To improve the survival rate in hepatoblastoma (HB), novel prognostic markers and therapeutic targets should be identified. Altered DNA methylation patterns are biologically and clinically important in HB. We evaluated the methylation status of RASSF1A, MST1R, OCIAD2, and PARP6, whose hypermethylation was associated with several clinicopathological characteristics in 132 patients with HB, using bisulfite pyrosequencing analysis. Hypermethylation in ≥2 of the four genes was significantly associated with poorer OS and EFS. Multivariate analysis indicated that ≥2 methylated genes was an independent prognostic factor. Moreover, it was associated with poorer OS in the CHIC-very low (VL)-/low (L)-risk group and CHIC-intermediate (I) risk group (3-year OS rates; 83% vs. 98% and 50% vs. 95%, respectively). The 3-year OS rates of the VL/L, I, and high-risk groups in the new stratification model (methylation-based CHIC-HS; mCHIC-HS) were 98%, 90%, and 63% (vs. CHIC-HS [96%, 82%, and 66%, respectively]), optimizing CHIC-HS. The proposed stratification system may improve the clinical management of HB according to individual risk in patients with HB.

CHARGE syndrome is a genetic disorder with congenital features, which is sometimes associated with immunodeficiency. We report a case of a patient with CHARGE syndrome with severe combined immunodeficiency (SCID) who underwent umbilical cord blood transplantation (CBT). The patient was referred for fatal growth retardation and delivered at 37 gestational weeks. He was diagnosed with CHARGE syndrome due to multiple malformations and deletion of CHD7. Since he was one month old, he had recurrent pneumonia and otitis media. Laboratory tests led to the diagnosis of T-B+NK+SCID. After the diagnosis, infections were effectively managed through intravenous immunoglobulin replacement therapy and prophylactic administration of antibiotics and antifungal agents. At 6 months old, he underwent 7/8 HLA allele-matched CBT without pre-conditioning. Tacrolimus and short methotrexate were used as graft-versus-host disease (GVHD) prophylaxis. Subsequently, T-cell counts increased and the flow cytometry analysis revealed CD45RA-positive naive T cells on day 28. Grade 2 cutaneous acute GVHD occurred on day 14; however, it was immediately resolved by administering 2 mg/kg prednisolone. The treatment was tapered off 2 months post CBT without GVHD recurrence. Although thymic transplantation is the most suitable therapy for CHARGE syndrome with SCID, it is unavailable in most countries, including Japan. Recent reports have shown that CBT can successfully restore immune function and is expected to become an alternative treatment for SCID in patients with CHARGE syndrome.

The treatment of children with cancer is a complex endeavor. The establishment of novel therapies entails a strong collaboration between basic research and translational research, including the integration of multi-institutional studies. Within a clinical setting, a multidisciplinary team approach is indispensable. Given the dynamic nature of children’s growth and development, a specialized technique for communicating information about the disease and its clinical consequences to parents becomes imperative. In reflecting on the historical progress described herein, understanding this evolution, coupled with a good sense of self-esteem, serves as the basis for the continuance of this invaluable vocation.

The main purposes of long-term follow-up for childhood cancer survivors (CCS) include prevention, early detection, and appropriate management of late complications to achieve long-term survival with a high quality of life. For this purpose, it is necessary to generate original evidence in Japan. To address the issues, the establishment of a nationwide long-term follow-up system is currently underway as a part of the Comprehensive Research Project for the Promotion of Cancer Control, known as the “Long-Term Follow-Up Matsumoto Group”. In this framework, we play a major role in the development of information infrastructure as a data center.

We intend to utilize a bidirectional database that enables both physicians and CCS to access and enter data. These data can be used to develop a prediction model to allow for long-term follow-up as a preemptive medicine.

In addition, we would like to establish a system to enable precision survivorship according to the individual risk of CCS by linking CCS’s clinical information and genomic data. Importantly, long-term follow-up should not be initiated after the completion of treatment but should begin with a cancer registry to recognize the presence of each case of CCS.

This article describes the progress of developing an information infrastructure for the Long-Term Follow-Up Matsumoto Group. Regarding the project, we discuss the strategy of the database and prospects for international collaboration.

In pediatric cancer, while the prognosis has been improving, some cancers still have poor outcomes. In treating pediatric cancer, besides aiming for a cure, minimizing late effects is crucial. Recently, oncolytic virotherapy (OV) has become promising as a novel therapy. Various types of OVs have been developed worldwide; however, they should have minimal adverse effects on normal cells, infect only tumor cells, and show antitumor effects when the virus replicates in the tumor cells and spreads successively to neighboring tumor cells. In addition to the direct cell-killing effect of the virus, OV is also expected to have an immunostimulatory effect by changing the tumor microenvironment from immunologically “cold” to “hot,” and the latter anti-tumor effect has been attracting more attention recently. Notably, in June 2021, ‘Tesevlatrex’ (Delictat; G47Δ) was the first OV therapy approved in Japan for malignant glioma treatment. We have modified adenovirus genes and developed OV targeting refractory PAX3::FOXO1-positive rhabdomyosarcoma and rhabdoid tumors, challenging pediatric cancers. First, this presentation provides an overview of the potential appeal of OV, from its therapeutic development history to its recent research and clinical applications. Subsequently, the status and prospects of OV for pediatric cancer will be reviewed.

