We have discussed Cancer Genomic Medicine (CGM) to establish a body of providing CGM, establish a body to aggregate and utilize genomic and clinical information, and promote research in accordance with the third phase of the basic plan. We established the Cancer Genomic Medicine Promotion Consortium in 2018, which aimed to set directions for the functions and roles of medical institutions providing CGM and played a role in providing opinions to the Ministry of Health, Labour and Welfare, Japan, about CGM. From June 2019, two genomic panel tests, the OncoGuide^TM Oncopanel System and FoudationOne CDx Cancer Genome Profile, were covered by Japan’s National Health Insurance. The Center for Cancer Genomics and Advanced Therapeutics (C-CAT) was established as a new hub for CGM. Sequencing data and clinical information are collected by C-CAT. The center constructs a Cancer Knowledge DataBase (CKDB) for cancer genomic medicine and promotes research, especially in clinical genomic medicine and immune therapeutics. There are 15 designated hospitals and two central institutes for pediatric patients in Japan. The central institutes play a core role in window service, providing support for diagnosis of pediatric cancer and human resources, and so on. Several of the designated hospitals can provide genomic panel tests for pediatric patients. Regarding whole-genome sequencing, we have developed technologies and enhanced systems for this sequencing. Now, we are working on a detailed action plan formulated in 2019, which includes numerical targets, human resource development, and system development among others.

Implementation of the Antimicrobial Stewardship Program (ASP), which provides guidance on antimicrobial use, is expected to reduce the prevalence of drug-resistant bacteria, reduce medical costs, and provide education to healthcare providers. We evaluated the effects of introducing the ASP in the hematology and oncology wards of our institute in September 2014. As part of this program, we aimed to administer cefepime (CFPM) for febrile neutropenia (FN) and restrict the use of tazobactam/piperacillin (TAZ/PIPC) and meropenem (MEPM). We retrospectively evaluated the day of therapy (DOT)/1,000 patient-days, antibiogram changes, and numbers of deaths caused by infectious diseases within the period from October 2010 to August 2018, divided into three phases: pre-ASP introduction, transitional phase, and mature phase. Compared with the pre-ASP introduction phase, the mature-phase DOT for CFPM increased 3.95 times; in contrast, the mature-phase DOT for TAZ/PIPC and MEPM decreased 0.34 and 0.13 times, respectively (p<0.01). The activity of CFPM against Gram-negative bacteria was about 70%. The cases in which CFPM was ineffective were presumably due to naturally resistant β-lactamase-producing bacteria. The susceptibility of Pseudomonas aeruginosa to TAZ/PIPC and MEPM was below 90% in the transient phase, but it increased to over 90% in the mature phase. Antibiotic selection was not found to affect the number of deaths caused by infectious diseases. Significant reductions in MEPM and TAZ/PIPC use for febrile neutropenia did not increase the number of cases of serious infectious diseases and did not affect infectious disease mortality. The usefulness of ASP, in close cooperation with infectious disease specialists, was demonstrated in our pediatric hematology and oncology wards.

Purpose: To determine the factors involved in facilitating the social life (educational achievement and employment) of AML survivors. Participants and Methods: Ten AML survivors aged 15 years or older who were treated in accordance with ANLL91 and AML99 protocols in their childhood and are currently undergoing follow-up at JACLS participating institutions underwent semistructured interviews. A descriptive and qualitative analysis was conducted on the basis of the contents of the interviews. Results: We extracted six categories and 23 subcategories. When AML survivors obtained educational achievement and employment, they “adjust and convince themselves” to have a “sense of purpose” and to “do things cautiously.” During their course of treatment, they also consulted with “those who supported them,” such as doctors, friends, and teachers, as well as “those who guided them,” including their brothers and sisters. “To maintain the wish to return to school and proceed to the next educational level” was an essential element for educational achievement and employment. Discussion: Doctors and nurses need to assess physical and social functioning among childhood cancer survivors and introduce them to those who can provide support, such as social workers and cancer support counselors, aside from providing continuous information and support for returning to school as an essential element for educational achievement and employment.

