Short summary

Acute lymphoblastic leukemia is the most common form of childhood cancer. Cure rates are improving, but the intensity of treatment is limited by toxicity. Colostrum is the first natural food produced by female mammals during the first hours after delivery of offspring. Colostrum is a complex fluid containing a range of immunomodulating components is rich in nutrients, and growth factors. We hypothesize that bovine colostrum supplementation during chemotherapy may have protective effects against chemotherapy-induced gastrointestinal toxicity and thus it may reduce derivative adverse effects such as infections and systemic inflammation.

Rationale

Acute lymphoblastic leukemia is the most common form of childhood cancer. Cure rates are improving, but the intensity of treatment is limited by toxicity. Two to five percent of patients die from treatment related complications, mostly due to therapy-induced toxicity and immune suppression. Gastrointestinal toxicity induced by chemotherapy is likely to play a key role in the pathogenesis of treatment related complications. Since the intestinal epithelium is in constant interaction with the microbiological flora of the gut it is essential for the maintenance of the immunological balance that the epithelial barrier is intact. Chemotherapy induced toxicity may disturb this balance through damaging effects on the epithelium leading translocation of bacterial components. This may result in both infections and systemic inflammatory responses with impact on post-chemotherapy immune recovery. Colostrum is the first natural food produced by female mammals during the first hours after delivery of offspring. Colostrum is a complex fluid containing a range of immunomodulating components is rich in nutrients, and growth factors. We hypothesize that bovine colostrum supplementation during chemotherapy may have protective effects against chemotherapy-induced gastrointestinal toxicity and thus it may reduce derivative adverse effects such as infections and systemic inflammation. The aim of the present study is to evaluate the ability a colostrum containing diet to limit gastrointestinal toxicity including chemotherapy induced inflammation and infections. The study is based on a combination of animal studies and human studies thus hoping to provide a translational understanding of the effect of bovine colostrum on gastrointestinal toxicity, systemic inflammation and infections during chemotherapeutic treatment for childhood cancer.

Description of the cohort

Inclusion criteria:

• Paediatric patients treated according to the NOPHO ALL2008 protocol are eligible for inclusions.

Exclusion criteria:

• Milk allergy
• Lactose intolerance

Active Hospital Sites:

• H.C. Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
• Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.

Data and biological material

Primary outcome measures:

Days with fever. Days with temperature at or above 38.5 degrees celsius.

Secondary outcome measures:

Days in intensive care unit.

Days in i.v. antibiotic treatment.

Duration of cytopenia (neutrocytes <1.0 and platelets <20)

Proven or suspected infections. Episodes of suspected or culture positive sepsis number of documented septic events either culture proven or those treated with a course of antibiotics.

Number of blood and platelet transfusions given during the course of treatment

Clinical and paraclinical indices of gastrointestinal toxicity. Clinical toxicity is scored using Common Toxicity Criteria for Adverse Effects (NCI-CTCAE), WHO and oral mucositis assessment scale (OMAS) grading schemes at inclusion and weekly during the treatment period. Furthermore the patients register toxicity using the oral mucositis daily questionnaire (OMDQ). Para-clinical indices are citruline, fecal calprotectin,

Collaborating researchers and departments

Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen

• Professor Klaus Müller, MD, DMSc
• Professor Kjeld Schmiegelow, MD, DMSc

Publications associated with the project

Chemotherapeutic treatment reduces circulating levels of surfactant protein-D in 

children with acute lymphoblastic leukemia / Rathe M, Sorensen GL, Wehner PS, Holmskov U, Sangild PT, Schmiegelow K, Müller K, Husby S; Pediatr Blood Cancer. 2017 Mar; 64(3). doi: 10.1002/pbc.26253.