Risk Factors For Hypersensitivity Reactions Research Articles

A survey of carboplatin desensitization therapy in Japan: A multicenter retrospective study.

Hypersensitivity reactions (HSRs) to chemotherapy are serious adverse events associated with cancer drug therapy and can occur with any antitumor drug. This study investigated the safety and efficacy of carboplatin desensitization therapy in Japan and established a method for treating carboplatin HSRs. Patients diagnosed with gynecological (ovarian, endometrial, or cervical) cancers who underwent carboplatin desensitization therapy between 2016 and 2020 at the Gynecologic Cancer Study Group of Japan Clinical Oncology Group were included. The carboplatin desensitization therapy at each institution and the implementation cases were registered in an online case report form. This retrospective study enrolled 136 patients (ovarian, 108; endometrial, 17; and cervical cancer, 11). Pre-existing allergies were present in 37 (27.2%) patients, and 32 (23.5%) patients exhibited prodromal symptoms during treatment before HSR onset. Erythema was the most common symptom at HSR onset, affecting 93 (68.4%) patients, followed by itching in 72 (52.9%) patients and decreased oxygen saturation in 43 (31.6%) patients. Loss of consciousness occurred in three (2.2%) patients. The most common timing of HSR onset was during the first recurrence treatment (47%). The mean total carboplatin dose until HSR onset was 7331 (2620-18,282) mg, and the mean number of doses was 14 (4-63). Desensitization treatment was completed in 75% of cases, and breakthrough HSRs occurred in 25% (34/136). No deaths occurred in the study cohort. The risk factors for HSRs were not identified. Although carboplatin desensitization therapy has high success rates in Japan, erythema and pruritus are important HSRs to consider.

Hypersensitivity to Intravenous Iron Preparations.

Intravenous iron is widely used for the treatment of iron deficiency anemia when adherence to oral iron replacement is poor. Acute hypersensitivity reactions during iron infusions are very rare but can be life threatening. Major risk factors for hypersensitivity reactions include a previous reaction to an iron infusion, a fast iron infusion rate, multiple drug allergies, atopic diseases, high serum tryptase levels, asthma, and urticaria. The management of iron infusions requires meticulous observation, and, in the event of an adverse reaction, prompt recognition and severity-related interventions by well-trained medical and nursing staff. Avoidance of IV iron products in patients with iron hypersensitivity reactions may not be considered as a standard practice.

Réactions d’hypersensibilité au fer intraveineux : le point de vue de l’allergologue

Intravenous iron infusions rarely result in severe hypersensitivity reactions. The primary suspected hypersensitivity mechanism is an abnormal complement activation by non-IgE antibodies to the carbohydrate moieties stabilizing iron formulations. A major risk factor for hypersensitivity reactions is related to the infusion speed. Fishbane-like reactions usually resolve after pausing the infusion, which can be resumed under medical surveillance and at a lower infusion rate. Yet, anaphylactic reactions require emergency first aid and subsequent strict avoidance of intravenous iron. Desensitization protocols can be implemented in selected cases and under strict medical surveillance to reduce the risks of severe reactions upon re-exposure.

Hypersensitivity reactions to vaccines in children: from measles to SARS-CoV-2.

Allergic individuals at risk for hypersensitivity reactions to measles vaccine marketed for a long time are well established. On the other hand, risk factors for hypersensitivity reactions to the new mRNA COVID‐19 vaccines currently include a history of allergy, allergy to excipient of the vaccine, or hypersensitivity reactions to the first dose of COVID‐19 vaccine. In the last two cases, the recipient should be assessed by an allergist before vaccination to share a decision on the choice of vaccination. Studies on skin testing accuracy and desensitization protocols to the COVID‐19 vaccines and the efficacy of potential alternatives in patients with confirmed hypersensitivity reactions to the first COVID‐19 vaccine are necessary to improve the safety of COVID‐19 vaccines.

Impact of carboplatin hypersensitivity and desensitization on patients with recurrent ovarian cancer.