Purpose: To disclose the impact of bereavement on adolescent patients after their friend’s death during hospitalization and make suggestions on supporting these adolescents with their grieving process. Method: Semistructured interviews were conducted on six adolescents (aged 10–18 years old when hospitalized in the pediatric hematology/oncology unit) after discharge. The data were analyzed qualitatively and inductively. Results: Participant experiences were analyzed from three aspects in time, and thirteen categories were extracted. Althouth the participants sensed their friend’s death, they did not talk about their anxieties with surrounding adults before they were notified of the death. They were perplexed by their friend’s death. However, all participants expressed gratitude that they were notified of their friend’s death and tried to take a step forward. None of the participants were worried about their own prognosis when hearing of their friend’s death; however, some participants were vaguely concerned about their own death when their physical condition was poor. Activities to deal with bereavement such as meeting friends after a death, attending funerals, and making presents were meaningful opportunities for participants to share their friend’s memories. Discussion: Because friendship is critical during adolescence, information about their friends, including their death, should be shared with them. Adolescents have complicated feelings regarding life and death, even when they are in good health. It is important to build relationships with patients and to talk about life and death without treating it as a forbidden subject. Giving patients the opportunity to share memories and thoughts of their friends will support their grieving process.

We report the case of a 32-day-old boy admitted to our hospital for hemophagocytic lymphohistiocytosis (HLH). When he was 27 days old, he had a fever, followed by pancytopenia, liver failure, and high levels of ferritin. When he was transported to our hospital, he required intensive care because of cardiorespiratory failure. Since a genetic test revealed PRF1 mutation, he was diagnosed as having familial hemophagocytic lymphohistiocytosis (FHL) type2. He was found to be a compound heterozygote for c.1090_1091delCT and c.658G>A mutations. The pathogenesis of the c.658G>A mutation has not yet been fully characterized. However, a homozygote for c.658G>A mutations was reported to express no perforin and develop FHL2. The combination of this compound heterozygote for a c.1090_1091delCT mutation and a c.658G>A mutation has not yet been reported. This is the first report of a case of FHL2 with a c.658G>A mutation in Japan. We carried out cord blood transplantation after non-myeloablative conditioning. He died on the day after his first transplant because of severe complications and high disease activity. FHL is a very rare disease. Therefore, pathogenic mutations associated with this disease should be widely studied by accumulating reports of novel gene mutations.

We present the case of a 32-year-old female diagnosed with moderate aplastic anemia at the age of 7 years. Owing to the progression of her disease, she became dependent on blood transfusion. She was unresponsive to immunosuppressive therapy and continued undergoing transfusion owing to the lack of an human leukocyte antigen (HLA)-matched donor. Iron chelation therapy was initiated at the age of 10 years. Although deferoxamine (DFO) was administered at every hospitalization for transfusion, it was ineffective, and her serum ferritin level increased to 5,000 ng/mL. At the age of 13 years, self-administration of continuous overnight subcutaneous infusion of DFO was initiated at home. The frequency of red blood cell (RBC) transfusion slowly decreased. At the age of 29 years, RBC transfusion became unnecessary and her serum ferritin level decreased to <500 ng/mL, allowing DFO treatment discontinuation. Continuous subcutaneous infusion of DFO may improve iron overload and be useful for bone marrow hematopoietic recovery.

We present the case of a 40-day-old female infant with acute lymphoblastic leukemia and KMT2 rearrangement. Laboratory data included a white blood cell (WBC) count of 1,730×10³/μL and leukocrit of 43%. We conducted mechanical ventilation, followed by exchange transfusion (ET) immediately after admission, because her leukostasis (symptomatic hyperleukocytosis) required emergency care. During the procedure, we observed hyperphosphatemia and hypocalcemia. The WBC count rapidly declined, and it decreased further to 3,100/μL on treatment day 9. We initiated multi-agent chemotherapy on the same day. We eventually conducted cord blood transplantation at 6 months of age, and she has remained in remission for 1 year since. Since subdural hematoma was observed, a slight developmental delay was noted (development quotient of 69 at 18 months of age), but she is gradually catching up with normal children. ET was effective for smooth transition of induction therapy. We emphasize the need for long-term follow-up since leukostasis might affect the brain microenvironment and, consequently, neurological development.

