Rapid Desensitization Protocol Research Articles

Rapid Drug Desensitization Protocol in Delayed Hypersensitivity Reactions to CFTR Modulator Drugs: When Every Day Counts.

Rapid Drug Desensitization Protocol in Delayed Hypersensitivity Reactions to CFTR Modulator Drugs: When Every Day Counts.

Successful desensitization in a patient with metastatic colorectal cancer presenting with regorafenib-mediated fix drug eruption.

Regorafenib is an oral protein kinase inhinitor approved fot the treatment of metastatic colorecral cancer. We present a first successful case of desensitization in regorafenib-related fix-drug eruption in the literature. A 44-year-old female patient was diagnosed with metastatic colorectal adenocarcinoma. The patient received regorafenib treatment for malignancy recurrence. The patient was admitted to adult allergy clinic with developing recurrent fix drug eruption in the second cycle, on the 10th day of regorafenib treatment. The patient was given the third cycle of regorafenib treatment with a 6-day desensitization protocol, the first day of which consisted of 6 steps and and the third cycle was successfully completed. Regorafenib-mediated delayed hypersensitivity reactions occur less frequently and and regorafenib hypersensitivity reactions are difficult to manage and experience is limited. This is the first successful desensitization protocol developed by us for regorafenib-related fix drug eruption and more cases are needed to be reported to confirm the desensitization protocol. There is only one successful regorafenib desensitization protocol for severe delayed hypersensivity reaction in the literature, but there is no protocol developed for mild type delayed hypersensivity reaction. The management of fix-drug eruption primarily involves discontinuation and avoidance of the offending drug but our patient had a mild delayed-type reaction and there was no alternative to regarofenib treatment. We developed the rapid 6-step desensitization protocol (Day 1). According to this protocol, the patient was able to continue regorafenib treatment successfully.

Rapid Desensitization to Antitumoral Agents. Result from a Retrospective Study, DESARCh

Antitumoral drugs (ADs) can induce drug hypersensitivity reactions (DHRs). Rapid drug desensitization (RDD) protocols represent an important option to mitigate recurrent DHRs thus allowing the safe administration of ADs at therapeutic doses. The aim of this retrospective study was to assess the effectiveness of the RDD protocols performed at our institution. The “DESARCh” study was a retrospective, observational study that included consecutive patients who underwent RDD protocols from January 2011 to December 2022 at IRCCS Ospedale Sacro Cuore Don Calabria in Negrar di Valpolicella, Verona, Italy. The RDD protocol consisted of a 5-step protocol with 5 different concentrations of the drugs at 1:1, 1:10, 1:100, 1:1,000 and 1:10,000 dilution given intravenously over a 1-hour infusion each, with concentrations increasing from the most diluted to the most concentrated form, preceded by a 30-min premedication regimen. A total of 66 RDD protocols were administered to 25 female patients with ovarian (64%; n = 16/25), breast (12%; n = 3/25), endometrium (8%; n = 2/25), cervix (8%; n = 2/25), uterine (4%; n = 1/25) and fallopian tubes (4%; n = 1/25) cancers. A known history of atopy/allergy was reported by 36% (n = 9/25) of patients. Patients received RDD protocols because of DHRs to carboplatin (n = 23/66, 34.85%), paclitaxel (n = 18/66, 27.27%), pegylated liposomal doxorubicin (n = 3/66, 4.55%), and trastuzumab (n = 22/66, 33.33%). DHRs were mild-moderate, severe and life-threatening in 60.72%, 28.57% and 10.71% of cases, respectively. The success rate of RDD protocols, defined as the rate of complete administration of full target dose with no breakthrough reactions, was 81.82% (n = 54/66). Success rate was lower for carboplatin compared to other drugs (65.22% vs 90.7%; P = .017678). The RDD protocol used in our institution was found to be safe, with a meaningful success rate. However, further research is needed to better understand the underlying mechanisms of DHRs and to enhance effectiveness, particularly for patients experiencing DHRs to platinum compounds. This study was approved by the ethics committee of Verona and Rovigo (Italy) with approval number 15476 on 10/03/2023 and it was registered with the Register of Observational Studies of the Italian Medicines Agency (AIFA) (available since 31 January 2023), with ID n. 109, on 28/02/2023 ( https://www.aifa.gov.it/en/registro-studi-osservazionali ).

