Historically, patients with T-cell acute lymphoblastic leukemia (ALL) had poorer outcomes than those with B-cell ALL. However, with intensive chemotherapy regimens, outcomes for both groups have become similar. From 2002 to 2008, the Japan Association of Childhood Leukemia Study (JACLS) conducted the prospective ALL-02 study, using a unique protocol for T-ALL (T-02). All T-ALL patients received the same induction therapy, and those who had < 25

BackgroundAcute lymphoblastic leukemia (ALL)-based therapeutic regimens have markedly improved the survival of children with ALL and lymphoblastic lymphoma (LBL). However, survivors are at risk of secondary neoplasms. Few studies on such secondary neoplasms have been conducted outside of Europe and the United States. The aim of this study was to evaluate the incidence of, risk factors for, and outcomes of secondary neoplasms in long-term survivors of ALL and LBL at a tertiary pediatric oncology center in Mie prefecture, Japan.ProcedureWe retrospectively reviewed 188 patients with ALL and LBL who were treated with an ALL-based therapeutic regimen at Mie University Hospital from January 1, 1977 to December 31, 2022 and followed up.ResultsTen patients developed secondary neoplasms, with 10-year and 20-year cumulative incidences of 2.9% [standard error (SE) = 1.5%] and 5.5% (SE = 2.3%), respectively. The median interval between the primary-cancer diagnosis and secondary-neoplasm diagnosis was 18.5 years (range: 7.8–41.7 years). All 10 secondary neoplasms were central nervous system (CNS) tumors (6 meningiomas and 4 high-grade gliomas). Radiotherapy (p = 0.007) and CNS involvement in the primary cancer (p < 0.001) increased the risk of secondary neoplasms among long-term survivors. Gliomas occurred significantly earlier than meningiomas (p = 0.047), and three patients died of secondary neoplasms (all gliomas).ConclusionsAs secondary gliomas occurred earlier than meningiomas and are associated with poor outcomes, physicians should take great pains to minimize their risk to improve long-term survival and quality of life.

In this second paper of a Series on childhood cancer in Asia, we provide an overview on the Paediatric Oncology Clinical Trials in Asia. Asia with a population of 4.7 billion constitutes about 60% of the world's population. The continent accounts for about half of the global paediatric cancer burden. Many Asian countries have consequently formed national professional societies in childhood cancer. Multicentre clinical trials are pivotal in advancing survival outcomes in paediatric oncology. The continent's diverse socioeconomic conditions may account for significant disparities in the development of such trials. However some countries with good financial resources are relatively deficient in developing clinical trials. In general, the countries show three distinct levels of clinical trials development: established, emerging and nascent. This article reports the landscape of multicentre clinical trials in Asia and the hurdles that clinicians face to actively engage in quality research and clinical trials. Although a ‘one-size-fits-all’ approach is not feasible, the successful development of clinical trials systems in some countries can offer valuable lessons and insights for others.This is the second in a Series of three papers on childhood cancer in Asia (Paper 3 appears in The Lancet Child and Adolescence Health).

According to the 2022 estimates of the Global Cancer Observatory, 280,000 children (aged 0-19 years) are diagnosed with cancer worldwide, with more than 105,000 dying from it. Asia, with its population of 1.4 billion children, accounts for about half of these figures. In 2018, the World Health Organization launched the Global Initiative for Childhood Cancer (WHO GICC) with the goal of achieving at least 60% survival for children with cancer globally by 2030. In Asia, the 5-year net survival based on microsimulation model was estimated to be 39.6%, which was lower than the estimates reported for Europe (74.3%) and North America (83.0%). Incidence and survival data are essential to understanding the burden of childhood cancer, however, less than 5% of the childhood population is covered by population-based cancer registries providing comparable data on incidence in Asia. In this first paper of a Series on childhood cancer in Asia, we provide an overview of the available information on the childhood cancer incidence, mortality, survival and prevalence of survivors in Central, Southern, Eastern and Southeastern Asia. We highlight lack of comparable data, the challenges associated with data collection and propose strategies to improve childhood cancer data in Asia. This is the first in a Series of three papers on childhood cancer in Asia (Paper 2 appears also in eClinicalMedicine and paper 3 appears in The Lancet Child and Adolescence Health).

