The Impact of Bleomycin Test Doses on the Development of Acute Hypersensitivity Reactions

The Impact of Bleomycin Test Doses on the Development of Acute Hypersensitivity Reactions | 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 Research Article The Impact of Bleomycin Test Doses on the Development of Acute Hypersensitivity Reactions Dennis Marjoncu, Kori Holman This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4565600/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 Sep, 2025 Read the published version in Supportive Care in Cancer → Version 1 posted 7 You are reading this latest preprint version Abstract Purpose Hypersensitivity reactions are a side effect of bleomycin. Test doses have been utilized to attempt to predict patients that would develop these reactions. Despite this, there is scant data available on whether these test doses actually predict the development of reactions. Commonly cited literature relies on lack of reporting of hypersensitivity reactions, rather than comparative data, to claim test doses may not be beneficial. The purpose of this analysis was to compare patients who received test doses against those who did not in the development of bleomycin hypersensitivity reactions. Methods 77 patients who had received bleomycin as part of their chemotherapy regimen were included in this retrospective analysis. Patients were stratified based on the receipt of a bleomycin test dose (either 1 or 2 units given prior to the full dose). The presence of hypersensitivities were assessed by documentation of emergency medications in the medical record shortly after bleomycin administration or through documentation by a provider note. Results There were no reactions reported with any of the 84 test doses administered. With the full dose of bleomycin administered, hypersensitivity reactions occurred in 3 patients in the test dose arm (5.5%) compared to no patients in the group that did not receive a test dose. Despite this difference, there was no statistical difference between the two arms (p = 0.264). Conclusion In this study, we observed no relation between a negative bleomycin test dose and the development of acute hypersensitivity reaction. Interestingly, there was a higher numerical incidence of hypersensitivity reactions in patients who received a test dose than those who did not receive a test dose, though this was not statistically significant. Larger studies would need to be conducted to verify these findings. Bleomycin test dose hypersensitivity Introduction Bleomycin is an antineoplastic medication with activity against lymphoma, germ cell tumors, and squamous cell carcinomas. It is a glycopeptide antibiotic synthesized from the fungus Streptomyces verticillus . The most notable adverse effects of bleomycin include rash, pulmonary toxicity, and, rarely, hypersensitivity reactions. 1,2 The mechanism by which bleomycin causes hypersensitivity reactions is not fully understood. One study found that bleomycin increases the production of leukotriene which can lead to profound pyrexia. 3 This pyrexia can cause significant endothelial damage which can lead to multi-organ dysfunction and can occur hours after the dose is administered. This is not indicative of an immunoglobulin E-mediated hypersensitivity reaction. 3,4 In order to assess if a particular patient population is at an increased risk, a review was completed by Blum et al. They found that patients most likely to experience hypersensitivity reactions resulting in death were patients with lymphoma. 4 Due to the potential of fatal hypersensitivity reactions, the package insert recommends utilizing a test dose for patients with lymphoma. 1 However, there are not consistent recommendations within guidelines, and there is limited data to support the use of a test dose in predicting a hypersensitivity reaction. 2 There have been no reported cases of fulminant hypersensitivity reactions since the 1980s, which also calls into question the utility of a test dose. 2,5–12 There is a paucity of comparative data to assess the predictive value of a test dose. The purpose of this analysis is to compare the development of bleomycin hypersensitivity reactions in patients who received test doses against those who did not receive a test dose. Methods Study Design A multi-center, retrospective analysis of patients greater than or equal to 18 years old who had received systemic bleomycin at Methodist Le Bonheur Healthcare facilities from 2008 to March 31, 2021 was conducted. Given the retrospective and de-identified nature of the data, this study was granted exemption status by the University of Tennessee Health Science Center (UTHSC) institutional review board (IRB) and consent was not needed. Patients were eligible if they had a confirmed cancer diagnosis and received a bleomycin-containing chemotherapy regimen. Patients who were younger than 18 years old and those who had only received intrapleural bleomycin were excluded. Test doses were defined as any dose of two