Abstract
Purpose
Oral ulcerative mucositis (UM) and gastrointestinal mucositis (GIM) have been associated with increased likelihood of systemic infection (bacteremia and sepsis) in patients being treated for hematological malignancies. To better define and contrast differences between UM and GIM, we utilized the United States 2017 National Inpatient Sample and analyzed patients hospitalized for the treatment of multiple myeloma (MM) or leukemia.
Methods
We utilized generalized linear models to assess the association between adverse events—UM and GIM—among hospitalized MM or leukemia patients and the outcome of febrile neutropenia (FN), septicemia, burden of illness, and mortality.
Results
Of 71,780 hospitalized leukemia patients, 1255 had UM and 100 GIM. Of 113,915 MM patients, 1065 manifested UM and 230 had GIM. In an adjusted analysis, UM was significantly associated with increased risk of FN in both the leukemia (aOR = 2.87, 95% CI = 2.09–3.92) and MM cohorts (aOR = 4.96, 95% CI = 3.22–7.66). Contrastingly, UM had no effect on the risk of septicemia in either group. Likewise, GIM significantly increased the odds of FN in both leukemia (aOR = 2.81, 95% CI = 1.35–5.88) and MM (aOR = 3.75, 95% CI = 1.51–9.31) patients. Similar findings were noted when we restricted our analysis to recipients of high-dose condition regimens in preparation for hematopoietic stem-cell transplant. UM and GIM were consistently associated with higher burden of illness in all the cohorts.
Conclusion
This first use of big data provided an effective platform to assess the risks, outcomes, and cost of care of cancer treatment-related toxicities in patients hospitalized for the management of hematologic malignancies.
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Data availability
We used data from the United States’ 2017 National Inpatient Sample database obtained from Healthcare Cost and Utilization Project (HCUP) of the Agency for Healthcare Research and Quality (AHRQ).
Code availability
Not applicable.
References
Jairam V, Lee V, Park HS et al (2019) Treatment-related complications of systemic therapy and radiotherapy. JAMA Oncol 5(7):1028–1035. https://doi.org/10.1001/jamaoncol.2019.0086
Blijlevens NM, Logan RM, Netea MG (2009) The changing face of febrile neutropenia-from monotherapy to moulds to mucositis. Mucositis: from febrile neutropenia to febrile mucositis. J Antimicrob Chemother 63(Suppl 1):i36-40. https://doi.org/10.1093/jac/dkp081
Tsuboi K, Tsuboi N, Sakamoto K et al (2021) Life-threatening oral mucositis following chemotherapy in a pediatric patient. Clin Case Rep 9(6):e04356. https://doi.org/10.1002/ccr3.4356
Wardill HR, de Mooij CEM, da Silva Ferreira AR et al (2021) Translational model of melphalan-induced gut toxicity reveals drug-host-microbe interactions that drive tissue injury and fever. Cancer Chemother Pharmacol 88(2):173–188. https://doi.org/10.1007/s00280-021-04273-7
van der Velden WJ, Herbers AH, Feuth T, Schaap NP, Donnelly JP, Blijlevens NM (2010) Intestinal damage determines the inflammatory response and early complications in patients receiving conditioning for a stem cell transplantation. PLoS One 5(12):e15156. https://doi.org/10.1371/journal.pone.0015156
Overview of the National (Nationwide) Inpatient Sample (NIS) (2021) Healthcare cost and utilization project. Available at: https://www.hcup-us.ahrq.gov/nisoverview.jsp. Accessed Feb 2020
NIS Description of Data Elements (2021) Healthcare cost and utilization project. Available at: https://www.hcup-us.ahrq.gov/db/nation/nis/nisdde.jsp. Accessed Feb 2020
Elixhausern A, Steiner C, Harris DR, Coffey RM (1998) Comorbidity measures for use with administrative data. Med Care 36(1):8–27 JSTOR, https://www.jstor.org/stable/3766985. Accessed 25 February 2020.
Bernhardt PW, Wang HJ, Zhang D (2015) Statistical methods for generalized linear models with covariates subject to detection limits. Stat Biosci 7(1):68–89. https://doi.org/10.1007/s12561-013-9099-4
McCullagh P, Nelder JA (1989) Generalized linear models. Chapman and Hall, London
Johansson JE, Brune M, Ekman T (2001) The gut mucosa barrier is preserved during allogeneic, haemopoietic stem cell transplantation with reduced intensity conditioning. Bone Marrow Transplant 28(8):737–742. https://doi.org/10.1038/sj.bmt.1703230
Blijlevens NM, Donnelly JP, de Pauw BE (2005) Prospective evaluation of gut mucosal barrier injury following various myeloablative regimens for haematopoietic stem cell transplant. Bone Marrow Transplant 35(7):707–711. https://doi.org/10.1038/sj.bmt.1704863
Blijlevens NM, Donnelly JP, de Pauw BE (2001) Empirical therapy of febrile neutropenic patients with mucositis: challenge of risk-based therapy. Clin Microbiol Infect 7(Suppl 4):47–52. https://doi.org/10.1046/j.1469-0691.2001.00058.x
Coron E, Esnaud E, Chevallier P et al (2021) Early remodeling of the colonic mucosa after allogeneic hematopoietic stem cells transplantation: an open-label controlled pilot study on 19 patients. United European Gastroenterol J 9(8):955–963. https://doi.org/10.1002/ueg2.12128
Zecha JAEM, Raber-Durlacher JE, Laheij AMGA, Westermann AM, de Lange J, Smeele LE (2022) The potential contribution of dental foci and oral mucositis to febrile neutropenia in patients treated with myelosuppressive chemotherapy for solid tumors and lymphoma. Front Oral Health 30(3):940044. https://doi.org/10.3389/froh.2022.940044