Successful rapid liposomal amphotericin B desensitization in pediatric case series.

Background: Liposomal amphotericin B (LAMB) is a crucial agent in the treatment of invasive fungal diseases caused by a wide variety of yeasts and molds. In the presence of an infection caused by a fungal agent resistant to alternative antifungal drugs, desensitization may be the only option to continue treatment. However, there is insufficient information and consensus with regard to amphotericin B desensitization protocols in the pediatric age group. Objective: We present our experience with five cases of patients in whom successful desensitization protocols were applied with LAMB, along with a review of the literature on pediatric cases. We also provide a sample desensitization protocol that we successfully applied. Methods: Pediatric patients who continued their treatment with the successful rapid desensitization protocol conducted at the Paediatric Allergy and Immunology Clinic of the Ministry of Health Ankara City Hospital between September 2019 and September 2023 were examined. Desensitization protocols were applied based on Castells' desensitization protocol. Results: Five patients ages between 5 and 12 years were referred to us due to the development of anaphylaxis during their treatment with LAMB. Anaphylaxis is diagnosed clinically, according to the European Academy of Allergy and Clinical Immunology guidelines: anaphylaxis (2021 update). A 16-step desensitization protocol was prepared by using LAMB solutions at four different dilutions (0.001, 0.01, 0.1, and 1 mg/mL). Each solution consisted of four steps, with a 15-minute infusion for each step. The patients were premedicated with 1 mg/kg/dose methylprednisolone and an antihistamine. Conclusion: The data we present on the successful application of a sample protocol to five cases, particularly in a pediatric setting, are noteworthy valuable contributions to the field, which demonstrates the feasibility and success of rapid desensitization with LAMB in pediatric patients. This can provide important insights and potentially serve as a reference for medical professionals working with similar cases in the future.

Prevention of allergic reactions during oxaliplatin desensitization through inhibition of Bruton tyrosine kinase

BackgroundAcute infusion reactions to oxaliplatin, a chemotherapeutic used to treat gastrointestinal cancers, are observed in about 20% of patients. Rapid drug desensitization (RDD) protocols often allow the continuation of oxaliplatin in patients with no alternative options. Break-through symptoms including anaphylaxis can still occur during RDDs. ObjectiveTo evaluate if pretreatment with acalabrutinib, a Bruton’s tyrosine kinase inhibitor, can prevent anaphylaxis during a RDD in a patient sensitized to oxaliplatin. MethodsA 52-year-old male with locally advanced gastric carcinoma developed anaphylaxis during his 5th cycle of oxaliplatin. As he required 6 additional cycles to complete his curative-intent treatment regimen, he underwent RDD to oxaliplatin but still developed severe acute reactions. The risks and benefits of adding acalabrutinib prior to and during a RDD, were reviewed and he elected to proceed. ResultsWith acalabrutinib taken prior to and during the RDD, the patient was able to tolerate oxaliplatin RDDs without complication. Consistent with its mechanism of action, acalabrutinib completely blocked the patient’s positive skin prick response to oxaliplatin. Acalabrutinib did not alter the percentage of circulating basophils (1.24% versus 0.98%) prior to the RDD but protected from basopenia (0.74% versus 0.09%) after the RDD. Acalabrutinib was associated with a drastic reduction in the ability of basophils to upregulate CD63 in vitro following incubation with oxaliplatin (0.11% versus 2.38%) or polyclonal anti-human IgE antibody (0.08% versus 44.2%). ConclusionsFive doses of acalabrutinib 100mg orally twice daily starting the evening 2 days before and continuing through a RDD allowed a sensitized patient to successfully and safely receive oxaliplatin.

