Adolescent and Young Adult (AYA) Oncology, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on considerations for the comprehensive care of AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.

Hemophagocytic lymphohistocytosis in trisomy 21: successful treatment with interferon inhibition.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune dysregulation primarily driven by the cytokine interferon gamma. It can be either a genetic or acquired disorder associated with infection, malignancy, and rheumatologic disorders. Trisomy 21 can express a wide range of phenotypes which include immune dysregulation and shares inherent pathophysiology with a group of disorders termed interferonopathies. Knowledge of this overlap in seemingly unrelated conditions could provide a basis for future research, and most importantly, alternative therapeutic interventions in acute life threatening clinical scenarios. Herein, we describe two patients with trisomy 21 presenting with HLH that was refractory to conventional treatment. Both patients were successfully managed with novel interventions targeting the interferon pathway. CASE PRESENTATION: We describe a 17-month-old male and 15-month-old female with trisomy 21 presenting with a myriad of signs and symptoms including fever, rash, cytopenias, and hyperferritinemia, both ultimately diagnosed with HLH. Each had relapsing, refractory HLH over time requiring several admissions to the hospital receiving conventional high dose corticosteroids and interleukin-1 inhibition therapy. Successful steroid-free remission was achieved after targeting interferon inhibition with emapalumab induction followed by long-term maintenance on baricitinib. CONCLUSION: To our knowledge, these are the first reported cases of relapsed, refractory HLH in patients with trisomy 21 successfully treated with emapalumab and transitioned to a steroid-sparing regimen with oral baricitinib for maintenance therapy. Trisomy 21 autoimmunity and HLH are both thought to be driven by interferon gamma. Targeting therapy toward interferon signaling in both HLH and autoimmunity in trisomy 21 may have potential therapeutic benefits. Further investigation is needed to determine if trisomy 21 may predispose to the development of HLH given this common pathway.

Successful Treatment of Splenic Vein Thrombosis Secondary to Acute Pancreatitis with Oral Anticoagulants: A Pediatric Case Series.

BACKGROUND Two Pediatric Patients with Splanchnic Venous Thrombosis as a Complication of Acute Pancreatitis Successfully Treated with Low-Molecular-Weight Heparin and Rivaroxaban CASE REPORT Case 1: A 13-year-old girl presented with a second attack of acute pancreatitis. She developed a non-occlusive splenic vein thrombosis diagnosed by CT scan on the sixth day of hospitalization. Injectable low-molecular-weight heparin was started during hospitalization and switched to oral rivaroxaban at discharge. Imaging at follow-up showed resolution of thrombosis. Case 2: A 9-year-old girl with history of acute recurrent pancreatitis presented with a third attack of acute pancreatitis. An occlusive splenic vein thrombosis with extension into the portal vein and superior mesenteric vein and necrotizing pancreatitis was seen on CT scan on the third day of hospitalization. Low-molecular-weight heparin was initiated during hospitalization and was switched to oral rivaroxaban at discharge. Imaging at follow-up demonstrated nearly complete resolution of the extensive thrombosis. CONCLUSIONS Splanchnic venous thrombosis remains a rare complication of pediatric pancreatitis. Anticoagulant use in patients with these complications remains controversial. Direct oral anticoagulants are as safe and effective as low-molecular-weight heparin and should be considered for use in children instead of low-molecular-weight heparin due to its advantages, including the availability of enteral forms of administration.

Effect of physical activity on fatigue in childhood cancer survivors: a systematic review.

PURPOSE: Many children, adolescents, and young adult survivors of childhood cancer experience fatigue following cancer treatment. Physical activity has been shown to be effective in improving cancer-related fatigue in adult survivors, but there is a lack of evidence on its effect in childhood cancer survivors. In addition, there are no guidelines for treatment of fatigue in childhood cancer survivors. The purpose of this study was to examine the existing literature on the effect of physical activity on fatigue in children, adolescents, and young adult survivors of childhood cancer. METHODS: We conducted a systematic review to examine the effect of physical activity on fatigue in children, adolescents, and young adult survivors of childhood cancer. RESULTS: Nine studies were included. Most of the studies included reported an increase in physical activity and a decline in fatigue in the target patient population. Interpretation of these findings is limited due to small sample sizes, inadequate length of follow-up, and variability among reviewed studies. Quantitative analysis was not conducted due to significant variability in both the type of physical activity implemented and in the measurement of fatigue. CONCLUSIONS: Further research, with a larger sample size and consistency in both physical activity interventions and measurement of fatigue, is needed to add greater precision and confidence in the effect of physical activity on fatigue in childhood cancer survivors. Results of this research will help guide future recommendations on physical activity for the treatment of cancer-related fatigue in children, adolescents, and young adult survivors of childhood cancer.

