To improve the treatment outcome and QOL of patients with pediatric hematological malignancy in Japan, the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG; now Japanese Children’s Cancer Group (JCCG)) was established in 2003. Registration and the central laboratory/diagnosis systems under the CHM-14 study have been used for all patients enrolled in clinical trials by JCCG. On the other hand, since 2006, epidemiological research on pediatric hematological diseases were started by the Japanese Society of Pediatric Hematology (now the Japanese Society of Pediatric Hematology/Oncology (JSPHO)) in 2006. Data on the current status of these patients, including their background, diagnosis, and outcome, have been collected under “Epidemiological research on hematological diseases and pediatric cancers developing in patients under 20 years of age” by the academic research committee of JSPHO. Compartmentalization of both studies has been carried out; that is, the collection of the annual number and outcome of the patients has been carried out by JSPHO, and the accurate diagnosis, assessment of the efficacy and safety of clinical studies, and research on sample analysis have been conducted by JCCG. A convenient method for the collection of overlapping data in both studies has been developed. However, the challenge lies in how to effectively reduce the effort involved in data entry. because of the annual accumulation of follow-up cases.

The association between coagulation (C) and fibrinolysis (F) potentials is such that thrombosis occurs when coagulation is predominant, and bleeding occurs when the opposite is true. In other words, a balance between C and F is crucial. Coagulopathy encountered in pediatric oncology includes sinusoidal obstruction syndrome (SOS) and thrombotic microangiopathy (TMA); however, its pathogenesis is not well understood. We developed a novel thrombin–plasmin generation assay (T/P-GA) that can simultaneously measure comprehensive C/F potential because hemostatic balance may offer a window into the pathophysiology of such coagulopathies. In SOS, a simultaneous decrease in thrombin generation and plasmin generation (PG) was found immediately before the onset of the disease, confirming that both C/F potentials were reduced. The same was true for TMA brought on by hematopoietic cell transplantation, and C/F potential improved as the condition improved. PG was increased in patients with metastasis of pediatric solid tumors, indicating a relationship between metastasis and fibrinolysis. When L-asparaginase was administered, PG in acute lymphoblastic leukemia considerably decreased, and in the last stages of induction therapy, a relative procoagulant state was seen. It has also been reported that the level of “total plasminogen activator inhibitor-1”, a fibrinolysis inhibitory factor, is increased in cases of the coagulopathy associated with cytokine release syndrome in chimeric antigen receptor-modified T-cell therapy for adult malignant lymphoma, and pathological analysis utilizing T/P-GA is warranted in novel immunotherapy. Therefore, it is anticipated that the pathological analysis of different coagulation disorders based on the balance of C/F potential will help develop a safe and efficient cancer treatment.

[Background] TCF3::HLF-positive acute lymphoblastic leukemia (ALL) is consistently resistant to conventional chemotherapy, whereas the efficacy of the graft-versus-leukemia (GVL) effect has been suggested. Recently, allogenic hematopoietic cell transplantation (allo-HCT) following blinatumomab has been reported to induce durable remissions in patients with TCF3::HLF-positive ALL. [Case] A 13-year-old female with a chief complaint of subcutaneous hemorrhage was diagnosed with TCF3::HLF-positive ALL. Although hypercalcemia and disseminated intravascular coagulation worsened owing to tumor lysis, remission induction therapy with aggressive supportive care resulted in complete remission, and minimal residual disease (MRD) was less than 10^–4. The patient became MRD-negative after one course of blinatumomab as a consolidation therapy. The transplantation of bone marrow from her HLA 5/8 allele-matched father was performed after conditioning with 12 Gy total body irradiation and etoposide 1.8 g/m². For graft-versus-host disease (GVHD) prophylaxis, post-transplant cyclophosphamide (PTCy) was used. Although she developed bronchiolitis obliterans, for which she is currently under treatment, she has been disease-free for more than two years after allo-HCT. [Discussion] Haploidentical HCT with PTCy did not increase the risk of relapse or GVHD in adults with ALL, suggesting that PTCy was an effective GVHD prophylaxis without attenuation of the GVL effect. Haploidentical HCT with PTCy in deep molecular remission after consolidation therapy with blinatumomab appears to be a promising strategy for TCF3::HLF-positive ALL.

Risk stratification is essential to the assignment of a patient to an appropriate therapy and prevention of excess toxicities, which has significantly contributed to an improvement in outcomes of pediatric acute myeloid leukemia (AML). Application of low-intensity chemotherapy to children with Down-syndrome-associated myeloid leukemia, whose normal and leukemic cells are both vulnerable to cytotoxic agents, is a good example. In children with de novo AML, cytogenetics and minimal/measurable residual disease evaluation are the most commonly used prognostic factors, which have been utilized to determine an indication of allogeneic hematopoietic stem cell transplantation. Additionally, with the recent advances in molecular biology and genetics, the identification of targetable lesions amenable to molecularly targeted therapy is becoming increasingly important. The introduction of all-trans-retinoic acid (ATRA) and/or arsenic trioxide to acute promyelocytic leukemia therapy is one of the advances successfully applied. With the expected near-future introduction of universal gene panel testing for hematological malignancies in Japan, further improvement of AML risk stratification is likely. However, the development of novel agents in Japan especially for children is lagging behind other countries, which should be urgently solved.