units or less, given IV, IM, or subcutaneous prior to any dose of bleomycin. Hypersensitivity reactions were defined as hypotension, chills, respiratory compromise, or high-grade fever within 24 hours after a dose of bleomycin. This study was conducted in accordance with the Declaration of Helsinki. Data Collection The electronic health record of all patients who received systemic bleomycin during the study period was assessed to screen for inclusion in the study. Administration of bleomycin doses were confirmed via the medication administration record (MAR). The development of bleomycin hypersensitivity reactions was confirmed by both review of clinical notes as well as assessment of the MAR for emergency medications such as corticosteroids, histamine antagonists, and/or epinephrine. The following information was collected: patient age, sex, race, indication, chemotherapy regimen, test dose (Y/N), number of test doses, strength of test dose in units, reaction to the test dose (Y/N), type of reaction to test dose if present, reaction to the full dose (Y/N), type of reaction to full dose if present, and which dose the patient had a reaction to if present. Study Assessments The primary endpoint of this study was to assess whether there was a relationship between the administration of a test dose and the development of a bleomycin hypersensitivity reaction with the full dose. A conditional secondary endpoint was to assess whether there was a specific dose associated with the development of bleomycin hypersensitivity reactions. Statistical Analysis Descriptive statistics were utilized for baseline characteristics in both arms. Parametric data was reported as means with a standard deviation (SD) and medians with inter-quartile ranges (IQR). Categorical variables were compared with the chi-squared (χ 2 ) test. Continuous variables were compared using the t-test. A p-value of less than 0.05 was considered statistically significant. Results Patient Characteristics Seventy-seven patients met the inclusion criteria and were included in the final analysis. Fifty-five (71.4%) patients received a test dose and 22 (28.6%) did not receive a test dose. The mean age was 36.9 ± 13.6 years, with no difference between the two arms (p = 0.288). There was no difference in sex (p = 1) or race (p = 0.076) between the two arms, although the group that did not receive a test dose had a numerically larger proportion of African American patients. The test dose arm had a larger number of patients with Hodgkin’s lymphoma (69% vs 36%; p = 0.047), which also resulted in more patients in the test dose arm receiving ABVD compared to those who did not receive a test dose (65% vs 36%). Conversely, the arm that did not receive a test dose had a larger number of patients receive the BEP regimen (59% vs 31%). This was likely due to the larger number of patients with testicular cancer and germ cell tumors. See Table 1 for a summary of baseline characteristics. Table 1 Baseline Characteristics Total (N = 77) Test Dose (N = 55) No Test Dose (N = 22) p-value Age Mean ± std dev Median (IQR) 36.9 ± 13.6 36 (26–47) 36.3 ± 12.3 36 (26.5–44) 38.5 ± 16.6 34.5 (24.5–52.5) 0.288 Sex Male, n (%) Female, n (%) 49 (64%) 28 (36%) 35 (64%) 20 (36%) 14 (64%) 8 (36%) 1 Race White, n (%) African American, n (%) Other, n (%) 34 (44%) 32 (42%) 11 (14%) 23 (42%) 21 (38%) 11 (20%) 11 (50%) 11 (50%) 0 (0%) 0.076 Indication, n (%) Hodgkin’s Testicular Granulosa Cell Germ Cell Malignant Teratoma DLBCL 46 (59.7%) 21 (27.2%) 3 (3.9%) 5 (6.5%) 1 (1.3%) 1 (1.3%) 38 (69%) 13 (24%) 1 (2%) 2 (4%) 1 (2%) 0 (0%) 8 (36%) 8 (36%) 2 (9%) 3 (14%) 0 (0%) 1 (5%) 0.047 Chemotherapy Regimen, n (%) ABVD BEP BEACOPP GOX (Gemcitabine, Carboplatin, bleomycin) 44 (57.1%) 30 (40%) 2 (2.6%) 1 (1.3%) 36 (65%) 17 (31%) 2 (4%) 0 (0%) 8 (36%) 13 (59%) 0 (0%) 1 (5%) 0.032 p-values are for comparison between test dose and no test dose Bleomycin Hypersensitivity Reactions There were 84 test doses given among 55 patients. Of these doses, 25 (29.8%) were the 1 unit of bleomycin and 59 (70.2%) were two units of bleomycin. There were no reactions reported with any of the test doses. Consequently, there were three cases of hypersensitivity reactions in this study. All three reactions were reported in the group that had received a test dose (5.5% of patients who received a test dose), and all occurred during the first infusion of bleomycin. Two patients who had Hodgkin’s lymphoma developed rigors and chills, while the third patient with a germ cell tumor developed a rash during the infusion. All three recovered with emergency medication administration. Despite this, there was no statistical difference in reaction rates between the two arms (p = 0.264). Table 2 Summary of Bleomycin Doses Total (N = 77) Test Dose (N = 55) No Test Dose (N = 22) p-value Number of Test Doses 84 84 0 N/A Strength of Test Dose, n (%) 1 unit 2 units 25 (29.8%) 59 (70.2%) 25 (29.8%) 59 (70.2%) N/A N/A Reaction with Test Dose Yes No 0 55 (71.4%) 0 (0%) 55 (100%) -- -- N/A Reaction with Full Dose Yes No 3 (3.9%) 74 (96.1%) 3 (5.5%) 52 (94.5%) 0 (0%) 22 (100%) 0.264 Discussion Bleomycin hypersensitivity reactions are infrequently reported in the literature. They are limited to case reports that occurred shortly after bleomycin was approved for use, and there are no cases reported in the literature after 2000. As noted by Lam, this could be attributed to several factors. One such factor may include the widespread use of antiemetic premedications, which often contain corticosteroids, in modern chemotherapy regimens. A second explanation may be due to modern processes for manufacturing bleomycin, contrasted with an older method of purifying bleomycin from fungus which may have resulted in contaminants present in the formulation. 2 Our analysis showed that bleomycin hypersensitivity reactions occur rarely and do not appear to be predicted with the use of test doses. This is evidenced by all three patients who developed a reaction had received a test dose with no reaction to those doses. This lends credence to the idea that the incidence of bleomycin hypersensitivity reactions do not typically occur in modern times. There were no differences in age, sex, or race in our study, however there were more patients in the test dose arm with Hodgkin’s lymphoma and a higher number of patients with testicular and germ cell tumors in the non-test dose arm. This did not appear to influence the results at all due to the low overall event rate in our analysis. Our study has several limitations. It is retrospective in nature and data collection was reliant on appropriate documentation in the electronic health record. Additionally, the timeframe of our study includes a time prior to computerized physician order entry (CPOE) at our institution when medication orders were written on paper and subsequently scanned into the computer system. This may have limited the ability to gather pertinent medications. This limitation was attenuated by reviewing documents up to one month after each bleomycin dose to account for delays in document uploading. Additionally, our trial was not powered to detect a difference between the two arms. Despite these limitations, our study also has several strengths. Prior to our study, any reports of bleomycin hypersensitivity reactions were limited to case reports and series. Ours is the first study to specifically compare the rate of bleomycin hypersensitivity reactions between those who received and did not receive a test dose. The benefit of this is to show actual rates between the two arms rather than relying on low incidence in the literature as evidence it does not happen. This most importantly shows that, even with low numbers, a test dose is not necessary. Our study also includes a large proportion of African Americans, an often under-represented group in clinical research. Conclusion The findings in this study did not show a correlation between bleomycin test dose reactions and the development of bleomycin hypersensitivity reactions. It is the first analysis of this relationship other than cases that have been reported shortly after the advent of bleomycin. Based on these findings, there appears to be a limited utility to continuing the practice of bleomycin test doses. Further studies are needed to confirm our findings. Declarations Ethics Declaration This is a retrospective observational study. The UTHSC IRB determined no ethical approval is required. Consent to Participate This is a retrospective observational study and was granted exemption status from formal consent by the UTHSC IRB Funding Acknowledgments The authors received no financial support for the research, authorship, and/or publication of this article. Conflicts of Interest The authors declare that there is no conflict of interest. References Bleomycin [prescribing information]. Lake Forest, IL: Hospira; May 2017. Lam MS. The need for routine bleomycin test dosing in the 21 st century. Ann Pharmacother. 2005; 39(11):1897-1902. Geuenich S, Haberl C, Egger D, Kaspers U, Hultner L, Wilmanns W. Induction of leukotriene production by bleomycin and asparaginase in mast cells in vitro and in patients in vivo. Biochem Pharmacol 1998; 55:447-53. Blum RH, Carter Sk, Agre K. A clinical review of bleomycin – a new antineoplastic agent. Cancer. 1973; 56:197-205. Rosenfelt F, Palmer J, Weinstein I, Rosenbloom B. A fatal hyperpyrexial response to bleomycin following prior therapy: A case report and literature review. Yale J Biol Med. 1982; 55:529-31 Ma DD, Isbister JP. Cytotoxic-induced fulminant hyperpyrexia. Cancer. 1980; 45:2249-51. Carter JJ, McLaughlin ML, Bern MM. Bleomycin-induced fatal hyperpyrexia. Am J Med. 1983; 74:523-5. Leung WH, Lau JY, Chan TK, et al. Fulminant hyperpyrexia-induced by bleomycin. Postgrad Med J. 1989; 65:417-9. Inbar MJ, Baratz M, Figer A, et al. Idiosyncratic reaction to bleomycin in an epithelial tumor. Cancer Chemother Pharmacol. 