ABSTRACT Enteric viruses are significantly associated with acute gastroenteritis globally. Despite a decrease in severe rotavirus associated diarrhoea, Ghana still records high diarrhoea burden. Meanwhile aetiological investigations in hospital settings do not routinely include viral testing. Rotavirus vaccination is thought to alter enteric viral populations and impact evolution. To better understand virus‐specific effects in acute gastroenteritis in both children and adults, we tested fecal samples from 228 patients at two hospitals in Accra from January to December 2019, using multiplex and singleplex PCR assays. The clinical impact of detected viruses was assessed using a modified Vesikari score system. Partial viral genome sequences were obtained by Sanger Sequencing and their genetic diversity and evolutionary history, traced by phylogenetic analyses. At least one enteric virus was found in 86 (37.7%) patient samples, with 36.9% of the population under five infected. Single infections of rotavirus, norovirus, adenovirus, sapovirus and astrovirus were 33, 14, 8, 6, and 1, respectively, while coinfections were 24. Rotavirus accounted for 33.3% of 24 clinically severe cases (modified Vesikari score > 7). Three out of 10 rotavirus cases with evidence of vaccination experienced severe gastroenteritis. Diverse genotypes, including RVA G2P[4], G1P[8], G12P[8] and G12P[6]; AdV F40 and F41; NoV GII.4 Sydney 2012, GII.6 and GI.3, several of which clustered with contemporary strains from the Americas, Europe and Asia, were detected. This study also provides the first report of SaV GI.1, GI.7 and GII.8 detection in humans in Ghana. RVA G2P[4] and AdV F were associated with higher proportions of hospitalizations. While RVA continues to have a profound clinical impact on gastroenteritis, AdV and SaV produce an equally severe disease. In contrast, NoV and AstV showed a generally mild to moderate impact on clinical disease severity.

Survival after childhood cancer has markedly improved over the past decades in Asia, leading to a growing number of survivors in the region. However, long-term care for these individuals remains a substantial challenge in Asia due to the insufficient availability of comprehensive childhood cancer survivorship programmes in the region. Many countries and regions of Asia are only beginning to acknowledge the significance of post-treatment care. In this third paper in a Series on childhood cancer control in Asia, we provide an overview of the challenges, disparities, and enablers in the provision of long-term follow-up care in Asia. These challenges include deficiencies in comprehensive care models that incorporate multidisciplinary approaches and insufficient support for school and social reintegration for childhood cancer survivors. To address these gaps, collaborative initiatives, such as twinning programmes and regional partnerships, can strengthen capacity and improve care delivery for low-income and lower-middle-income countries. Specific to some Asian cultures, the use of traditional complementary medicine underscores the need for further research to evaluate its efficacy in survivors. Leveraging existing networks and fostering regional collaboration will be pivotal in advancing equitable and sustainable survivorship care across the region.

In Asia, a few countries have a long and established history of collaborative clinical trials successfully formed national children's cancer study groups, but many still do not have such groups. The process of forming national children's cancer groups is fraught with many hurdles, which varies among the countries. One of the basic requirements for running clinical trials is an affordable health care system in which most of the children with cancer can receive the proposed treatment. The health insurance coverage for children with cancer varies from <20% to as high as 100% among Asian countries, and the operation of clinical trials must also be adjusted accordingly. Shortage of research personnel is common, including medical, nursing, research coordinators, and data managers. The establishment of the Asian Pediatric Hematology and Oncology Group aims to provide a good platform for promotion of international clinical trials in the Asian countries.

Hematopoietic stem cell transplantation (HSCT) is only indicated for acute lymphoblastic leukemia (ALL) patients for whom other treatments are unlikely to be curative. However, outcomes of patients not in complete remission (CR) at HSCT remain very poor. To improve the outcomes of patients receiving HSCT, it is important to obtain detailed clinical information about patients with ALL receiving HSCT in CR and not in CR. Patients enrolled in the Japan Association of Childhood Leukemia Study ALL-02 who underwent HSCT and were not in CR (non-CR patients, n = 55) were examined. The 1-year overall survival (OS) rate of non-CR patients was 27.3%. Compared with CR patients, non-CR patients experienced very early and early relapse significantly more frequently and had poorer prognostic factors. Most interestingly, high hyperdiploid (HHD) patients showed an excellent 1-year OS of 80%. In addition, long-term survival among surviving HHD patients was longer than 5 years. All eight patients who survived after undergoing HSCT while not in CR were younger than 10 years at initial diagnosis and were negative for central nervous system involvement. While limited, these results suggest that a subset of patients may benefit from HSCT while not in CR.

