Guideline for Children With Cancer Receiving General Anesthesia for Procedures and Imaging.

Children with cancer and those undergoing hematopoietic stem cell transplantation frequently require anesthesia for imaging as well as diagnostic and therapeutic procedures from diagnosis through follow-up. Due to their underlying disease and side effects of chemotherapy and radiation, they are at risk for complications during this time, yet no published guideline exists for preanesthesia preparation. A comprehensive literature review served as the basis for discussions among our multidisciplinary panel of oncologists, anesthesiologists, nurse practitioners, clinical pharmacists, pediatric psychologists, surgeons and child life specialists at the Children's Hospital of Philadelphia. Due to limited literature available, this panel created an expert consensus guideline addressing anesthesia preparation for this population.

Risk Factors for Subtherapeutic Tacrolimus Levels after Conversion from Continuous Intravenous Infusion to Oral in Children after Allogeneic Hematopoietic Cell Transplantation.

Tacrolimus (FK506) is a calcineurin inhibitor and is an essential component of many immunosuppressive regimens. The oral bioavailability of tacrolimus may be affected by many factors, including patient age and gender, as well as by drug-drug interactions or genetic polymorphisms in drug metabolism. The dosing recommendations for pediatric allogeneic hematopoietic cell transplantation (alloHCT) recipients have been derived from tacrolimus use in adult solid-organ transplantation patients. Data describing the impact of conversion of i.v. tacrolimus to oral on the incidence of acute graft-versus-host disease (aGVHD) are limited in children after alloHCT. In this study, we describe the incidence of grades II to IV aGVHD after conversion from i.v. tacrolimus to oral tacrolimus and study the clinical factors associated with delayed achievement of therapeutic blood levels. In this retrospective analysis, 68 pediatric patients (median age, 6.7 years; range, .25 to 22 years), underwent alloHCT for malignant and nonmalignant diseases and received tacrolimus and mycophenolate mofetil for aGVHD prophylaxis. Among all patients, the median number of days to achieve therapeutic tacrolimus trough concentration (10 ng/mL to 20 ng/mL) was 7 days (range, 0 to 37 days). Twenty-two patients developed grades II to IV aGVHD and the cumulative incidence of grades II to IV aGVHD in all patients was 32.4% (standard error, .06). On multivariate analysis ethnicity (white versus others: odds ratio [OR], -4.5; 95% confidence interval [95% CI], 1.091 to 18.91; P = .038) and ≥ 10 days of subtherapeutic tacrolimus levels in first 30 days on i.v. (OR, -3.8; 95% CI, 1.276 to 11.43; P = .017) were significantly associated with delay in achieving therapeutic tacrolimus trough concentration. The impact of race/ethnicity on therapeutic tacrolimus trough concentration in pediatric alloHCT recipients should be further studied prospectively so that individualized dosing plans can be developed.

Efficacy of tacrolimus/mycophenolate mofetil as acute graft-versus-host disease prophylaxis and the impact of subtherapeutic tacrolimus levels in children after matched sibling donor allogeneic hematopoietic cell transplantation.

Only a few studies in children have evaluated the efficacy of prophylactic regimens using tacrolimus on acute graft-versus-host disease (aGVHD). As a result, optimal tacrolimus levels in children after matched sibling donor allogeneic hematopoietic cell transplantation (alloHCT) are not well defined. We measured the association between subtherapeutic levels (<10 ng/mL) during weeks 1 to 4 after alloHCT and the cumulative incidence of grades II to IV aGVHD in children. Additionally, we identified optimal lower cutoff levels for tacrolimus. Sixty patients (median age, 8 years) received tacrolimus/mycophenolate mofetil between March 2003 and September 2012. Twenty-three had a malignant disease and 37 nonmalignant disorders. The stem cell source included peripheral blood stem cells (n = 12) and bone marrow or cord blood (n = 48). Conditioning regimen varied. Specifically, 38.3% received a myeloablative regimen, 36.7% receiving a reduced-toxicity regimen, and 25% receiving a reduced-intensity regimen. Tacrolimus was initiated at .03 mg/kg/day via continuous i.v. infusion or .12 mg/kg/day orally. The dose was adjusted to maintain daily steady state concentrations within a range of 10 to 20 ng/mL. The overall incidence of grades II to IV aGVHD was 33.3%. On multivariate analysis, a mean tacrolimus level < 10 ng/mL during week 3 (P = .042; 95% confidence interval, 1.051 to 14.28) was significantly associated with increased incidence of grades II to IV aGVHD. Using weekly receiver operator curves, the optimal lower cutoff for tacrolimus levels was 10 to 11.2 ng/mL. Further prospective studies are warranted to study the incidence of aGVHD comparing the conventional tacrolimus levels of 5 to 15 versus 10 to 15 ng/mL.

