[Current Status and Perspective of Medical Setting for Pediatric Cancers in Japan].

In accordance with the Basic Plan to Promote Cancer Control Programs, a medical setting for providing patients with pediatric cancers sufficient medical treatments and supports has been assigned as one of the central issues in Japan. The Japanese Ministry of Health, Labour and Welfare designated 15 Pediatric Cancer Core Hospitals, and National Center for Child Health and Development as a central center in February 2013. A medical setting for pediatric cancers has been progressed to achieve the consolidation of patients who need specialized therapies and equalization of patients who need standard therapies for cure. Pediatric cancers are typical rare cancers in terms of the disease frequency. Therefore, there is a limitation to conduct systemic clinical studies in a few centers. To overcome this situation, JCCG(Japanese Children's Cancer Group)and JPLSG(Japanese Pediatric Leukemia/Lymphoma Study Group)were organized to conduct more than 30 clinical studies nationwide in each disease of pediatric solid tumors and hematological malignancies, respectively. They contributed to better outcome achieving more than 80% overall survival rates. While clinical trials to reduce therapeutic intensity in patients with better prognosis, molecular targeted therapies based on comprehensive genetic analysis and CAR-T therapy have been provided as effective therapeutic options in patients with refractory diseases. However, we still have limitations to provide patients such new therapeutic agents without delay covered by health insurance. Comprehensive supportive care for the patients and their family members by multi-disciplinary medical stuffs are required for their better quality of life. Long-term follow-ups for cancer survivors, learning supporting system for high school students, cares for their siblings, supports for the generation of adolescent and young adults (AYA) and fertility preservation have been provided in each hospital. In this paper, I summarized these current status and future perspective for medical settings of pediatric cancers in Japan.

Characteristic phenotypes of ADH5/ALDH2 deficiency during childhood.

ADH5/ALDH2 deficiency is a rare inherited syndrome characterized by short stature, microcephaly, delayed mental development, and hematopoietic dysfunction and has recently been proposed as a disease paradigm. Acute and severe presentations include aplastic anemia, myelodysplastic syndrome, or leukemia, requiring bone marrow transplantation during childhood. Conversely, non-hematological manifestations may exhibit a prolonged and nonspecific clinical trajectory, with growth failure and developmental delay, most of which are often overlooked, particularly in patients with milder symptoms. Here, we describe the clinical course of a girl with a wide spectrum of clinical presentations, including nonspecific hematopoietic disorders, growth retardation, mild developmental delay, amblyopia, hemophagocytic lymphohistiocytosis, and verruca vulgaris, culminating in a genetic diagnosis of AMeD syndrome at 12 years of age. We also summarized the clinical manifestations of previously reported cases of AMeD syndrome. Cumulatively, 13 females and 5 males have been documented, with a cardinal triad of symptoms, aplastic anemia, short stature, and intellectual disability. Additional characteristic observations included pigmentary deposition in approximately half of the cases and skeletal difficulties in one-quarter. We propose that early diagnosis of patients who exhibit relatively mild phenotypes of skin or skeletal lesions is important for managing and improving the quality of life of patients with AMeD syndrome.

Highly sensitive detection of Epstein-Barr virus-infected cells by EBER flow FISH.

When Epstein-Barr virus (EBV) infection is suspected, identification of infected cells is important to understand the pathogenesis, determinine the treatment strategy, and predict the prognosis. We used the PrimeFlow™ RNA Assay Kit with a probe to detect EBV-encoded small RNAs (EBERs) and multiple surface markers, to identify EBV-infected cells by flow cytometry. We analyzed a total of 24 patients [11 with chronic active EBV disease (CAEBV), 3 with hydroa vacciniforme lymphoproliferative disorder, 2 with X-linked lymphoproliferative disease type 1 (XLP1), 2 with EBV-associated hemophagocytic lymphohistiocytosis, and 6 with posttransplant lymphoproliferative disorder (PTLD)]. We compared infected cells using conventional quantitative PCR methods and confirmed that infected cell types were identical in most patients. Patients with CAEBV had widespread infection in T and NK cells, but a small amount of B cells were also infected, and infection in patients with XLP1 and PTLD was not limited to B cells. EBV-associated diseases are believed to be complex pathologies caused by EBV infecting a variety of cells other than B cells. We also demonstrated that infected cells were positive for HLA-DR in patients with CAEBV. EBER flow FISH can identify EBV-infected cells with high sensitivity and is useful for elucidating the pathogenesis.