Attention Deficit Hyperactivity Disorder in Children With Sickle Cell Disease Referred for an Evaluation.

Neuropsychological deficits, including difficulties with attention, are well described in children with sickle cell disease (SCD). Very little is known about attention deficit hyperactivity disorder (ADHD) in children with SCD. The objective of this study was to determine the proportion of ADHD in children with SCD referred for neuropsychological evaluation. This prospective, cross-sectional study included patients (age, 4 to 18 y) with SCD and completion of a neuropsychological evaluation between December 2013 and March 2016. Patients were referred for neuropsychological evaluation because of concern regarding school performance, development, and/or behavior. The diagnosis of ADHD was made by a neuropsychologist on the basis of the diagnostic criteria in the Diagnostic Statistical Manual-Fourth or Fifth Editions. ADHD medication usage rate was obtained by medical record review. Of the 89 patients with SCD referred for neuropsychological evaluation, 25% (95% confidence interval, 16%-35%) met diagnostic criteria for ADHD. Only 21% of the patients with SCD and ADHD were prescribed an ADHD medication. Our study supports routine ADHD screening in children with SCD who have poor school performance or behavioral concerns. Despite the benefits of pharmacologic treatment, the majority of patients with SCD and ADHD did not receive a medication for management of their ADHD.

Patient-reported neuropathic pain in adolescent and young adult cancer patients.

BACKGROUND: Neuropathic pain, a known complication of cancer and its treatments, negatively impacts quality of life. There are limited data using screening tools to aid in the diagnosis of neuropathic pain in cancer patients. Our primary objective was to determine the proportion of adolescent and young adult cancer patients reporting neuropathic pain on a patient-completed, neuropathic pain screening tool. PROCEDURES: This prospective, cohort study enrolled patients 14-39 years of age who were receiving therapy for primary cancer diagnosis, cancer relapse, or had recently completed treatment. The painDETECT, a patient-completed, neuropathic pain screening tool used down to age 14, was administered a maximum of three times in on-therapy patients and once in off-therapy patients. Provider documentation of neuropathic pain at the corresponding visit was abstracted from the medical record. RESULTS: Seventy-eight patients participated. Median (interquartile range) age at study enrollment was 18.1 (16-19.4) years and 47% were female. Cancer diagnoses included 41% leukemia, 26% solid tumor, 23% lymphoma, and 10% central nervous system tumor. The proportion of patients reporting neuropathic pain was 26% (95% confidence interval [CI] 16-40%) in on-therapy patients and 11% (95% CI 3-27%) in off-therapy patients. In patients reporting neuropathic pain, only 26% had a clinical diagnosis of neuropathic pain documented in the medical record at the corresponding visit. CONCLUSIONS: Neuropathic pain occurs in one in four adolescents and young adults receiving cancer therapy. Use of screening tools may increase the detection of neuropathic pain in adolescents and young adults receiving cancer therapy and could ultimately improve pain treatment.

Liver transplant for congenital factor VII deficiency.

Congenital factor VII (FVII) deficiency is a rare, autosomal recessive bleeding disorder with a spectrum of phenotypes ranging from asymptomatic to life-threatening intra-cranial hemorrhage (ICH). Orthotopic liver transplantation has been described for definitive treatment in a few patients with severe manifestations. We report a patient with congenital FVII deficiency and recurrent ICH, despite twice-weekly prophylaxis with recombinant activated FVII. At 17 months of age, he underwent an orthotopic liver transplant. He is now 1-year post-transplant, on maintenance immunosuppression with no hemorrhage or other complications.

Refractory autoimmune hemolytic anemia after intestinal transplant responding to conversion from a calcineurin to mTOR inhibitor.

AIHA is a rare and serious complication of solid organ transplantation. Herein, we report four cases of warm or mixed AIHA in pediatric patients following combined liver, small bowel and pancreas transplant. The hemolysis was refractory to multiple treatment modalities including steroids, rituximab, IVIG, plasmapheresis, cytoxan, discontinuation of prophylactic penicillin, and a change in immunosuppression from tacrolimus to cyclosporine. All patients had resolution or marked improvement of hemolysis after discontinuation of maintenance of CNI and initiation of sirolimus immunosuppression. One patient developed nephrotic syndrome but responded to a change in immunosuppression to everolimus. Three of the four patients continue on immunosuppression with sirolimus or everolimus without further hemolysis, evidence of rejection or medication side effects. Based on our experience and review of similar cases in the literature, we have proposed a treatment algorithm for AIHA in the pediatric intestinal transplant patient population that recommends an early change in immunosuppressive regimen from CNIs to sirolimus therapy.