Hypersensitivity reactions with first-line antituberculosis drugs and outcomes of rapid desensitizations

BackgroundData about drug hypersensitivity reactions with first-line antituberculosis drugs and their management is limited. Rapid drug desensitization seems to be an appropriate management. ObjectiveEvaluate the efficacy of the rapid desensitization protocols in patients who had a reaction phenotypically compatible with immediate-type drug hypersensitivity with first-line antituberculosis drugs and identify possible risk factors of breakthrough reactions during the protocols. MethodsThis is a retrospective study of active tuberculosis patients who had a reaction phenotypically compatible with immediate-type drug hypersensitivity with first-line antituberculosis drugs and underwent desensitization with the drugs used during the reaction. Characteristics of drug hypersensitivity and breakthrough reactions, and outcomes of rapid desensitizations were recorded. ResultsOne hundred and seventy-nine patients were included in the study. Most of the initial reactions (n = 132, 73.7%) occurred within the first week of treatment and were mild (n = 146, 81.6%). A total of 690 desensitizations were performed. Desensitizations were successfully completed without any breakthrough reaction in 103 (57.5%) patients and in 29 of 36 (80.6%) patients after a breakthrough reaction. The overall success of desensitizations were found to be 95% (132 of 139 patients). Most of the breakthrough reactions (84%) were mild. Sixteen patients had breakthrough reactions with multiple drugs. Although pyrazinamide was the most common culprit of breakthrough reactions and had the lowest desensitization success, it had the highest rate of a single breakthrough reaction (p < 0.001). Timing of the initial reaction and concomitant breakthrough reaction with ethambutol were found to have increased the risk for breakthrough reaction caused by rifampicin (p = 0.017 and p = 0.010 respectively). ConclusionThe rapid desensitization protocols used in this study provide a successful and effective management of the patients with a reaction phenotypically compatible with immediate-type drug hypersensitivity with first-line antituberculosis drugs.

THU655 Methimazole Desensitization As An Effective Alternative To Ablation Therapy In Patients With Graves’ Disease Experiencing Thionamide-induced Type IV Hypersensitivity Reactions

Abstract Disclosure: J. Arguinchona: None. A. Mahajan: None. A. Gonzalez-Estrada: None. E. De Filippis: None. Introduction: Patients with newly diagnosed Graves’ disease often choose treatment with methimazole (MMI) over traditional ablation therapies. However, MMI can result in adverse reactions including skin rash, pruritus, and urticaria. We present a case of Graves’ thyrotoxicosis with a type IV hypersensitivity reaction while on MMI. The patient was successfully treated with a novel, individualized, 27-day desensitization protocol which resulted in tolerance of MMI with subsequent improvement in thyroid indices. Clinical Case: A 42-year-old female presented for abnormal thyroid studies with associated insomnia, heat intolerance, palpitations, resting tremor, and weight loss. Lab work revealed a thyroid-stimulating hormone &amp;lt;0.005 (0.450-4.500 μIU/mL), free thyroxine 3.28 (0.82-1.77 ng/dL), triiodothyronine 310 (71-180 ng/dL), thyroid peroxidase antibody (Ab) 62 (0-34 IU/mL), thyroid-stimulating immunoglobulin 0.67 (0.00 -0.55 IU/L), and thyrotropin receptor Ab of 6.00 (0.00-1.75 IU/L). She was started on MMI, 10 mg daily for Graves’ disease. Three weeks later, T3 and T4 remained elevated prompting an increase in MMI dose to 10 mg twice daily. Two weeks later, she developed a diffuse, pruritic maculopapular exanthema over her trunk, neck, and extremities. Methimazole was discontinued while prednisone was initiated that subsided her rash. Unfortunately, the patient’s symptoms recurred upon repeat MMI exposure. The patient declined propylthiouracil due to concerns of hepatotoxicity and elected to avoid ablation therapy with iodine or surgery. With the assistance of an allergist, a novel, 10-step, 27-day desensitization protocol was developed specifically for her reaction to MMI with plans to taper prednisone once desensitization was completed. The patient underwent desensitization with development of mild lower extremity exanthema that was successfully treated with high dose antihistamines. Three months later, she was tolerating MMI at 15 mg daily without further adverse reactions and tapered off prednisone. While on MMI, her immune titers normalized with euthyroid clinical and biochemical restoration. Conclusion: Many patients and clinicians initially prefer medical management over definitive ablation therapies in the treatment of Graves’ disease. This case demonstrates with the assistance of an allergist, desensitization to MMI is a viable option in the setting of a known hypersensitivity reaction when it is the first line treatment and no equally efficacious alternatives exist. In addition, patient’s preferences should also be considered during medical decision making. Previous literature has offered various rapid desensitization protocols for MMI for immediate type hypersensitivity reactions. However, in non-immediate, type IV hypersensitivity reactions, a slower desensitization protocol can be considered, as demonstrated in this case. Presentation: Thursday, June 15, 2023

