Acute lymphoblastic leukemia (ALL) is the most common form of pediatric leukemia in Japan and presents significant treatment challenges owing to variable patient sensitivity to the key therapeutic agent, 6-mercaptopurine. This variability is often linked to genetic differences, particularly variants of NUDT15, which can lead to severe myelosuppression and an increased risk of second malignancies. Current methods for assessing NUDT15 variants must be improved for precise dosage adjustments. However, there is no reliable analytical method to determine the diplotype of NUDT15. Therefore, we aimed to develop a practical diplotyping method using digital PCR to enhance clinical outcomes and reduce complications. We performed a retrospective observational analysis of 38 pediatric ALL cases, employing digital PCR for NUDT15 genotyping and diplotyping. Nine patients had single NUDT15 variants, and two had multiple variants. We utilized digital PCR with four variant-specific probes and successfully detected compound heterozygosity in one patient who had multiple variants with variants in both exons 1 and 3. Collectively, our method enables detailed diplotype analysis and establishes digital PCR as a valuable tool for assessing NUDT15 variants. This approach has potential for tailoring treatment strategies for pediatric ALL and could substantially reduce treatment-related toxicity and enhance patient management outcomes.

We conducted a cross-sectional study using a questionnaire to explore the late effects in survivors of juvenile myelomonocytic leukemia (JMML). The attending pediatric hematologist oncologists completed the questionnaires. All survivors (N=30) had undergone allogeneic hematopoietic stem cell transplantation. Approximately 83% survivors showed more than one late effect. The identified late effects included endocrine, dental, skin, ophthalmologic, musculoskeletal, pulmonary, neurocognitive, and cardiovascular dysfunction. The prevalence of short stature and cardiovascular and kidney dysfunction was significantly elevated among survivors aged ≥18 years. Therefore, a multidisciplinary follow-up system for survivors of JMML is crucial.

We evaluated the peptide-specific immunoglobulin G (IgG) response and the safety of the personalized peptide vaccine in four children with refractory solid cancer. Although the pre-vaccination IgG responses were suppressed compared to those observed in children with upper respiratory tract infection, IgG levels against the vaccinated peptides after 12 times vaccination increased in all the three cases tested. Vaccination-related adverse effects were grade 1 injection-site local skin lesions. One patient had maintained remission for 37 months. The remaining three patients exhibited progressive disease. These results indicate the next steps in phase II studies considering their immune boosting effect and safety.