Whole-genome sequencing reveals genetic backgrounds in Japanese patients with hemophagocytic lymphohistiocytosis treated with the HLH-2004 protocol.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition triggered by a combination of genetic predispositions and environmental factors. Reports of previous outcomes from the HLH-2004 protocol in Japan revealed patients with idiopathic HLH who had poor prognoses. This study aimed to reevaluate the genetic background of such patients to identify potential novel genetic variants.

Retrospective nationwide survey of pediatric RDD in Japan: a high prevalence of mutations in the kinase pathway genes.

Background: Rosai-Dorfman-Destombes disease (RDD) is a rare form of histiocytosis, characterized by the accumulation of S100 protein-positive and CD1a-negative histiocytes with emperipolesis. Recently, oncogenic mutations in mitogen-activated protein kinase pathway genes were reported in nearly half of RDD patients.

Methods: We conducted a nationwide retrospective survey of childhood RDD in Japan.

Dexamethasone palmitate for children with Epstein-Barr virus associated hemophagocytic lymphohistiocytosis.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) has a wide range of clinical presentations and is sometimes life-threatening. It is often treated with systemic corticosteroids and etoposide, but no optimal treatment has been identified. Dexamethasone palmitate (DP) contains a combination of dexamethasone and a lipid emulsion and is selectively taken up by activated macrophages.

Trametinib for a child with refractory Rosai-Dorfman-Destombes disease harboring a novel somatic mutation in MAP2K1.

Rosai-Dorfman-Destombes disease (RDD) is a rare histiocytosis characterized by accumulation of S100 + , CD68 + , and CD1a- histiocytes, with emperipolesis. It occurs predominantly in black adolescents and young adults, but rarely in Japanese children. Recently, oncogenic mutations in mitogen-activated protein kinase (MAPK) pathway genes were reported in 30-50% of patients with RDD, and several studies have described treatment of adult patients with MAPK inhibitors.

Cerebellar peduncle damage in Langerhans cell histiocytosis-associated neurodegenerative disease revealed by diffusion tensor imaging.

Purpose: To confirm the hypothesis that brain white matter damage is involved in the pathogenesis and disease progression of Langerhans cell histiocytosis (LCH)-associated neurodegenerative disease (ND), we aimed to analyze pediatric patients with LCH using diffusion tensor imaging (DTI).

Methods: We enrolled 33 patients with LCH and obtained 33 DTI datasets. Using DTI-based tractography, fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were measured in the cerebral and cerebellar white matter tracts.

Detection of BRAF V600E mutation in radiological Langerhans cell histiocytosis-associated neurodegenerative disease using droplet digital PCR analysis.

Langerhans cell histiocytosis-associated neurodegenerative disease (LCH-ND) is the most serious late complication secondary to LCH and is gradually progressive, destructive, and irreversible. Detection of the BRAF V600E mutation in peripheral blood mononuclear cells (PBMCs), even in the absence of active LCH lesions, is considered a sign of clinical LCH-ND, presenting with both abnormal imaging findings and neurological symptoms. However, the detection of the BRAF V600E mutation in PBMCs of patients with asymptomatic radiological LCH-ND (rLCH-ND) without active LCH lesions who present only with abnormal imaging findings is unknown.

Intensification of treatment with vinca alkaloid does not improve outcomes in pediatric patients with Langerhans cell histiocytosis: results from the JPLSG LCH-12 study.

Chemotherapy with cytarabine, vincristine (VCR), and prednisolone has achieved low mortality rates in pediatric patients with Langerhans cell histiocytosis (LCH). However, relapse rates remain high, making event-free survival (EFS) rates unsatisfactory. A nationwide clinical trial, LCH-12, tested a modified protocol in which the early maintenance phase was intensified with increasing dosages of VCR.

The efficacy and safety of allogeneic stem cell transplantation in Mevalonate Kinase Deficiency.

Objectives: Mevalonate kinase deficiency (MKD) is a rare autoinflammatory syndrome. Several reports have described allogeneic hematopoietic stem cell transplantation in severely affected patients, sometimes with promising results. In view of the scarcity of data, this study aims to analyse the efficacy and safety of allogeneic hematopoietic stem cell transplantation (HSCT) to give a more complete overview of this treatment.

New biomarker paves the way for a clinical trial for neurodegeneration in Langerhans cell histiocytosis.

Neurodegeneration in Langerhans cell histiocytosis (ND-LCH) is a major clinical issue requiring urgent resolution. Sveijer et al. showed that plasma neurofilament light protein is a promising biomarker for screening patients with ND-LCH and determining the therapeutic effect of a mitogen-activated protein kinase inhibitor.

[Elucidated pathogenesis and therapeutic prospects in Langerhans cell histiocytosis].

Langerhans cell histiocytosis (LCH) is characterized by immature dendritic cell proliferation, which is currently classified as an inflammatory myeloid neoplasm. Clinical features and outcomes vary from spontaneously regressing isolated bone disease to fatal liver, spleen, or hematopoietic system (risk organ) involvement-positive multisystem disease. LCH cells have the only mutation in the mitogen-activated protein kinase (MAPK) signaling pathway gene, represented by the BRAF V600E mutation, which is the driver mutation.

Reliability and Validity of the Japanese Pediatric Version of Memorial Symptom Assessment Scale.

Context: Few instruments in Japanese assess health-related quality of life in pediatric cancer patients.

Objectives: To translate the Memorial Symptom Assessment Scale (MSAS) into Japanese pediatric and proxy versions (MSAS-J 7-12, MSAS-J 13-18, and MSAS-J-Proxy) and assess validity and reliability.

Methods: Phase I comprised forward-backward translation and pilot testing in 13 children and 16 guardians.

Prognostic value of the revised International Prognostic Scoring System five-group cytogenetic abnormality classification for the outcome prediction of hematopoietic stem cell transplantation in pediatric myelodysplastic syndrome.

Cytogenetic abnormalities are a major risk factor for relapse after hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS). We aimed to evaluate the value of the five-group cytogenetic classification according to the revised International Prognostic Scoring System (R-IPSS) for predicting the outcome after HSCT in pediatric patients with MDS. We retrospectively analyzed the Japanese registration data of 242 pediatric patients with MDS.

Central diabetes insipidus developing in a 6-year-old patient 4 years after the remission of unifocal bone Langerhans cell histiocytosis.

A six-year-old boy was referred with a one-and-a-half months history of polyuria and polydipsia. At the age of two, he had a single lytic bone lesion in his femoral head, diagnosed as Langerhans cell histiocytosis (LCH) by biopsy at another hospital. As no other affected organs were detected and the affected bone lesion was self-limited, he was not followed up afterward and was doing well.