title: The Incidence and Severity of Oral Mucositis among Allogeneic Hematopoietic Stem Cell Transplantation Patients: A Systematic Review.
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 = .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 = .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 = .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 allogeneic HSCT clinical trials.
authors.affiliation: Mayo Medical School, Rochester, Minnesota. Electronic address: chaudhry.hafsa@mayo.edu.
authors.forename: Hafsa M
authors.initials: HM
authors.lastname: Chaudhry
authors.affiliation: Department of Dermatology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Bruce
authors.affiliation: Division of Pharmacy, Mayo Clinic, Rochester, Minnesota.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Wolf
authors.affiliation: Division of Hematology, Blood & Marrow Transplantation, Mayo Clinic, Rochester, Minnesota.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Litzow
authors.affiliation: Division of Hematology, Blood & Marrow Transplantation, Mayo Clinic, Rochester, Minnesota.
authors.forename: William J
authors.initials: WJ
authors.lastname: Hogan
authors.affiliation: Division of Hematology, Blood & Marrow Transplantation, Mayo Clinic, Rochester, Minnesota.
authors.forename: Mrinal S
authors.initials: MS
authors.lastname: Patnaik
authors.affiliation: Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Walter K
authors.initials: WK
authors.lastname: Kremers
authors.affiliation: Hematology and Oncology Comprehensive Cancer Center, Wake Forest Baptist Health, Winston-Salem, North Carolina.
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Phillips
authors.affiliation: Division of Hematology, Blood & Marrow Transplantation, Mayo Clinic, Rochester, Minnesota.
authors.forename: Shahrukh K
authors.initials: SK
authors.lastname: Hashmi
mesh_terms: D002066:Busulfan / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D015994:Incidence; D008727:Methotrexate / Q000627:therapeutic use; D009061:Mouth Mucosa / Q000382:microbiology / Q000473:pathology; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013280:Stomatitis / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008727:Methotrexate
keywords: Allogeneic hematopoietic stem cell transplantation; Mucosal barrier injury; Oral mucositis; Transplantation-related toxicity