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

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).

[1]  F. A. de Orange,et al.  Low-level laser therapy prevents severe oral mucositis in patients submitted to hematopoietic stem cell transplantation: a randomized clinical trial , 2016, Supportive Care in Cancer.

[2]  Li-li Wang,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 , 2015, PloS one.

[3]  Xuedong Zhou,et al.  Oral microbiota: an overlooked etiology for chemotherapy-induced oral mucositis? , 2015, Journal of the Formosan Medical Association = Taiwan yi zhi.

[4]  A. Stringer,et al.  The role of oral flora in the development of chemotherapy-induced oral mucositis. , 2015, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[5]  Xuedong Zhou,et al.  Oral Microbiota Distinguishes Acute Lymphoblastic Leukemia Pediatric Hosts from Healthy Populations , 2014, PloS one.

[6]  D. McGuire,et al.  MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy , 2014, Cancer.

[7]  V. Raina,et al.  Comparison of BEAM vs. LEAM regimen in autologous transplant for lymphoma at AIIMS , 2013, SpringerPlus.

[8]  G. Campus,et al.  Effect of a daily dose of Lactobacillus brevis CD2 lozenges in high caries risk schoolchildren , 2013, Clinical Oral Investigations.

[9]  S. Gujjari,et al.  Evaluation of the effect of probiotic (inersan®) alone, combination of probiotic with doxycycline and doxycycline alone on aggressive periodontitis - a clinical and microbiological study. , 2013, Journal of clinical and diagnostic research : JCDR.

[10]  M. Vidyasagar,et al.  Low level laser therapy for concurrent chemoradiotherapy induced oral mucositis in head and neck cancer patients - a triple blinded randomized controlled trial. , 2012, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[11]  B. Mohanti,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. , 2012, European journal of cancer.

[12]  A. Shamshiri,et al.  The effect of zinc sulfate in the prevention of high‐dose chemotherapy‐induced mucositis: a double‐blind, randomized, placebo‐controlled study , 2012, Hematological oncology.

[13]  S. Carlo,et al.  Use of Lozenges Containing Lactobacillus brevis CD2 in Recurrent Aphthous Stomatitis: A Double-Blind Placebo-Controlled Trial , 2011 .

[14]  Bernard Coulie,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. , 2010, Oral oncology.

[15]  A. Polimeni,et al.  The arginine-deiminase enzymatic system on gingivitis: preliminary pediatric study. , 2010, Annali di stomatologia.

[16]  S. Sonis.  Mucositis: The impact, biology and therapeutic opportunities of oral mucositis. , 2009, Oral oncology.

[17]  R. Hariprasad,et al.  High-dose chemotherapy with autologous stem cell transplantation for multiple myeloma: what predicts the outcome? Experience from a developing country , 2009, Bone Marrow Transplantation.

[18]  A. Polimeni,et al.  Anti-inflammatory effects of Lactobacillus brevis (CD2) on periodontal disease. , 2007, Oral diseases.

[19]  F. Eduardo,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 , 2007, Supportive Care in Cancer.

[20]  D. McGuire,et al.  Clinical Practice Guidelines for the Prevention and Treatment of Mucositis , 2007 .

[21]  C. De Simone,et al.  Lactobacilli lozenges in the management of oral ulcers of Behçet's syndrome. , 2006, Clinical and experimental rheumatology.

[22]  R. Duan.  Alkaline sphingomyelinase: an old enzyme with novel implications. , 2006, Biochimica et biophysica acta.

[23]  B. George,et al.  Randomized trial of two different conditioning regimens for bone marrow transplantation in thalassemia – the role of busulfan pharmacokinetics in determining outcome , 2005, Bone Marrow Transplantation.

[24]  R. Herrmann,et al.  Prospective randomised trial of amifostine cytoprotection in myeloma patients undergoing high-dose melphalan conditioned autologous stem cell transplantation , 2005, Bone Marrow Transplantation.

[25]  T. Shea,et al.  Palifermin for oral mucositis after intensive therapy for hematologic cancers , 2017 .

[26]  C. De Simone,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 , 2001, Nutrition and cancer.

[27]  J. Knox,et al.  Chemotherapy-Induced Oral Mucositis , 2000, Drugs & aging.

[28]  G. Jayson,et al.  Prospective evaluation of oral mucositis in patients receiving myeloablative conditioning regimens and haemopoietic progenitor rescue , 2000, British journal of haematology.

[29]  B. D. de Pauw,et al.  Mucosal barrier injury: biology, pathology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview , 2000, Bone Marrow Transplantation.

[30]  P. Naccache,et al.  Mucositis: Its Occurrence, Consequences, and Treatment in the Oncology Setting. , 1998, The oncologist.

[31]  L. Grochow,et al.  Patterns of mucositis and pain in patients receiving preparative chemotherapy and bone marrow transplantation. , 1993, Oncology nursing forum.

[32]  S. Sonis,et al.  A longitudinal study of oral ulcerative mucositis in bone marrow transplant recipients , 1993, Cancer.

[33]  L. McManus,et al.  Radiation-induced increased platelet-activating factor activity in mixed saliva. , 1993, Laboratory investigation; a journal of technical methods and pathology.

[34]  J. Donnelly,et al.  A scheme for daily monitoring of oral mucositis in allogeneic BMT recipients. , 1992, Bone marrow transplantation.