Review Articles The Incidence and Severity of Oral Mucositis among Allogeneic Hematopoietic Stem Cell Transplantation Patients: A Systematic Review Hafsa M. Chaudhry 1 , * , Alison J. Bruce 2 , Robert C. Wolf 3 , Mark R. Litzow 4 , William J. Hogan 4 , Mrinal S. Patnaik 4 , Walter K. Kremers 5 , Gordon L. Phillips 6 , Shahrukh K. Hashmi 4 1 Mayo Medical School, Rochester, Minnesota 2 Department of Dermatology, Mayo Clinic, Rochester, Minnesota 3 Division of Pharmacy, Mayo Clinic, Rochester, Minnesota 4 Division of Hematology, Blood & Marrow Transplantation, Mayo Clinic, Rochester, Minnesota 5 Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota 6 Hematology and Oncology Comprehensive Cancer Center, Wake Forest Baptist Health, Winston-Salem, North Carolina Article history: Received 18 July 2015 Accepted 16 September 2015 Key Words: Oral mucositis Mucosal barrier injury Transplantation-related toxicity Allogeneic hematopoietic stem cell transplantation abstract Oral mucositis (OM) is a debilitating early adverse effect of allogeneic hematopoietic stem cell transplantation (HSCT). The intensity of the conditioning regimen correlates with the incidence and severity of OM, but no studies have analyzed this relationship among various conditioning regimens. We performed a systematic review on the incidence and outcomes of OM in allogeneic HSCT patients and analyzed this association. A comprehensive search of several databases (Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Cochrane CRCT, Cochrane DSR, Scopus) from 1990 to 2014 for studies of OM in allogeneic HSCT patients was conducted. Professional societies’ meeting abstracts were also searched. Grade of OM was analyzed based on the World Health Organization (WHO) or National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events scales. Severe mucositis was defined as either grades 2 to 4 or grades 3 and 4, depending on the studies’ definition of severity. Cohorts were analyzed based on regimen intensity; ie, reduced-intensity conditioning (RIC) (including nonmyeloablative) and myeloablative (MA). Random effect (RE) and standard logistic models weighted by the number of patients in each cohort were used for comparisons. A total of 624 studies were generated from the search. Of the 395 patients in 8 eligible MA regimen studies, 73.2% experienced any OM, whereas in 245 patients in the 6 eligible RIC regimen studies, 86.5% experienced any OM (chi-square P < .0001; RE, P ¼ .05). Severe (grades 2 to 4) OM occurred among 79.7% of the WHO/NCI-graded MA patients and 71.5% of RIC patients (chi-square, P ¼ .0421; RE, P < .01). In comparing graft-versus-host disease (GVHD) prophylaxis, only 55.4% of patients receiving nonmethotrexate regimens experienced OM; this was lower (chi-square, P < .0001; RE, P ¼ .06) than that found among patients who received methotrexate (83.4%), either standard or reduced dose. Besides NCI and WHO grading scales, other scales included in the studies were Oral Mucositis Index, the Southwest Oncology Group Criteria, and Eastern Cooperative Oncology Group scale. To our knowledge, this is the first analysis on OM in allogeneic HSCT patients with respect to conditioning regimens, and we observed that RIC regimens led to a high incidence of OM similar to that of MA regimens. Clinical trials on treatment of OM are lacking, emphasizing the essential need for prospective studies in this arena. A significant variance in the criteria for grading OM underscores the importance of establishing a standard grading system for OM measurement in future allo- geneic HSCT clinical trials. Ó 2016 American Society for Blood and Marrow Transplantation. INTRODUCTION Oral mucositis (OM) is a debilitating adverse effect of treatment during allogeneic hematopoietic stem cell trans- plantation (HSCT) [1] and its incidence varies between 47% [22] and 100% [26], depending on a multitude of factors. Furthermore, OM is 1 of the most common complications and Financial disclosure: See Acknowledgments on page 615. * Correspondence and reprint requests: Hafsa M. Chaudhry, 200 First Street SW, Rochester, MN 55905. E-mail address: chaudhry.hafsa@mayo.edu (H.M. Chaudhry). http://dx.doi.org/10.1016/j.bbmt.2015.09.014 1083-8791/Ó 2016 American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 22 (2016) 605e616 Biology of Blood and Marrow Transplantation journal homepage: www.bbmt.org