A safe, effective, and single-day protocol for rapid drug desensitization to intravenous iron dextran.

A safe, effective, and single-day protocol for rapid drug desensitization to intravenous iron dextran.

A Pilot Experience Using a 1-Bag Intravenous Rapid Desensitization Protocol for Chemotherapy and Biologics in a Cohort of Patients With Access to a Delabeling Pathway.

A Pilot Experience Using a 1-Bag Intravenous Rapid Desensitization Protocol for Chemotherapy and Biologics in a Cohort of Patients With Access to a Delabeling Pathway.

Oxaliplatin-induced hypersensitivity reactions: risk factors and management.

Chemotherapy-related adverse reactions have been steadily increasing in recent years. In patients who develop oxaliplatin-induced hypersensitivity reactions (HSRs), prognosis and quality of life are adversely affected. Proper management of cancer patients enables them to safely receive first-line treatments. This study aimed to assess the risk factors in oxaliplatin-induced HSRs and the effectiveness of the rapid desensitization protocol. In the study, 57 patients treated with oxaliplatin between October 2019 and August 2020 in the Medical Oncology Department of Elazig City Hospital were retrospectively evaluated. We analyzed patients' clinical histories to reveal any associations with the development of oxaliplatin-induced HSRs. Moreover, we re-evaluated 11 patients with oxaliplatin-induced HSRs through infusion time or desensitization procedures. Of 57 patients treated with oxaliplatin, 11 (19.3%) had HSRs. Patients with HSRs were younger and had higher peripheral blood eosinophil counts than those without HSRs (p=0.004, p=0.020, respectively). Prolongation of the infusion time was effective in the re-administration of oxaliplatin in six of the hypersensitive patients. Rapid desensitization protocol was performed for a total of 11 cycles in four patients with recurrent HSRs, and their chemotherapy regimens were successfully completed. This retrospective study has revealed that younger ages and higher peripheral eosinophil counts could be predictive for oxaliplatin-induced HSR. Furthermore, the study confirms that prolongation of the infusion time and rapid desensitization protocol are effective in patients with HSRs.

Toxicity management and efficacy of carboplatin desensitization therapy for recurrent epithelial ovarian carcinoma: A real-world study.

