Extracellular vesicle small RNA cargo discriminates non-cancer donors from pediatric B-lymphoblastic leukemia patients.

Pediatric B-acute lymphoblastic leukemia (B-ALL) is a disease of abnormally growing B lymphoblasts. Here we hypothesized that extracellular vesicles (EVs), which are nanosized particles released by all cells (including cancer cells), could be used to monitor B-ALL severity and progression by sampling plasma instead of bone marrow. EVs are especially attractive as they are present throughout the circulation regardless of the location of the originating cell.

Residual meta-iodobenzyl guanidine (MIBG) positivity following therapy for metastatic neuroblastoma: Patient characteristics, imaging, and outcome.

Background: Meta-iodobenzylguanidine(MIBG) scans are used to detect neuroblastoma metastatic lesions at diagnosis and during posttreatment surveillance. MIBG positivity following induction chemotherapy correlates with poor outcome; however, there are reports of patients with progression-free survival despite MIBG positivity at the end of therapy. The factors distinguishing these survivors from patients who progress or relapse are unclear.

Deciphering the messages carried by extracellular vesicles in hematological malignancies.

Extracellular vesicles (EVs) are nanosized membrane-bound particles released from all living cells examined thus far. EVs can transfer information in the form of proteins, nucleic acids, and lipids from donor cells to recipient cells. Here we summarize recent advances in understanding the role(s) EVs play in hematological malignancies (HM) and outline potential prognostic and diagnostic strategies using EVs.

Recombinant Factor VIII Fc Inhibits B Cell Activation via Engagement of the FcγRIIB Receptor.

The development of neutralizing antibodies (inhibitors) against factor VIII (FVIII) is a major complication of hemophilia A treatment. The sole clinical therapy to restore FVIII tolerance in patients with inhibitors remains immune tolerance induction (ITI) which is expensive, difficult to administer and not always successful. Although not fully understood, the mechanism of ITI is thought to rely on inhibition of FVIII-specific B cells (1).

Standardizing the categorizations of models of aftercare for survivors of childhood cancer.

Background: With significant improvements in the survival rates for most childhood cancers, there is increased pressure to determine how follow-up or aftercare for survivors is best structured.

Main Body: Previous work in this area has not been consistent in how it categorizes models of aftercare, which risks confusion between studies and evaluations of different models. The adoption of a standardized method for classifying and describing different models of aftercare is necessary in order to maximize the applicability of the available evidence.

Conservative Management of Hyperferritinemia in Hemolytic Disease of the Fetus and Newborn: A Case Report and Review of the Literature.

We report a newborn with hemolytic disease of the fetus and newborn (HDFN) with rapid resolution of extreme hyperferritinemia without chelation. An infant born at 35+3 weeks with HDFN and a history of 3 intrauterine transfusions developed severe hyperferritinemia (maximum, 8258 mcg/L) without evidence of toxic iron deposition on liver biopsy. Her hyperferritinemia was managed with observation alone, and ferritin levels normalized rapidly.

A Practical Guide to the Management of the Fetus and Newborn With Hemophilia.

Newborns with hemophilia are at risk of intracranial hemorrhage, extracranial hemorrhage, and other bleeding complications. The safe delivery of a healthy newborn with hemophilia is a complex process that can begin even before conception, and continues throughout pregnancy, birth, and the newborn period. This process involves the expectant parents and a wide variety of health-care professionals: genetic counselors, obstetricians, neonatologists, pediatricians, radiologists, adult and pediatric hematologists, and nurses with expertise in hemophilia.

Correction to: The association of venous thromboembolism with survival in pediatric cancer patients: a population-based cohort study.

The Figure 1 used in the originally published version of this article was incorrect.

The association of venous thromboembolism with survival in pediatric cancer patients: a population-based cohort study.

Venous thromboembolism (VTE) is a well-recognized complication in pediatric oncology patients. Studies in adult oncology patients have suggested a potential negative association between VTE and survival, but this association has not been examined in pediatric patients yet. The aim of this study was to assess the association of VTE with survival in pediatric oncology patients.

Dexamethasone promotes durable factor VIII-specific tolerance in hemophilia A mice via thymic mechanisms.

The development of inhibitory antibodies to factor VIII is the most serious complication of replacement therapy in hemophilia A. Activation of the innate immune system during exposure to this protein contributes to inhibitor development. However, avoidance of factor VIII exposure during innate immune system activation by external stimuli (e.

A Prospective Study of the Association Between Clinically Significant Bleeding in PICU Patients and Thrombocytopenia or Prolonged Coagulation Times.

Objective: There are no proven methods to predict the risk of clinically significant bleeding in the PICU. A retrospective study identified platelet count as a risk marker for clinically significant bleeding. We conducted a study to examine any association of platelet count, international normalized ratio, and activated partial thromboplastin time with bleeding risk in PICU patients.

Generation and optimization of the self-administered pediatric bleeding questionnaire and its validation as a screening tool for von Willebrand disease.

Objective: Our objective was to generate, optimize, and validate a self-administered pediatric bleeding questionnaire (Self-PBQ) as a screening tool for von Willebrand disease (VWD) in children referred to the hematology clinic for the first time.

Study Design: The Self-PBQ was generated by combining the validated expert-administered PBQ and the International Society on Thrombosis and Hemostasis (ISTH) bleeding assessment tool (BAT). Medical terminology was translated into lay language requiring a grade 4 reading level.

Concurrent influenza vaccination reduces anti-FVIII antibody responses in murine hemophilia A.

Inflammatory signals such as pathogen- and danger-associated molecular patterns have been hypothesized as risk factors for the initiation of the anti-factor VIII (FVIII) immune response seen in 25% to 30% of patients with severe hemophilia A (HA). In these young patients, vaccines may be coincidentally administered in close proximity with initial exposure to FVIII, thereby providing a source of such stimuli. Here, we investigated the effects of 3 vaccines commonly used in pediatric patients on FVIII immunogenicity in a humanized HA murine model with variable tolerance to recombinant human FVIII (rhFVIII).

Rapid acquisition of immunologic tolerance to factor VIII and disappearance of anti-factor VIII IgG4 after prophylactic therapy in a hemophilia A patient with high-titer factor VIII inhibitor.

We report an 11-month-old boy with severe hemophilia A who had regular exposure to factor VIII (FVIII) intended to reduce the risk of developing an inhibitor. He developed a high-titer inhibitor (peak titer 19 BU) that disappeared within 6 weeks of starting immune tolerance induction (ITI). Anti-FVIII IgG4 peaked briefly compared with anti-FVIII IgG1 and the Bethesda titer.

A survey of the management of newborns with severe hemophilia in Canada.

Objective: To determine the practice patterns of Canadian hematologists and neonatologists/paediatricians who care for newborns with hemophilia, with regard to vitamin K administration, use of empirical clotting factor replacement therapy, neuroimaging and timing of hematology consultation.

Methods: Hematologists and neonatologists/paediatricians, identified from membership lists of Canadian professional organizations, were provided electronic and/or paper versions of the survey instrument. Questions were posed in the context of specific clinical scenarios.

An evidence-based threshold for thrombocytopenia associated with clinically significant bleeding in pediatric intensive care unit patients.

Objective: To determine the epidemiology and identify the risk factors for clinically significant bleeding in the pediatric intensive care unit.

Design: A retrospective cohort study over 6 months with up to 7 days of observation for each patient.

Setting: The pediatric intensive care unit in a tertiary care children's hospital.