1984; 13:71-2. Levy RL, Chiarillo S. Hyperpyrexia, allergic-type response and death occurring with low-dose bleomycin administration. Oncology. 1980; 37:316-7. Khansur T, Little D, Tavassoli M. Fulminant and fatal angioedema caused by bleomycin treatment. Arch Intern Med. 1984; 144:2267. Brodsky A, Aparici I, Argeri C, et al. Stevens-Johnson syndrome, respiratory distress, and renal failure due to synergistic bleomycin-cisplatin toxicity. J Clin Pharmacol. 1989; 29:821-3. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 08 Sep, 2025 Read the published version in Supportive Care in Cancer → Version 1 posted Editorial decision: Accepted 28 Aug, 2025 Reviews received at journal 27 Aug, 2024 Reviewers agreed at journal 25 Aug, 2024 Reviewers invited by journal 21 Aug, 2024 Editor assigned by journal 25 Jul, 2024 Submission checks completed at journal 19 Jun, 2024 First submitted to journal 11 Jun, 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-4565600","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":321818808,"identity":"a47e3565-b234-4b4e-b77e-18feb37cb2a5","order_by":0,"name":"Dennis Marjoncu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8UlEQVRIiWNgGAWjYDCCA0CcAGGCKTkGdh4StRgzMBOjBRkkNhDSwne899iDB38YovlnH3j4uKDmcPraZt4DDB/31OLUInnmXLpBYhtD7oxzCcnGM44dzt12mC+Bccaz4zi1GNzIMZNIbGDIbTjDkCbN2wDSwmPAzHPgGG4t99+YSST8YcidD9WSbkZQyw0eoBY2htwNUC0JUC01ePwCclibRO7GMwzJxjzH0g1BDjs448ABnFr4jp8xk/zxxyZ33hmexMc8NdbyZsd7DB98OFCHUwsUSAAxTwKcC7TiMCEtIMCO4haCtoyCUTAKRsHIAQBxK1ib0t3YSwAAAABJRU5ErkJggg==","orcid":"","institution":"Methodist University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Dennis","middleName":"","lastName":"Marjoncu","suffix":""},{"id":321818810,"identity":"1ce74ac6-3296-40e6-b30a-47376d1dedb8","order_by":1,"name":"Kori Holman","email":"","orcid":"","institution":"Methodist University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kori","middleName":"","lastName":"Holman","suffix":""}],"badges":[],"createdAt":"2024-06-11 16:47:45","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4565600/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4565600/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00520-025-09902-y","type":"published","date":"2025-09-08T15:57:34+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":91359031,"identity":"2f9ad338-3bb1-4198-9f27-78b3570ca426","added_by":"auto","created_at":"2025-09-15 16:04:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":446589,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4565600/v1/77acd155-a660-4f88-8761-3e363111d2fd.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Impact of Bleomycin Test Doses on the Development of Acute Hypersensitivity Reactions","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBleomycin is an antineoplastic medication with activity against lymphoma, germ cell tumors, and squamous cell carcinomas. It is a glycopeptide antibiotic synthesized from the fungus \u003cem\u003eStreptomyces verticillus\u003c/em\u003e. The most notable adverse effects of bleomycin include rash, pulmonary toxicity, and, rarely, hypersensitivity reactions.\u003csup\u003e1,2\u003c/sup\u003e The mechanism by which bleomycin causes hypersensitivity reactions is not fully understood. One study found that bleomycin increases the production of leukotriene which can lead to profound pyrexia.\u003csup\u003e3\u003c/sup\u003e This pyrexia can cause significant endothelial damage which can lead to multi-organ dysfunction and can occur hours after the dose is administered. This is not indicative of an immunoglobulin E-mediated hypersensitivity reaction.\u003csup\u003e3,4\u003c/sup\u003e In order to assess if a particular patient population is at an increased risk, a review was completed by Blum et al. They found that patients most likely to experience hypersensitivity reactions resulting in death were patients with lymphoma.\u003csup\u003e4\u003c/sup\u003e Due to the potential of fatal hypersensitivity reactions, the package insert recommends utilizing a test dose for patients with lymphoma.\u003csup\u003e1\u003c/sup\u003e However, there are not consistent recommendations within guidelines, and there is limited data to support the use of a test dose in predicting a hypersensitivity reaction.\u003csup\u003e2\u003c/sup\u003e There have been no reported cases of fulminant hypersensitivity reactions since the 1980s, which also calls into question the utility of a test dose.\u003csup\u003e2,5\u0026ndash;12\u003c/sup\u003e There is a paucity of comparative data to assess the predictive value of a test dose. The purpose of this analysis is to compare the development of bleomycin hypersensitivity reactions in patients who received test doses against those who did not receive a test dose.