Epithelial Ovarian cancer (EOC) is the most lethal gynecologic cancer worldwide. Carboplatin (CP) is the main chemotherapeutic agent in the treatment of ovarian cancer. However, the development of a hypersensitivity reaction (HSR) in 10% to 15% of patients with EOC is an important limiting factor for the clinical use of CP. Herein, we aimed to investigate the efficacy and safety of CP-desensitization (CP-D) therapy in the treatment of recurrent patients with EOC. Forty-seven ovarian cancer cases treated with CP-desensitization at the Istanbul University Oncology Institute were retrospectively analyzed between 01.01.2017 and 01.01.2022. The decision for CP-D was based on the patients' history of HSR and/or a positive skin test. For all patients, a 6-hour 12-step rapid drug desensitization protocol with a 30-minutes premedication regimen was used. Forty-seven patients were included in this study, and the median age at diagnosis was 53 years (range; 27-80). Twenty-one (43.7%) patients had 1 or more comorbid diseases, and 12.7% had a previous history of drug allergy. On average, HSR due to carboplatin was identified after 9 (7-16) cycles, and carboplatin was administered n = 11 (range, 3-36) times to patients. The overall survival from the first desensitization procedure (0S2) was 42.2 months (range: 25.3-59.1), and the 1-, 2-, and 5-years survival rates were 92.6%, 75.6%, and 47.2%, respectively. The objective response rate (ORR) was 78.5%. Cumulatively, 496 CP-D procedures were performed, of which 478 (96.3%) were successfully completed. None of the patients included in this study developed severe (grade 3-4) HSR during CP administration (no adrenaline was used, no need for intensive care). No deaths due to CP-D were noted. CP-D is a beneficial and safe method in treating platinum-sensitive recurrent EOC patients with CP-induced HSR.

Novel approach to idursulfase and laronidase desensitization in type 2 and type 1 S mucopolysaccharidosis (MPS)

Background:Idursulfase and laronidase are drugs used to treat Hunter syndrome (mucopolysaccharidosis type 2) and Scheie syndrome (mucopolysaccharidosis type 1 S), respectively. These are rare lysosomal storage disorders, leading to accumulation of glycosaminoglycans within lysosomes. Failure of early recognition of the disease and/or delay in starting the appropriate treatment result in severe clinical impairment and death. For almost 20 years, enzyme replacement therapy with recombinant proteins has represented the first line therapeutic option. However, administration of idursulfase and laronidase is associated with infusion-related hypersensitivity reactions, in approx. 20% of patients. In these patients, rapid desensitization by intravenous administration protocols has been used in order to avoid treatment discontinuation. This approach proved effective and safe. However, long-term tolerance could not be achieved. Thus, we decided to combine rapid desensitization with allergen immunotherapy-like desensitization.Results:Two patients with Hunter syndrome and one patient with Scheie syndrome developed severe allergy to idursulfase and laronidase, respectively, preventing them from continuing the otherwise indispensable therapy. In all three patients, the possible IgE-mediated nature of the reactions suffered was suggested by positive skin tests with the two enzymes, respectively. By devising 12-step, 3-dilution rapid desensitization protocols, we resumed the enzyme replacement therapy. However, the prolonged time required for administration (a not negligible pitfall, since therapy should be given weekly for life) and the persistent occurrence of reactions (mild but still requiring anti-allergic medication at full dosage) led us to combine rapid desensitization with a compact 11-step, 24-day allergen immunotherapy-like desensitization protocol. Thus, idursulfase and laronidase were injected subcutaneously, with a 500-fold increase from step 1 to step 11 for idursulfase and a 222-fold increase for laronidase. This strategy led to restoration of long-term tolerance, allowing weekly intravenous therapy administration under standard conditions, according to the manufacturer instructions, in the absence of side effects and with only precautionary low-dose premedication.Conclusion:Rapid desensitization is a suitable and safe option in the case of idursulfase and laronidase allergy. Combination with subcutaneous allergen immunotherapy-like desensitization afforded restoration of enzyme replacement therapy given by the normal administration schedule, by inducing sustained tolerance.

