Objective: This study aimed to establish a comprehensive evaluation system for health quality and education during long-term follow-up of childhood cancer survivors (CCS).

Participants: The participants were 1) aged ≥ 18 years upon obtaining consent, 2) aged ≥ 10 years after childhood cancer diagnosis and not receiving treatment for the current disease for ≥ 5 years, and 3) have a treatment summary.

Methods: Participants completed a pre-assessment questionnaire and underwent a half-day evaluations at the Preventive Medicine Center, at the hospital, and by a clinical psychologist. On the following day, the participants received a report and health education. Late effects were assessed using modified CTCAE v4.0.

Results: We compared the late effects of 58 participants (active screening group: A) who participated in the St. Luke’s AYA cohort study between February 2016 and September 2019 with those of 110 participants (regular follow-up group: R) who underwent health checkups and examinations at the discretion of their attending physician between December 2010 and December 2015.

The detection rate of grade ≥ 1 late complications was 93.1% in group A and 67.3% in group R. The detection frequency of organ-­specific late complications was significantly higher in group A for respiratory function and ophthalmologic, dental, and cognitive function abnormalities (p<0.001). Notably, psychiatric complications were detected regardless of treatment intensity.

Conclusion: Late complications, such as pulmonary function, ophthalmologic, dental, cognitive function, and psychiatric abnormalities, are easily overlooked.

Since its approval in Japan more than five years ago, the Japan CAR-T Consortium has developed a database to evaluate real-world outcomes in children and young adults with relapsed or refractory B-ALL treated with tisagenlecleucel. This retrospective registry study, initiated after May 22, 2019, analyzed data from 11 Japanese centers encompassing 42 patients who had received tisagenlecleucel by February 1, 2022.

The analysis revealed that the best overall response rate was 93%. At one year post-infusion, the event-free survival (EFS) and overall survival rates were 56% and 82%, respectively. Notably, 27 (64%) patients had low disease burden (LB), defined as <5% bone marrow (BM) lymphoblasts, upon infusion. LB was associated with significantly better outcomes, with a one-year EFS rate of 80%, compared to 24% in patients with a high disease burden (≥5% BM lymphoblasts) (p<0.0001).

Multivariate analysis indicated that previous hematopoietic stem cell transplantation (HSCT) (n=23, 55%) was linked to improved outcomes, with a hazard ratio of 0.084 (95% CI; 0.02–0.3, p<0.001). Patients who underwent HSCT achieved a one-year EFS rate of 75% compared with 24% in those without previous HSCT.

Extended follow-up and more detailed analyses of patient samples may provide deeper insights into the biology of CAR-T cell therapy and inform strategies for improving outcomes in this patient population.

The Platelet Committee of the Japanese Society of Pediatric Hematology/Oncology published the Guidelines for Childhood Immune Thrombocytopenia in 2022. Besides changes in the name and stage of a disease, a modified Buchanan Bleeding Severity Classification system was introduced to assess bleeding symptoms. Based on a multidimensional assessment of platelet count, bleeding symptoms, activity level, lifestyle, and access to healthcare, the guidelines propose therapeutic interventions aimed at improving patients’ health-­related quality of life. Presently, a more individualized approach is required. Aside from differential diagnosis recommendations, a system that facilitates collaboration with hematologists to determine treatment options is needed.

In Japan, the TPO receptor agonist rituximab, positioned as second-line therapy, has not yet received a dosage regimen for pediatric ITP, and each institution was forced to consider its introduction in accordance with its ethical guidelines. However, with the support of these guidelines, these drugs were approved for pediatric use in April of the same year. None of the treatments after third-line therapy are indicated for children, and new drugs that are safer and more effective should be developed. Target molecules for new drugs include spleen tyrosine kinase, Bruton’s tyrosine kinase inhibitors, and fetal Fc receptor inhibitors. We look forward to future developments in the treatment of pediatric ITP.

We will continue to disseminate these guidelines, examine the changes in clinical practice choices, and reflect on these changes in the following revision of the guidelines.

