Context Complementary and alternative medicine (CAM) provides clinical benefits to hospice patients, including decreased pain and improved quality of life. Yet little is known about the extent to which U.S. hospices employ CAM therapists. Objectives To report the most recent national data regarding the inclusion of art, massage, and music therapists on hospice interdisciplinary teams and how CAM therapist staffing varies by hospice characteristics. Methods A national cross-sectional survey of a random sample of hospices (n=591; 84% response rate) from September 2008 to November 2009. Results Twenty-nine percent of hospices (169 of 591) reported employing an art, massage, or music therapist. Of those hospices, 74% employed a massage therapist, 53% a music therapist, and 22% an art therapist, and 42% expected the therapist to attend interdisciplinary staff meetings, indicating a significant role for these therapists on the patient’s care team. In adjusted analyses, larger hospices compared with smaller hospices had significantly higher odds of employing a CAM therapist (adjusted odds ratio (AOR) = 6.38, 95% CI 3.40, 11.99) and forprofit hospices had lower odds of employing a CAM therapist compared with nonprofit hospices (AOR = 0.52, 95% CI 0.32, 0.85). Forty-four percent of hospices in the Mountain/Pacific region reported employing a CAM therapist versus 17% in the South Central region. Conclusion Less than one-third of U.S. hospices employ art, massage, or music therapists despite the benefits these services may provide to patients and families. A higher proportion of large hospices, nonprofit hospices and hospices in the Mountain/Pacific region employ CAM therapists, indicating differential access to these important services.

Direct oral anticoagulants (DOACs), including direct factor Xa (FXa) inhibitors, have become the preferred treatment for thrombosis in adults due to their efficacy, safety, and convenience. Recent studies show promising results for rivaroxaban and dabigatran use in children [1][2][3][4] ; there were no major bleeding events in the rivaroxaban phase 3 pediatric clinical trial and the rate of clinically relevant nonmajor bleeding was 3%. 2 Dabigatran has been FDA approved for pediatrics while rivaroxaban has been submitted for review, and trials are ongoing for other agents. [5][6][7][8][9][10] The use of DOACs for children with thrombosis is therefore anticipated to increase.

Introduction: Primary hemophagocytic lymphohistiocytosis (HLH) has historically been associated with a number of genetic mutations resulting in impaired lymphocyte cytotoxicity. More recently, we have learned that defects of the inflammasome immune complex, such as in X-linked inhibitor of apoptosis (XIAP) deficiency, cause an HLH phenotype with normal cytotoxic function and that patients with XIAP deficiency have a high risk of peri-transplant HLH flare and mortality. This study aims to further elucidate the differential peri-transplant courses of HLH patients depending on their underlying genetic backgrounds. Methods: We retrospectively extracted data from medical records of patients who underwent allogeneic hematopoietic cell transplant (HCT) for HLH or an HLH-predisposing immunodeficiency at UCSF Benioff Children's Hospital between 2006-2018. Event-free survival (EFS) was defined as successful engraftment without rejection or failure of initial transplant. HLH recurrence was defined by HLH-2004 diagnostic criteria. All time ranges were measured from the date of HCT admission. Log rank tests were used for statistical testing of survival data. Results: We identified 23 subjects, median age 4 years (0.4-22.5 years). 13/23 (57%) were found to have a pathogenic variant in a non-inflammasome, HLH-associated gene ("Proven Typical HLH"), 2/23 (9%) had mutations involving the inflammasome ("Proven Atypical HLH," both with XIAP deficiency), and 8/23 (35%) had no identified genetic defect ("Possible Atypical HLH"). The latter two groups were analyzed as "Atypical HLH." The majority of patients received conditioning with busulfan, fludarabine, and alemtuzumab. With median follow up of 4.3 years, 3-year overall survival was 82% (95% CI, 65-98%). The 3-year EFS was 69% (95% CI, 50-88%). In engrafted patients (21/23, 91%), median donor myeloid chimerism (30-day, 100%; 180-day, 100%; 365-day 99%) and T cell chimerism (30-day, 76%; 180-day, 97%, 365-day 99%) were high. The cumulative incidence of grade II-IV acute GvHD in transplant recipients was 15% (95% CI, 0-30%). 3-year OS and EFS were both significantly higher in Typical HLH patients at 100% (95% CI, 75-100%) and 92% (95% CI, 78-100%), respectively, compared to Atypical HLH patients whose OS and EFS were 56% (95% CI, 23-90%) and 40% (95% CI, 10-70%), respectively (p=0.006 and 0.011). The only event in the Typical HLH group was a primary graft rejection, salvaged with second HCT. Peri-transplant mortality occurred only in patients without a known mutation (53%; 95% CI, 16-90%) compared to those with known mutations (0%; 95% CI, 0-25%; p=0.002). 3-year HLH-free survival was also significantly (p<0.001) higher in Typical HLH patients (100%; 95% CI, 75-100%) compared to Atypical HLH patients (30%; 95% CI, 2-58%), as peri-transplant HLH flares occurred only in the Atypical HLH group, with half (3/6) surviving the flare. All flares occurred within 1 year of HCT admission (range 2-291 days), and all events occurred within 3 years of admission (range 5-993 days). Conclusions: HLH is a clinical phenotype with significant underlying genetic heterogeneity, manifested in differential peri-transplant outcomes. Patients with proven Typical HLH have improved survival and EFS as well as decreased risk of peri-transplant HLH compared to those with proven or possible Atypical HLH. Given limitations in current testing, it is possible that patients without a known defect in the cytotoxic pathway may have underlying inflammasome mutations. Defects in XIAP and the resulting loss of apoptosis protection appear to put patients at higher risk of chemotherapy complications. These results demonstrate the need for thorough genetic testing in all HLH patients prior to HCT, as well as close monitoring for development of a peri-HCT flare in patients without proven Typical HLH. If validated in a larger dataset, patients with proven or possible Atypical HLH may be considered for trials of anti-cytokine therapy in the peri-transplant period. Disclosures Shimano: Pfizer: Research Funding; Novartis: Research Funding; Daiichi Sankyo: Research Funding. Huang:Novartis: Research Funding. Dvorak:Alexion Inc: Consultancy; Jazz Pharmaceuticals: Consultancy.

Li-Fraumeni syndrome (LFS) is one of the most common cancer predisposition syndromes that affects both children and adults. Individuals with LFS are at an increased risk of developing various types of cancer over their lifetime including soft tissue sarcomas, osteosarcomas, breast cancer, leukemia, brain tumors, and adrenocortical carcinoma. Heterozygous germline pathogenic variants in the tumor suppressor gene TP53 are the known causal genetic defect for LFS. Single nucleotide variants (SNVs) including missense substitutions that occur in the highly conserved DNA binding domain of the protein are the most common alterations, followed by nonsense and splice site variants. Gross copy number changes in TP53 are rare and account for less than 1% of all variants. Using next-generation sequencing (NGS) panels, we identified a paternally inherited germline intragenic duplication of TP53 in a child with metastatic osteosarcoma who later developed acute myeloid leukemia (AML). Transcriptome sequencing (RNA-Seq) demonstrated the duplication was tandem, encompassing exons 2-6 and 28 nucleotides of the untranslated region (UTR) upstream of the start codon in exon 2. The inclusion of the 28 nucleotides is expected to result in a frameshift with a stop codon 18 codons downstream of the exon 6, leading to a loss-of-function allele. This case highlights the significance of simultaneous identification of both significant copy number variants as well as SNVs/indels using NGS panels.