Background Childhood cancer survivors lacking awareness on their potential risks of late effects often fail to seek adequate follow-up care. Patient education matching their preference is of great importance to improve their adherence to survivorship care. In this study, we developed two age-dependent game-based learning programs, which enable continuous approaches for childhood cancer survivors along their intellectual maturation. Then, we assessed the effectiveness of the programs. Methods Childhood cancer survivors over 10 years of age who regularly visited a long-term follow-up clinic were enrolled in this study. They were requested to play either of two different types of game tools, one for school children and another for adolescents and young adults, for one month at home. To evaluate the educational effects of the programs, they were examined for health management awareness, self-esteem, and knowledge on cancer-related late effects before and after the intervention with age-based questionnaires and knowledge tests. Results Among 83 participants, 49 (59.0%) completed the assessments over the period of 12 months. The health management awareness and knowledge levels increased significantly at 1-month after the intervention as compared to the baseline in both school children and adolescents/young adults (for health management awareness, p = 0.011 in elementary school children; p = 0.007 in junior high school children; p < 0.001 in adolescents/young adults; for knowledge levels, p < 0.001 in school children; p < 0.001 in adolescents/young adults). The effect was maintained for 12 months in school children while it decreased in adolescents and young adults with time. Self-esteem significantly increased at 1-month ( p = 0.002 in school children; p = 0.020 in adolescents/young adults) and was maintained for 12 months in both age groups. Conclusion The game-based learning programs enhanced health locus of control and self-esteem in childhood cancer survivors. The game-based learning programs could be applied effectively to survivorship care as a new modality of patient education. Trial registration This study was retrospectively registered in UMIN-CTR ( UMIN000043603 ) on March 12, 2021.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. As overall cure rates of childhood ALL have improved, reduction of overall treatment intensity while still ensuring excellent outcomes is imperative for low-risk patients. We report the outcomes of patients treated following the standard-risk protocol from the prospective Japan Association of Childhood Leukemia Study (JACLS) ALL-02 study, which was conducted between 2002 and 2008 for patients with newly diagnosed ALL aged 1–18 years. Of 1138 patients with B-cell precursor ALL, 388 (34.1%) were allocated to this protocol. Excellent outcomes were achieved despite the overall treatment intensity being lower than that of most contemporary protocols: 4 years event-free survival (EFS) was 92.3% and 4 years overall survival 98.2%. Patients with high hyperdiploidy (HHD) involving triple trisomy (trisomy of chromosomes 4, 10, and 17) or ETV6-RUNX1 had even better outcomes (4 years EFS 97.6% and 100%, respectively). Unique characteristics of this protocol include a selection of low-risk patients with a low initial WBC count and good early treatment response and reduction of cumulative doses of chemotherapeutic agents while maintaining dose density. In Japan, we are currently investigating the feasibility of this protocol while incorporating minimal residual disease into the patient stratification strategy.

In Japan, clinical genetic services became available in the 1970s, and genomic medicine, including genetic counseling (GC), developed rapidly. However, research on the outcomes of GC in Japan is limited. Japan has a unique cultural context, and appropriate GC methods have not yet been optimized for this population. The current study aimed to evaluate the psychological status of Japanese patients and their companions undergoing GC and the outcomes of GC. We used the Quality of Care Through the Patients' Eyes-gene cancer (QUOTE-gene(CA)), the Genetic Counseling Outcome Scale-24 (GCOS-24), and the State-Trait Anxiety Inventory (STAI) to evaluate patients and their companions' needs and preferences regarding GC, empowerment, and anxiety, respectively. We evaluated stress status during GC by measuring saliva cortisol levels. QUOTE-gene(CA) results for patients (n = 69) and a group of patients and their companions (n = 96) revealed that participants felt that it was important that skilled medical staff explained medical information and provided advice in an easily understandable manner. Japanese patients and their companions regarded the procedural aspects of counseling as most important and their autonomy in decision-making as less important. GCOS-24 results revealed a significant increase in empowerment scores in 38 patients (by 9.63 points) from pre- to post-GC (p < 0.001; Cohen's d = 0.79). STAI results revealed a significant decrease in state anxiety for patients (6.11 points; p < 0.001; Cohen's d = 0.66). Cortisol levels in patients significantly decreased after GC (p = 0.001). The improvement of empowerment scores from pre- to post-GC among patients and their companions were significantly negatively correlated with pre-GC empowerment scores (p < 0.001), trait anxiety scores (p = 0.001), and the number of people living together (p = 0.011). The change of cortisol levels during GC in patients and their companions was significantly positively correlated with trait anxiety score (p = 0.027). This study suggested that these characteristics of Japanese patients and their companions may predict GC outcomes.