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eA multi-center, retrospective analysis of patients greater than or equal to 18 years old who had received systemic bleomycin at Methodist Le Bonheur Healthcare facilities from 2008 to March 31, 2021 was conducted. Given the retrospective and de-identified nature of the data, this study was granted exemption status by the University of Tennessee Health Science Center (UTHSC) institutional review board (IRB) and consent was not needed. Patients were eligible if they had a confirmed cancer diagnosis and received a bleomycin-containing chemotherapy regimen. Patients who were younger than 18 years old and those who had only received intrapleural bleomycin were excluded.\u003c/p\u003e \u003cp\u003eTest doses were defined as any dose of two units or less, given IV, IM, or subcutaneous prior to any dose of bleomycin. Hypersensitivity reactions were defined as hypotension, chills, respiratory compromise, or high-grade fever within 24 hours after a dose of bleomycin. This study was conducted in accordance with the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData Collection\u003c/h2\u003e \u003cp\u003eThe electronic health record of all patients who received systemic bleomycin during the study period was assessed to screen for inclusion in the study. Administration of bleomycin doses were confirmed via the medication administration record (MAR). The development of bleomycin hypersensitivity reactions was confirmed by both review of clinical notes as well as assessment of the MAR for emergency medications such as corticosteroids, histamine antagonists, and/or epinephrine. The following information was collected: patient age, sex, race, indication, chemotherapy regimen, test dose (Y/N), number of test doses, strength of test dose in units, reaction to the test dose (Y/N), type of reaction to test dose if present, reaction to the full dose (Y/N), type of reaction to full dose if present, and which dose the patient had a reaction to if present.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStudy Assessments\u003c/h2\u003e \u003cp\u003eThe primary endpoint of this study was to assess whether there was a relationship between the administration of a test dose and the development of a bleomycin hypersensitivity reaction with the full dose. A conditional secondary endpoint was to assess whether there was a specific dose associated with the development of bleomycin hypersensitivity reactions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eDescriptive statistics were utilized for baseline characteristics in both arms. Parametric data was reported as means with a standard deviation (SD) and medians with inter-quartile ranges (IQR). Categorical variables were compared with the chi-squared (χ\u003csup\u003e2\u003c/sup\u003e) test. Continuous variables were compared using the t-test. A p-value of less than 0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePatient Characteristics\u003c/h2\u003e \u003cp\u003eSeventy-seven patients met the inclusion criteria and were included in the final analysis. Fifty-five (71.4%) patients received a test dose and 22 (28.6%) did not receive a test dose. The mean age was 36.9\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6 years, with no difference between the two arms (p\u0026thinsp;=\u0026thinsp;0.288). There was no difference in sex (p\u0026thinsp;=\u0026thinsp;1) or race (p\u0026thinsp;=\u0026thinsp;0.076) between the two arms, although the group that did not receive a test dose had a numerically larger proportion of African American patients. The test dose arm had a larger number of patients with Hodgkin\u0026rsquo;s lymphoma (69% vs 36%; p\u0026thinsp;=\u0026thinsp;0.047), which also resulted in more patients in the test dose arm receiving ABVD compared to those who did not receive a test dose (65% vs 36%). Conversely, the arm that did not receive a test dose had a larger number of patients receive the BEP regimen (59% vs 31%). This was likely due to the larger number of patients with testicular cancer and germ cell tumors. See Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e for a summary of baseline characteristics.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal (N\u0026thinsp;=\u0026thinsp;77)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTest Dose (N\u0026thinsp;=\u0026thinsp;55)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo Test Dose (N\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;std dev\u003c/p\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.9\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6\u003c/p\u003e \u003cp\u003e36 (26\u0026ndash;47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.3\u0026thinsp;\u0026plusmn;\u0026thinsp;12.3\u003c/p\u003e \u003cp\u003e36 (26.5\u0026ndash;44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.5\u0026thinsp;\u0026plusmn;\u0026thinsp;16.6\u003c/p\u003e \u003cp\u003e34.5 (24.5\u0026ndash;52.