A case report of anaphylaxis caused by initial administration of rasburicase resulting in death just before the treatment of diffuse large B cell lymphoma

A case report of anaphylaxis caused by initial administration of rasburicase resulting in death just before the treatment of diffuse large B cell lymphoma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A case report of anaphylaxis caused by initial administration of rasburicase resulting in death just before the treatment of diffuse large B cell lymphoma Yoshikazu Utsu, Natsuho Kaneda, Makio Kawakami, Shin-ichi Masuda, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4204004/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Oct, 2024 Read the published version in Allergy, Asthma & Clinical Immunology → Version 1 posted 10 You are reading this latest preprint version Abstract Background: Rasburicase has potent efficacy in controlling uric acid and is widely used to prevent tumor lysis syndrome in high-risk patients owing to its low toxicity profile. However, the safety of rasburicase re-administration has not been established due to the risk of anaphylaxis mediated by antibody production. However, reports of such reactions upon the initial administration of rasburicase are scarce. Case presentation: A 71-year-old Japanese female who had been diagnosed with diffuse large B cell lymphoma with a large tumor burden experienced anaphylactic shock leading to death that occurred upon initial administration of rasburicase just before the chemotherapy. The patient had several unfavorable characteristics that resulted in a fatal outcome, including a predisposition to allergies. Moreover, there was a large tumor in the posterior mediastinum that, although it would not cause a significant issue under normal circumstances, could severely impact hemodynamics if the patient entered into a state of shock. Chest compressions during cardiopulmonary resuscitation resulted in crushing of the tumor. The pre-and postmortem examination revealed that the cause of death was a cascade of events starting with anaphylaxis-induced distributive shock leading to obstructive shock due to collapse of the heart, which was compressed by the tumor. This was further compounded by massive bleeding from the tumor and tension hemothorax, resulting in circulatory collapse. Conclusions: Anaphylaxis can lead to lethal outcomes when unfavorable conditions overlap. Clinicians need to carefully assess the indication for rasburicase, considering both the risk of tumor lysis syndrome and the patient’s background risks simultaneously. rasburicase anaphylaxis initial administration lymphoma shock asthma Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Rasburicase, a recombinant form of urate oxidase, has demonstrated potent efficacy in controlling uric acid in several trials of pediatric and adult patients with hematologic malignancy [1, 2]. Although rasburicase is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency because of the risk of hemolysis [3, 4], its safety profile has been demonstrated in clinical trials of patients without glucose-6-phosphate dehydrogenase deficiency. Currently, with the accumulation of experience on its use, rasburicase has become widely recommended and is used as a prophylactic agent for high-risk patients (and some intermediate-risk patients) with tumor lysis syndrome (TLS) with various types of malignant tumor [5–7]. As rasburicase is a recombinant enzyme that does not naturally exist in humans, antibody production occurs at a rate of approximately 2–10% after administration [8, 9], and regulatory authorities in Japan (Pharmaceuticals and Medical Devices Agency), as well as the supplier (Sanofi K.K., Tokyo), do not recommend the re-administration of rasburicase owing to its unestablished safety in the package insert of their distributed product Rasuritek. Although the frequency of anaphylaxis upon re-administration is reported to be 0–6.2% [10, 11], there has only been one report of a patient with anaphylaxis upon the first administration of rasburicase [3], while there have been no case reports of fatalities due to anaphylaxis. Herein, we report our experience of a patient with anaphylaxis following the initial administration of rasburicase before the treatment of malignant lymphoma, finally leading to death. We have also reviewed relevant published reports. Case presentation A 71-year-old Japanese female was admitted to the hematology unit of our hospital to undergo chemotherapy for newly diagnosed diffuse large B cell lymphoma (DLBCL). She had complained of dry cough and back pain that gradually worsened over 1 month. She consulted a local doctor and underwent a computed tomography (CT) scan, which revealed a posterior mediastinal mass with a diameter of 12 cm compressing the heart (Fig. 1 ). She underwent a bronchoscopic biopsy at our institution 10 days before her admission and was diagnosed with stage II DLBCL not otherwise specified, with a bulky mass. She had been undergoing treatment for bronchial asthma, taking steroids orally and via inhalation, and her condition was well controlled. She had a history of drug-induced rash with ambroxol and oral third-generation cephalosporin antibiotics. She had little to no impairment in her daily activities, with