Among western African countries, the Republic of Ghana has maintained an economic growth rate of 5% since the 1980s and is now categorized as a middle-income country. However, as with other developing countries, Ghana still has challenges in the effective implementation of surveillance for infectious diseases. Facing public health emergencies of international concern (PHEIC), it is crucial to establish a reliable sample transportation system to the referral laboratory. Previously, surveillance capacity in Ghana was limited based on Integrated Disease Surveillance and Response, and therefore the "Surveillance and Laboratory Support for Emerging Pathogens of Public Health Importance in Ghana (SLEP)" was introduced to strengthen diarrhea surveillance. The SLEP project started with a sentinel diarrhea survey supported by SATREPS/JICA in collaboration with National Public Health Reference Laboratory (NHPRL) and Noguchi Memorial Institute of Medicine (NMIMR). The base-line survey revealed the limited capacity to detect diarrhea pathogens and to transfer samples from health centers to NHPRL. The involvement of private clinic/hospital facilities into the surveillance network is also crucial to strengthen surveillance in Ghana. The strong and interactive relationship between the two top referral laboratories, NHPRL under the Ministry of Health NMIMR and under the Ministry of Education, enables Ghana Health Services and is critical for the rapid response against PHEIC. In future, we hope that the outcome of the SLEP surveillance project could contribute to building a surveillance network with more timely investigation and transfer of samples to referral labs.

Objectives: This study aimed to assess the perception of PBL among Japanese medical students.Methods: Learning effects and challenges of PBL from the students' viewpoint were assessed with an exploratory se-quential mixed method. Focus group discussions followed by thematic analysis were conducted with 27 students and resi-dents. Then a questionnaire survey was carried out. A total of 119 out of 258 students (46.1%) responded. The results from 24 questions were analyzed with a residual analysis.Results: Thematic analysis extracted 14 themes from four discussion topics. The participants in focus group discussion regarded the PBL program as a better learning method than lectures. But some key phrases on the challenge of social in-teraction, including reluctance to actively discuss and collab-orate with unfamiliar peers, were found. The questionnaire survey revealed a significantly lower adjusted standardized residual (ASR) for the positive response in five of six ques-tions in the category of social interaction; improvement of communication skills (ASR =-3.303, n = 118, p < .001), en-hancement of responsibility at group discussions (ASR =-2.078, n = 119, p = .038), building social networking (ASR =-3.006, n = 119, p = .003), becoming to sympathize with patients (ASR =-2.449, n = 119, p = .014) and under-standing social aspects of clinical practice (ASR =-5.790, n = 119, p < .001). Conclusion: The Japanese medical students perceived PBL as an effective learning strategy. However, they had a prob-lem with social interactions.

Background Social awareness of cancer can be changed with cancer education and proper distribution of cancer information. This study addressed the current situation and historical changes to children's perception of cancer. Methods Questionnaire surveys were conducted among healthy school children aged 10-15 years in 2008 and 2018. Knowledge of cancer was surveyed and compared with that of asthma, tuberculosis, and measles. The children were asked about their health information resources. Results The numbers of participants and collection rates were 438 and 63.9% in 2008, and 320 and 44.7% in 2018. Children's perception of cancer changed significantly in the last decade. The proportion of respondents answering "cancer affects children" changed from 78.3 to 89.5% (P = 0.0001), "cancer is preventable" from 42.0 to 49.7% (P = 0.0425), and "cancer is curable," from 52.4 to 66.0% (P = 0.0003). Significantly more junior high school students answered that cancer is preventable than elementary school children in 2018 (55.9 vs 42.7%, P = 0.0028). The major resources of information on health were television, parents, and books. The proportion of children choosing the Internet significantly increased from 15.3 to 47.8% (P < 0.0001). Significantly more junior high school students selected television and the Internet than elementary school children (94.5 vs 86.9%, P = 0.0202 for television; 57.1 vs 37.9%, P = 0.0007 for the Internet). Conclusions The proportion of children correctly perceiving cancer information had increased in the last decade. Junior high school students better understood the information. The Internet is of increasing importance as an information resource for school children.

Acute gastroenteritis associated with diarrhea is considered a serious disease in Africa and South Asia. In this study, we examined the trends in the causative pathogens of diarrhea and the corresponding gut microbiota in Ghana using microbiome analysis performed on diarrheic stools via 16S rRNA sequencing. In total, 80 patients with diarrhea and 34 healthy adults as controls, from 2017 to 2018, were enrolled in the study. Among the patients with diarrhea, 39 were norovirus-positive and 18 were rotavirus-positive. The analysis of species richness (Chao1) was lower in patients with diarrhea than that in controls. Beta-diversity analysis revealed significant differences between the two groups. Several diarrhea-related pathogens (e.g., Escherichia-Shigella, Klebsiella and Campylobacter) were detected in patients with diarrhea. Furthermore, co-infection with these pathogens and enteroviruses (e.g., norovirus and rotavirus) was observed in several cases. Levels of both Erysipelotrichaceae and Staphylococcaceae family markedly differed between norovirus-positive and -negative diarrheic stools, and the 10 predicted metabolic pathways, including the carbohydrate metabolism pathway, showed significant differences between rotavirus-positive patients with diarrhea and controls. This comparative study of diarrheal pathogens in Ghana revealed specific trends in the gut microbiota signature associated with diarrhea and that pathogen-dependent dysbiosis occurred in viral gastroenteritis.