Vascular anomalies (hemangiomas and malformations) are characterized by abnormal blood or lymphatic vessels in the skin or soft ­tissues. In pediatric hematology/oncology, we encounter challenging cases, such as the Kasabach–Merritt phenomenon, lymphatic diseases, venous malformations, and Klippel–Trenaunay syndrome. Treatment varies depending on the lesion size and symptoms, ranging from observation to surgical resection or sclerotherapy. A standard therapy for intractable cases with large, unresectable lesions remains unavailable. Recent studies have identified genetic abnormalities in the PI3K/AKT/mTOR and RAS/MAPK/MEK pathways as key ­contributors to these conditions, and advancements have been made in novel therapies. In January 2024, sirolimus, an mTOR inhibitor, was approved for use in Japan. It has shown efficacy in reducing lesion size and alleviating symptoms, such as bleeding and pain; ­however, uncertainties remain regarding its mechanisms, usage, and indications. This review outlines the refractory vascular anomalies and discusses the therapeutic applications of sirolimus.

With the remarkable progress in the treatment of hemophilia in recent years, preventing bleeding and improving the quality of life (QOL) of patients and their families have become important indicators of treatment efficacy. Emicizumab, an antibody preparation, has distinct characteristics from coagulation factor VIII concentrates, such as a subcutaneous route of injection and a long half-life, which are expected to improve QOL. International clinical trials including the HAVEN trials; clinical trials in Japanese patients, such as the phase 1/2 trial of emicizumab and HOHOEMI study; and other surveys have reported that emicizumab improved QOL in children and adult patients regardless of the presence or absence of inhibitors. Furthermore, the Emicizumab Preference Survey showed that the treatment was highly preferred by both pediatric and adult patients, which was related to the aforementioned characteristics of emicizumab. Experiences at Miyagi Children’s Hospital have shown that emicizumab may contribute to the improvement of the QOL of children with ­hemophilia A and their families. In the future, widespread use of emicizumab is anticipated, and advances in new drugs will further improve the QOL of children with hemophilia and their families.

Total body irradiation (TBI) is important in identifying residual tumor cells and reducing the risk of graft failure during allogeneic hematopoietic cell transplantation in pediatric patients with various hematological malignancies and non-malignant diseases (NMDs). Contrastingly, based on the effects of TBI-related adverse effects on long-term quality of life, non-irradiation conditioning or reduced-­intensity conditioning (RIC) has been developed, especially in pediatric patients.

High-dose TBI-based myeloablative conditioning (MAC) remains the major conditioning regimen for pediatric hematological malignancies to elucidate residual tumor cells. Conversely, low-dose irradiation-based RIC has been the mainstay conditioning regimen for various NMDs to reduce the risk of TBI-related adverse effects without increasing the frequency of graft failure. TBI-related adverse effects are serious problems, particularly for infants and patients with diseases showing high radiosensitivity. Therefore, there are high expectations for the development of novel radiation technology considering these pediatric features.

A widespread clinical implementation of cancer genome analysis and the development of new anticancer agents, such as molecular-targeted therapy and immune checkpoint inhibitors, promise substantial benefits for patients with cancer. However, most of these drugs are not approved for pediatric patients in Japan, and systems enabling ready access to pediatric patients have not been well established; therefore, patients’ chances of receiving these therapies are limited. In contrast, these drugs can be used on a compassionate basis in Canada, allowing for high accessibility to innovative therapies and actual clinical benefits for pediatric patients. This paper introduces drug access in clinical practice of pediatric oncology in Canada.

Post-hematopoietic stem cell transplantation (HSCT) vaccination is recommended. However, the current status of posttransplant vaccination in Japanese children remains unclear.

