR but did not affect long-term allograft outcomes. HLA-incompatible kidney transplantation in the context of XM-negative HLA-DSA appears to be feasible with careful monitoring and ensuring appropriate management of any occurrence of ABMR. Furthermore, considering the characteristics of pre-transplant XM-negative HLA-DSA, the development of a more detailed and standardized desensitization protocol is warranted.

Hypersensitivity reactions to anticancer chemotherapy and monoclonal antibodies: Safety and efficacy of desensitization.

Hypersensitivity reactions to anticancer chemotherapy and monoclonal antibodies may lead to discontinuation of first-line treatment options. Identification of these reactions can provide specific diagnosis and treatment by rapid drug desensitizations. To determine the hypersensitivity reactions involved in anticancer chemotherapy and monoclonal antibodies, and the safety and efficacy of rapid drug desensitization. We conducted an observational study of hypersensitivity reaction presented after the administration of anticancer chemotherapy and monoclonal antibodies in Mexico. We documented the symptoms of initial reaction and their severity, and the results of skin tests. We also report our experience of the administration of 12-step (mild-moderate reactions) and 16-step (severe reactions) desensitization protocols in these patients. Overall, 93 patients received 336 rapid drug desensitization; 105 to taxanes, 115 to platinum drugs, 101 to monoclonal antibodies, and 15 other anticancer chemotherapy. Hypersensitivity reaction to taxanes occurred in the first or second administration, platinum drugs after the sixth cycle, and rituximab in the first cycle. The most common symptom in carboplatin was urticaria, paclitaxel back pain, oxaliplatin and docetaxel dyspnea, and in the monoclonal antibodies cardiovascular symptoms. Skin tests were positive in 75% of the carboplatin group, and only 16.7% in docetaxel. There was a rapid drug desensitization success rate of 99.4% and 85.7% did not present any related hypersensitivity reaction. The diagnosis of hypersensitivity reaction to anticancer chemotherapy and monoclonal antibodies offers a panorama in the management of oncological diseases. Our standardized desensitization protocol is safe and effective and can be reproduced in other centers to treat patients who need to maintain first-line treatment.

Simplified Graded Infusion Strategy for Mitigation of Oxaliplatin Hypersensitivity

BackgroundHypersensitivity reactions (HSRs) to oxaliplatin present a therapeutic challenge. The standard desensitization protocol consists of 12 infusion steps with 3 drug dilutions, often in an inpatient setting. Several years ago we implemented a simplified outpatient graded infusion protocol for oxaliplatin with 2 drug dilutions and 3 infusion steps. Materials and MethodsWe performed a retrospective analysis of our experience to define the safety and outcomes associated with this simplified, ambulatory, graded infusion strategy. ResultsBetween January 1, 2011 and December 1, 2020, 374 patients who had experienced an oxaliplatin-related HSR were treated via a 3-step graded infusion in the outpatient setting. Of these 374 patients, 283 (76%) did not experience a subsequent HSR, while 91 (24%) did experience a breakthrough HSR. Of the 374 patients, 19 (5%) experienced a grade 3 or 4 HSR. Three patients (0.8%) were hospitalized. There was no grade 5 (fatal) HSRs. Overall, the 374 patients received a median additional 3 cycles of oxaliplatin (range 1-41). The most common reasons for treatment discontinuation were disease progression (35%), breakthrough HSRs (24%), completion of treatment (21%), and toxicity other than HSR (20%). Fifteen patients who experienced breakthrough HSRs during a graded infusion were subsequently treated with the standard 12-step desensitization. Five of these 15 patients had an HSR during their initial desensitization and 5 developed an HSR on subsequent 12-step desensitizations. Thus, treatment was discontinued in 67% of these 15 patients due to persistent HSRs. ConclusionOur data indicate that the simplified 3-step graded infusion protocol is a safe outpatient strategy for patients with a history of HSR to oxaliplatin.

Tocilizumab and Desensitization in Kidney Transplant Candidates: Personal Experience and Literature Review.

Desensitization (DES) allows kidney transplantation for highly HLA-sensitized subjects. Due to the central role of IL-6 in the immunological response, tocilizumab may improve DES efficacy. Thus, we conducted a PubMed systematic review using the MeSH terms tocilizumab, interleukin-6, kidney transplantation, and desensitization. Tocilizumab (TCZ) was first studied for DES as the second-line treatment after failure of a standard DES protocol (SP) (apheresis, rituximab +/− IVIg). Although TCZ (as a monotherapy) attenuated anti-HLA antibody rates, it did not permit transplantation. However, lymphocyte immuno-phenotyping has shown that TCZ hinders B-cell maturation and thus could improve the long-term efficacy of DES by limiting anti-HLA rebound and so avoid antibody-mediated rejection. This hypothesis is supported by a recent study where clazakizumab, a monoclonal antibody directed against IL-6, was continued after kidney transplantation in association with an SP. Nine out of ten patients were then eligible for transplantation, and there were no donor-specific antibodies at 6 months post-transplantation. In association with an SP, tocilizumab does not seem to significantly improve kidney-allograft access (short-term efficacy) vs. a SP only. However, it could improve the long-term prognosis of HLA-incompatible transplantation by hindering B-cell maturation and, thereby, avoiding donor-specific antibody rebounds post-transplantation.

