Lactobacillus brevis CD2 lozenges prevent oral mucositis in patients undergoing high dose chemotherapy followed by haematopoietic stem cell transplantation

Atul Sharma, Tvsvgk Tilak, Sameer Bakhshi, Vinod Raina, Lalit Kumar, SurendraPal Chaudhary, RanjitKumar Sahoo, Ritu Gupta, Sanjay Thulkar, Atul Sharma, Tvsvgk Tilak, Sameer Bakhshi, Vinod Raina, Lalit Kumar, SurendraPal Chaudhary, RanjitKumar Sahoo, Ritu Gupta, Sanjay Thulkar

Abstract

Background: Oral mucositis is a common inflammatory complication in patients undergoing high-dose chemotherapy and radiation followed by haematopoietic stem cell transplantation (HSCT). Lactobacillus brevis CD2 has been proven efficacious in preventing chemoradiotherapy-induced oral mucositis in squamous cell carcinoma of head and neck.

Methods: This phase II study aimed to evaluate the safety and efficacy of L. brevis CD2 lozenges in preventing oral mucositis in patients undergoing HSCT. Eligible patients received four to six lozenges of L. brevis CD2 per day, beginning from 4 to 7 days before initiation of chemotherapy and continuing until resolution of mucositis or till day +24.

Results: Of 31 patients enrolled, 7 (22.6%) patients did not develop any mucositis, 6 (19.4%) patients developed grade 1, 12 (38.7%) patients developed grade 2, 4 (12.9%) and 2 (6.5%) patients developed grade 3 and grade 4 mucositis, respectively. Median time to onset and for resolution of mucositis were 6 days and 8 days, respectively. No adverse events were reported with usage of study drug. However, one patient died of Klebsiella sepsis.

Conclusion: Promising results from the study encourage the use of L. brevis CD2 lozenges as a supportive care treatment option; however, a randomised, double-blind, multicentric trial in a larger population is warranted.

Trials registration number: NCT01480011 at https://www.clinicaltrials.gov/ (Registered on Nov 04, 2011).

Keywords: haematopoietic stem cell transplantation; high dose chemotherapy; lactobacillus brevis CD2; oral mucositis; supportive care.

Conflict of interest statement

Competing interests: None declared.