The HSCT Committee of the Japanese Society of Pediatric Hematology/Oncology conducted a nationwide multicenter questionnaire survey on posttransplant vaccination. Of the 85 centers that requested participation in the surveillance, 57 responded to the questionnaire. All centers were aware of the Japanese Society for Transplantation and Cellular Therapy guidelines, and 49 centers (88%) implemented posttransplant vaccination policies. The criteria for initiating inactivated and live vaccines included improving chronic graft-versus-host disease (34/49 and 39/49 centers, respectively), completing immunosuppressive therapy (34/49 and 40/49 centers, respectively), and progressing two years post-HSCT (36/49 for live vaccines only). Immunological indicators were used in 27/49 and 37/49 facilities for inactivated and live vaccines, respectively. Based on the number of vaccinations, many centers administer measles-rubella, varicella, and other vaccines according to the guidelines. Contrastingly, the number of unspecified vaccinations in the guidelines, such as the Japanese encephalitis vaccines, remains unknown.

This study revealed that many facilities followed the posttransplant vaccination guidelines. Although there are no specific regulations for these guidelines, many facilities use immunological indicators. With various transplantations, further information is necessary to tailor vaccinations according to an individual’s immune status.

Molecular classification using DNA methylation profiling had a great impact on the diagnosis and classification of central nervous system (CNS) tumors; however, nationwide data remain limited. Methods: We uploaded IDAT files from archived samples from the Illumina Infinium Human MethylationEPIC BeadChip array at our institution to the methylation classifier on the webpage of the German Cancer Center to obtain the molecular classification and copy number plot. Results: Sixty-one samples from 53 patients were collected. Twenty-eight samples (46%) showed calibrated scores of ≥0.9. Among them, one case suggested a diagnostic change (level of usefulness A), four were diagnosed according to the revised WHO classification (level of usefulness B), 18 obtained prognostic information from molecular classification or copy number analysis (level of usefulness C), and five supported a pathological diagnosis (level of usefulness D). Thirteen cases with calibrated scores <0.9 but ≥0.5 presented a level of usefulness of A in one case, B in one case, C in five cases, and D in six cases. Multivariate analysis showed a statistical significance in the diagnosis of medulloblastomas with a higher calibrated score (odds ratio; 12.56, p=0.004). Conclusion: Methylation classifiers can support pathological diagnosis, thereby providing additional valuable information for predicting the prognosis of childhood CNS tumors. In Japan, prospective clinical studies are underway.

An 11-year-old girl with worsening shortness of breath and a pale complexion presented with anemia (hemoglobin; 6.8 g/dL). Abdominal computed tomography revealed a small intestinal mass. The small intestine was resected partially. Intraoperative findings revealed a mass protruding from the intestinal wall, primarily in the jejunal submucosa. Histopathological examination revealed an inflammatory myo­fibroblastic tumor (IMT), which is an intermediately malignant tumor that can occur anywhere in the body. Pathological immunohistochemical staining, especially for ALK positivity, is useful for diagnosis. Complete resection is crucial for successful treatment of IMT, and prognosis after resection is good. As local recurrence and metastasis have been reported, long-term follow-up using imaging is required. Ten months after resection without adjuvant therapy, the patient was well and did not experience any recurrence.

We report a case in which mycophenolate mofetil (MMF) was effective in refractory immune thrombocytopenia (ITP) with bleeding tendency. An 8-year-old girl presented with purpura and epistaxis and was diagnosed with ITP. Screening for secondary ITP revealed no significant findings. For the patient’s family history, her mother has Evans syndrome and a maternal relative has thrombocytopenia. As she did not respond to immunoglobulin, corticosteroids, and steroid pulse therapy, she received thrombopoietin receptor agonists (TPO-RA) and rituximab with the approval of the Ethics Committee in our hospital; however, its effect was temporary. After MMF was introduced, the platelet count became stable and she finished the administration of corticosteroid, TPO-RA, and MMF after five, six, 14 months, respectively, from start of MMF. The combination of MMF for pediatric refractory ITP may be an effective option for stabilized platelet count.