Hypersensitivity reactions (HSRs) to chemotherapy is an ongoing issue in cancer treatments. Strategies to induce tolerance and maximize chemotherapy efficacy include desensitization protocols. The precise impact of these protocols, however, in the long-term treatments remains unclear. We aim to compare overall survival (OS) in hypersensitive patients treated with carboplatin desensitization to patients without hypersensitivity reactions. We also sought to identify new risk factors for HSRs and reconfirm that the DNA repair enzyme, germline BRCA1/2 (gBRCA1/2), is a risk factor for hypersensitivity. Retrospective study in patients with ovarian cancer tested for gBRCA1/2 mutations who received more than six infusions of carboplatin from August 2005 to November 2016. Two-sided Fisher exact, Student's t test and Gehan-Breslow-Wilcoxon test were used for statistical analysis. Univariate and multivariate analyses were completed to identify independent predictors of survival. Statistical significance was set with a two-sided p value of 0.05. Ninety-one patients with gBRCA1/2 testing met inclusion. Forty patients (44%) were gBRCA1/2-deficient and 51 (56%) were gBRCA1/2-proficient. Patients with gBRCA1/2 deficiencies had a higher likelihood of developing carboplatin hypersensitivity, HR 6.433 (95% CI: 1.868-22.149). None of the patients with carboplatin hypersensitivity were given PARP inhibitors prior to the development of HSRs. The patients with recurrent advanced stage (III-IV) ovarian cancer had a higher likelihood of developing carboplatin hypersensitivity, HR 4.783 (1.008-22.689). Moreover, we found that hypersensitive patients who underwent carboplatin desensitization had a 48-month longer OS than patients without hypersensitivity to carboplatin not undergoing carboplatin desensitization (p = 0.0094). A subgroup analysis indicated that gBRCA1/2-proficient hypersensitive patients undergoing carboplatin desensitization had a 43-month longer OS than gBRCA1/2-proficient patients without HSRs (p = 0.034). We confirmed that gBRCA1/2 deficiency and advanced stage are independent risk factors for development of carboplatin hypersensitivity in ovarian cancer patients. Our study also shows improved OS in hypersensitive patients receiving CD compared to non-hypersensitive patients, independent of gBRCA1/2.

Risk factors for hypersensitivity reactions to tocilizumab introduction in systemic juvenile idiopathic arthritis

Objectives: The objective of this study is to identify risk factors for hypersensitivity reaction (HSR) to tocilizumab (TCZ) in systemic juvenile idiopathic arthritis (sJIA).Methods: Clinical records of 40 patients with sJIA administered TCZ at one center were retrospectively reviewed. Patients were divided into HSR or non-HSR groups depending on the presence of HSR between the first and third TCZ administrations; clinical and laboratory assessments, including serum cytokine profile, were compared.Results: Five patients displayed HSR following the third TCZ administration. They were significantly younger, shorter, and lighter, with a higher peak body temperature than non-HSR patients following the third administration. Their serum C-reactive protein (CRP) level was undetectable following the first administration but detectable by the third administration. Before the third administration, the white blood cell counts and serum levels of CRP and sTNFRII were significantly higher in the HSR group than in the non-HSR group. The serum levels of interleukin-18 and -6 before the third TCZ administration were higher and lower than those before the first administration in the HSR and non-HSR groups, respectively.Conclusion: Patients with sJIA having a younger age, shorter stature, and lighter weight and those showing increased disease activity in the early period of TCZ administration may be at higher risk of TCZ-induced HSR.

Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies.

We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2%) experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease (P < 0.001, Kruskal-Wallis test), serous and mixed histological types (P = 0.003, Kruskal-Wallis test), malignant ascites (P = 0.009, chi-square test), and history of other drug allergy (P < 0.001, chi-square test). Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P < 0.001, independent sample t-test) and dose (6,816 vs. 3,844 mg, P < 0.001, independent sample t-test). The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications.

P035 Atopy as a risk factor for hypersensitivity to L-Asparaginase in pediatric patients with leukemia

L-Asparaginase (ASNase) is a chemotherapeutic agent used in the treatment of children and young adults with acute lymphoblastic leukemia (ALL). ASNase is known to cause hypersensitivity reactions. Atopy as a risk factor for hypersensitivity reactions to ASNase in pediatric leukemia patients has not been previously studied.

