Adjunctive effects of eltrombopag on immunosuppressive therapy for childhood aplastic anemia.

Eltrombopag is used with first-line immunosuppressive therapy for adult aplastic anemia, although its practical utility in childhood remains unclear. We retrospectively analyzed the outcomes of pediatric patients who received eltrombopag in Japan. Of the 27 eligible patients, 23 (85%) were previously treated, and 15 (56%) had severe or very-severe disease.

Real-world Outcomes of Commercial Tisagenlecleucel for Children, Adolescents, and Young Adults With Acute Lymphoblastic Leukemia in Japan.

Chimeric antigen receptor (CAR) T cells are a major new treatment option for children, adolescents, and young adults (CAYA) patients with relapsed and refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL). Therefore, accumulating evidence from real-world experiences of CAR-T outcomes in various regions worldwide is important, particularly when comparing outcomes of patients with differing medical and ethnic backgrounds. More than 5 years have passed since tisagenlecleucel was approved in Japan.

Cord Blood Transplantation Using Myeloablative Conditioning for Pediatric Advanced Myelodysplastic Syndrome in AMeD Syndrome With a Novel ADH5 Variant.

Aplastic anemia, mental retardation, and dwarfism syndrome (AMeDS) is a rare inherited bone marrow failure syndrome. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only possible treatment option for hematological complications in AMeDS; however, there are no reports addressing allo-HSCT for AMeDS. A 6-year-old female diagnosed with AMeDS accompanying myelodysplastic syndrome with increased blast was successfully treated with cord blood transplantation followed by myeloablative conditioning (MAC).

Endoscopic characteristics to differentiate SSLs and microvesicular hyperplastic polyps from goblet cell-rich hyperplastic polyps.

Among colorectal serrated polyps (SPs), sessile serrated lesions (SSLs) and hyperplastic polyps (HPs) have a similar endoscopic appearance. However, the endoscopic distinctions between those two categories, microvesicular HPs (MVHPs) and goblet cell-rich HPs (GCHPs), are not well understood. Therefore, we compared the endoscopic features of SSLs, MVHPs, and GCHPs.

Increased response to granulocyte-macrophage colony-stimulating factor in peripheral blood cells and transient manifestations mimicking juvenile myelomonocytic leukemia in a male patient with NEMO deficiency caused by a deep intronic pathogenic variant of IKBKG.

X-linked NF-κB essential modulator (NEMO) deficiency is a primary immunodeficiency characterized by combined immunodeficiency and ectodermal dysplasia. Monocytes from the patients demonstrate a severely impaired response to tissue necrosis factor or lipopolysaccharide, whereas hyper-inflammation is found in some patients. Juvenile myelomonocytic leukemia (JMML) is a pediatric malignancy caused by hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) and aberrant RAS signaling activation.

High threshold of total developmental quotient at 3 years for follow-up in extremely preterm infants.

Aim: To investigate the relationship between the developmental quotient (DQ) at age 3 years and the need for educational support at school age in extremely preterm infants.

Methods: A total of 176 infants with a gestational age of <28 weeks were analyzed. The total DQ and subscales were evaluated using the Kyoto Scale of Psychological Development (KSPD) test.

Risk factors of bloodstream infection after allogeneic hematopoietic cell transplantation in children/adolescent and young adults.

Allogeneic hematopoietic cell transplantation (HCT) is a crucial treatment for various diseases, including hematological malignancies, solid tumors, and genetic disorders. Despite its curative potential, HCT is associated with severe complications, notably infections, graft-versus-host disease, and organ damage. Infections, particularly bloodstream infections (BSIs), pose a significant threat in the initial weeks post-HCT, necessitating effective management strategies.

Ruxolitinib for pediatric patients with treatment-naïve and steroid-refractory acute graft-versus-host disease: the REACH4 study.