an Eastern Cooperative Oncology Group Performance Status of 1. On blood examination, lactate dehydrogenase and soluble interleukin-2 receptors showed mild elevation (379 U/L and 578.0 U/mL, respectively). All other parameters were within normal ranges. Although we planned to administer polatuzumab, rituximab, cyclophosphamide, doxorubicin, and prednisolone (Pola-R-CHP) as the initial therapy, we decided to administer rasburicase for the prevention of TLS prior to chemotherapy, considering the large tumor burden. Immediately after rasburicase administration, the patient complained of dyspnea, and generalized erythema and wheezing were observed. Shortly thereafter, her blood pressure plummeted and became unmeasurable, and she went into cardiopulmonary arrest (CPA). Immediate cardiopulmonary resuscitation (CPR) measures, such as chest compressions and artificial ventilation by ward physicians and nurses, were initiated. Pharmacological interventions, including repetitive adrenaline, high-volume extracellular fluid, steroids, and antihistamines, were also administered. The resuscitation efforts were appropriately continued by specialized staff following the Immediate Life Support protocol [12], but it took 20 minutes to achieve recovery of the self-circulation. Subsequently, CPA occurred again and recovery of the self-circulation was achieved; however, the circulation remained extremely unstable, necessitating the placement of a percutaneous cardiopulmonary support device. However, little improvement was observed. CT revealed massive pleural effusion compressing the right lung and the heart (Fig. 2 ). The patient died 5 days after the administration of rasburicase despite maximal supportive care. Postmortem pathological examination revealed massive hemothorax filling the right pleural cavity and crushed lymphoma of the posterior mediastinum, which was speculated to have resulted from major bleeding due to mechanical injury of the tumor by chest compressions during CPR (Fig. 3 ). The right lung and heart had collapsed due to hemothorax. Discussion and Conclusions Anaphylaxis caused by rasburicase is rare, with past reports suggesting a rate of 0–6.2% in the setting of re-administration [8,9], and only one case of anaphylaxis has been described upon initial administration of rasburicase [3]. The estimated lifetime prevalence of anaphylaxis, regardless of the cause, is 0.3–5.1% [13], and its mortality is estimated at 0.5–1 per million population [14]. The mortality rate of patients diagnosed with anaphylaxis is estimated at 0.2–2.5% [15, 16]. Although these epidemiological data must be considered in light of information bias, it is undeniable that fatal anaphylaxis following the initial administration of rasburicase is extremely rare. The patient in the present case received an immediate diagnosis of anaphylaxis and immediate care from the medical staff, so it is extremely unfortunate that her death could not be avoided. The cardiopulmonary pathophysiology of severe anaphylaxis involves a combination of loss of intravascular volume due to increased vascular permeability, hypotension due to vasodilation, myocardial depression, and bradycardia, resulting in cardiovascular collapse, otherwise known as distributive shock [17]. The patient was compounded by obstructive shock, which manifested as distributive shock, and intracardiac pressures could not be maintained because of mechanical compression of the heart by the tumor. Therefore, even with the immediate administration of adrenaline and vigorous fluid resuscitation, cardiovascular collapse could not be reversed. Moreover, massive bleeding from the crushed tumor was followed by tension hemothorax, leading to hypovolemic shock and reinforcing obstructive shock (Fig. 4 ). The patient’s allergic predisposition should have been more strongly considered when evaluating the indication for rasburicase. Asthma is a known risk factor for anaphylaxis, mainly induced by food [18]. Although there are no comprehensive reports describing the relationship between drug-induced anaphylaxis and asthma, most past clinical trials administering rasburicase have excluded patients with an apparent history of asthma from the study cohort [1–3, 8, 9, 19, 20]. Although there is no literature concerning rasburicase and asthma, Allen reported that one of six patients who developed anaphylaxis after repeated courses of rasburicase had comorbid asthma, which indicated that anaphylaxis did not occur at the initial administration [10]. We do not believe that rasburicase should be contraindicated in all patients with an allergic predisposition because there must be a life that can be saved from TLS. However, clinicians must bear in mind that the safety of rasburicase in patients with asthma has not been established. The only way to have saved the patient’s life would have been to not administer rasburicase. In conclusion, clinicians should consider the possibility of anaphylaxis, even with the initial administration of rasburicase, especially in patients with an allergic predisposition. Anaphylaxis can lead to lethal outcomes when unfavorable conditions overlap. Therefore, the appropriateness of rasburicase should be thoroughly evaluated, considering both the risk of TLS and the patient’s underlying risks. Abbreviations CPA cardiopulmonary arrest CPR cardiopulmonary resuscitation CT computed tomography DLBCL diffuse large B cell lymphoma TLS tumor lysis syndrome. Declarations Competing Interests: The authors have no relevant financial or non-financial interests to disclose. Ethics approval: This is a case report. The Japanese Red Cross Narita Hospital Research Ethics Committee has confirmed that no ethical approval is required. Consent for publication: Written informed consent was obtained from the next of kin to publish this case report and the accompanying images or data. Funding: No funds, grants, or other support was received. Author Contribution Author contributions: YU, NK, SM, HA, SS, RM, TT, KT, KM, CK, SK, and NA were involved in the patient’s clinical management and collected the clinical and literature data. MK performed the postmortem examination and prepared the images. YU, NK, and SM wrote and edited the manuscript. All authors have read and approved the final manuscript. Acknowledgement The authors would like to thank the patient’s family for giving consent to publish the details of this case. We thank Emily Woodhouse, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript. Data availability: All data generated and/or analyzed during this study are included in the published article. References Goldman SC, Holcenberg JS, Finklestein JZ, Hutchinson R, Kreissman S, Johnson FL, Tou C, Harvey E, Morris E, Cairo MS: A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis . Blood 2001, 97 (10):2998–3003. Coiffier B, Mounier N, Bologna S, Ferme C, Tilly H, Sonet A, Christian B, Casasnovas O, Jourdan E, Belhadj K et al : Efficacy and safety of rasburicase (recombinant urate oxidase) for the prevention and treatment of hyperuricemia during induction chemotherapy of aggressive non-Hodgkin's lymphoma: results of the GRAAL1 (Groupe d'Etude des Lymphomes de l'Adulte Trial on Rasburicase Activity in Adult Lymphoma) study . J Clin Oncol 2003, 21 (23):4402–4406. Jeha S, Kantarjian H, Irwin D, Shen V, Shenoy S, Blaney S, Camitta B, Pui CH: Efficacy and safety of rasburicase, a recombinant urate oxidase (Elitek), in the management of malignancy-associated hyperuricemia in pediatric and adult patients: final results of a multicenter compassionate use trial . Leukemia 2005, 19 (1):34–38. Relling MV, McDonagh EM, Chang T, Caudle KE, McLeod HL, Haidar CE, Klein T, Luzzatto L, Clinical Pharmacogenetics Implementation C: Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for rasburicase therapy in the context of G6PD deficiency genotype . Clin Pharmacol Ther 2014, 96 (2):169–174. Coiffier B, Altman A, Pui CH, Younes A, Cairo MS: Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review . J Clin Oncol 2008, 26 (16):2767–2778. Cairo MS, Coiffier B, Reiter A, Younes A, Panel TLSE: Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus . Br J Haematol 2010, 149 (4):578–586. Howard SC, Jones DP, Pui CH: The tumor lysis syndrome . N Engl J Med 2011, 364 (19):1844–1854. Ishizawa K, Ogura M, Hamaguchi M, Hotta T, Ohnishi K, Sasaki T, Sakamaki H, Yokoyama H, Harigae H, Morishima Y: Safety and efficacy of rasburicase (SR29142) in a Japanese phase II study . Cancer Sci 2009, 100 (2):357–362. Cortes J, Moore JO, Maziarz RT, Wetzler M, Craig M, Matous J, Luger S, Dey BR, Schiller GJ, Pham D et al : Control of plasma uric acid in adults at risk for tumor Lysis syndrome: efficacy and safety of rasburicase alone and rasburicase followed by allopurinol compared with allopurinol alone–results of a multicenter phase III study . J Clin Oncol 2010, 28 (27):4207–4213. Allen KC, Champlain AH, Cotliar JA, Belknap SM, West DP, Mehta J, Trifilio SM: Risk of anaphylaxis with repeated courses of rasburicase: a Research on Adverse Drug Events and Reports (RADAR) project . Drug Saf 2015, 38 (2):183–187. Kobayashi S, Yasu T, Akazawa M: Survey of Anaphylaxis during Rasburicase Re-Administration in Patients with Hematological Malignancies Using a Japanese Claims Database . Curr Oncol 2022, 29 (12):9826–9832. Hatada T, Tanbo A, Satou A, Shima Y, Toyoda H, Hayashi H: ICLS Course Guide Book by Japanese Association for Acute Medicine , Revised 5th edn. Tokyo, Japan: Yodo-sha; 2022. Cardona V, Ansotegui IJ, Ebisawa M, El-Gamal Y, Fernandez Rivas M, Fineman S, Geller M, Gonzalez-Estrada A, Greenberger PA, Sanchez Borges M et al : World allergy organization anaphylaxis guidance 2020 . World Allergy Organ J 2020, 13 (10):100472. Turner PJ, Campbell DE, Motosue MS, Campbell RL: Global Trends in Anaphylaxis Epidemiology and Clinical Implications . J Allergy Clin Immunol Pract 2020, 8 (4):1169–1176. Jeppesen AN, Christiansen CF, Froslev T, Sorensen HT: Hospitalization rates and prognosis of patients with anaphylactic shock in Denmark from 1995 through 2012 . J Allergy Clin Immunol 2016, 137 (4):1143–1147. Sugizaki C, Sato S, Yanagida N, Ebisawa M: Analysis of drug-induced anaphylaxis cases using the Japanese Adverse Drug Event Report (JADER) database - secondary publication . Allergol Int 2023, 72 (4):580–587. Bochner BS, Lichtenstein LM: Anaphylaxis . N Engl J Med 1991, 324 (25):1785–1790. Bock SA, Munoz-Furlong A, Sampson HA: Fatalities due to anaphylactic reactions to foods . J Allergy Clin Immunol 2001, 107 (1):191–193. Pui CH, Mahmoud HH, Wiley JM, Woods GM, Leverger G, Camitta B, Hastings C, Blaney SM, Relling MV, Reaman GH: Recombinant urate oxidase for the prophylaxis or treatment of hyperuricemia in patients With leukemia or lymphoma . J Clin Oncol 2001, 19 (3):697–704. Pui CH, Jeha S, Irwin D, Camitta B: Recombinant urate oxidase (rasburicase) in the prevention and treatment of malignancy-associated hyperuricemia in pediatric and adult patients: results of a compassionate-use trial . Leukemia 2001, 15 (10):1505–1509. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 26 Oct, 2024 Read the published version in Allergy, Asthma & Clinical Immunology → Version 1 posted Editorial decision: Revision requested 07 Sep, 2024 Reviews received at journal 01 Sep, 2024 Reviews received at journal 28 Aug, 2024 Reviewers agreed at journal 27 Aug, 2024 Reviewers agreed at journal 23 Aug, 2024 Reviewers agreed at journal 15 May, 2024 Reviewers invited by journal 29 Apr, 2024 Submission checks completed at journal 03 Apr, 2024 Editor assigned by journal 03 Apr, 2024 First submitted to journal 02 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4204004","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":288690264,"identity":"5485705b-d334-4a95-bfdb-ade765ef57d9","order_by":0,"name":"Yoshikazu 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05:29:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4204004/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4204004/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13223-024-00920-9","type":"published","date":"2024-10-26T15:57:44+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":54519939,"identity":"8decf5f5-15cb-42de-a054-679a092d266d","added_by":"auto","created_at":"2024-04-11 17:52:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":431782,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChest X-ray and CT scan at diagnosis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea:\u003c/strong\u003eChest X-ray showing atelectasis of the middle and lower lobes of the right lung.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb:\u003c/strong\u003eAxial computed tomography showing a posterior mediastinal mass with a diameter of 12 cm (blue arrows) compressing the heart (red arrows). CT: computed tomography.\u003c/p\u003e","description":"","filename":"Slide1.png","url":"https://assets-eu.researchsquare.com/files/rs-4204004/v1/a8bfa5bcbe8dd1a870d135e9.png"},{"id":54519942,"identity":"bb7e7095-c1ac-4091-b453-e97c5511e520","added_by":"auto","created_at":"2024-04-11 17:52:20","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":582210,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChest X-ray and CT scan after resuscitation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea:\u003c/strong\u003eChest X-ray showing atelectasis of the entire right lung and deviation of the mediastinum to the left.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb:\u003c/strong\u003e Axial computed tomography showing massive fluid in the right pleural cavity. The heart had collapsed (red arrows). The yellow arrows show the devascularization catheter for percutaneous cardiopulmonary support in the inferior vena cava. The green arrows show the nasogastric tube in the esophagus. CT: computed tomography.\u003c/p\u003e","description":"","filename":"Slide2.png","url":"https://assets-eu.researchsquare.com/files/rs-4204004/v1/0d3f79e88891ebd71dfdb219.png"},{"id":54519938,"identity":"2fdc0755-e79e-46b0-b94b-fed6f03447a2","added_by":"auto","created_at":"2024-04-11 17:52:19","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1017393,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGross pathological findings of the mediastinum\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea:\u003c/strong\u003e The blue arrows show the crushed lymphoma in the posterior mediastinum. The green and purple arrows show the esophagus and the trachea, respectively. The black arrow shows the descending aorta.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb:\u003c/strong\u003eEnlarged tumor section. Blood stains are visible on the surface of the crushed wound.\u003c/p\u003e","description":"","filename":"Slide3.png","url":"https://assets-eu.researchsquare.com/files/rs-4204004/v1/81d170d1f7651404dc76cb76.png"},{"id":54520314,"identity":"fb3d0e6c-04fc-460e-9b9e-cac032c4c32d","added_by":"auto","created_at":"2024-04-11 18:00:19","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":67706,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSchematic diagram of the cascade of shock and cardiopulmonary collapse\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea:\u003c/strong\u003eT: tumor; H: heart (cardiovascular system).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb:\u003c/strong\u003eDistributive shock mediated by anaphylaxis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ec:\u003c/strong\u003eObstructive shock due to defeating intracardial pressure by mechanical compression of the tumor.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ed:\u003c/strong\u003eHypovolemic shock due to bleeding from the tumor.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ee:\u003c/strong\u003eReinforced obstructive shock by tension hemothorax.\u003c/p\u003e","description":"","filename":"Slide4.png","url":"https://assets-eu.researchsquare.com/files/rs-4204004/v1/5fc279b68605a5db5ae5f08a.png"},{"id":67681869,"identity":"f9716d76-2f57-40e7-961f-9e9adf874911","added_by":"auto","created_at":"2024-10-28 16:10:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3100079,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4204004/v1/208b0d8a-302d-4aa1-aa8b-d5416cb979ab.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A case report of anaphylaxis caused by initial administration of rasburicase resulting in death just before the treatment of diffuse large B cell lymphoma","fulltext":[{"header":"Background","content":"\u003cp\u003eRasburicase, a recombinant form of urate oxidase, has demonstrated potent efficacy in controlling uric acid in several trials of pediatric and adult patients with hematologic malignancy [1, 2]. Although rasburicase is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency because of the risk of hemolysis [3, 4], its safety profile has been demonstrated in clinical trials of patients without glucose-6-phosphate dehydrogenase deficiency. Currently, with the accumulation of experience on its use, rasburicase has become widely recommended and is used as a prophylactic agent for high-risk patients (and some intermediate-risk patients) with tumor lysis syndrome (TLS) with various types of malignant tumor [5\u0026ndash;7].\u003c/p\u003e \u003cp\u003eAs rasburicase is a recombinant enzyme that does not naturally exist in humans, antibody production occurs at a rate of approximately 2\u0026ndash;10% after administration [8, 9], and regulatory authorities in Japan (Pharmaceuticals and Medical Devices Agency), as well as the supplier (Sanofi K.K., Tokyo), do not recommend the re-administration of rasburicase owing to its unestablished safety in the package insert of their distributed product Rasuritek. Although the frequency of anaphylaxis upon re-administration is reported to be 0\u0026ndash;6.2% [10, 11], there has only been one report of a patient with anaphylaxis upon the first administration of rasburicase [3], while there have been no case reports of fatalities due to anaphylaxis.\u003c/p\u003e \u003cp\u003eHerein, we report our experience of a patient with anaphylaxis following the initial administration of rasburicase before the treatment of malignant lymphoma, finally leading to death. We have also reviewed relevant published reports.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 71-year-old Japanese female was admitted to the hematology unit of our hospital to undergo chemotherapy for newly diagnosed diffuse large B cell lymphoma (DLBCL).\u003c/p\u003e \u003cp\u003eShe had complained of dry cough and back pain that gradually worsened over 1 month. She consulted a local doctor and underwent a computed tomography (CT) scan, which revealed a posterior mediastinal mass with a diameter of 12 cm compressing the heart (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). She underwent a bronchoscopic biopsy at our institution 10 days before her admission and was diagnosed with stage II DLBCL not otherwise specified, with a bulky mass. She had been undergoing treatment for bronchial asthma, taking steroids orally and via inhalation, and her condition was well controlled. She had a history of drug-induced rash with ambroxol and oral third-generation cephalosporin antibiotics. She had little to no impairment in her daily activities, with an Eastern Cooperative Oncology Group Performance Status of 1. On blood examination, lactate dehydrogenase and soluble interleukin-2 receptors showed mild elevation (379 U/L and 578.0 U/mL, respectively). All other parameters were within normal ranges.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAlthough we planned to administer polatuzumab, rituximab, cyclophosphamide, doxorubicin, and prednisolone (Pola-R-CHP) as the initial therapy, we decided to administer rasburicase for the prevention of TLS prior to chemotherapy, considering the large tumor burden. Immediately after rasburicase administration, the patient complained of dyspnea, and generalized erythema and wheezing were observed. Shortly thereafter, her blood pressure plummeted and became unmeasurable, and she went into cardiopulmonary arrest (CPA). Immediate cardiopulmonary resuscitation (CPR) measures, such as chest compressions and artificial ventilation by ward physicians and nurses, were initiated. Pharmacological interventions, including repetitive adrenaline, high-volume extracellular fluid, steroids, and antihistamines, were also administered. The resuscitation efforts were appropriately continued by specialized staff following the Immediate Life Support protocol [12], but it took 20 minutes to achieve recovery of the self-circulation. Subsequently, CPA occurred again and recovery of the self-circulation was achieved; however, the circulation remained extremely unstable, necessitating the placement of a percutaneous cardiopulmonary support device. However, little improvement was observed. CT revealed massive pleural effusion compressing the right lung and the heart (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The patient died 5 days after the administration of rasburicase despite maximal supportive care.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePostmortem pathological examination revealed massive hemothorax filling the right pleural cavity and crushed lymphoma of the posterior mediastinum, which was speculated to have resulted from major bleeding due to mechanical injury of the tumor by chest compressions during CPR (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The right lung and heart had collapsed due to hemothorax.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion and Conclusions","content":"\u003cp\u003eAnaphylaxis caused by rasburicase is rare, with past reports suggesting a rate of 0\u0026ndash;6.2% in the setting of re-administration [8,9], and only one case of anaphylaxis has been described upon initial administration of rasburicase [3]. The estimated lifetime prevalence of anaphylaxis, regardless of the cause, is 0.3\u0026ndash;5.1% [13], and its mortality is estimated at 0.5\u0026ndash;1 per million population [14]. The mortality rate of patients diagnosed with anaphylaxis is estimated at 0.2\u0026ndash;2.5% [15, 16]. Although these epidemiological data must be considered in light of information bias, it is undeniable that fatal anaphylaxis following the initial administration of rasburicase is extremely rare. The patient in the present case received an immediate diagnosis of anaphylaxis and immediate care from the medical staff, so it is extremely unfortunate that her death could not be avoided.\u003c/p\u003e \u003cp\u003eThe cardiopulmonary pathophysiology of severe anaphylaxis involves a combination of loss of intravascular volume due to increased vascular permeability, hypotension due to vasodilation, myocardial depression, and bradycardia, resulting in cardiovascular collapse, otherwise known as distributive shock [17]. The patient was compounded by obstructive shock, which manifested as distributive shock, and intracardiac pressures could not be maintained because of mechanical compression of the heart by the tumor. Therefore, even with the immediate administration of adrenaline and vigorous fluid resuscitation, cardiovascular collapse could not be reversed. Moreover, massive bleeding from the crushed tumor was followed by tension hemothorax, leading to hypovolemic shock and reinforcing obstructive shock (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe patient\u0026rsquo;s allergic predisposition should have been more strongly considered when evaluating the indication for rasburicase. Asthma is a known risk factor for anaphylaxis, mainly induced by food [18]. Although there are no comprehensive reports describing the relationship between drug-induced anaphylaxis and asthma, most past clinical trials administering rasburicase have excluded patients with an apparent history of asthma from the study cohort [1\u0026ndash;3, 8, 9, 19, 20]. Although there is no literature concerning rasburicase and asthma, Allen reported that one of six patients who developed anaphylaxis after repeated courses of rasburicase had comorbid asthma, which indicated that anaphylaxis did not occur at the initial administration [10]. We do not believe that rasburicase should be contraindicated in all patients with an allergic predisposition because there must be a life that can be saved from TLS. However, clinicians must bear in mind that the safety of rasburicase in patients with asthma has not been established. The only way to have saved the patient\u0026rsquo;s life would have been to not administer rasburicase.\u003c/p\u003e \u003cp\u003eIn conclusion, clinicians should consider the possibility of anaphylaxis, even with the initial administration of rasburicase, especially in patients with an allergic predisposition. Anaphylaxis can lead to lethal outcomes when unfavorable conditions overlap. Therefore, the appropriateness of rasburicase should be thoroughly evaluated, considering both the risk of TLS and the patient\u0026rsquo;s underlying risks.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCPA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecardiopulmonary arrest\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCPR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecardiopulmonary resuscitation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecomputed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDLBCL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ediffuse large B cell lymphoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTLS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etumor lysis syndrome.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eCompeting Interests:\u003c/h2\u003e \u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e \u003ch2\u003eEthics approval:\u003c/h2\u003e \u003cp\u003eThis is a case report. The Japanese Red Cross Narita Hospital Research Ethics Committee has confirmed that no ethical approval is required.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication:\u003c/strong\u003e \u003cp\u003e Written informed consent was obtained from the next of kin to publish this case report and the accompanying images or data.\u003c/p\u003e \u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eNo funds, grants, or other support was received.