References

    1. Blijlevens NM, Donnelly JP, De Pauw BE. Mucosal barrier injury: biology, pathology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview. Bone Marrow Transplant 2000;25:1269–78.10.1038/sj.bmt.1702447
    1. Gautam AP, Fernandes DJ, Vidyasagar MS, et al. . Low level laser therapy for concurrent chemoradiotherapy induced oral mucositis in head and neck cancer patients - a triple blinded randomized controlled trial. Radiother Oncol 2012;104:349–54.10.1016/j.radonc.2012.06.011
    1. Chandy M, Balasubramanian P, Ramachandran SV, et al. . Randomized trial of two different conditioning regimens for bone marrow transplantation in thalassemia--the role of busulfan pharmacokinetics in determining outcome. Bone Marrow Transplant 2005;36:839–45.10.1038/sj.bmt.1705151
    1. Donnelly JP, Muus P, Schattenberg A, et al. . A scheme for daily monitoring of oral mucositis in Allogeneic BMT recipients. Bone Marrow Transplant 1992;9:409–13.
    1. Kumar L, Ghosh J, Ganessan P, et al. . High-dose chemotherapy with autologous stem cell transplantation for multiple myeloma: what predicts the outcome? experience from a developing country. Bone Marrow Transplant 2009;43:481–9.10.1038/bmt.2008.343
    1. McGuire DB, Altomonte V, Peterson DE, et al. . Patterns of mucositis and pain in patients receiving preparative chemotherapy and bone marrow transplantation. OncolNurs Forum 1993;20:1493–502.
    1. Pico JL, Avila-Garavito A, Mucositis NP, et al. . And treatment in the oncology setting. Oncologist 1998;3:446–51.
    1. Sadasivan R. Chemotherapy-induced oral mucositis. Oncology & Hematology Review 2010;06:13e6.10.17925/OHR.2010.06.0.13
    1. Wardley AM, Jayson GC, Swindell R, et al. . Prospective evaluation of oral mucositis in patients receiving myeloablative conditioning regimens and haemopoietic progenitor rescue. Br J Haematol 2000;110:292–9.10.1046/j.1365-2141.2000.02202.x
    1. Woo SB, Sonis ST, Monopoli MM, et al. . A longitudinal study of oral ulcerative mucositis in bone marrow transplant recipients. Cancer 1993;72:1612–7.10.1002/1097-0142(19930901)72:5<1612::AID-CNCR2820720520>;2-Q
    1. Sharma A, Kayal S, Iqbal S, et al. . Comparison of BEAM vs LEAM regimen in autologous transplant for Lymphoma at AIIMS. Springerplus 2013;2:489–95.10.1186/2193-1801-2-489
    1. Keefe DM, Schubert MM, Elting LS, et al. . Mucositis study section of the multinational association of supportive care in cancer and the international society for oral oncology. updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer 2007;109:820–31.
    1. Lalla RV, Bowen J, Barasch A, et al. . Mucositis guidelines leadership group of the multinational association of supportive care in cancer and international society of oral oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 2014;120:1453–61.
    1. Spielberger R, Stiff P, Bensinger W, et al. . Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med 2004;351:2590–8.10.1056/NEJMoa040125
    1. Sharma A, Rath GK, Chaudhary SP, et al. . Lactobacillus brevis CD2 lozenges reduce radiation- and chemotherapy-induced mucositis in patients with head and neck cancer: a randomized double-blind placebo-controlled study. Eur J Cancer 2012;48:875–81.10.1016/j.ejca.2011.06.010
    1. Di Marzio L, Russo FP, D'Alò S, et al. . Apoptotic effects of selected strains of lactic acid bacteria on a human T leukemia cell line are associated with bacterial arginine deiminase and/or sphingomyelinase activities. Nutr Cancer 2001;40:185–96.10.1207/S15327914NC402_16
    1. Riccia DN, Bizzini F, Perilli MG, et al. . Anti-inflammatory effects of Lactobacillus brevis (CD2) on periodontal disease. Oral Dis 2007;13:376–85.10.1111/j.1601-0825.2006.01291.x
    1. Duan R. Alkaline sphingomyelinase: An old enzyme with novel implications. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 2006;1761:281–91.10.1016/j.bbalip.2006.03.007
    1. McManus LM, Ostrom KK, Lear C, et al. . Radiation-induced increased platelet-activating factor activity in mixed saliva. Lab Invest 1993;68:118–24.
    1. Ierardo G, Bossù M, Tarantino D, et al. . The arginine-deiminase enzymatic system on gingivitis: preliminary pediatric study. Ann Stomatol 2010;1:8–13.
    1. Tasli L, Mat C, De Simone C, et al. . Lactobacilli lozenges in the management of oral ulcers of Behçet's syndrome. Clin Exp Rheumatol 2006;24(5 Suppl 42):S83–6.
    1. Ferreira B, da Motta Silveira FM, de Orange FA, et al. . Low-level laser therapy prevents severe oral mucositis in patients submitted to hematopoietic stem cell transplantation: a randomized clinical trial. Support Care Cancer 2016;24:1035–42.10.1007/s00520-015-2881-8
    1. Schubert MM, Eduardo FP, Guthrie KA, et al. . A phase III randomized double-blind placebo-controlled clinical trial to determine the efficacy of low level laser therapy for the prevention of oral mucositis in patients undergoing hematopoietic cell transplantation. Support Care Cancer 2007;15:1145–54.10.1007/s00520-007-0238-7
    1. Spencer A, Horvath N, Gibson J, et al. ; Australasian Leukemia and Lymphoma Group. Prospective randomised trial of amifostine cytoprotection in myeloma patients undergoing high-dose melphalan conditioned autologous stem cell transplantation. Bone Marrow Transplant 2005;35:971–7.10.1038/sj.bmt.1704946
    1. Mansouri A, Hadjibabaie M, Iravani M, et al. . The effect of zinc sulfate in the prevention of high-dose chemotherapy-induced mucositis: a double-blind, randomized, placebo-controlled study. Hematol Oncol 2012;30:22–6.10.1002/hon.999
    1. Wang L, Gu Z, Zhai R, et al. . Efficacy of oral cryotherapy on oral mucositis prevention in patients with hematological malignancies undergoing hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials. PLoS One 2015;10:e012876310.1371/journal.pone.0128763
    1. Wang Y, Xue J, Zhou X, et al. . Oral microbiota distinguishes acute lymphoblastic leukemia pediatric hosts from healthy populations. PLoS One 2014;9:e10211610.1371/journal.pone.0102116
    1. Wang Y, Zhou X, Xu X. Oral microbiota: an overlooked etiology for chemotherapy-induced oral mucositis? J Formos Med Assoc 2015;114:297–9.10.1016/j.jfma.2013.10.014
    1. Stringer AM, Logan RM. The role of oral flora in the development of chemotherapy-induced oral mucositis. J Oral Pathol Med 2015;44:81–7.10.1111/jop.12152
    1. Sonis ST. The impact, biology and therapeutic opportunities of oral mucositis. Oral Oncol 2009;45:1015–20.10.1016/j.oraloncology.2009.08.006
    1. Caluwaerts S, Vandenbroucke K, Steidler L, et al. . AG013, a mouth rinse formulation of Lactococcus lactis secreting human Trefoil Factor 1, provides a safe and efficacious therapeutic tool for treating oral mucositis. Oral Oncol 2010;46:564–70.10.1016/j.oraloncology.2010.04.008
    1. Campus G, Cocco F, Carta G, et al. . Effect of a daily dose of Lactobacillus brevis CD2 lozenges in high caries risk schoolchildren. Clin Oral Investig 2014;18:555–61.10.1007/s00784-013-0980-9
    1. Shah MP, Gujjari SK, Chandrasekhar VS. Evaluation of the effect of probiotic (Inersan®) alone, combination of probiotic with doxycycline and doxycycline alone on aggressive periodontitis – a clinical and microbiological study. J Clin Diagn Res 2013;7:595–600.10.7860/JCDR/2013/5225.2834
    1. Trinchieri V, Di Carlo S, Bossù M, et al. . Use of lozenges containing Lactobacillus brevis CD2 in recurrent aphthous stomatitis: a double-blind placebo-controlled trial. Oral Ulcers 201110.1155/2011/439425

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner