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The Incidence and Outcomes of Oral Mucositis Among Allogeneic Stem Cell Transplantation Patients: A Systematic Review and Meta-Analysis

Hafsa Myedah Chaudhry, Alison J. Bruce, Robert Wolf, Mark R. Litzow, William Hogan, et al.

Biology of Blood and Marrow Transplantation, Volume 21, Issue 2, Supplement, February 2015, Pages S245-S246

Editors’ comment: Dr Ricardo Caponero

Oral mucositis remains the major problem with great impact on the quality of life in patients during stem cell transplantation and may be the cause of prolonged hospitalization time. Hafsa Myedah Chaudhry and cols. performed a systematic review and a meta-analysis about the incidence and outcomes of this uncomfortable symptom.

Abstract

Background
Oral mucositis (OM) is the most debilitating adverse effect of treatment from patient perspective during Allogeneic Stem Cell Transplantation (ASCT).The intensity of the conditioning regimen relates to both incidence & severity of OM; however no previously published study has analyzed this relationship. We sought to perform a meta-analysis and systemic review on the incidence and outcomes of OM in ASCT patients, and analyze this association.

Methods
A comprehensive search of several databases (Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane CRCT, Ovid Cochrane DSR and Scopus) from 1990-2014 for studies of OM in ASCT patients was conducted by an experienced medical librarian. To avoid file-drawer bias, professional society meeting (ASH, EHA, ASBMT, EBMT, AAD) abstracts were searched. Studies were included with strict eligibility - if they reported the grade & incidence of OM with validated scales, and provided details of conditioning regimen and Graft-versus-host-disease (GVHD) prophylaxis (including doses e.g. methotrexate). Grade of OM was analyzed based on the WHO or NCI-CTCAE scales. For studies not utilizing these scales, only overall incidence of OM was reported. Severe mucositis was defined as either Grade 2-4 or Grade 3-4 depending on the studies' definition of severity. Cohorts were analyzed based on regimen intensity i.e. Reduced Intensity Conditioning (RIC) [including Non-myeloablative] and Myeloablative (MA).

Results
A total of 624 studies generated from the search were reviewed. Of the 582 patients in 14 eligible MA regimen studies, 75.4% experienced any OM, while in 245 patients reviewed in the 6 eligible RIC regimen studies, 86.1% experienced any OM (figures 1&2). A majority of studies utilized the WHO or NCI-CTCAE scales. Severe OM occurred in 73.3% of the WHO/NCI graded MA conditioning patients and 67.8% of WHO/NCI graded RIC conditioned patients. Other grading scales included in the studies were Oral Mucositis Index, the Southwest Oncology Group (SWOG) Criteria, and the Eastern Cooperative Oncology Group (ECOG) scale. Due to the lack of randomized controlled trials focusing on OM as the primary outcome variable and heterogeneity of scales used to measure OM, a meta-analysis could not be performed; however pooled analysis indicated significant differences in incidence of OM with respect to different conditioning regimens (figures 1&2).

Conclusions
To our knowledge, this is the first analysis on OM in ASCT patients and we found that RIC regimens led to a very 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 undermines the importance of establishing standard grading system for OM measurement in future ASCT clinical trials globally.

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