Frequency and severity of reactions to a 325-mg aspirin dose during desensitization

BackgroundThe frequency with which patients with aspirin-exacerbated respiratory disease (AERD) react to 325 mg of aspirin during aspirin desensitization, or fail to react at all, is not fully known. ObjectiveTo determine the rate and type of reaction at 325 mg of aspirin during desensitization. MethodsA retrospective study of 104 patients who underwent aspirin desensitization from 2010 to 2016 was performed. A standard desensitization protocol (starting at 20–40 mg, progressing through 325 mg, and extinguishing reactions by dose repetition) was used. Reactions were defined by upper respiratory tract symptoms, lower respiratory tract symptoms, and/or forced expiratory volume in 1 second decrease of 15% or greater. Patients who did and did not react were compared by logistic regression. ResultsEighty-four patients reacted (81%) and 20 did not (19%). Seventy-seven patients who had a provoking reaction at 162 mg of aspirin or less subsequently extinguished their reactions before they reached a dose of 325 mg and had no problems at that dose; one subsequent 325-mg reaction occurred during a protocol violation. One initial provoking reaction to 325 mg occurred. Both 325-mg reactions were mild, and neither met the forced expiratory volume in 1 second criterion for a clinically meaningful change. The remaining 5 patients could not complete the protocol because of persistent reactions or social reasons. Reactors were more likely to have had asthma for more than 10 years than nonreactors (odds ratio, 3.2; 95% confidence interval, 1.0–10.3; P = .05). ConclusionDuring aspirin desensitization for AERD, provoking reactions at the 325-mg dose are rare (1%) and mild. Patients who react at 162 mg or less and extinguish their reactions may be able to administer the 325-mg dose at home.

An Alternative Aspirin Desensitization Protocol for Patients with Aspirin- Exacerbated Respiratory Disease

Background:Aspirin exacerbated respiratory disease (AERD) affects up to 5% to 15% of asthmatics. While aspirin desensitization is a safe treatment option and allows for aspirin to be used to control AERD symptoms, not all patients diagnosed with AERD are able to complete the standard desensitization protocol. Objective: For patients who cannot complete the standard desensitization protocol, we sought to create an alternative method that allows patients to reach a therapeutic maintenance dose of aspirin. Methods: We retrospectively analyzed patients that underwent AERD desensitization, identifying 5 patients that failed the standard desensitization protocol and 6 that elected to complete the alternative aspirin desensitization. Subjects started at a dose lower than their reaction dose and subsequently increased their dosage by 40.5 mg or 81 mg every 2 to 4 weeks, with the goal of reaching a dose of 325 mg BID. Results: Among the five patients that initially failed the standard desensitization protocol, our alternative desensitization protocol took an average of 6.1 months to reach a maintenance dose of 307 mg BID with an increase of 47.5 mg aspirin every two weeks. Of the six patients who elected to complete our alternative protocol, it took an average of 4.6 months to reach a maintenance dose of 244 mg BID with an increase of 38.7 mg every two weeks. Six patients successfully increased their aspirin dosage to 325 mg BID by following the alternative protocol. Conclusion: Based on the data, it seems possible that a graduated approach to the administration of aspirin could benefit a majority of those who fail or do not wish to complete the standard desensitization protocol.

Infusion‐related reactions to Rituximab: pathogenic mechanism and proposal of a new modified desensitization protocol

Background Rituximab is a chimeric monoclonal antibody against the surface protein CD20 of B cells, used in the treatment of hematologic malignances and autoimmune diseases. Some patients develop hypersensitivity reactions after the infusion. It is unknown the percentage of these which are due to an IgE allergic mechanism. Also, there is not a standardized desensitization protocol that allows us to induce tolerance to this drug in patients.

307: The Effectiveness of a Standardized Desensitization Protocol in Reducing Calculated Panel Reactive Antibodies (cPRA) in Sensitized Heart Transplant Candidates: Does It Make Sense To Desensitize?

307: The Effectiveness of a Standardized Desensitization Protocol in Reducing Calculated Panel Reactive Antibodies (cPRA) in Sensitized Heart Transplant Candidates: Does It Make Sense To Desensitize?

Rapid desensitization for hypersensitivity reactions to paclitaxel and docetaxel: a new standard protocol used in 77 successful treatments

Objective Administration of paclitaxel is associated with hypersensitivity reactions (HSRs) in up to 9% of patients despite premedication. The purpose of this study was to evaluate the effectiveness of a standardized desensitization protocol in patients with HSRs to taxanes, based on our experience with carboplatin desensitization. Methods We analyzed seventeen consecutive patients with documented HSRs to taxanes who required continued treatment with a taxane agent. The patients were treated with either paclitaxel or docetaxel using the 6- to 7-h standard desensitization protocol. Results Seventeen patients who previously had severe taxane HSRs successfully completed 77 planned cycles of desensitization to paclitaxel or docetaxel, 72 of which were without reactions. Four patients developed HSRs during the desensitization protocol that were much less severe than their original HSRs and tolerated the re-administration of infusions without further reactions. Of these four patients, the first had palmar erythema 8 h after her 1st desensitization. The second patient had mild abdominal pain during her 1st cycle, and the third patient developed mild chest burning during her 2nd and 4th cycles. These three patients also completed subsequent desensitization cycles without reactions. The fourth patient developed a delayed urticaria reaction and gastrointestinal symptoms 6 h after completing her 1st desensitization. She elected to be treated with an alternative chemotherapy and did not receive additional courses of desensitization. Conclusion The rapid standard desensitization protocol provides a safe and effective strategy for the re-administration of paclitaxel or docetaxel even after severe HSRs.