Recently, the efficacy and safety of venetoclax/azacitidine (VEN/AZA) for adult acute myelogenous leukemia (AML) have been reported; however, only few reports focus on their efficacy in pediatric AML. Here, we report four cases of pediatric relapsed/refractory AML, who were treated with VEN/AZA. One patient experienced induction failure, whereas three patients relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median number of VEN/AZA courses was three (2–4). Complete hematological remission was achieved in two patients after the first course and in all four patients after the second course; three patients subsequently received allo-HSCT. Grade 4 neutropenia was observed in nine out of 12 (75%) courses. Neutropenia of less than 100/µL was common in the first course; however, it was only in one of eight courses in subsequent courses. No serious non-hematological toxicities were observed. All four patients were successfully remitted and side effects other than myelosuppression were minimal. This suggests that VEN/AZA may be a promising and novel treatment option for induction therapy in relapsed/refractory pediatric AML and could be used safely even for patients in poor conditions after allo-HSCT.

We retrospectively analyzed the incidence, risk factors, and response to treatment of post-allogeneic hematopoietic cell transplant (HCT) immune-mediated cytopenias (IMC) in 89 patients (103 HCTs) who underwent HCT at age below 20 years, between January 2010 and March 2023. The 2-year cumulative incidence of IMC was 4.8%. Multivariate analysis identified younger age at HCT (below 1 year) as the sole independent and significant risk factor for the development of post-HCT IMC (P=0.039). Four patients, all with non-malignant diseases, developed IMCs (2 cases of autoimmune hemolytic anemia and 2 of immune thrombocytopenia) at a median of 95 days post-HCT (range, 56–432 days). These patients had undergone HCT from unrelated donors utilizing a reduced-intensity conditioning regimen. Rituximab in combination with mTOR inhibitor everolimus or anti-CD38 monoclonal antibody daratumumab was effective for two patients who were refractory for prednisolone and intravenous immunoglobulin. All patients obtained complete responses; however, one patient experienced a recurrence of IMC. Nationwide surveys are essential to gain insights into the prevalence of post-HCT IMC in Japan.

Although the relationship between pediatric cancer patients and their former classmates, during hospitalization has various benefits, the recognition of interactions between both parties has not been clarified. Herein, we conducted semi-structured interviews with seven adult survivors of childhood cancer and three of their former classmates, to clarify their recognition of interactions during hospitalization. According to the results, the survivors felt a dilemma in disclosing information about their illness to their classmates, and the classmates felt a dilemma about getting involved with the survivors. Additionally, five categories of support including informing classmates and sharing information among adults, were generated. Although maintaining relationships between pediatric cancer patients and their former classmates is important, the time when the need for such support increases varies depending on the developmental stage and situation of the patient. It was also suggested that the classmates made assumptions regarding the kind of hope the survivor may have from the relationship with them and tried to respond accordingly. Healthcare professionals should play a bridging role in understanding both situations by continuously recognizing and supporting the needs of both pediatric cancer patients and their classmates.

This study aimed to explore how mothers helped their children understand retinoblastoma and highlight the challenges they faced. Semi-structured interviews were conducted with 11 mothers with 3- to 7-year-old children diagnosed with retinoblastoma. The median age of these mothers was 42 years. Following the analysis, the study identified 12 categories of methods employed by mothers to help their children understand their medical condition and two categories of challenges mothers face.

In post-diagnosis periods, mothers “tailored information to their children’s understanding, avoiding in-depth discussions on the disease or treatment”. As the children grew, the mothers associated hospital visits with the eye disease while “stating that they were going to see the doctor for examination and testing of their eye disease”. Eye enucleation often prompted explanations of the treatment’s necessity. The mothers tended to “avoid using the word ‘cancer’ when explaining the disease’s impact on visual impairment or its life-threatening nature”. They carefully timed and curated discussions on “cancer”, prosthetic eyes, and visual impairment. Ultimately, addressing the topic of death was also necessary. Some mothers contemplated providing explanations that considered genetics and its implications for adulthood. Some mothers confessed to “experiencing feelings of shock and guilt”. To help children understand their illnesses better, the findings recommend a timely implementation of a well-planned explanation process, following the children’s growth and the emotional well-being of mothers from the early stages of their child’s diagnosis. Moreover, an interdisciplinary support system that encourages cooperation between different clinical departments and disciplines should be established.