A SUCCESSFUL 4-HOUR ACETYLSALICYLIC ACID DESENSITIZATION PROTOCOL IN AN ATOPIC PATIENT WITH ACUTE CORONARY SYNDROME

<h3>Introduction</h3> Acetylsalicylic acid (ASA) is the world's most widely used drug, essential for treating patients with cardiovascular diseases, in particular acute coronary syndrome (ACS) and chronic ischemic heart disease. ASA and other non-steroidal anti-inflammatory drugs (NSAIDs), especially those that inhibit cyclo-oxygenase-1, can cause hypersensitivity reactions. A history of ASA hypersensitivity typically leads to the avoidance of this potentially lifesaving therapy in patients with coronary artery disease (CAD). ASA desensitization is crucial in patients with ACS and a history of ASA hypersensitivity reactions. <h3>Case Description</h3> A 58-year-old male with a long history of hypertension and unspecified arrythmia was admitted due to acute chest pain. He referred previous hypersensitivity reactions to NSAIDs (ASA, acetaminophen, ibuprofen and metamizole) from hives to angioedema, as well as previous history of allergic rhinitis, fruit-latex syndrome, eosinophilic esophagitis, chronic spontaneous urticaria and angioedema. Initial work-up confirmed the diagnosis of acute myocardial infarction without ST elevation and the patient underwent early coronary angiography with drug-eluting stent placement. Due to previous reactions to ASA and the indication of dual anti-platelet therapy, bedside desensitization was performed including pretreatment with montelukast and cetirizine. The patient successfully completed the oral ASA desensitization protocol in 8 steps, reaching a cumulative dose of 308 mg (Figure 1). Nine months after the procedure the patient continued with 100 mg of ASA daily without adverse reactions. <h3>Discussion</h3> ASA rapid desensitization protocols have proven to be safe and effective in patients with CAD, including ACS, independent of the type of ASA hypersensitivity, reducing associated morbimortality.

Safety and efficacy of rapid drug desensitization in children.

Any drug taken at the recommended dosage may cause hypersensitivity reactions (DHR). Rapid drug desensitization (RDD) protocols have been developed in the case of a confirmed or highly suspected HSR to allow safe administration of the medicine when there is no alternative drug or in the presence of a less effective or more toxic alternative. The aim of this study was to evaluate the characteristics of children who underwent desensitization, the safety and efficacy of RDD in children, as well as, the characteristics and management of breakthrough reactions. This retrospective study concerned children who underwent RDD due to physician-diagnosed HSRs during or up to 48hours after the infusion of various drugs between February 2010-February 2021. Patients with a chronic disease needing chronic drug usage and acute infections seen in patients with chronic diseases were included. The results of RDD were documented. The study included 48 patients [8.1(IQR = 3.32-13.4) years, 60.4% male] with 58 HSRs of which 62.1% were classified as moderate and 5.2% as severe. Most of the patients were being treated for leukemia (41.7%), solid tumors (29.2%), and infections (6.3%). Skin tests were done for 41 out of 58 HSRs in 35 patients, and twenty of them were positive. A total of 269 RDDs were performed for 18 different drugs. Ninety percent of desensitizations were achieved with no reaction, and 3.7% and 5.6% with mild and moderate reactions, respectively. In multivariate analysis, skin test positivity was the only risk factor for breakthrough reactions (OR = 8.5, CI = 1.72-42.15, p = .009). We demonstrated the safety and efficacy of RDD in childhood, thereby offered the first line treatment options to children with chronic diseases with hypersensitivity reactions (HSRs).

Management and Successful Desensitization in a Patient with Abatacept-Induced Anaphylaxis

ABSTRACT Abatacept is a fusion protein that blocks T cell activation. It is used in a variety of conditions including organ transplantation, immune deficiency, and autoimmune diseases. Even though abatacept-induced adverse events are observed, hypersensitivity reactions are rare. Desensitization protocols that can be implemented in the case of hypersensitivity reactions are present in the literature for many biological agents. However, a desensitization protocol for abatacept has not yet been established. Our patient, who was started on one of the biological agents, abatacept, for rheumatoid arthritis due to insufficient response to disease- modifying antirheumatic drugs, developed immediate hypersensitivity reaction with the first dose. Since it was planned to continue the treatment, abatacept desensitization was performed. The rapid desensitization protocol performed with prior premedication was successful and the patient was able to receive subsequent doses of abatacept using the same protocol. Keywords: Abatacept, anaphylaxis, desensitization