Hyperleukocytosis is a life-threatening complication of acute leukemia and requires early treatment. Exchange transfusion may be an effective treatment for infants and older children who are ineligible for apheresis. A 9-year-old girl was presented to our hospital with headache, vomiting, and progressive somnolence for 10 days. Laboratory examination revealed an extremely high white blood cell count (1,106.0×10³/µL), anemia, and thrombocytopenia. The patient was diagnosed with KMT2A::AFF1-positive B-cell precursor acute lympho­blastic leukemia based on morphological and molecular genetic analyses. The patient experienced multiple intracranial hemorrhages. Hyperinfusion and corticosteroids were administered immediately and exchange transfusion was initiated 6 h after presentation. Hyperleukocytosis was corrected without severe tumor lysis syndrome, and the patient returned after two days. She was treated with multi-agent chemotherapy according to the JPLSG-ALL-B12 protocol and achieved complete remission after induction chemotherapy. The patient’s neurological symptoms resolved without any neurological sequelae.

Studies have yet to report on extranodal NK/T-cell lymphoma (ENKL) after remission of chronic active Epstein–Barr virus (CAEBV) disease and specify its treatment. Here, we report a case of ENKL in the subcutaneous right lower leg during clinical remission of CAEBV that was successfully treated with SMILE therapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT). A 14-year-old boy was diagnosed with CAEBV and underwent allo-HSCT at 10 years of age. Recently, he developed a subcutaneous mass in the right lower leg and skin ulcers, which were biopsied and diagnosed as ENKL. The patient exhibited partial metabolic response after two courses of SMILE therapy. We performed allo-HSCT after an additional SMILE therapy course. The patient is alive and disease-free 19 months post-transplantation, indicating that SMILE therapy is effective for ENKL that develops subcutaneously after CAEBV remission and allo-HSCT may be effective as a consolidation therapy for long-term survival.

A healthy 9-year-old girl complained of pain in the right buttock and lower extremity, which led us to detect an intradural extramedullary tumor in the lumbar spinal canal. The patient underwent tumor resection. The tumor was grossly resected and histologically diagnosed as a mesenchymal chondrosarcoma (MCS). NCOA2 breaks detected by fluorescence in situ hybridization supported this diagnosis. The patient received alternate doses of vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide, and local proton irradiation for a total dose of 50.4 Gy. She was recurrence-free at one year and two months after diagnosis. Intradural extramedullary MCS is extremely rare, with 60% of the previously reported cases occurring in children. Diagnosis is primarily based on histology. However, a disease-specific fusion gene, HEY1::NCOA2, has been identified and is useful for diagnosis. The clinical characteristics of intraspinal MCS may differ from those of common MCS, and further accumulation of cases is required.

Ecthyma gangrenosum (EG) is an uncommon cutaneous infection characterized by an initial painful erythema with vesicles and pustules that progresses to central necrotic ulcers. EG is often associated with Pseudomonas aeruginosa bacteremia in immunocompromised patients. Here, we report two cases of pseudomonal EG that developed during chemotherapy-induced neutropenia in patients with acute lymphoblastic leukemia. Case 1 involved a nine-year-old girl who presented with EG on her right arm after consolidation therapy. She was treated with tazobactam-piperacillin, and the lesion improved within two weeks following neutrophil recovery. Case 2 involved a 12-year-old girl who developed EG in her left thigh during induction therapy. She was treated with cefepime; however, EG progressed to deep ulcers and granulomatous lesions, which required local debridement. Complete healing was not achieved after five months because antileukemic chemotherapy was administered concurrently. Thus, EG should be considered in febrile patients who develop painful erythema, induration, and blistering during chemotherapy-induced neutropenia.

A 4-year-old girl with T-cell acute lymphoblastic leukemia achieved first remission after induction therapy and negative minimal residual disease after early intensification chemotherapy. However, she was identified as carrying a TCF7::SPI1 fusion, predicting a poor prognosis. She underwent unrelated cord blood transplantation with reduced-intensity conditioning during the first complete remission. On day 3 after transplantation, the patient developed a fever and was diagnosed with COVID-19. Chest computed tomography revealed left lower lung pneumonia. The patient was treated with remdesivir for 10 days and recovered without disease progression. Despite engraftment on day 23 after transplantation, the polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 remained positive for 89 days. Although early onset COVID-19 after hematopoietic cell transplantation is associated with a high severity risk, early therapeutic intervention prevented disease progression in this case, in which delayed viral clearance was observed during post-transplant immunosuppression. This was consistent with previous reports.