This qualitative, descriptive study explored how children with retinoblastoma understand their eyes and vision, and how their mothers facilitate this understanding. Data from semi-structured interviews with the mothers of three- to seven-year-old children with retinoblastoma were analyzed. Ten categories of children’s understanding of their eyes and vision were obtained, with 26 subcategories. Thirteen categories were generated from 23 subcategories relating to the approach used in understanding. Children seemed to experience no discomfort with their vision, noticed and expressed difficulties in their vision and differences in visual perception between each eye, and learned to cope with their difficulties. They were aware of differences in visual perception and in the physical appearances of self and others, while questioning their own eyes and envying those with normal ones. Mothers observed their children’s behavior and repeatedly explained the need for attention to the invisible. They also provided behavioral precautions to avoid accidents. While fostering their children’s awareness of things they could do without feeling their visual impairment as a weakness, the mothers encouraged their children to protect the remaining eyeball and their vision. Along with assessment-based advice on early childhood visual cognitive development, this study indicates a need to initiate developmental support of visual impairments, in collaboration with specialists in the field.

Infantile B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is generally associated with a poor prognosis, especially in the presence of KMT2A rearrangement or in early onset cases, with patients younger than 6 months at diagnosis. However, KMT2A-wildtype ALL is associated with better prognoses. In 2021, a worldwide study including Japan found nuclear protein in the testis member 1 (NUTM1) fusion gene-positive cases among KMT2A-wildtype infantile ALL, for which the 4-year overall survival rate was 100%.

We encountered a case of infantile BCP-ALL with NUTM1 fusion gene, diagnosed at 4 months. The patient was referred to our hospital for hepatosplenomegaly. She was diagnosed as having BCP-ALL. The initial bone marrow examination was negative for KMT2A gene rearrangement. Chromosome analysis revealed t(14;15)(q24;q15), which led to detection of the NUTM1 fusion gene. The presence of the NUTM1 fusion gene might be clinically important for infantile BCP-ALL with chromosome 15q abnormality.

Corticosteroid is a vital drug in the management of acute lymphoblastic leukemia (ALL). Repeated lumbar punctures (LPs) are required for intrathecal injections in patients with ALL. Spinal epidural lipomatosis (SEL), an overgrowth of adipose tissue in the extradural space, is a rare complication of intensified corticosteroid treatment for pediatric ALL. Among patients with SEL, difficulty in performing LP is identified as one of clinical manifestiations. We describe the case of a five-year-old boy who immediately developed SEL in the re-remission induction phase. Spinal cord magnetic resonance imaging was performed due to the unsuccessful LP for his thirteenth intrathecal administration. Although no neurological symptoms were observed, he met the diagnostic criteria for SEL. Follow-up imaging performed one month later revealed resolution of the epidural fat deposition, with sufficient space in the spinal cavity, enabling a successful intrathecal injection. This case highlights that SEL should be considered in cases of difficult LP as a possible complication of ALL treatment.

Ovarian mature teratomas are prevalent benign tumors in childhood, often necessitating tumor enucleation to preserve fertility in cases of recurrence or metachronous growth. This study presents the case of a 2-year-and-2-month-old girl who was referred due to an abdominal tumor discovered during a fever examination. Tumor markers were negative, and CT scans revealed an 8 cm calcifying cystic tumor, indicating ovarian mature teratoma. A left ovarian tumor enucleation was performed and pathologically confirmed. At the age of 9 years and 1 month, a contralateral tumor was enucleated from the right ovary, recurring at 10 years and 10 months. While menarche occurred at 12 years and 1 month, another left ovarian tumor recurrence appeared at 12 years and 5 months. The disease progressed to amenorrhea at 13 years and 9 months, leading to premature ovarian failure by 14 years and 6 months. This study emphasizes the significance of fertility preservation in cases of bilateral ovarian teratomas.

Introduction: Since April 2016, pediatric cancer proton therapy is been covered by public insurance. This development has not only facilitated the elimination of disparities but also improved collaboration between pediatric cancer treatment facilities and proton beam facilities. Methods: Ten patients were linked to proton beam facilities following initial treatment at our hospital between April 2019 and May 2021. We analyzed the collaborative methods employed within the proton therapy facility, the need for adjustments to the treatment schedule, and the occurrence of adverse events. Results: Ten patients diagnosed with medulloblastoma, ependymoma, Ewing sarcoma, pineal tumor, and Hodgkin lymphoma underwent proton therapy within an acceptable schedule delay. Conclusion: The implementation of borderless, sequential cooperation covering all of Japan holds the potential to provide equal opportunities for the multidisciplinary treatment of pediatric cancers using proton beam therapy.