Pharmacogenomic Score Effectively Personalizes Treatment of Acute Myeloid Leukemia.

Purpose: Cytarabine (also known as ara-C) has been the backbone of acute myeloid leukemia (AML) chemotherapy for more than five decades. Recent pharmacogenomics-based 10-SNP ara-C (ACS10) scores showed low ACS10 (≤0) to be associated with poor outcomes in patients with AML treated with standard chemotherapy. Here, we evaluated the ACS10 score in the context of three different induction I regimens in patients with pediatric AML.

Pharmacogenomics, Race, and Treatment Outcome in Pediatric Acute Myeloid Leukemia.

Importance: Disparities in outcomes exist between Black and White patients with acute myeloid leukemia (AML), with Black patients experiencing poorer prognosis compared with their White counterparts.

Objective: To assess whether varying intensity of induction therapy to treat pediatric AML is associated with reduced disparities in treatment outcome by race.

Design, Setting, And Participants: A comparative effectiveness analysis was conducted of 86 Black and 359 White patients with newly diagnosed AML who were enrolled in the AML02 trial from 2002 to 2008 or the AML08 trial from 2008 to 2017.

Acute Promyelocytic Leukemia With Torque Teno Mini Virus::RARA Fusion: An Approach to Screening and Diagnosis.

Acute promyelocytic leukemia (APL) with variant RARA translocation is linked to over 15 partner genes. Recent publications encompassing 6 cases have expanded the spectrum of RARA partners to torque teno mini virus (TTMV). This entity is likely underrecognized due to the lack of clinician and pathologist familiarity, inability to detect the fusion using routine testing modalities, and informatic challenges in its recognition within next-generation sequencing (NGS) data.

Langerhans cell histiocytosis: NACHO update on progress, chaos, and opportunity on the path to rational cures.

Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder characterized by lesions with CD1a-positive/Langerin (CD207)-positive histiocytes and inflammatory infiltrate that can cause local tissue damage and systemic inflammation. Clinical presentations range from single lesions with minimal impact to life-threatening disseminated disease. Therapy for systemic LCH has been established through serial trials empirically testing different chemotherapy agents and durations of therapy.

Acute infusion-related reactions in pediatric patients receiving etoposide at a tertiary cancer center.

Introduction: Etoposide is a key component of many pediatric chemotherapy regimens for both hematologic and solid tumors. It is well documented that patients receiving etoposide may experience infusion-related reactions.

Methods: In this study, total doses of etoposide and etoposide phosphate were identified, and infusion-related reactions were retrospectively evaluated at a large pediatric oncology ambulatory clinic.

Hemophagocytic lymphohistiocytosis as an etiology of bone marrow failure.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of multiorgan system dysfunction that is caused by hypercytokinemia and persistent activation of cytotoxic T lymphocytes and macrophages. A nearly ubiquitous finding and a diagnostic criterion of HLH is the presence of cytopenias in ≥ 2 cell lines. The mechanism of cytopenias in HLH is multifactorial but appears to be predominantly driven by suppression of hematopoiesis by pro-inflammatory cytokines and, to some extent, by consumptive hemophagocytosis.

The added value of skeletal surveys in the initial evaluation of children diagnosed with Langerhans cell histiocytosis in the era of staging F-FDG PET/CT: A retrospective study.

Objective: Currently, there is no consensus protocol on the initial staging evaluation for Langerhans cell histiocytosis (LCH). Our institutional protocol consists of a skeletal survey and a whole-body positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography (FDG PET/CT) study. The utility of the PET/CT lies in its sensitivity in detecting osseous and extra-osseous lesions, and in determining the baseline metabolic activity of LCH lesions to assess treatment response.

An Evidence-Based Guideline Improves Outcomes for Patients With Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome.

Objective: To compare clinical outcomes in children with hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) who were managed before and after implementation of an evidence-based guideline (EBG).

Methods: A management algorithm for MAS-HLH was developed at our institution based on literature review, expert opinion, and consensus building across multiple pediatric subspecialties. An electronic medical record search retrospectively identified hospitalized patients with MAS-HLH in the pre-EBG (October 15, 2015, to December 4, 2017) and post-EBG (January 1, 2018, to January 21, 2020) time periods.

Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis.

Background: Primary hemophagocytic lymphohistiocytosis is a rare syndrome characterized by immune dysregulation and hyperinflammation. It typically manifests in infancy and is associated with high mortality.

Methods: We investigated the efficacy and safety of emapalumab (a human anti-interferon-γ antibody), administered with dexamethasone, in an open-label, single-group, phase 2-3 study involving patients who had received conventional therapy before enrollment (previously treated patients) and previously untreated patients who were 18 years of age or younger and had primary hemophagocytic lymphohistiocytosis.

Pediatric leukemia cutis: A case series.

Background: Pediatric leukemia cutis (LC) is often difficult to diagnose due to similarity in appearance to other dermatologic diseases. Several case reports and smaller case series have been published in the medical literature, but studies on larger cohorts of children with LC are lacking.

Objective: This study aimed to better characterize the clinical features, course, and prognosis of LC in the pediatric population.

Clofarabine Can Replace Anthracyclines and Etoposide in Remission Induction Therapy for Childhood Acute Myeloid Leukemia: The AML08 Multicenter, Randomized Phase III Trial.

