Mucositis In Patients With Hematologic Malignancies: Prophylaxis Or Treatment - That Is The Question!
Authors: Pereira Dulcineia , Chacim Sergio Pereira , Martinez Jose , Mesquita Edgar , Sousa Ines , Martins Angelo , Mariz Jose Mario 
Published: October 2019

Abstract

Introduction
Oral and gastrointestinal mucositis in the context of high dose chemotherapy (CT) and/or radiotherapy (RT) remains one of the most problematic side effects that influences quality of life (QOL). Mucositis may lead to clinical deterioration with significant weight loss and reduction of chemotherapy doses with lower effectiveness, prolongation of hospitalization and increased costs.

Objectives
Epidemiological characterization of mucositis secondary to CT. Prognostic impact of the type of hematologic malignancy in the mucositis' risk. Impact of conservative treatment (MASCC/ISSO) in the risk of mucositis and hospitalization days.

Methods
Observational study of sequencial 30 patients with acute leukemia (AL) and aggressive B-cell non-Hodgkin lymphoma (B-NHL), indicated for CT (1st or 2nd line), followed at our center between February and August 2012. Patients admitted to the study underwent daily assessment by trained nurse staff for the degree of mucositis (WHO), pain and diarrhea, according to well-established scales, and for the presence of neutrophils, need for analgesics, basic oral prophylactic care (BOC) - guidelines MASCC / ISSO - vs BOC and therapeutic treatment (Caphosol ® and/or Gelclair ®) of mucositis. The evaluation was carried out up to day 20th of CT, or until mucositis resolved to grade ≤ 2 for 2 consecutive days or until day 12thof CT in patients who had mucositis ≤ grade 1. Patient characteristics were compared by the χ2 test for binary variables and by the Mann-Whitney test for continuous variables. Data was modeled according to longitudinal procedures, regarding continuous and multinomial dependent variables. We used R software with packages lme and VGAM. The remaining data were analyzed by using SPSS version 17.0. A p value less than 0,01 was considered to be statistically significant.

Results
30 patientes were included, corresponding to 75 episodes/admissions of patients with hematologic malignancy, of which 22,7% (n = 17) developed mucositis. The median follow-up was 23 days (min.5-máx.35). 64,7% (n = 11) patients were diagnosed with AL and 35,3% (n = 6) patients diagnosed with Burkitt NHL, median age was 61 years (min.35-máx.68) and 41,5 years (min.37-máx.47), respectively. Regarding the treatment phase, 72,7% (n = 8) patients with AL were evaluated during induction, 18,2% (n = 2) during consolidation and 9,1% (n = 1) during aplasia. 33,3% (n = 2) patients with B-NHL were evaluated under CT and 66,7 (n = 4) under aplasia.
Through the application of a multinomial logistic model with a longitudinal component and analyzing the variation of the degree of mucositis over time we found that, in patients with AL, the period of greatest frequency of mucositis in spline curves occurs from the 10thday from starting CT, with a median time to mucositis development of 12 days (mín.0-máx.24). In patients with B-NHL, the frequency of mucositis is higher in the first 10 days of treatment, the median time until installation of mucositis was 5 days (min.1-máx.12). In both diagnostic groups, few patients had grade 3 mucositis (18,2% in AL and 16,7% in B-NHL), since most patients with B-NHL and AL show grade 1 mucositis.
The risk of developing grade 1 mucositis is higher in AL vs B-NHL patients (HR 0.328444, p <0.01). For B-NHL, the degree of oral mucositis tends to the development of gastrointestinal mucositis (HR 72.46, p <0.001). Neutropenia involves an increased risk of mucositis: in patients with AL increases the risk of grade 2 mucositis in 5.99 (p<0.001), in B-NHL patients increases the risk of grade 2 mucositis in 207.58 (p<0.001). Patients with grade 3 mucositis had an increased number of hospitalization days, on average increase of 0.57 days (p<0,05). Our results suggest that patients who did not initiate early prophylaxis with conservative measures, developed mucositis earlier, with an average reduction of 0,967 days (p<0,05).

Conclusion
Studies of epidemiological characterization of mucositis are scarce. In this study, it is demonstrated that the incidence of mucositis in AL patients is higher than in patients with B-NHL. In patients with B-NHL and AL, neutropenia entails an increased risk of mucositis (p <0.001). Our results suggested that grade 3 mucositis leads to prolonged hospitalization (p<0,05). Patients who did not initiate early prophylaxis with conservative measures, developed mucositis earlier (p<0,05). Prospective randomized trials should validate this findings.

Disclosures:
No relevant conflicts of interest to declare.