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAuthor contributions: YU, NK, SM, HA, SS, RM, TT, KT, KM, CK, SK, and NA were involved in the patient\u0026rsquo;s clinical management and collected the clinical and literature data. MK performed the postmortem examination and prepared the images. YU, NK, and SM wrote and edited the manuscript. All authors have read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors would like to thank the patient\u0026rsquo;s family for giving consent to publish the details of this case. We thank Emily Woodhouse, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.\u003c/p\u003e\u003ch2\u003eData availability:\u003c/h2\u003e \u003cp\u003eAll data generated and/or analyzed during this study are included in the published article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eGoldman SC, Holcenberg JS, Finklestein JZ, Hutchinson R, Kreissman S, Johnson FL, Tou C, Harvey E, Morris E, Cairo MS: \u003cstrong\u003eA randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis\u003c/strong\u003e. \u003cem\u003eBlood\u003c/em\u003e 2001, \u003cstrong\u003e97\u003c/strong\u003e(10):2998\u0026ndash;3003.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eCoiffier B, Mounier N, Bologna S, Ferme C, Tilly H, Sonet A, Christian B, Casasnovas O, Jourdan E, Belhadj K \u003cem\u003eet al\u003c/em\u003e: \u003cstrong\u003eEfficacy 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and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus\u003c/strong\u003e. \u003cem\u003eBr J Haematol\u003c/em\u003e 2010, \u003cstrong\u003e149\u003c/strong\u003e(4):578\u0026ndash;586.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHoward SC, Jones DP, Pui CH: \u003cstrong\u003eThe tumor lysis syndrome\u003c/strong\u003e. \u003cem\u003eN Engl J Med\u003c/em\u003e 2011, \u003cstrong\u003e364\u003c/strong\u003e(19):1844\u0026ndash;1854.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eIshizawa K, Ogura M, Hamaguchi M, Hotta T, Ohnishi K, Sasaki T, Sakamaki H, Yokoyama H, Harigae H, Morishima Y: \u003cstrong\u003eSafety and efficacy of rasburicase (SR29142) in a Japanese phase II study\u003c/strong\u003e. \u003cem\u003eCancer Sci\u003c/em\u003e 2009, \u003cstrong\u003e100\u003c/strong\u003e(2):357\u0026ndash;362.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eCortes J, 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Yasu T, Akazawa M: \u003cstrong\u003eSurvey of Anaphylaxis during Rasburicase Re-Administration in Patients with Hematological Malignancies Using a Japanese Claims Database\u003c/strong\u003e. \u003cem\u003eCurr Oncol\u003c/em\u003e 2022, \u003cstrong\u003e29\u003c/strong\u003e(12):9826\u0026ndash;9832.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHatada T, Tanbo A, Satou A, Shima Y, Toyoda H, Hayashi H: \u003cstrong\u003eICLS Course Guide Book by Japanese Association for Acute Medicine\u003c/strong\u003e, Revised 5th edn. Tokyo, Japan: Yodo-sha; 2022.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eCardona V, Ansotegui IJ, Ebisawa M, El-Gamal Y, Fernandez Rivas M, Fineman S, Geller M, Gonzalez-Estrada A, Greenberger PA, Sanchez Borges M \u003cem\u003eet al\u003c/em\u003e: \u003cstrong\u003eWorld allergy organization anaphylaxis guidance 2020\u003c/strong\u003e. \u003cem\u003eWorld Allergy Organ J\u003c/em\u003e 2020, \u003cstrong\u003e13\u003c/strong\u003e(10):100472.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eTurner PJ, Campbell DE, Motosue MS, Campbell RL: \u003cstrong\u003eGlobal Trends in Anaphylaxis Epidemiology and Clinical Implications\u003c/strong\u003e. \u003cem\u003eJ Allergy Clin Immunol Pract\u003c/em\u003e 2020, \u003cstrong\u003e8\u003c/strong\u003e(4):1169\u0026ndash;1176.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eJeppesen AN, Christiansen CF, Froslev T, Sorensen HT: \u003cstrong\u003eHospitalization rates and prognosis of patients with anaphylactic shock in Denmark from 1995 through 2012\u003c/strong\u003e. \u003cem\u003eJ Allergy Clin Immunol\u003c/em\u003e 2016, \u003cstrong\u003e137\u003c/strong\u003e(4):1143\u0026ndash;1147.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eSugizaki C, Sato S, Yanagida N, Ebisawa M: \u003cstrong\u003eAnalysis of drug-induced anaphylaxis cases using the Japanese Adverse Drug Event Report (JADER) database - secondary publication\u003c/strong\u003e. \u003cem\u003eAllergol Int\u003c/em\u003e 2023, \u003cstrong\u003e72\u003c/strong\u003e(4):580\u0026ndash;587.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBochner BS, Lichtenstein LM: \u003cstrong\u003eAnaphylaxis\u003c/strong\u003e. \u003cem\u003eN Engl J Med\u003c/em\u003e 1991, \u003cstrong\u003e324\u003c/strong\u003e(25):1785\u0026ndash;1790.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBock SA, Munoz-Furlong A, Sampson HA: \u003cstrong\u003eFatalities due to anaphylactic reactions to foods\u003c/strong\u003e. \u003cem\u003eJ Allergy Clin Immunol\u003c/em\u003e 2001, \u003cstrong\u003e107\u003c/strong\u003e(1):191\u0026ndash;193.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003ePui CH, Mahmoud HH, Wiley JM, Woods GM, Leverger G, Camitta B, Hastings C, Blaney SM, Relling MV, Reaman GH: \u003cstrong\u003eRecombinant urate oxidase for the prophylaxis or treatment of hyperuricemia in patients With leukemia or lymphoma\u003c/strong\u003e. \u003cem\u003eJ Clin Oncol\u003c/em\u003e 2001, \u003cstrong\u003e19\u003c/strong\u003e(3):697\u0026ndash;704.