Title: Obesogenic microbial signatures and the development of obesity in childhood acute lymphoblastic leukemia.

Childhood acute lymphoblastic leukemia (ALL) is the most common childhood cancer with survival exceeding 90% for standard-risk groups. A debilitating side-effect of treatment is the development of overweight/obesity (OW/OB), which develops in approximately 40% of children by the end of treatment. The microbiome has been associated with the development of OW/OB. We examined fluctuations in the microbiome with the development of OW/OB during the first six months of treatment at diagnosis, and two subsequent timepoints (N = 62). Shotgun metagenomic sequencing was performed on Illumina Nextseq system, and taxa and functional pathways were extracted from sequences using kraken2 and humann2, respectively. An association of increased presence of several species (e.g., Klebsiella pneumoniae, Escherichia coli) was observed in children with OW/OB, while lean-promoting species (Veillonella, Haemophilus, and Akkermansia) were increased in children who maintained a normal weight. Pathway analysis revealed purine nucleotide biosynthesis, sugar nucleotide biosynthesis, and enzyme cofactor biosynthesis were positively correlated with Bacteroides spp. among children with OW/OB. We identified several taxa and functional pathways that may confer increased risk for the development of OW/OB. The associations observed in this pilot are preliminary and warrant further research in the microbiome and the development of OW/OB in childhood ALL.

The safety and feasibility of probiotics in children and adolescents undergoing hematopoietic cell transplantation.

Hematopoietic cell transplantation (HCT) has become a standard treatment for many adult and pediatric conditions. Emerging evidence suggests that perturbations in the microbiota diversity increase recipients' susceptibilities to gut-mediated conditions such as diarrhea, infection and acute GvHD. Probiotics preserve the microbiota and may minimize the risk of developing a gut-mediated condition; however, their safety has not been evaluated in the setting of HCT. We evaluated the safety and feasibility of the probiotic, Lactobacillus plantarum (LBP), in children and adolescents undergoing allogeneic HCT. Participants received once-daily supplementation with LBP beginning on day -8 or -7 and continued until day +14. Outcomes were compliance with daily administration and incidence of LBP bacteremia. Administration of LBP was feasible with 97% (30/31, 95% confidence interval (CI) 83-100%) of children receiving at least 50% of the probiotic dose (median 97%; range 50-100%). We did not observe any case of LBP bacteremia (0% (0/30) with 95% CI 0-12%). There were not any unexpected adverse events related to LBP. Our study provides preliminary evidence that administration of LBP is safe and feasible in children and adolescents undergoing HCT. Future steps include the conduct of an approved randomized, controlled trial through Children's Oncology Group.

The development, testing, and preliminary feasibility of an adaptable pediatric oncology nutrition algorithm for low-middle income countries.

BACKGROUND: Survivors of childhood cancer are at increased risk for several cardiometabolic complications. Obesity/overweight and metabolic syndrome have been widely reported in Western literature, but data from India are lacking. AIMS: To perform an objective assessment of nutritional status in a cohort of childhood cancer survivors (CCSs) and to find risk factors for extremes in nutritional status. SETTINGS AND DESIGN: The study was a retrospective chart review of CCSs who attended the late effects clinic of a referral pediatric oncology center over the period of 1 year. MATERIALS AND METHODS: An objective assessment of nutritional status was done, and results were analyzed in two groups: Adult survivors (present age <18 years) and child and adolescent survivors (CASs) (<18 years). The data were then analyzed for possible risk factors. RESULTS: Six hundred and forty-eight survivors were included in the study; of these, 471 were <18 years at follow-up, and 177 were 18 years or older. The prevalence of obesity, overweight, normal, and undernutrition was 2.6%, 10.8%, 62.7%, and 28.8% (CASs) and 0%, 8.5%, 62.7%, and 28.8% (adult survivors), respectively. Factors predictive of overweight/obesity were an initial diagnosis of acute lymphoblastic leukemia, or brain tumor and follow-up duration of >20 years or current age >30 years in adult survivors. CONCLUSIONS: The prevalence of obesity/overweight is lower in our cohort when compared to Western literature. It remains to be clarified whether this reflects the underlying undernutrition in our country, or whether our cohort of survivors is indeed distinct from their Western counterparts. Comparison with age/sex-matched normal controls and baseline parameters would yield more meaningful results.

An international survey of nutritional practices in low- and middle-income countries: a report from the International Society of Pediatric Oncology (SIOP) PODC Nutrition Working Group.

BACKGROUND/OBJECTIVES: Optimal nutritional status is important in children with cancer, as it can influence clinical outcomes. To improve the nutritional health of children and adolescents receiving treatment for cancer residing in low income and middle-income countries (LMIC), we investigated nutrition practices among these nations' institutions providing treatment for childhood cancer. SUBJECT/METHODS: A cross-sectional survey of nutrition practice was administered to staff members at institutions providing treatment for children with cancer between 2011 and 2012. Countries classified as low income and middle income were divided by geographical region. Final analysis was performed with 96 surveys, which included 27 institutions from Asia, 27 institutions from Latin America and Caribbean, 27 institutions from Africa and 15 institutions from Europe. RESULTS: The study found that 55% of institutions had a dietician available on their service. Access to dieticians, lack of nutrition resources and lack of nutrition education of staff were the main barriers to providing nutrition care in LMIC. Half of the institutions performed nutritional assessment at diagnosis, and the methods used varied widely. Twenty-nine percent of all institutions used complementary and alternate therapies within their clinical practice, and 35% of institutions reported that nutrition education was provided to patients and families. CONCLUSIONS: Priority areas for improving the nutritional management in LMIC include the following: (1) improved nutrition education and assessment tools for doctors and nurses; (2) increased availability of nutrition education resources for families and patients; and (3) identification of the role of complementary and alternative therapies in closing gaps in symptom management in these institutions.

Topical Yunnan Baiyao administration as an adjunctive therapy for bleeding complications in adolescents with advanced cancer.

PURPOSE: Yunnan Baiyao (White Medicine from Yunnan, YNB) is a Chinese herbal medicinal powder used to stop bleeding and improve circulation in traumatic injuries. We describe the use of YNB in adolescents with cancer as an adjunct to uncontrolled bleeding in the palliative care setting. METHODS: Through a retrospective chart review of all patients receiving integrative medicine consultations at the Integrative Therapies Program at Columbia University from January 1, 2007 to January 31, 2012, we describe the outcome of patients treated with YNB for management of uncontrolled bleeding. RESULTS: Four patients were identified who received topical YNB for uncontrolled bleeding; patients included two males and two females with diagnoses of solid tumors (n = 3) and Burkitt's lymphoma (n = 1). Mean age was 15.5 years (range 15-17). Fifty percent had life-threatening bleeding from the tumor site and 50 % experienced uncontrollable epistaxis. All patients received preceding therapy with packed red blood cells and platelet transfusions, topical thrombin, and oral aminocaproic acid. Two patients used YNB in the inpatient setting, and all four patients used YNB as outpatients. In all patients, bleeding control improved with the addition of YNB to conventional hemostatic interventions. Two patients using YNB in their home reported control of bleeding episodes. There were no adverse events reported. CONCLUSIONS: YNB may be an efficacious agent for uncontrolled bleeding in conjunction with conventional hemostatic agents in adolescents with advanced cancer. It is well accepted by patients. YNB may be especially valuable in the outpatient setting to prevent the recurrence of hemorrhage.