In REACH4, a phase 1/2, open-label, single-arm, multicenter study, the pharmacokinetics (PK), efficacy, and safety of ruxolitinib were evaluated in treatment-naïve and steroid-refractory pediatric patients with grade 2 to 4 acute graft-versus-host disease (aGVHD; n = 45). Ruxolitinib dosing was based on age and targeted the exposure in adults receiving 10 mg twice daily; group 1 (aged ≥12 to <18 years) received 10 mg twice daily and preliminary starting doses for groups 2 (aged ≥6 to <12 years) and 3 (aged ≥2 to <6 years) were 5 mg twice daily and 4 mg/m2 twice daily, respectively. The phase 1 primary objective was to assess ruxolitinib PK parameters and define an age-appropriate recommended phase 2 dose (RP2D) for patients aged <12 years.

Ruxolitinib in treatment-naive or corticosteroid-refractory paediatric patients with chronic graft-versus-host disease (REACH5): interim analysis of a single-arm, multicentre, phase 2 study.

Background: Chronic graft-versus-host disease (GVHD) is a debilitating, and sometimes life threatening, complication of allogeneic haematopoietic stem-cell transplantation (HSCT). We aimed to investigate the activity, pharmacokinetics, and safety of ruxolitinib added to corticosteroids in paediatric patients (ie, <18 years) with moderate-to-severe chronic GVHD.

Methods: In this single-arm, phase 2 study, patients were recruited at 21 hospitals or clinics across 14 countries in Asia, Europe, and Canada.

Clinical features of immature leukemias in children.

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL), mixed phenotypic acute leukemia (MPAL), and acute myeloid leukemia with minimal differentiation (AML-M0) all originate from immature hematopoietic progenitor cells and have a poor prognosis. We investigated the clinical characteristics of these immature leukemias in 17 children (ETP-ALL: 8, MPAL: 5, AML-M0: 4) at seven institutions. Clinical and laboratory findings were comparable across disease types.

Single-Cell Transcriptomic Analysis of Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis.

Epstein-Barr virus (EBV) infection can lead to infectious mononucleosis (EBV-IM) and, more rarely, EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), which is characterized by a life-threatening hyperinflammatory cytokine storm with immune dysregulation. Interferon-gamma (IFNγ) has been identified as a critical mediator for primary HLH; however, the detailed role of IFNγ and other cytokines in EBV-HLH is not fully understood. In this study, we used single-cell RNA sequencing to characterize the immune landscape of EBV-HLH and compared it with EBV-IM.

IL-33-ST2 signaling in fibro-adipogenic progenitors alleviates immobilization-induced muscle atrophy in mice.

Background: The regenerative and adaptive capacity of skeletal muscles reduces with age, leading to severe disability and frailty in the elderly. Therefore, development of effective therapeutic interventions for muscle wasting is important both medically and socioeconomically. In the present study, we aimed to elucidate the potential contribution of fibro-adipogenic progenitors (FAPs), which are mesenchymal stem cells in skeletal muscles, to immobilization-induced muscle atrophy.

Nanopore sequencing in distinguishing between wild-type and vaccine strains of Varicella-Zoster virus.

Background: The introduction of varicella vaccines into routine pediatric immunization programs has led to a considerable reduction in varicella incidence. However, there have been reports of varicella, herpes zoster, and meningitis caused by the vaccine strain of varicella-zoster virus (VZV), raising concerns. Establishing the relationship between the wild-type and vaccine strains in VZV infections among previously vaccinated individuals is crucial.

Harmonizing definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism in allogeneic hematopoietic cell transplantation: a report on behalf of the EBMT, ASTCT, CIBMTR, and APBMT.

Despite emergence of novel therapies to treat hematologic malignancies, allogeneic hematopoietic cell transplantation (allo-HCT) remains an essential treatment modality capable of curing these diseases. Allo-HCT has been also shown to be curative in benign hematologic disorders such as aplastic anemia, sickle cell disease, and thalassemia, among others. Recently, the American Society for Transplantation and Cellular Therapy (ASTCT) published standardized definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism.