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.

Burden of Oral Mucositis: A Systematic Review and Implications for Future Research

“…Incidence of OM/stomatitis of all grades in patients with hematopoietic stem cell transplantation (HSCT) was between 70% and 86.8% when considering only the 3 studies/meta-analyses with an evidence level rated as ‘high' [3,5,19]. OM grade 3 was reported to be 12.9% [5] and 30.5% [3] and OM grade 4 to be 8.2% [5] and 13.7% [3], respectively, in 2 of these studies.…”

“…1 Studies on oral mucositis (OM). Incidence of OM was investigated in patients with hematopoietic stem cell transplantation (HSCT) in 14 studies (32.6%) [3,5,14,17,19,28,31,36,37,39,44,56,62,67], in head and neck cancer (HNC) patients in 13 studies (30.2%) [18,21,29,40,50,51,55,59,60,61,63,70,73], in patients with chemotherapy in 13 studies (30.2%) [15,16,22,23,24,25,30,34,38,46,48,58,71], with mixed tumor types and treatment in 1 study (2.3%) [13] and with palliative care in 2 studies (4.7%) [32,57]. Cost related to OM in patients undergoing HSCT was the focus in 4 studies [7,14,17,54], in HNC patients in 2 studies [43,47], in patients with chemotherapy in 6 studies [9,10,11,12,42,49,68], and in patients with mixed tumor types and treatment in 2 studies [20,45].…”

“…There were 7 studies covering 2 topics each [3,13,14,15,16,17,18] and 7 meta-analyses [19,20,21,22,23,24,25]. 20 studies (29.4%) were from Europe [3,5,9,10,11,12,15,22,26,27,28,29,30,31,32,33,34,35,36,37,38,] 20 from the US [4,14,17,19,20,24,39,40,41,42,43,44,45,46,47,48,49,50,51,52], 3 studies (4.4%) from US plus Europe [23,53,54], 6 studies (8.8%) from Japan [16,55,56,57,58,59], 6 studies (8.8%) from China [18,25,60,61,62,63], 2 studies (3.0%) from Hong Kong [13,64,65], 3 studies (4.4%) from Canada [66,67,68], 3 studies (4.4%) from India [21,69,70] and 5 studies (7.4%) from other countries [7,71,72,73,74]. 21 studies (30.9%) used the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale for assessment of OM.…”

Bacterial bloodstream infections in the allogeneic hematopoietic cell transplant patient: new considerations for a persistent nemesis

“…109 Chemotherapy and irradiation not only damage the gastrointestinal tract, allowing bacterial constituents to enter the systemic circulation (that is, bacterial transmigration and subsequent bacteremia), but also activate aGvHD, an inflammatory cytokine-associated alloreactivity that causes further insult to gastrointestinal epithelium. 110 Surprisingly, mucositis severity does not correlate with incidence of BSI. For example, prospective studies evaluating interventions that are effective in reducing mucositis like keratinocyte growth factor 111 and cryotherapy 112 have not shown a beneficial effect in reducing BSI rates.…”

Complete prevention and rapid sustained elimination of chemoradiation toxic mucositis, a case series with implications for mucositis pathobiology, cost of care, morbidity and premature cancer deaths

“…Over this period of time, fifteen generations of medical oncologists and correspondingly six generations of radiation oncologists have been trained to accept toxic mucositis as an irreversible and unpreventable complication of chemoradiation. Overall, treatment-induced mucositis has been documented to occur in 37% of patients receiving chemotherapy (CT) [5,6], in 89.5% of head neck cancer patients (HNC) receiving radiation [7][8][9] and in 100% of patients undergoing human stem cell transplantation patient (HSCT) [10,11].…”