Purpose: To identify effective and less toxic therapy for children with acute myeloid leukemia, we introduced clofarabine into the first course of remission induction to reduce exposure to daunorubicin and etoposide.

Patients And Methods: From 2008 through 2017, 285 patients were enrolled at eight centers; 262 were randomly assigned to receive clofarabine and cytarabine (Clo+AraC, n = 129) or high-dose cytarabine, daunorubicin, and etoposide (HD-ADE, n = 133) as induction I. Induction II consisted of low-dose ADE given alone or combined with sorafenib or vorinostat.

Pediatric CNS-isolated hemophagocytic lymphohistiocytosis.

Objective: To highlight a novel, treatable syndrome, we report 4 patients with CNS-isolated inflammation associated with familial hemophagocytic lymphohistiocytosis (FHL) gene mutations (CNS-FHL).

Methods: Retrospective chart review.

Results: Patients with CNS-FHL are characterized by chronic inflammation restricted to the CNS that is not attributable to any previously described neuroinflammatory etiology and have germline mutations in known FHL-associated genes with no signs of systemic inflammation.

A phase II clinical trial of adoptive transfer of haploidentical natural killer cells for consolidation therapy of pediatric acute myeloid leukemia.

Consolidation therapies for children with intermediate- or high-risk acute myeloid leukemia (AML) are urgently needed to achieve higher cure rates while limiting therapy-related toxicities. We determined if adoptive transfer of natural killer (NK) cells from haploidentical killer immunoglobulin-like receptor (KIR)-human leukocyte antigen (HLA)-mismatched donors may prolong event-free survival in children with intermediate-risk AML who were in first complete remission after chemotherapy. Patients received cyclophosphamide (Day - 7), fludarabine (Days - 6 through - 2), and subcutaneous interleukin-2 (Days - 1, 1, 3, 5, 7, and 9).

Calm in the midst of cytokine storm: a collaborative approach to the diagnosis and treatment of hemophagocytic lymphohistiocytosis and macrophage activation syndrome.

Background: Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) were historically thought to be distinct entities, often managed in isolation. In fact, these conditions are closely related. A collaborative approach, which incorporates expertise from subspecialties that previously treated HLH/MAS independently, is needed.

Central nervous system-restricted familial hemophagocytic lymphohistiocytosis responds to hematopoietic cell transplantation.

Familial HLH can present as chronic isolated neuroinflammation. CNS-isolated HLH responds to hematopoietic cell transplantation.

Histopathologic Correlates of Familial Hemophagocytic Lymphohistiocytosis Isolated to the Central Nervous System.

Familial hemophagocytic lymphohistiocytosis (HLH) is an immune hyperactivation syndrome caused by mutations in genes associated with cytotoxic T-cell and NK-cell function. While neurological manifestations frequently accompany systemic inflammation at initial presentation, isolated central nervous system (CNS) involvement is rare, and the histological correlates are not well described. We present 3 patients (ages 5, 6, and 7 years) with CNS-isolated familial HLH, who presented with a variety of neurological symptoms and underwent brain biopsies for multifocal enhancing supratentorial and infratentorial lesions.

Acute lymphoblastic leukemia in a patient with MonoMAC syndrome/GATA2 haploinsufficiency.

Patients with GATA2 haploinsufficiency have a significant predisposition to developing cytopenias, unique infectious manifestations, and myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). We report a unique case of a patient who presented with B-cell acute lymphoblastic leukemia (B-ALL) and was subsequently diagnosed with monocytopenia and mycobacterium avium complex (MonoMAC) syndrome/GATA2 haploinsufficiency. The development of MDS/AML in patients with GATA2 haploinsufficiency is well described, however, the development of ALL has not been reported in the literature.

Familial Hemophagocytic Lymphohistiocytosis.

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare heritable disorder of immune regulation that is typically characterized by sudden onset of severe systemic illness. Functional impairment or absence of 1 or more of several proteins that participate in lymphocyte cytotoxicity underlies the disease. Although FHL usually presents in infancy, age of onset is variable and dependent on genetic and environmental factors.

Management and Outcome of Patients With Langerhans Cell Histiocytosis and Single-Bone CNS-Risk Lesions: A Multi-Institutional Retrospective Study.

Background: Children with Langerhans cell histiocytosis (LCH) and single-bone CNS-risk lesions have been reported to be at increased risk of diabetes insipidus (DI), central nervous system neurodegeneration (CNS-ND), and recurrence of disease. However, it is unknown whether the addition of chemotherapy or radiotherapy changes outcomes in these patients.

Methods: Ten pediatric institutions across North America and Europe contributed data of their patients with LCH and single-bone CNS-risk lesions.

Ethnicity, race, and socioeconomic status influence incidence of Langerhans cell histiocytosis.

Background: Langerhans cell histiocytosis (LCH) is a rare disease, and its etiology is not well understood. Population-based studies may contribute to etiologic research by defining incidence patterns. This study was designed to evaluate the descriptive epidemiology of disseminated LCH in the United States, using data from population-based cancer registries.

Bone marrow engraftment and associated dermatologic sequelae in a three-yr-old after liver transplantation.

We present a case of a three-yr-old child with a history of multisystem Langerhans cell histiocytosis treated with systemic chemotherapy, who developed progressive liver failure and received an orthotopic split liver transplant while continuing on chemotherapy. One month following transplant, he developed acute graft-vs.-host disease of the skin and gastrointestinal tract.