Facchini L, Martino R, Ferrari A, Piñana JL et al (2012) Degree of mucositis and duration of neutropenia are the major risk factors for early post-transplant febrile neutropenia and severe bacterial infections after reduced-intensity conditioning. Eur J Haematol 88(1):46–51. https://doi.org/10.1111/j.1600-0609.2011.01724.x
Sonis ST, Oster G, Fuchs H et al (2001) Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation. J Clin Oncol 19(8):2201–2205. https://doi.org/10.1200/JCO.2001.19.8.2201
Lee SJ, Klar N, Weeks JC, Antin JH (2000) Predicting costs of stem-cell transplantation. J Clin Oncol 18(1):64–71. https://doi.org/10.1200/JCO.2000.18.1.64
Chaudhry HM, Bruce AJ, Wolf RC et al (2016) The incidence and severity of oral mucositis among allogeneic hematopoietic stem cell transplantation patients: a systematic review. Biol Blood Marrow Transplant 22(4):605–616. https://doi.org/10.1016/j.bbmt.2015.09.014
Bacigalupo A, Ballen K, Rizzo D, Horowitz M et al (2009) Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant 15(12):1628–33. https://doi.org/10.1016/j.bbmt.2009.07.004
Miaskowski C (2001) Biology of mucosal pain. J Natl Cancer Inst Monogr 29:37–40. https://doi.org/10.1093/oxfordjournals.jncimonographs.a003438
Quinn B, Potting CM, Stone R et al (2008) Guidelines for the assessment of oral mucositis in adult chemotherapy, radiotherapy and haematopoietic stem cell transplant patients. Eur J Cancer 44(1):61–72. https://doi.org/10.1016/j.ejca.2007.09.014
Sonis ST, Eilers JP, Epstein JB et al (1999) Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or chemotherapy. Mucositis Study Group. Cancer 85(10):2103–2113. https://doi.org/10.1002/(sici)1097-0142(19990515)85:10%3c2103::aid-cncr2%3e3.0.co;2-0
Epstein JB, Beaumont JL, Gwede CK et al (2007) Longitudinal evaluation of the oral mucositis weekly questionnaire-head and neck cancer, a patient-reported outcomes questionnaire. Cancer 109(9):1914–1922. https://doi.org/10.1002/cncr.22620
Kushner JA, Lawrence HP, Shoval I et al (2008) Development and validation of a Patient-Reported Oral Mucositis Symptom (PROMS) scale. J Can Dent Assoc 74(1):59
Le Bourgeois A, Mohr C, Guillaume T et al (2013) Comparison of outcomes after two standards-of-care reduced-intensity conditioning regimens and two different graft sources for allogeneic stem cell transplantation in adults with hematologic diseases: a single-center analysis. Biol Blood Marrow Transplant 19(6):934–939. https://doi.org/10.1016/j.bbmt.2013.03.009
Eduardo FP, Bezinelli LM, Gobbi M et al (2019) Retrospective study of the digestive tract mucositis derived from myeloablative and non-myeloablative/reduced-intensity conditionings with busulfan in hematopoietic cell transplantation patient. Support Care Cancer 27(3):839–848. https://doi.org/10.1007/s00520-018-4362-3
Nakagaki M, Kennedy GA, Gavin NC, Clavarino A, Whitfield K (2022) The incidence of severe oral mucositis in patients undergoing different conditioning regimens in haematopoietic stem cell transplantation. Support Care Cancer 26:1–9. https://doi.org/10.1007/s00520-022-07328-4
Silva FC, Marto JM, Salgado A, Machado P, Silva AN, Almeida AJ (2017) Nystatin and lidocaine pastilles for the local treatment of oral mucositis. Pharm Dev Technol 22(2):266–274. https://doi.org/10.1080/10837450.2016.1221424
Napeñas JJ, Brennan MT, Bahrani-Mougeot FK, Fox PC, Lockhart PB (2007) Relationship between mucositis and changes in oral microflora during cancer chemotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103(1):48–59. https://doi.org/10.1016/j.tripleo.2005.12.016
Stringer AM, Logan RM (2015) The role of oral flora in the development of chemotherapy-induced oral mucositis. J Oral Pathol Med 44(2):81–87. https://doi.org/10.1111/jop.12152
Vozza I, Caldarazzo V, Ottolenghi L (2015) Changes in microflora in dental plaque from cancer patients undergoing chemotherapy and the relationship of these changes with mucositis: a pilot study. Med Oral Patol Oral Cir Bucal 20(3):e259–e266. https://doi.org/10.4317/medoral.19934
Damiani A, Onder G, Valentini V (2018) Large databases (Big Data) and evidence-based medicine. Eur J Intern Med 53:1–2. https://doi.org/10.1016/j.ejim.2018.05.019
Parikh RB, Gdowski A, Patt DA, Hertler A, Mermel C, Bekelman JE (2019) Using big data and predictive analytics to determine patient risk in oncology. Am Soc Clin Oncol Educ Book 39:e53–e58. https://doi.org/10.1200/EDBK_238891
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S. K. contributed to the design, conception, acquisition, interpretation of the data, drafting, and critical revision of the manuscript; S. S. contributed to the design, conception, acquisition, interpretation of the data, drafting, and critical revision of the manuscript; and N. B. contributed to the design and critical revision of the manuscript.
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Satheeshkumar, P.S., Blijlevens, N. & Sonis, S.T. Application of big data analyses to compare the impact of oral and gastrointestinal mucositis on risks and outcomes of febrile neutropenia and septicemia among patients hospitalized for the treatment of leukemia or multiple myeloma. Support Care Cancer 31, 199 (2023). https://doi.org/10.1007/s00520-023-07654-1
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DOI: https://doi.org/10.1007/s00520-023-07654-1