Effective use of tocilizumab for the treatment of steroid-refractory gastrointestinal acute graft versus host disease in a child with very high levels of serum interleukin-6.

Steroid-refractory acute graft versus host disease (SR-aGVHD) is associated with poor prognosis. A three year old male with severe sickle cell disease (SCD) received a 7/8 HLA-matched unrelated bone marrow transplant. He developed grade III acute graft versus host disease (aGVHD) of the gut, which was refractory to methylprednisolone and five other treatment regimens. Due to very high serum Interleukin-6 (IL-6) levels, he received salvage therapy with tocilizumab with resolution of aGVHD. It may be reasonable to further prospectively study routine monitoring of IL-6 levels and the use of tocilizumab in such patients. Pediatr Blood Cancer 2015;62:362-363. © 2014 Wiley Periodicals, Inc.

Culture-Independent Analysis of Pediatric Bronchoalveolar Lavage Specimens.

RATIONALE: The clinical utility of culture-independent testing of pediatric BAL specimens is unknown. In addition, the variability of the pediatric pulmonary microbiome with patient characteristics is not well understood. OBJECTIVES: To compare testing with 16S rRNA gene-based sequencing to conventional cultures of BAL specimens in children Methods: Study subjects were not more than 22 years old and underwent BAL from May 2013 to August 2015 as part of clinical care. DNA extracted from BAL specimens was used for 16S rRNA gene-based analysis, and results were compared with routine cultures from the same samples. Indices of microbial diversity and relative taxon abundances were compared on the basis of subject characteristics (diagnosis and antibiotic use). RESULTS: From 81 participants (male, 51%; median age, 9 yr), 89 samples were collected. The 16S rRNA genes of 77 samples (86.5%) from 70 subjects were successfully analyzed. These 70 subjects included 23 with cystic fibrosis, 19 who were immunocompromised, and 28 who were nonimmunocompromised. Of 68 organisms identified in culture, 16S rRNA gene-based analyses detected corresponding taxa in 66 (97.1%) and also identified potentially clinically significant organisms missed by cultures (e.g., Staphylococcus, Legionella, and Pseudomonas). Taxa that varied significantly with diagnosis and antibiotic use included Veillonella, Corynebacterium, Haemophilus, and Streptococcus. The microbiota of cystic fibrosis samples was less diverse. A "core" group of 15 taxa present in all three diagnosis groups was identified. CONCLUSIONS: Culture-independent analysis was concordant with routine cultures and showed the potential to detect noncultured pathogens. Although culture-independent testing identified relative changes in organism abundance associated with clinical characteristics, distinct microbiome profiles associated with disease states were not identified.

Bacterial bloodstream infections in pediatric allogeneic hematopoietic stem cell recipients before and after implementation of a central line-associated bloodstream infection protocol: A single-center experience.

INTRODUCTION: There are only few reports describing the influence of central line-associated bloodstream infection (CLABSI) prevention strategies on the incidence of bacterial bloodstream infections (BBSIs). METHODS: We performed a retrospective cohort study among pediatric recipients of allogeneic hematopoietic stem cell transplantation (allo-HCT) to assess potential changes in BBSI rates during 3 time periods: pre-CLABSI prevention era (era 1, 2004-2005), CLABSI prevention implementation era (era 2, 2006-2009), and maintenance of CLABSI prevention era (era 3, 2010-2012). BBSI from day 0-365 following allo-HCT were studied. The comparison of person-years incidence rates among different periods was carried out by Poisson regression analysis. RESULTS: The mean age of patients was 10.0 years. During the study period, 126 (65%) of 190 patients had at least a single BBSI. From day 0-30, day 31-100, day 101-180, and day 181-365, 20%, 28%, 30%, and 17% of patients, respectively, experienced BBSIs. The rate of Staphylococcus epidermidis and gram-negative pathogens significantly declined from 3.16-0.93 and 6.32-2.21 per 100 person-months during era 1 and era 3, respectively (P = .001). CONCLUSIONS: Patients undergoing allo-HCT during era 3 were associated with decreased risk of BBSI (P = .012). Maintenance of CLABSI protocols by nursing staff and appropriate education of other care providers is essential to lower incidence of BBSI in this high-risk population, and further strategies to decrease infection burden should be studied.