Background: Tumor lysis syndrome (TLS) is a potentially fatal complication associated with the treatment of childhood leukemia. A practical guideline by the Japanese Society of Pediatric Hematology/Oncology in 2016 indicates the standard therapy for TLS; it does not recommend urinary alkalization as a premise for the use of rasburicase. However, the current situation regarding supportive care for patients with TLS has not been clarified in Japan. Therefore, we conducted a nationwide survey of the institutions participating in the Japanese Pediatric Leukemia/Lymphoma Study Group.

Method: From February to June 2016, we conducted a web survey of practitioners at 155 facilities using SurveyMonkey^®.

Results: We received valid responses from 99 facilities (64%). Urinary alkalinization was performed at initiation of induction therapy in 54% of the institutions, and it was conducted in 67% of the facilities where five or fewer new hematopoietic tumors were reported per year. Uric acid production inhibitors were administered prophylactically in 75% of the facilities. Rasburicase was used in most institutions to treat TLS with an average continuous duration of 5.4 days. Regarding the re-administration of rasburicase, 45% of the respondents reported no adverse effects; however, data from the period between the initial administration and re-administration were not investigated.

Conclusions: This survey showed that rasburicase was widely used for the prevention and treatment of TLS, but that 54% of the institutions utilized urinary alkalinization. It is important that TLS is appropriately managed in all childhood cancer treatment facilities in the rasburicase era.

Background: Childhood cancer survivors (CCSs) should understand health promotion in relation to the risk of late effects, but few reports are available on their health literacy (HL). Methods: Patients who received treatment for childhood cancer at University of the Tsukuba Hospital from 1976 to 2018 and who were diagnosed more than 5 years ago and aged 16 years or older at the time of the survey were included. The participants completed a self-administered questionnaire received through the post. We investigated the relationships between the participants’ HL and backgrounds and compared the results with those of healthy individuals. Results: Of the 249 individuals who were sent the questionnaires, 54 (21.6%) responded. Although no statistically significant difference was revealed, CCSs had higher HL than the healthy controls. The HL tends to be high in those who were 0–4 years old at the time of diagnosis, vocational school graduates, and students, whereas the HL tends to be low in those who were diagnosed at 15 years of age or older. The difficulty in attaining HL was greater in CCSs than in healthy controls. In CCSs the greater difficulty in attaining HL was observed in determining the need to seek a second opinion and to understand the reliability of the information on health risks obtained from the media. Discussion/Conclusion: Although HL of CCSs may be affected by their life events, parents and others, our results that indicate equal to or better HL in CCSs than in healthy controls suggests that the experiences of childhood cancer do not worsen but can raise health awareness.

Chronic active Epstein–Barr virus (EBV) infection (CAEBV) has an indolent clinical course and a highly variable presentation, with symptoms including fever, lymphadenopathy, and hepatosplenomegaly. The clonality of CAEBV, which frequently involves T and/or natural killer (NK) cells, has been suggested by the monoclonal patterns of the virus. Extranodal NK/T-cell lymphoma, nasal type (ENKL), is an EBV-associated lymphoma and is most common among people in their 40s to 50s, but rare in children. A 12-year-old boy was diagnosed as having ENKL, which was complicated owing to a high number of EBV-DNA copies and EBV titer in the peripheral blood. ENKL resolved with radiochemotherapy, but the number of EBV-DNA copies did not decrease. Thus, ENKL with CAEBV as a background disease was diagnosed and hematopoietic stem-cell transplantation was performed. Complete remission of CAEBV was achieved. Thus, when diagnosing childhood-onset ENKL, CAEBV should always be considered as a possible underlying disease.

Paroxysmal nocturnal hemoglobinuria (PNH) in childhood occasionally develops into aplastic anemia (AA) during the progression of the disease (AA-PNH syndrome). Here, a case of a 12-year-old female AA patient treated with immunosuppressive therapies is presented. She developed PNH but was asymptomatic other than hemolysis for 8 years. Because she experienced thrombosis with severe abdominal symptoms, eculizumab was initiated at 20 years of age. After the treatment, her hemolysis and symptoms of thrombosis were dramatically improved. Subsequent medication switching from eculizumab to ravulizumab led to a prolongation of the period between hospital visits and high quality of life. In childhood-onset AA, it is very important to prevent the development of the pathological condition over a long period of time and to choose treatments suitable for the patient’s life stages.