Comparison between hypersensitivity reactions to cycles of modified FOLFOX6 and XELOX therapies in patients with colorectal cancer

PurposeAlthough hypersensitivity reactions (HSRs) to oxaliplatin (L-OHP) therapy are well-documented, few reports have compared different therapies in terms of HSR occurrence. In this study, we compared the frequency and pattern of HSRs to modified FOLFOX6 (mFOLFOX6; 5-fluorouracil, levofolinate calcium and L-OHP infusions) and XELOX (capecitabine and L-OHP) therapies, and sought to identify risk factors associated with HSRs.MethodsPatients who had received mFOLFOX6 or XELOX chemotherapeutic regimens for unresectable colon or rectal cancer or as adjuvant chemotherapy following colon cancer surgery between April 2012 and August 2015 were included. Potential correlation between treatment modalities (regimen, dosage and route of administration of L-OHP, and injection timing for dexamethasone administration) and HSRs was assessed.ResultsAmong the 240 patients included in the study, 136 had received mFOLFOX6 therapy and 104 had received XELOX therapy. Although the frequency of HSRs did not differ between the two groups, incidence of HSRs in the first cycle was higher in the XELOX therapy group. Treatment method or cumulative dosage was not identified as a risk factor for HSR; however, the incidence of ≥grade-2 HSR was higher in cases where the cumulative L-OHP dosage was ≥600 mg/m2 and in patients in whom dexamethasone was not co-infused with L-OHP.ConclusionAlthough HSR rates were comparable among patients treated with mFOLFOX6 and XELOX, HSRs tended to occur more frequently during the first cycle of XELOX therapy as compared to that with mFOLFOX6 therapy. Our findings warrant careful assessment of ≥grade-2 HSRs in patients who are prescribed cumulative L-OHP dosages of ≥600 mg/m2.

Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management.

Intravenous iron is widely used for the treatment of iron deficiency anemia when oral iron is inappropriate, ineffective or poorly tolerated. Acute hypersensitivity reactions during iron infusions are very rare but can be life-threatening. This paper reviews their frequency, pathogenesis and risk factors, and provides recommendations about their management and prevention. Complement activation-related pseudo-allergy triggered by iron nanoparticles is probably a more frequent pathogenetic mechanism in acute reactions to current formulations of intravenous iron than is an immunological IgE-mediated response. Major risk factors for hypersensitivity reactions include a previous reaction to an iron infusion, a fast iron infusion rate, multiple drug allergies, severe atopy, and possibly systemic inflammatory diseases. Early pregnancy is a contraindication to iron infusions, while old age and serious co-morbidity may worsen the impact of acute reactions if they occur. Management of iron infusions requires meticulous observation, and, in the event of an adverse reaction, prompt recognition and severity-related interventions by well-trained medical and nursing staff.

Multicenter evaluation of the administration of crotalid antivenom in cats: 115 cases (2000–2011)

To evaluate use of crotalid antivenom, frequency of hypersensitivity reactions, and risk factors for hypersensitivity reactions and death in envenomed cats. Retrospective multicenter case series. 115 envenomed cats treated with antivenom and 177 envenomed cats treated without antivenom. Procedures-Medical records from 5 institutions were searched by means of a multiple-choice survey with standardized answers for patient data including signalment, diagnosis, antivenom administration criteria, premedication, product, dose, administration rate, hypersensitivity reactions, and mortality rate. 95 of 115 (82.6%) cats received whole IgG antivenom, 11 (9.57%) received F(ab')2 antivenom, and 4 (3.48%) received Fab antivenom. The majority (101/115 [878%]) of cats received 1 vial of antivenom. In all cats, the median dilution of antivenom was 1:60 (range, 1:10 to 1:250) administered over a median period of 2.0 hours (range, 0.3 to 9.0 hours). There was no mortality rate difference between cats that did (6.67%) or did not (5.08%) receive antivenom. A type I hypersensitivity reaction was diagnosed in 26 of 115 (22.6%) cats. The use of premedications did not decrease type I hypersensitivity or improve mortality rate. Cats that had a type I hypersensitivity reaction were 10 times as likely to die as were those that did not have such a reaction. The mortality rate of cats treated with antivenom was low. The administration of premedications did not improve mortality rate or prevent hypersensitivity reactions. The only variable associated with mortality rate was development of a type I hypersensitivity reaction. The rate of antivenom administration should be further evaluated as a possible risk factor for type I hypersensitivity reactions.

Hypersensitivity Reactions to Oxaliplatin: Clinical Features and Risk Factors in Koreans

Oxaliplatin hypersensitivity is a well-known adverse reaction but the prevalence varies and data for frequency and clinical features have not been reported for Korea. Here we evaluates the prevalence and risk factors for hypersensitivity reactions to oxaliplatin after chemotherapy. Clinical information on all patients treated with oxaliplatin was retrospectively reviewed in electronic medical records between August 2009 and July 2010 in Seoul National University Bundang Hospital. Patients who experienced hypersensitivity reactions to oxaliplatin were compared with those who did not. A total of 393 patients received oxaliplatin, with 42 (10.7%) experiencing hypersensitivity reactions including three cases of anaphylaxis. Median cycle of the first hypersensitivity reaction was 8. Reactions correlated with lower dexamethasone doses. Other variables were not significant. The prevalence of hypersensitivity reactions was 10.7%, symptoms being mostly mild and cutaneous. Lower dexamethasone doses could be a predictor for hypersensitivity reactions to oxaliplatin.

Race and albuterol premedication are risk factors for hypersensitivity reactions to cetuximab

20503 Background: Cetuximab (C-mab) is a recombinant (human/mouse) epidermal growth factor receptor antibody indicated for use in patients with colorectal cancer (CRC) and head and neck cancer (HNC). Serious grade 3–4 hypersensitivity reactions (HSR) to C-mab have been reported in the frequency of 0.5%-22%. The purpose of this paper is to study risk factors for HSR to C-mab at our institution. Methods: A retrospective record review was performed of serial patients treated with C-mab at the Siteman Cancer Center, St. Louis, MO for CRC from July 2004 to July 2006 and HNC from June 2005 to August 2007. HSR were defined as allergic reactions to C-mab and were graded 1–5 according to severity, based on the Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Data regarding demographics and premedication history was collected from patient charts. Results: Fifty-one patients (27 males and 24 females) with CRC and 50 patients (38 males and 12 females) with HNC treated with C-mab were identified and their mean age was 60 ±12.07 years. Seventy (69.3%) patients were Caucasian and 31 (30.7%) were African American. All patients were pre-medicated with benadryl prior to C-mab administration. Data regarding pepcid, dexamethasone and solucortef premedication was available for 84 patients. Of these, 14(16.7%) received pepcid, 32 (38.1%) received dexamethasone and 25 (29.8%) received solucortef. Twenty four (48%) of HNC patients also received albuterol. Eleven patients (10.9%) developed HSR. Serious grade 3–4 HSR were seen in 9 patients (8.9%). Race was strongly associated with HSR. All 11 patients who developed HSR were Caucasian (Fisher’s exact p=0.017). No grade 3–4 HSR were seen in the group who received albuterol (Fisher’s exact p=0.077). There was no statistically significant effect of dexamethasone, pepcid or solucortef premedication on the risk of HSR, although the small numbers were limiting. Age and gender had no effect on the risk of HSR. Conclusions: Race is a strong predictor for HSR. Additional pre-medication with albuterol may prevent grade 3–4 HSR. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Abraxis Oncology, Amgen, Bristol-Myers Squibb, Genentech™ BioOncology, ImClone Systems Incorporated, Pfizer Oncology, sanofi-aventis

Unusually high rates of hypersensitivity to cetuximab in the middle-southern United States: Association with atopic phenotype