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003ePui CH, Jeha S, Irwin D, Camitta B: \u003cstrong\u003eRecombinant urate oxidase (rasburicase) in the prevention and treatment of malignancy-associated hyperuricemia in pediatric and adult patients: results of a compassionate-use trial\u003c/strong\u003e. \u003cem\u003eLeukemia\u003c/em\u003e 2001, \u003cstrong\u003e15\u003c/strong\u003e(10):1505\u0026ndash;1509.\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"allergy-asthma-and-clinical-immunology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aaci","sideBox":"Learn more about [Allergy, Asthma \u0026 Clinical Immunology](http://aacijournal.biomedcentral.com/)","snPcode":"13223","submissionUrl":"https://submission.nature.com/new-submission/13223/3","title":"Allergy, Asthma \u0026 Clinical Immunology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"rasburicase, anaphylaxis, initial administration, lymphoma, shock, asthma","lastPublishedDoi":"10.21203/rs.3.rs-4204004/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4204004/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRasburicase has potent efficacy in controlling uric acid and is widely used to prevent tumor lysis syndrome in high-risk patients owing to its low toxicity profile. However, the safety of rasburicase re-administration has not been established due to the risk of anaphylaxis mediated by antibody production. However, reports of such reactions upon the initial administration of rasburicase are scarce.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 71-year-old Japanese female who had been diagnosed with diffuse large B cell lymphoma with a large tumor burden experienced anaphylactic shock leading to death that occurred upon initial administration of rasburicase just before the chemotherapy. The patient had several unfavorable characteristics that resulted in a fatal outcome, including a predisposition to allergies. Moreover, there was a large tumor in the posterior mediastinum that, although it would not cause a significant issue under normal circumstances, could severely impact hemodynamics if the patient entered into a state of shock. Chest compressions during cardiopulmonary resuscitation resulted in crushing of the tumor. The pre-and postmortem examination revealed that the cause of death was a cascade of events starting with anaphylaxis-induced distributive shock leading to obstructive shock due to collapse of the heart, which was compressed by the tumor. This was further compounded by massive bleeding from the tumor and tension hemothorax, resulting in circulatory collapse.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnaphylaxis can lead to lethal outcomes when unfavorable conditions overlap. Clinicians need to carefully assess the indication for rasburicase, considering both the risk of tumor lysis syndrome and the patient’s background risks simultaneously.\u003c/p\u003e","manuscriptTitle":"A case report of anaphylaxis caused by initial administration of rasburicase resulting in death just before the treatment of diffuse large B cell lymphoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-11 17:52:15","doi":"10.21203/rs.3.rs-4204004/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-08T02:59:51+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-01T12:43:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-29T01:57:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"77292215794445983806836941670366811206","date":"2024-08-28T01:22:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"153886133775053033443515641892854533136","date":"2024-08-23T15:23:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"133802800983717744159996186928482190135","date":"2024-05-15T21:52:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-30T02:48:49+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-03T07:45:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-03T07:45:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"Allergy, Asthma \u0026 Clinical Immunology","date":"2024-04-02T05:23:01+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"allergy-asthma-and-clinical-immunology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aaci","sideBox":"Learn more about [Allergy, Asthma \u0026 Clinical Immunology](http://aacijournal.biomedcentral.com/)","snPcode":"13223","submissionUrl":"https://submission.nature.com/new-submission/13223/3","title":"Allergy, Asthma \u0026 Clinical Immunology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7e10d02f-21eb-4b29-8f35-2fb190be773e","owner":[],"postedDate":"April 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-10-28T16:02:40+00:00","versionOfRecord":{"articleIdentity":"rs-4204004","link":"https://doi.org/10.1186/s13223-024-00920-9","journal":{"identity":"allergy-asthma-and-clinical-immunology","isVorOnly":false,"title":"Allergy, Asthma \u0026 Clinical Immunology"},"publishedOn":"2024-10-26 15:57:44","publishedOnDateReadable":"October 26th, 2024"},"versionCreatedAt":"2024-04-11 17:52:15","video":"","vorDoi":"10.1186/s13223-024-00920-9","vorDoiUrl":"https://doi.org/10.1186/s13223-024-00920-9","workflowStages":[]},"version":"v1","identity":"rs-4204004","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4204004","identity":"rs-4204004","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}