Parental Attitudes Towards Prenatal Genetic Testing For Sickle Cell Disease Uptake of prenatal genetic testing (PGT) is low among those with sickle cell disease (SCD). This study evaluated the association of knowledge and attitudes towards prenatal genetic counseling (PGC), awareness of posttesting intervention options and omission bias with attitudes towards PGT. In addition, we explored changes among knowledge, attitudes, and awareness of options following exposure to an educational, clinical vignette among parents of children with SCD. Parents (n=44) completed a questionnaire and an educational, clinical vignette presenting a detailed account of a pregnant woman with sickle cell trait seeking PGT and PGC was read to each participant. t Tests, Spearman correlations, multivariable regressions, and moderation/mediation analyses were used. More positive attitudes towards PGC (P=0.01), lesser tendency of omission bias (P<0.01) and private insurance (P=0.04) were significant correlates of more positive attitudes towards PGT. Omission bias mediated the relationship of attitudes towards PGC and attitudes towards PGT (95% confidence interval: 0.13, 3.03). Awareness of options (P=0.02), knowledge of PGC (P=0.01) and knowledge of PGT (P=0.01) significantly improved after exposure to the clinical vignette. Patients and families with SCD can benefit from education about the importance of prenatal diagnosis to improve attitudes, address omission bias and promote more informed decisions of PGT.

Neuroblastoma in Adolescents and Children Older than 10 Years: Unusual Clinicopathologic and Biologic Features Neuroblastoma (NB) in children older than 10 years is rare. We reviewed our archives for patients with NB aged 10 to 18 years and summarized their clinicopathologic/genetic records. Of 96 patients, 4 patients were identified in this age group. Four tumors were abdominal; 1 patient had 2 tumors at diagnosis, one of which was presacral. Tumor sizes ranged from 3 to 20 cm. All tumors were high risk at clinical stages 3 and 4, with metastasis to bone marrow and other areas. Four tumors were poorly differentiated with unfavorable histology and one patient with bilateral adrenal disease had an intermixed ganglioneuroblastoma on one side. Another tumor exhibited pheochromocytoma-like morphology. MYCN amplification was present in bone marrow metastasis in one case. Complex chromosomal gains and 19p deletions were common. Exome sequencing revealed ALK variants in 2 cases and previously unreported MAGI2, RUNX1, and MLL mutations. All patients received standard chemotherapy and 2 patients received ALK-targeted trial therapy. Three patients died of disease, ranging 18 to 23 months after diagnosis. One patient has active disease and is receiving trial therapy. In conclusion, NB in children older than 10 years may exhibit unusual clinicopathologic and genetic features with large tumors, bilateral adrenal disease, rare morphologic features, complex DNA microarray findings and novel mutations. Patients often have grim prognoses despite genomic profiling-guided targeted therapy.

Diagnosis of Invasive Fungal Infection Among Pediatric Oncology Patients Introduction: The diagnosis of pulmonary invasive fungal infection (IFI) in the pediatric oncology patient is challenging. Consensus criteria developed in 2008 state that bronchioalveolar lavage (BAL) results cannot confirm this diagnosis. A video-assisted thoracoscopic biopsy (VATS-biopsy) of lungs has been increasingly used to assist in evaluating these children for IFI. Our goal was to evaluate the impact of BAL and VATS-biopsy results on the management of IFI among pediatric oncology patients. Methods: A retrospective review of all oncology patients evaluated for IFI with VATS-biopsy and/or BAL over 9 years was carried out at a single free-standing children’s hospital. The primary outcome was management changes in the use of antifungal therapy on the basis of diagnostic procedure, fungal culture results, lung imaging, and serological markers. Results: A total of 102 patients underwent 122 diagnostic evaluations for IFI. Ninety-one workups included only BAL, 17 evaluations involved only VATS-biopsy, and 14 cases involved both BAL and VATS-biopsy. The diagnostic yield of VATS-biopsy (38.7%) was superior to that of BAL (27.6%). There was poor concordance between VATS-biopsy and BAL results in the 14 cases where both were performed. Upon workup completion, IFI was proven in 12 children, probable in 29, and possible in 52. The odds of continuing antifungals increased 3-fold for patients with probable IFI and 12.7 times for those with the proven disease. Discussion: On the basis of the inferior diagnostic yield of BAL, we believe that VATS-biopsy may be a more useful diagnostic adjuvant in the diagnosis of IFI in the immunocompromised pediatric oncologic patient population.

How Does Comprehensive Care Impact Life of Pediatric Patients With Hemophilia? Results From a Center in a Developing Country Background: Quality of life (QoL) has been included as a marker of treatment effectiveness in pediatric patients with chronic diseases. We believe that frequent multidisciplinary interventions and patient education could lead to an improvement in QoL. Aims: Determine the QoL and economic impact of monthly interventions in multidisciplinary treatment. Materials and Methods: The Haemo-QoL questionnaire was applied to patients who attended the hemophilia center of the University Hospital “Dr. José Eleuterio González,” Monterrey, Mexico, at the time of enrollment and 1 year later. Results: Male patients between 4 and 16 years diagnosed with hemophilia were included. The score results presented are based on Haemo-QoL versions that classify patients by their age group: group 1 (4 to 7 y) and group 2 (8 to 12 y). Statistical significant improvement was observed in the overall score (sociodemographic, psychosocial, etc.) after 1 year of follow-up in both groups (P<0.05). Conclusions: Impact on the QoL of patients receiving this approach was favorable. Improvement was observed regardless of severity and in those who were already in prophylaxis, suggesting that this type of approach could be causing the improvement. Results support the application of multidisciplinary treatment as the gold standard, and it should be considered in all centers including those with limited resources.