9051 Purpose: To confirm the anecdotal observation that pts in North Carolina (NC) and Tennessee (TN) treated with cetuximab (C-mab) experience hypersensitivity reactions (HSR) at a much higher rate than that reported nationally and internationally (= 3%). Methods: Data from pts treated with C-mab on clinical trials (CTs, n = 88) at 3 research sites in TN and NC were analyzed for grade 3 or 4 HSR. Additional information was obtained from medical records under IRB approval at the University of North Carolina (UNC) for 90 pts (including 35 pts on CTs) to determine whether history of other significant allergy was a risk factor for HSR. Prior allergy was defined as history of H1 antagonist use, or notation in the medical record of significant drug allergy (excluding narcotic allergies), bee sting allergy, eczema, allergic reactive airways disease, or food allergy. Pearson's or Fisher's exact tests were used for comparison of proportions. Results: Data for 88 pts on CTs and an additional 55 pts treated outside of CTs was included in this analysis. Pts had a variety of tumor types, the most frequent being colorectal and lung For the CT group (n = 88), the overall rate of grade 3 to 4 HSR was 21.6%, significantly higher than the rate noted in any large published trial (p &lt; 0.0001 for comparison to data from Cunningham et al). All HSRs occurred during the first dose. There was no apparent protection from HSR afforded by premedication with dexamethasone in either the CT cohort or the overall UNC cohort. Upon examination of medical records of 90 pts treated at UNC (14.4% gr 3/4 HSR overall), there was a strong relationship between prior allergy history and chance of HSR; 10/28 pts with any HSR vs. 7/62 without allergy history (p = 0.006), and grade 3/4 HSR occurred in 8/28 versus 5/62, respectively (p = 0.01). Conclusions: At the sites in neighboring Southern US states studied, HSR was far more common than reported in national studies. History of prior allergy is a strong predictor of HSR, although is not specific enough to be used as the sole means of excluding pts from therapy. Further investigation of more specific predictors of HSR in the US Middle South is warranted, and pts being treated with C-mab in the region should be observed particularly closely during their first infusion. No significant financial relationships to disclose.

Epidemiological risk factors for hypersensitivity reactions to abacavir.

We investigated risk factors for hypersensitivity reactions (HSR) to abacavir in a case-control study. In a multivariate analysis, white race [odds ratio (OR), 5.16; 95% confidence interval (CI), 1.16-22.97] and a higher CD8 cell count at initiation of abacavir (>850 vs. < or =850 cells: OR, 3.74; 95% CI, 1.19-11.77) were found to be significantly associated with the development of HSR. Age, gender, stage of disease, prior antiretroviral exposure and type of concurrent antiretroviral therapy were not associated with HSR. Differences in predisposition to HSR according to ethnicity and baseline CD8 cell count may be explained by the reported MHC genetic associations with HSR.

Role of polymorphic and monomorphic human arylamine N-acetyltransferases in determining sulfamethoxazole metabolism

Sulfonamides are associated with a variety of adverse reactions, some of which have been linked with the classical acetylator phenotypes. Although the slow acetylator phenotype has been identified as a risk factor for hypersensitivity reactions to sulfamethoxazole (SMX), the disposition of this compound appears not to be affected by the acetylation polymorphism in vivo in humans. We therefore investigated the acetylation of SMX by monomorphic (NAT1) and polymorphic (NAT2) arylamine N-acetyltransferases in humans with the objective of determining their role in the metabolism of SMX. SMX was acetylated by both NAT1 and NAT2. K m values determined in hepatic cytosol for NAT1- and NAT2-mediated acetylation of SMX were 1.2 mM and approximately 5 mM, respectively, at an acetyl coenzyme A concentration of 100 μM. Mononuclear leukocytes, which contain only NAT1, had a K m value of 1.2 mM. K m values determined with recombinant NAT1 and NAT2 proteins expressed in Escherichia coli were 1.5 mM and approximately 15 mM, respectively. The higher affinity of NAT1 for SMX indicates that acetylation by this enzyme will predominate at therapeutic plasma concentrations, in agreement with the observed in vivo monomorphic acetylation of SMX. NAT1 may be the primary determinant of SMX systemic metabolic clearance. However, in the hepatocyte NAT2 variation may be an important competitive pathway which influences the extent of oxidative metabolism of SMX to its reactive hydroxylamine metabolite. Therefore, variation in both monomorphic and polymorphic N-acetyltransferases may play a role in determining susceptibility to sulfamethoxazole toxicity.