Bovine Colostrum Against Chemotherapy‐Induced Gastrointestinal Toxicity in Children With Acute Lymphoblastic Leukemia: A Randomized, Double‐Blind, Placebo‐Controlled Trial

Abstract

Background The toxic effect of chemotherapy on the gastrointestinal tract may lead to mucositis and is associated with the pathogenesis of other treatment‐related complications. We hypothesized that nutrition supplementation with bovine colostrum, rich in bioactive factors, would ameliorate gastrointestinal toxicity and reduce the incidence of fever and infectious complications during induction treatment for childhood acute lymphoblastic leukemia (ALL). Methods Children with newly diagnosed ALL were included in a 2‐center, randomized, double‐blind, placebo‐controlled clinical trial. Patients were randomized to receive a daily colostrum or placebo supplement during 4 weeks of induction treatment. Data on fever, bacteremia, need for antibiotics, and mucosal toxicity were prospectively collected. (Trial registration: http://www.clinicaltrials.gov NCT01766804). Results Sixty‐two patients were included. No differences were found for the primary outcome (number of days with fever). No difference was observed for neutropenic fever, intravenous antibiotics, or incidence of bacteremia. Peak severity of oral mucositis was significantly reduced by colostrum (7/29 patients, 24% mild; 6/29, 21% moderate; 1/29, 3% severe) compared with placebo (12/31, 39% mild; 1/31, 3% moderate; 7/31, 23% severe) (P = 0.02). Among patients receiving at least 1 dose of supplement (colostrum: n = 22; placebo: n = 30), the peak weekly self‐reported oral mucositis score was overall significantly less severe in the colostrum group (P = 0.009). Conclusion The use of prophylactic bovine colostrum showed no effect on fever, infectious morbidity, or inflammatory responses. Nevertheless, these data may suggest protective effects on the oral mucosa during induction therapy in childhood ALL, encouraging additional studies confirming these findings.

Citrulline as a biomarker of bacteraemia during induction treatment for childhood acute lymphoblastic leukaemia

“…We included 61 children ( All patients participated in a randomised, placebo-controlled clinical trial investigating the effect of dietary supplementation with bovine colostrum against gastrointestinal toxicity. 18,21 In these patients, colostrum was not found to influence citrulline levels or IM scores significantly.…”

“…We included 61 children (1‐18 years old) diagnosed with ALL who completed induction treatment according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL‐2008 protocol between March 2013 and November 2016 at the Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, and Rigshospitalet, University Hospital of Copenhagen, Denmark. All patients participated in a randomised, placebo‐controlled clinical trial investigating the effect of dietary supplementation with bovine colostrum against gastrointestinal toxicity 18,21 . In these patients, colostrum was not found to influence citrulline levels or IM scores significantly.…”

“…OM was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI‐CTCAE) 4.0 criteria 24 . IM was scored as Grade 0, I or II based on the severity of diarrhoea and abdominal pain according to the NCI‐CTCAE 4.0 criteria, as described earlier 21 . Absolute neutrophil count (ANC) was measured on treatment days 1, 8, 15, 22 and 29 (± 3 days from the scheduled time point) by routine methods, with a median of five (range three to five) measurements per patient.…”

Bovine Colostrum: Its Constituents and Uses

“…In addition, the immune modulatory components within BC are probably also relevant in limiting excess inflammatory responses (as shown in Figure 2). BC shows therapeutic potential for a variety of GI conditions, including nonsteroidal anti-inflammatory drug (NSAID) gut injury [2], short bowel syndrome, chemotherapy induced mucositis (particularly oral mucositis) [133], and inflammatory bowel disease [134,135]. In addition, preclinical studies using BC or its hyperimmune variants show promise for several gastrointestinal infectious diseases, such as Clostridium difficile [136].…”

Therapeutic Applications of Human and Bovine Colostrum in the Treatment of Gastrointestinal Diseases and Distinctive Cancer Types: The Current Evidence

“…According to global cancer statistics data, gastric cancer is the fourth most common cancer worldwide. Serious vital organ deleterious effects happen when gastric cancer is treated by chemotherapy ( Rugge et al., 2015 ; Rathe et al., 2019 ). Therefore, there is an urgent need for the development of less toxic therapeutic agents for the prevention and cure of stomach cancer ( Farziyan et al., 2016 ).…”