Effect of Sickle Cell Anemia Therapies on the Natural History of Growth and Puberty Patterns As pediatric patients with sickle cell anemia (SCA) have impaired growth and puberty patterns, we studied the effect of disease-modifying therapies on growth and puberty patterns for patients with SCA receiving hydroxyurea (HU), transfusions, or no therapy. We performed a retrospective study of children with SCA in whom anthropometric measurements and therapy type were recorded. Penalized smoothing splines were fitted to estimate growth curves and growth velocity, and linear mixed models were used to examine differences across treatment groups. Across group analyses were divided into early childhood (4.0 to 7.9 y) and peripubertal (8.0 to 12.0 y). We analyzed growth data on 157 SCA patients. From 8.0 to 12.0 years, girls on transfusion therapy were significantly taller than girls on HU (range, 5.7 to 7.2 cm; P-value range 0.002 to 0.01). From 10.0 to 12.0 years, boys on transfusion therapy were significantly taller than boys on HU (range, 4.1 to 9.4 cm; P-value range <0.0001 to 0.04). In addition, boys on transfusion therapy had an earlier peak height velocity as compared with boys on either HU or no therapy. In conclusion, children receiving transfusions tended to be taller than children on HU or no therapy. Children on HU did not demonstrate superior growth pattern when compared with children on no therapy in the peripubertal years.

Bone Marrow Failure in Fanconi Anemia: Clinical and Genetic Spectrum in a Cohort of 20 Pediatric Patients Prognostic refinement in Fanconi anemia (FA) is needed, especially when considering allogeneic hematopoietic stem cell transplantation (HCT). We studied 20 children with FA and bone marrow failure from a single center. According to Hôpital Saint-Louis risk classification for FA, patients were classified in stage A (no or mild cytopenia/dysplasia), B (single non–high-risk cytogenetic abnormality), C (severe cytopenia and/or significant dysplasia and/or high-risk cytogenetic abnormality), and D (myelodysplastic syndrome with excess of blasts/acute myeloid leukemia) in 4, 2, 13, and 0 cases, respectively. Nine patients received androgens +/− steroids, with a response rate of 30%, and 11 patients underwent HCT. Ten-year cumulative incidence (CI) of myelodysplastic syndrome/acute myeloid leukemia and overall survival (OS) were 21.9% and 45.3%, respectively, in the entire cohort, whereas cumulative incidence of transplantation-related mortality and OS were 27% and 63%, respectively, in patients who underwent HCT. Patients with significant dysplasia at diagnosis (stages C and D) had significantly shorter OS post-HCT as compared with patients without dysplasia. All patients in stages C and D at diagnosis or during evolution died from their disease. HCT in recent years was associated with more favorable outcomes. Larger cohorts could validate homogenous reporting of risk and help decision-making, particularly for HCT.

Asymptomatic Pulmonary Artery Embolization by a Port-a-Cath Fragment in a Child With Acute Lymphoblastic Leukemia Broken catheter embolism is a rare but often fatal complication of implantable venous access devices. Prompt removal is key to avoiding an adverse outcome.

Immune Thrombocytopenia in a Child With Refractory Langerhans Cell Histiocytosis Following Cladribine Containing Therapy In this report, we present a young infant with multisystem Langerhans cell histiocytosis, who after cladribine and cytarabine salvage treatment developed immune thrombocytopenia (IT). On review of the literature, there were no previous reports of Langerhans cell histiocytosis–associated IT. Treatment of the IT with intravenous immunoglobulin and oral corticosteroids was unsuccessful. Eltrombopag, in combination with a 4-day course of dexamethasone was commenced as second-line therapy. Platelet recovery occurred 10 days after initiation of eltrombopag. The immune thrombocytopenia remains in long-term remission despite cessation of eltrombopag. Eltrombopag was safe and well tolerated.

Catastrophic Delayed Hemolytic Transfusion Reaction in a Patient With Sickle Cell Disease Without Alloantibodies: Case Report and Review of Literature While packed red blood cell (PRBC) transfusion therapy is a mainstay in the treatment of certain patients with sickle cell disease (SCD) and the standard of care for preoperative management, there are associated risks. Delayed hemolytic transfusion reaction (DHTR) is a risk of PRBC transfusion occurring 2 to 20 days from transfusion and typically presents with severe pain characteristic of vaso-occlusive crisis, fever, and hemolytic anemia. DHTRs are uncommon, occurring in only 4% to 11% of transfused patients with SCD, but may be catastrophic in nature with progression to multiorgan failure within hours. Here, we describe a case of a 20-year-old female with sickle cell SS disease who developed a severe DHTR 5 days following an elective preoperative PRBC transfusion, and rapidly progressed to multiorgan failure and death. This is the first reported case of a catastrophic DHTR in a patient with SCD without any detectable known or new alloantibodies.

Intrapelvic Retroperitoneal Synovial Sarcoma in a 15-Year-Old Adolescent Girl: A Case Report and Review of the Literature Synovial sarcomas are a rare subtype of soft tissue sarcomas mostly located in the lower extremities. The authors report a case of synovial sarcoma in a 15-year-old adolescent girl with several unusual features including age, intrapelvic retroperitoneal location of the primary tumor, and presentation with right abdominal tenderness and compression of the iliac vessels with thrombosis of the right iliac and femoral vein.