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.288\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003cp\u003eMale, n (%)\u003c/p\u003e \u003cp\u003eFemale, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (64%)\u003c/p\u003e \u003cp\u003e28 (36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (64%)\u003c/p\u003e \u003cp\u003e20 (36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (64%)\u003c/p\u003e \u003cp\u003e8 (36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRace\u003c/p\u003e \u003cp\u003eWhite, n (%)\u003c/p\u003e \u003cp\u003eAfrican American, n (%)\u003c/p\u003e \u003cp\u003eOther, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (44%)\u003c/p\u003e \u003cp\u003e32 (42%)\u003c/p\u003e \u003cp\u003e11 (14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (42%)\u003c/p\u003e \u003cp\u003e21 (38%)\u003c/p\u003e \u003cp\u003e11 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (50%)\u003c/p\u003e \u003cp\u003e11 (50%)\u003c/p\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.076\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndication, n (%)\u003c/p\u003e \u003cp\u003eHodgkin\u0026rsquo;s\u003c/p\u003e \u003cp\u003eTesticular\u003c/p\u003e \u003cp\u003eGranulosa Cell\u003c/p\u003e \u003cp\u003eGerm Cell\u003c/p\u003e \u003cp\u003eMalignant Teratoma\u003c/p\u003e \u003cp\u003eDLBCL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 (59.7%)\u003c/p\u003e \u003cp\u003e21 (27.2%)\u003c/p\u003e \u003cp\u003e3 (3.9%)\u003c/p\u003e \u003cp\u003e5 (6.5%)\u003c/p\u003e \u003cp\u003e1 (1.3%)\u003c/p\u003e \u003cp\u003e1 (1.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (69%)\u003c/p\u003e \u003cp\u003e13 (24%)\u003c/p\u003e \u003cp\u003e1 (2%)\u003c/p\u003e \u003cp\u003e2 (4%)\u003c/p\u003e \u003cp\u003e1 (2%)\u003c/p\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (36%)\u003c/p\u003e \u003cp\u003e8 (36%)\u003c/p\u003e \u003cp\u003e2 (9%)\u003c/p\u003e \u003cp\u003e3 (14%)\u003c/p\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003cp\u003e1 (5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.047\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy Regimen, n (%)\u003c/p\u003e \u003cp\u003eABVD\u003c/p\u003e \u003cp\u003eBEP\u003c/p\u003e \u003cp\u003eBEACOPP\u003c/p\u003e \u003cp\u003eGOX (Gemcitabine, Carboplatin, bleomycin)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (57.1%)\u003c/p\u003e \u003cp\u003e30 (40%)\u003c/p\u003e \u003cp\u003e2 (2.6%)\u003c/p\u003e \u003cp\u003e1 (1.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (65%)\u003c/p\u003e \u003cp\u003e17 (31%)\u003c/p\u003e \u003cp\u003e2 (4%)\u003c/p\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (36%)\u003c/p\u003e \u003cp\u003e13 (59%)\u003c/p\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003cp\u003e1 (5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ep-values are for comparison between test dose and no test dose\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eBleomycin Hypersensitivity Reactions\u003c/h2\u003e \u003cp\u003eThere were 84 test doses given among 55 patients. Of these doses, 25 (29.8%) were the 1 unit of bleomycin and 59 (70.2%) were two units of bleomycin. There were no reactions reported with any of the test doses. Consequently, there were three cases of hypersensitivity reactions in this study. All three reactions were reported in the group that had received a test dose (5.5% of patients who received a test dose), and all occurred during the first infusion of bleomycin. Two patients who had Hodgkin\u0026rsquo;s lymphoma developed rigors and chills, while the third patient with a germ cell tumor developed a rash during the infusion. All three recovered with emergency medication administration. Despite this, there was no statistical difference in reaction rates between the two arms (p\u0026thinsp;=\u0026thinsp;0.264).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e Summary of Bleomycin Doses\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal (N\u0026thinsp;=\u0026thinsp;77)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTest Dose (N\u0026thinsp;=\u0026thinsp;55)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo Test Dose (N\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of Test Doses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStrength of Test Dose, n (%)\u003c/p\u003e \u003cp\u003e1 unit\u003c/p\u003e \u003cp\u003e2 units\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (29.8%)\u003c/p\u003e \u003cp\u003e59 (70.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (29.8%)\u003c/p\u003e \u003cp\u003e59 (70.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReaction with Test Dose\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e55 (71.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003cp\u003e55 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e--\u003c/p\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReaction with Full Dose\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.9%)\u003c/p\u003e \u003cp\u003e74 (96.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (5.5%)\u003c/p\u003e \u003cp\u003e52 (94.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003cp\u003e22 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.264\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eBleomycin hypersensitivity reactions are infrequently reported in the literature. They are limited to case reports that occurred shortly after bleomycin was approved for use, and there are no cases reported in the literature after 2000. As noted by Lam, this could be attributed to several factors. One such factor may include the widespread use of antiemetic premedications, which often contain corticosteroids, in modern chemotherapy regimens. A second explanation may be due to modern processes for manufacturing bleomycin, contrasted with an older method of purifying bleomycin from fungus which may have resulted in contaminants present in the formulation.\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOur analysis showed that bleomycin hypersensitivity reactions occur rarely and do not appear to be predicted with the use of test doses. This is evidenced by all three patients who developed a reaction had received a test dose with no reaction to those doses. This lends credence to the idea that the incidence of bleomycin hypersensitivity reactions do not typically occur in modern times.\u003c/p\u003e \u003cp\u003eThere were no differences in age, sex, or race in our study, however there were more patients in the test dose arm with Hodgkin\u0026rsquo;s lymphoma and a higher number of patients with testicular and germ cell tumors in the non-test dose arm. This did not appear to influence the results at all due to the low overall event rate in our analysis.\u003c/p\u003e \u003cp\u003eOur study has several limitations. It is retrospective in nature and data collection was reliant on appropriate documentation in the electronic health record. Additionally, the timeframe of our study includes a time prior to computerized physician order entry (CPOE) at our institution when medication orders were written on paper and subsequently scanned into the computer system. This may have limited the ability to gather pertinent medications. This limitation was attenuated by reviewing documents up to one month after each bleomycin dose to account for delays in document uploading. Additionally, our trial was not powered to detect a difference between the two arms.\u003c/p\u003e \u003cp\u003eDespite these limitations, our study also has several strengths. Prior to our study, any reports of bleomycin hypersensitivity reactions were limited to case reports and series. Ours is the first study to specifically compare the rate of bleomycin hypersensitivity reactions between those who received and did not receive a test dose. The benefit of this is to show actual rates between the two arms rather than relying on low incidence in the literature as evidence it does not happen. This most importantly shows that, even with low numbers, a test dose is not necessary. Our study also includes a large proportion of African Americans, an often under-represented group in clinical research.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe findings in this study did not show a correlation between bleomycin test dose reactions and the development of bleomycin hypersensitivity reactions. It is the first analysis of this relationship other than cases that have been reported shortly after the advent of bleomycin. Based on these findings, there appears to be a limited utility to continuing the practice of bleomycin test doses. Further studies are needed to confirm our findings.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is a retrospective observational study. The UTHSC IRB determined no ethical approval is required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is a retrospective observational study and was granted exemption status from formal consent by the UTHSC IRB\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Acknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no financial support for the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there is no conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBleomycin [prescribing information]. Lake Forest, IL: Hospira; May 2017.\u003c/li\u003e\n\u003cli\u003eLam MS. The need for routine bleomycin test dosing in the 21\u003csup\u003est\u003c/sup\u003e century. \u003cem\u003eAnn Pharmacother.\u003c/em\u003e 2005; 39(11):1897-1902.\u003c/li\u003e\n\u003cli\u003eGeuenich S, Haberl C, Egger D, Kaspers U, Hultner L, Wilmanns W. Induction of leukotriene production by bleomycin and asparaginase in mast cells in vitro and in patients in vivo. Biochem Pharmacol 1998; 55:447-53.\u003c/li\u003e\n\u003cli\u003eBlum RH, Carter Sk, Agre K. A clinical review of bleomycin \u0026ndash; a new antineoplastic agent. Cancer. 1973; 56:197-205.\u003c/li\u003e\n\u003cli\u003eRosenfelt F, Palmer J, Weinstein I, Rosenbloom B. A fatal hyperpyrexial response to bleomycin following prior therapy: A case report and literature review. \u003cem\u003eYale J Biol Med.\u003c/em\u003e 1982; 55:529-31\u003c/li\u003e\n\u003cli\u003eMa DD, Isbister JP. Cytotoxic-induced fulminant hyperpyrexia. \u003cem\u003eCancer.\u003c/em\u003e 1980; 45:2249-51.\u003c/li\u003e\n\u003cli\u003eCarter JJ, McLaughlin ML, Bern MM. Bleomycin-induced fatal hyperpyrexia. \u003cem\u003eAm J Med.