Ewing sarcoma (ES) is a malignant tumor originating from bone and soft tissue, and it frequently occurs in children and young adults. Although patients with localized ES normally have a disease-free survival rate of 70%, those with metastatic ES and who are refractory to primary chemotherapy have an extremely poor prognosis. We report on the case of a 19-year-old male diagnosed as having ES, who had an EWSR1-FLI1 chimeric transcript originating from the right iliac bone. Chest computed tomography revealed multiple pulmonary metastases. He received VDC-IE consisting of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide, followed by high-dose chemotherapy including busulfan and melphalan with autologous peripheral blood stem cell rescue and local radiotherapy. Afterwards, several lines of additional chemotherapy were performed; however, they failed to achieve a complete response. The administration of pazopanib induced a transient response, which allowed him to survive for an additional 7 months. Pazopanib is thus an available treatment option for refractory ES.

A 4-year-old girl presented with an abdominal mass to her previous physician. She had right kidney tumor as revealed by CT and underwent tumor resection. Pathologically, the tumor had features of both focal anaplasia and blastemal predominant type of Wilms tumor, and had a para-aortic lymph node metastasis. She was diagnosed as having stage 3 Wilms tumor and received adjuvant chemotherapy with the DD4A regimen and abdominal irradiation with JWiTS-2. During the treatment with the DD4A regimen, masses were newly documented in the tumor excision site and liver and were judged as recurrence. Two cycles of salvage chemotherapy with the ICE regimen were effective, and she received additional chemotherapy with Regimen I of JWiTS-2. She is alive without evidence of disease 18 months after the completion of therapy. Although focal anaplasia and blastemal predominant types are not clearly defined as high-risk subtypes in the JWiTS protocol, there is room for consideration in the choice of the chemotherapeutic regimen for patients with Wilms tumor.

An abdominal mass was detected in an 11-year-old girl who presented with anemia and hyperlipidemia. A liver tumor was confirmed; hence, she was referred to our hospital. Enhanced computed tomography revealed that the tumor was located in both segment 4 and the right lobe (PRETEXT III); it stained deeper in the early phase and washed out in the equilibrium phase. The α-fetoprotein (AFP) level was 1,178 ng/mL. Owing to the patient’s age, AFP level, and imaging findings, hepatocellular carcinoma was strongly suspected. Therefore, one-stage extended right lobectomy was performed owing to biopsy-dissemination-related concerns, and hepatoblastoma was diagnosed pathologically. Tumor dissemination is a concern in biopsies for suspected hepatocellular carcinoma, but preoperative chemotherapy for hepatoblastoma is known to be useful. Therefore, although distinguishing primary liver tumors before biopsy is extremely difficult, the propriety of biopsy should be carefully evaluated according to each patient’s background characteristics.

Trisomy 18 (T18) is a chromosomal disorder with poor prognosis, and more than 90% of T18 patients have congenital heart disease (CHD). Some patients develop malignant tumors such as hepatoblastoma (HB) and Wilms tumor. Recently, the application of radical or palliative surgery for CHD has improved patient prognosis, and an increasing number of patients have received home healthcare. Here, we describe the cases of two T18 patients diagnosed in the fetal period who developed HB during the clinical course. Both patients progressed to home healthcare without selecting surgical treatment for CHD. In addition, nontreatment supportive care was selected for HB. The natural clinical course of HB with T18 is unclear, but both patients survived for more than 2 years after diagnosis. There are few reports on the natural clinical course of HB associated with T18, and thus we believe that this report may provide information that can be used as a reference for future treatment policy selection.