A 6-step rapid desensitization protocol to hydroxychloroquine

A 6-step rapid desensitization protocol to hydroxychloroquine

A New Successful Rapid Desensitization Protocol for Hypersensitivity Reactions to Carboplatin and Rituximab in the Pediatric Setting

Introduction Hypersensitivity reactions (HSRs) can be induced by many medications, including chemotherapy agents and monoclonal antibodies (mAbs). Virtually all chemotherapeutics have the potential to initiate infusion reactions. Allergies to chemotherapeutics and biologic agents usually manifest with skin symptoms (rash, itching, and swelling), angioedema, or even potentially fatal anaphylactic reactions. Medication allergies may lead to discontinuation of life-prolonging therapies and therefore worsen prognosis. For clinical situations where hypersensitivity reactions prevent administration of a critical medication, desensitization can be an extremely useful addition to the clinical toolkit. In the early 2000s, multiple clinical trials showed that Rapid Drug Desensitization (RDD) for chemotherapy and mAbs was safe and effective in improving clinical outcomes and allowing patients to remain on preferred first-line therapy. Desensitization is challenging however, and this is reflected in variable success rates reported in the literature. One recent review noted successful desensitization in anywhere from 20 to 75% of cases (Ruggiero et al. 2017). This wide range is likely due to different methods of desensitization used in various studies. There are multiple variables influencing the success of desensitization, including the starting dose, the infusion rate, and the number of increments. Desensitization protocols are often complex requiring multiple changes in the rate and volume of medication administered between steps--making it difficult to complete them correctly. We have developed a new, simpler desensitization method that does not require multiple changes in the infusion rate and volume, thus reducing clinical confusion and leading to improved patient outcomes. Methods We developed a standardized protocol for rapid desensitization in patients who had hypersensitivity reactions to carboplatin or rituximab. This new desensitization method utilizes the same rate, administration time, and volume for each dose, only changing the drug concentration gradually between steps. This method helps minimize the chance of errors that occur due to repeatedly reprogramming the rate and volume of the infusion. A total of 10 patients were treated under this desensitization protocol between November 2017 and June 2020 for a total of 76 desensitization episodes. Initial desensitization occurred in the medical intensive care unit and subsequent infusions of carboplatin took place in an outpatient hematology-oncology setting. We retrospectively analyzed safety and efficacy of this novel desensitization protocol through review of treatment records. Results Of the 76 desensitizations performed, no adverse reactions occurred during desensitization and patients received their full target dose in all cases. No breakthrough reactions were noted during subsequent infusions of carboplatin or rituximab in desensitized patients. To prevent breakthrough reactions, antihistamines, corticosteroids and a leukotriene modifier were administered as pre-medications. Patients undergoing carboplatin desensitization were able to be switched from a 12-step protocol to a 10-step protocol with the same 100 % success rate in completing the entire planned cycle of chemotherapy. Discussion This retrospective analysis demonstrated a statistically and clinically significant reduced rate of breakthrough reactions in comparison to previous reports (Brennan et al. 2009). The other benefits of this novel method include improvement in safety of administration and cost savings. Disclosures No relevant conflicts of interest to declare.