Approximately 90% of pediatric acute lymphoblastic leukemia (ALL) cases are curable with intensified chemotherapy, but very high-risk patients may require hematopoietic stem cell transplantation (HSCT). A suitable indication for HSCT in the first complete remission (CR1) should be defined to protect patients from long-term complications. We report the outcomes of HSCT in CR1 from the Japan Association of Childhood Leukemia Study (JACLS) ALL-02 study and reassess indications for HSCT. Of 1114 patients, 71 (6.4%) received HSCT in CR1. Indications included high-risk cytogenetic abnormalities and non-CR on day 33. Patients with B-cell precursor (BCP) ALL and a prednisolone poor response (PPR) received HSCT when leukocyte antigen-matched siblings were available. The 4-year overall survival (OS) of transplanted patients was 78.8% (confidence interval 67.3–86.6). Multivariate analysis revealed that cord blood transplantation was associated with poor OS. For BCP-ALL patients with PPR who achieved CR1 after induction therapy, HSCT in CR1 showed excellent outcomes (4-year OS 90.9%) but demonstrated no survival advantage as the outcome with chemotherapy was also excellent (4-year OS 97.0%). This study suggests that in BCP-ALL patients PPR is not an indication for HSCT in CR1. Precise evaluation of treatment responses would increase sophistication of indications for HSCT in CR1.

PURPOSE:ImmunoCAP® (ImmunoCAP) and IMMULITE® 2000 3gAllergy™ (3gAllergy) systems are major quantitative allergen-specific immunoglobulin E (sIgE) assay methods. Due to the heterogeneous nature of allergenic extracts and differences in the assay format, quantitation of allergen-sIgEs is not expected to correlate well between different methods. However, we have recently reported good agreement between the methods in the diagnosis of egg allergy. This study aimed to determine and correlate the predictive values of sIgE by the two systems in the diagnosis of milk and wheat allergies.METHODS:Children who had undergone oral food challenge (OFC) for the diagnosis of milk and wheat allergies were enrolled. The OFCs were performed to diagnose either true allergy in the 1-year-old group (A) or tolerance in the 2- to 6-year-old group (B). Milk, casein and β-lactoglobulin, and wheat and ω-5 gliadin sIgE values were measured using the 2 systems. The predictive accuracy of each sIgE for the OFC outcome was assessed using receiver operating characteristic (ROC) curves. The probability of a positive OFC outcome was estimated by logistic regression analysis.RESULTS:A total of 395 patients were recruited from 7 primary care clinics and 19 hospitals in Japan. Milk and wheat OFCs were performed for 87 and 102 group A patients, and 124 and 82 group B patients, respectively. ROC analysis yielded similar areas under the curve for the 2 assays (0.7-0.9). The log-transformed sIgE data showed a strong linear correlation with the estimated probabilities (R > 0.9).CONCLUSIONS:The 2 systems may be interchangeable for diagnosis of milk and wheat allergies in young children.

We conducted this study to reveal the historical changes of parents' perception of diagnosis disclosure of childhood cancer to children. Parents having school children were recruited for questionnaire surveys conducted in 1998, 2008 and 2018. They were questioned about their perception of cancer, cancer diagnosis disclosure to children and advantages and disadvantages of the diagnosis disclosure. The historical changes were analyzed by comparing the responses at each survey with a Chi-square test and a residual analysis. Parents perceiving “cancer is incurable” decreased from 40.0% (an adjusted standardized residual [ASR] = 12.002 P < 0.01) in 1998 to 10.4% (ASR = -6.334, P < 0.01) in 2018. Parents agreeing to disclose cancer diagnosis increased from 34.5% (ASR = −3.549, P < 0.01) in 1998 to 53.7% (ASR = 5.546, P < 0.01) in 2018. In 2018, more parents chose “avoiding secrets” (57.7%, ASR = 2.430, P < 0.05) and “respecting children's rights” (54.6%, ASR = 5.966, P < 0.01) for the advantages. Many parents manifested concerns on anxiety and mental shock of children irrespective of the survey year. Parents changed their perception of diagnosis disclosure of childhood cancer to children in the last 20 years.