\u003c/em\u003e 1983; 74:523-5.\u003c/li\u003e\n\u003cli\u003eLeung WH, Lau JY, Chan TK, et al. Fulminant hyperpyrexia-induced by bleomycin. \u003cem\u003ePostgrad Med J.\u003c/em\u003e 1989; 65:417-9.\u003c/li\u003e\n\u003cli\u003eInbar MJ, Baratz M, Figer A, et al. Idiosyncratic reaction to bleomycin in an epithelial tumor. \u003cem\u003eCancer Chemother Pharmacol.\u003c/em\u003e 1984; 13:71-2.\u003c/li\u003e\n\u003cli\u003eLevy RL, Chiarillo S. Hyperpyrexia, allergic-type response and death occurring with low-dose bleomycin administration. \u003cem\u003eOncology.\u003c/em\u003e 1980; 37:316-7.\u003c/li\u003e\n\u003cli\u003eKhansur T, Little D, Tavassoli M. Fulminant and fatal angioedema caused by bleomycin treatment. \u003cem\u003eArch Intern Med.\u003c/em\u003e 1984; 144:2267.\u003c/li\u003e\n\u003cli\u003eBrodsky A, Aparici I, Argeri C, et al. Stevens-Johnson syndrome, respiratory distress, and renal failure due to synergistic bleomycin-cisplatin toxicity. \u003cem\u003eJ Clin Pharmacol.\u003c/em\u003e 1989; 29:821-3.\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":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Bleomycin, test dose, hypersensitivity","lastPublishedDoi":"10.21203/rs.3.rs-4565600/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4565600/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eHypersensitivity reactions are a side effect of bleomycin. Test doses have been utilized to attempt to predict patients that would develop these reactions. Despite this, there is scant data available on whether these test doses actually predict the development of reactions. Commonly cited literature relies on lack of reporting of hypersensitivity reactions, rather than comparative data, to claim test doses may not be beneficial. The purpose of this analysis was to compare patients who received test doses against those who did not in the development of bleomycin hypersensitivity reactions.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e77 patients who had received bleomycin as part of their chemotherapy regimen were included in this retrospective analysis. Patients were stratified based on the receipt of a bleomycin test dose (either 1 or 2 units given prior to the full dose). The presence of hypersensitivities were assessed by documentation of emergency medications in the medical record shortly after bleomycin administration or through documentation by a provider note.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThere were no reactions reported with any of the 84 test doses administered. With the full dose of bleomycin administered, hypersensitivity reactions occurred in 3 patients in the test dose arm (5.5%) compared to no patients in the group that did not receive a test dose. Despite this difference, there was no statistical difference between the two arms (p\u0026thinsp;=\u0026thinsp;0.264).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn this study, we observed no relation between a negative bleomycin test dose and the development of acute hypersensitivity reaction. Interestingly, there was a higher numerical incidence of hypersensitivity reactions in patients who received a test dose than those who did not receive a test dose, though this was not statistically significant. Larger studies would need to be conducted to verify these findings.\u003c/p\u003e","manuscriptTitle":"The Impact of Bleomycin Test Doses on the Development of Acute Hypersensitivity Reactions","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-09 09:28:24","doi":"10.21203/rs.3.rs-4565600/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accepted","date":"2025-08-28T16:52:50+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-27T14:53:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"139400839493018501581183361211584157042","date":"2024-08-25T13:17:46+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-21T18:11:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-25T20:31:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-20T00:20:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"Supportive Care in Cancer","date":"2024-06-11T16:46:29+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"f56de4b0-f2d8-432c-b43d-50bd0d9a80ce","owner":[],"postedDate":"July 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-09-15T16:00:44+00:00","versionOfRecord":{"articleIdentity":"rs-4565600","link":"https://doi.org/10.1007/s00520-025-09902-y","journal":{"identity":"supportive-care-in-cancer","isVorOnly":false,"title":"Supportive Care in Cancer"},"publishedOn":"2025-09-08 15:57:34","publishedOnDateReadable":"September 8th, 2025"},"versionCreatedAt":"2024-07-09 09:28:24","video":"","vorDoi":"10.1007/s00520-025-09902-y","vorDoiUrl":"https://doi.org/10.1007/s00520-025-09902-y","workflowStages":[]},"version":"v1","identity":"rs-4565600","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4565600","identity":"rs-4565600","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}