Novel Protocol for Rapid Desensitization of Melphalan in a 5-Year-Old Boy Undergoing Conditioning for Hematopoietic Stem Cell Transplantation: A Case Report

Hematopoietic stem cell transplantation is a potentially life-saving therapy under certain conditions. Hypersensitivity reaction to chemotherapeutic drugs may interfere with this treatment. Griscelli syndrome type 2 is a rare autosomal recessive disease characterized by hypopigmentation of skin and hair, causing silver gray hair; this disease may develop a fatal condition called hemophagocytic lymphohistiocytosi. The main curative treatment for hemophagocytic lymphohistiocytosi is hematopoietic stem cell transplantation. Melphalan is an important drug in hematopoietic stem cell transplantation preparation regimen. This drug is only stable for 60 minutes following reconstitution with normal saline. There is a recommended 12- to 20-step desensitization protocol for moderate to severe hypersensitivity reaction to chemotherapeutic drugs. However, due to the short term stability of melphalan, this protocol cannot be employed in desensitization. In this case report, we presented a novel protocol for rapid desensitization of melphalan in a 5-year-old boy with immediate, moderate to severe hypersensitivity reaction, during hematopoietic stem cell transplantation. To obtain 50 mg total melphalan , we prepared solutions of drug in two bags; one with 12.5mg in 35 cc normal saline, and other with 25 mg in 35 cc normal saline. Each solution was infused during 60 minutes by incremental infusion rate, and the total of 50 mg melphalan was successfully infused.

Rapid Desensitization with Intravenous Insulin in a Patient with Diabetic Ketoacidosis and Insulin Allergy

We report a case of insulin desensitization in a patient with known allergy to multiple insulin preparations who presented with diabetic ketoacidosis (DKA). Clinical and laboratory data, and desensitization protocols are presented. A 65-year-old woman with type 2 diabetes and a documented insulin allergy presented with severe DKA. She was managed initially with intravenous (IV) fluids, sodium bicarbonate, and hemodialysis. An intradermal skin test was positive for 0.01 units/mL of human regular insulin. A rapid desensitization protocol for IV human regular insulin was initiated after pretreatment with methylprednisolone, ranitidine, montelukast, and cetirizine. An initial dilution of 1 unit of insulin in 100,000 mL of 0.9% sodium chloride was started at 5 mL/hour IV. The dilution was increased at 60-minute intervals to 1 unit/10,000 mL, 1 unit/1,000 mL, 1 unit/100 mL, 1 unit/10 mL, then 1 unit/1 mL. The dose was then increased from 1 to 7 units/hour (0.1 units/kg body weight/hour). The anion gap closed after 24 hours, and overlapping desensitization was started for subcutaneous (SC) human regular insulin starting with 0.00001 units with a gradual increase to 7 units before meals and 6 units at bedtime over 5 days. There were no anaphylactic reactions to IV or SC insulin. She was discharged with human regular insulin SC 4 times daily, oral montelukast, cetirizine, diphenhydramine as needed, and an epinephrine pen. No allergic reactions were reported at follow-up visits. Rapid insulin desensitization is possible to allow treatment of DKA with human regular insulin IV in patients with known insulin allergy.

A rapid desensitization protocol in a case of drotaverine-induced serum sickness-like reaction in a pregnant woman: A case report.

Drotaverine is an antispasmodic drug used to treat gastrointestinal and genitourinary smooth muscle spasms. There are very few hypersensitivity reactions reported. Serum sickness-like disease is an immune-complex-mediated hypersensitivity reaction that presents with some typical features that include rash, fever and articular impairment sometimes associated with liver and renal dysfunctions, beginning 1-2 weeks after exposure to a culprit drug. Diagnosis is a clinical one, made usually on the basis of knowledge obtained by medical history and physical examination. Desensitization usually is recommended for type I reaction, but may be a solution for this type of immunological reaction when other therapeutic alternatives are ineffective or do not exist. We report the case of a 29-year-old pregnant female who developed serum sickness-like reaction after 5 days of daily drotaverine oral administration. The patient required antispasmodic treatment, with this drug, having a pregnancy with an imminent risk of abortion and the other therapeutic alternatives being ineffective. She underwent a rapid 7-step oral drotaverine desensitization protocol without recurrence of serum sickness-like reaction. To our knowledge, this is the first case report of desensitization to drotaverine, previously involved in a serum sickness-like reaction.