Amanda Grimes

Activating MAPK1 (ERK2) mutation in an aggressive case of disseminated juvenile xanthogranuloma

Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder that is usually benign and self-limiting. We present a case of atypical, aggressive JXG harboring a novel mitogen-activated protein kinase (MAPK) pathway mutation in the MAPK1 gene, which encodes mitogen-activated protein kinase 1 or extracellular signal-regulated 2 (ERK2). Our analysis revealed that the mutation results in constitutive ERK activation that is resistant to BRAF or MEK inhibitors but susceptible to an ERK inhibitor. These data highlight the importance of identifying specific MAPK pathway alterations as part of the diagnostic workup for patients with histiocytic disorders rather than initiating empiric treatment with MEK inhibitors.

Evaluation of maternal and perinatal characteristics on childhood lymphoma risk: A population-based case-control study.

Lymphoma is one of the most common pediatric malignancies; however, there are few well‐established risk factors. Therefore, we investigated if maternal and perinatal characteristics influenced the risk of childhood lymphoma.

Megaloblastic Anemia Progressing to Severe Thrombotic Microangiopathy in Patients with Disordered Vitamin B12 Metabolism: Case Reports and Literature Review

We describe 2 children with cobalamin G disease, a disorder of vitamin B12 metabolism with normal serum B12 levels. They presented with megaloblastic anemia progressing rapidly to severe thrombotic microangiopathy. In infants presenting with acute thrombotic microangiopathy, cobalamin disorders should be considered early as diagnosis and targeted treatment can be lifesaving.

Rapid infusion of rituximab is well tolerated in children with hematologic, oncologic, and rheumatologic disorders

Traditional administration of rituximab requires careful titration and may involve many hours to minimize the risk of reactions. The objective of this study was to evaluate the safety of rapid infusions of rituximab in a pilot group of children with hematologic, oncologic, and rheumatologic disorders, and to determine the incidence of rate‐related infusion reactions. Twenty patients enrolled in the study. All patients tolerated the rapid infusion of rituximab and no patient had an infusion‐related reaction. We conclude that rapid infusions of rituximab are well tolerated and safe in our pilot group of patients.

Thrombopoietin Receptor Agonists: Characteristics, Adverse Effects, and Indications

While the most commonly utilized first-line therapeutics for the treatment of immune thrombocytopenia (ITP) target the peripheral destruction of platelets, a preponderant second-line therapeutic agent targeting increased megakaryopoiesis and/or platelet production has now emerged, in the form of thrombopoietin receptor agonists (TPO-RAs). These TPO-RAs, eltrombopag and romiplostim, have been proven safe and effective in treating ITP in both children and adults and have also been approved for use in severe aplastic anemia and chronic hepatitis, with ongoing investigation in the treatment of other clinical entities as well, including myelodysplastic syndrome and acute myelogenous leukemia, chemotherapy-induced thrombocytopenia, congenital thrombocytopenia, and other diseases. This chapter will detail TPO-RA use in all of these different clinical settings.

Evans Syndrome: Background, Clinical Presentation, Pathophysiology, and Management

Evans syndrome (ES) is a descriptive diagnostic term encompassing autoimmune disorders which affect two or more blood cell lines, resulting most commonly in autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) but also autoimmune neutropenia (AIN) in some cases. Since Evans and colleagues first described this phenomenon in the 1940s, classically defined ES has expanded to include the occurrence of multilineage autoimmune cytopenias either concurrently or sequentially. Furthermore, advances in the understanding of disease pathogenesis have uncovered many of the underlying etiologies responsible for the autoimmune cytopenias which define this syndrome, such that “idiopathic” is no longer a defining feature of the syndrome. Some of the most common pathologies now known to drive ES include autoimmune lymphoproliferative syndrome (ALPS), common variable immunodeficiency (CVID), and other systemic autoimmune diseases, all with the commonality of a dysregulated immune system in which autoreactive lymphocytes are poorly controlled, ultimately predisposing to autoimmunity. The recent advances in understanding of the pathologies driving ES have allowed for improved insight into optimal diagnostic and management strategies, although work is ongoing in the quest for continued improvement in understanding of disease pathogenesis and better outcomes for patients with ES.