A Pilot Study of Efficacy of Lactobacillus CD2 Lozenges in Preventing High-Dose Chemotherapy Induced Oral Mucositis in Patients Undergoing Haematopoietic Stem Cell Transplantation

More than 70% of patients receiving high dose chemotherapy and haematopoietic stem cell transplantation (HSCT) are likely to develop grade III or IV mucositis causing significant morbidity. Palifermin, which helps in reducing duration and severity, is expensive and not available in many countries. Probiotic Lactobacillus CD 2 has been shown to reduce incidence and severity of chemo-radiotherapy induced mucositis in squamous cell carcinoma of head and neck (Sharma A, et al. Eur J Cancer 2012: 875–81). The objective of this study was to determine the efficacy of this probiotic in preventing grade III/IV mucositis in patients undergoing HSCT.

Lozenges containing not less than 2×10⁹ viable cells of Lactobacillus CD2 as active ingredient were started 4–7 days prior to commencing conditioning regimen of HSCT and continued till resolution of mucositis or Day+24 post stem cell infusion, whichever was earlier. The lozenges were supposed to be kept in mouth for it to be dissolved by itself. Mucositis (NCI-CTCAE V 4.03) was assessed daily till recovery; number of lesions, localization in the oral cavity, bleeding, erythema and ulceration were recorded. Photographs of the mucosal lesions (oral cavity) were taken once a week and saliva samples of patients was collected weekly till complete recovery or day +24 of the treatment to analyze the levels of pro-inflammatory cytokines.

Twenty-one patients (17 autologous and 4 RIC-allogeneic) in the age group of 10–70 years undergoing high dose chemotherapy and HSCT were enrolled. Median age was 29 years (range11–64 yrs). Multiple myeloma constituted 9 (43%) of cases. Others included HL (5), NHL (3), AML (3), and RMS (1). Fourteen patients had received at least 2 lines of prior therapy. Conditioning regimens used were high dose melphalan, BEAM, CBV, or melphalan treosulfan. Four patients received RIC (fludarabine with melphalan). One patient could not continue study drug beyond one day because of nausea, however, rest tolerated lozenges well. Eighteen patients took at least 3 or 4 lozenges daily for an average duration of 8 days. Six patients (28.6%) had no mucositis, 4 (19%) had grade I, 7 (33.3%) had grade II, and 2 (9.5%) patients each had grade III or IV mucositis (one of these was post autologous HSCT and another one was on long term methotrexate for rheumatoid arthritis). Seventeen patients had < grade 2 dysphagia. Median duration of IV antibiotic use was 8 days (range 5–18). Median days to onset of mucositis and time to recovery were 6 (range 3–8) and 8 days (range 5–40), respectively. No adverse events except occasional grade I/II nausea due to study drug were noted.

This study suggests that the use of Lactobacillus CD2 significantly reduced events of severe mucositis in patients undergoing HSCT as only 19% developed grade III or IV mucositis compared to the expectation of >60%. This needs confirmation in randomized studies.

ClinicalTrials.gov Identifier: NCT01480011

No relevant conflicts of interest to declare.