Introduction: The five-year survival rate of pediatric acute lymphoblastic leukemia (ALL) patients has increased to approximately 90%, but the late effects of cancer treatment have become an issue in recent years. As the incidence of the late effects increases with time, long-term follow-up is important. However, patients and their parents do not have sufficient information about the late effects of the treatment, and some pediatric cancer patients withdraw voluntarily from outpatient attendance. We surveyed the outpatient attendance records of pediatric ALL patients at our hospital. Methods: Follow-up data of 107 pediatric ALL patients treated at our hospital from 1986 to 2016 were available and surveyed retrospectively. Patients not attending for one year or more after their last appointment were assigned to the discontinued attendance group. Results: Thirteen of the 107 patients were assigned to the discontinued attendance group, of whom 12 had withdrawn voluntarily. The outpatient attendance rate was 91% at 10 years after treatment but fell to 43% at 20 years. In terms of age at final observation, although the outpatient attendance rate was 93% for age 19, it was only 43% for age 30. Five patients in the 19 or below age group discontinued attendance, of whom two withdrew voluntarily after therapy completion. Conclusion: Our findings suggest that it is necessary on completion of therapy to educate patients and their families regarding the importance of long-term follow-up, with renewed emphasis at 10 years after diagnosis and at age 19.

Despite the improved outcome of Ph-positive acute lymphoblastic leukemia (Ph+ ALL) with tyrosine kinase inhibitors in children, side effects and complications of treatment are still major concerns. In this report, we describe the case of a 13-year-old boy who was diagnosed as having Ph+ ALL and treated with chemotherapy including imatinib. He developed febrile neutropenia on day 14 after the re-induction therapy. An antibiotic agent was immediately administered to the patient, but septic shock and, following acute renal failure, intestinal edema and acute respiratory distress syndrome progressed. He died on day 62. Autopsy findings showed that the cause of death was multiple organ failure from septic shock. E. coli was detected in his blood culture. The mechanism of sepsis was considered as a bacterial translocation from his intestine. These findings show that the immediate use of antibiotics in the case of prolonged febrile neutropenia is recommended, because bacterial translocation will be induced by the imatinib-containing chemotherapy in Ph+ ALL patients.

The patient described in this report is a 25-year-old woman. She developed chronic myelogenous leukemia (CML) at the age of 14 years and was treated with imatinib mesylate (IM), resulting in complete remission. At the age of 18 years, she elected to receive a human leukocyte antigen-identical allogenic bone marrow transplantation from her sister. However, after 3 months, she relapsed. She was again treated with IM and underwent donor lymphocyte infusion from the same donor. She developed chronic graft-versus-host disease (cGVHD) on her skin that gradually worsened in terms of skin pigmentation, scleroderma, and joint contracture. She was treated with prednisolone, but it was ineffective as a single agent; thus, she was treated with etretinate and mycophenolate mofetil, but they were also ineffective. Other treatments were also tried, but they were stopped because of various severe side effects. Subsequently, IM was initiated at a dose of 100  mg/day, and her symptoms markedly improved. Our experience with this patient, along with prior reports, suggests that IM therapy is effective for refractory sclerodermatous cGVHD, although further confirmation is warranted.

X-linked lymphoproliferative syndrome (XLP) is a rare primary immunodeficiency disease (PID) characterized by vulnerability to the Epstein-Barr virus (EBV). XLP is divided into XLP1 caused by SH2D1A mutation and XLP2 caused by XIAP mutation. Approximately 60% of patients with XLP1 present with EBV-associated hemophagocytic lymphohistiocytosis (HLH), which may be fatal despite treatment with etoposide and cyclosporine A. EBV mainly infects CD8⁺ T cells in sporadic EBV-HLH, whereas it mainly infects B cells in PIDs including XLP1. Treatment with an anti-CD20 monoclonal antibody (rituximab) may be effective in patients with EBV-HLH accompanied by XLP1. Here, we describe a 3-year-old boy with XLP1, who presented with severe EBV-HLH and was successfully treated with rituximab.

A 6-year-old boy with acute lymphoblastic leukemia developed disseminated mucormycosis caused by Rhizopus microsporus during induction therapy. Despite the presence of intestinal perforation and the formation of multiple abscesses, surgical resection and intravenous administration of liposomal amphotericin B were effective, and the patient recovered. Because the prognosis of mucormycosis is very poor, early diagnosis and treatment are important. In cases of patients with risk factors for mucormycosis, physicians must consider the possibility of mucormycosis. Moreover, the empirical administration of liposomal amphotericin B could be a good treatment option before a definitive diagnosis of mucormycosis is made.

Cyclic neutropenia (CyN) and severe congenital neutropenia (SCN) are disorders of neutrophil production leading to recurrent bacterial infections. Mutations of ELANE, which encodes neutrophil elastase, have been mostly associated with CyN and SCN. We report the case of a 21-month-old girl who showed severe neutropenia and maturation arrest of myeloid lineage at the promyelocyte/myeloid stage in the bone marrow at her first presentation. Heterozygous in-frame deletion (IVS4+1G>A) of ELANE was identified by genetic analysis, and she was tentatively diagnosed as having SCN. However, her neutrophil count gradually increased, and her bone marrow reexamination did not show maturation arrest 4 months after the initial visit. Finally, we concluded that regular fluctuations of neutrophil count and bone marrow findings are consistent with CyN. The frequency of recurrent bacterial infections decreased as neutrophil count gradually increased. Confirming the fluctuation of neutrophil count and bone marrow reexamination are significant for discriminating between CyN and SCN.

In a 5-month-old boy with a history of horizontal nystagmus and vomiting, computed tomography and magnetic resonance imaging (MRI) demonstrated bilateral subdural hygroma and contrast-enhanced lesions in the suprasellar region, medulla oblongata, and the spinal axis. Histopathological examination of a suprasellar tumor biopsy specimen revealed a World Health Organization (WHO) grade I desmoplastic infantile astrocytoma (DIA). A regimen of vincristine and carboplatin (VC) chemotherapy for low-grade astrocytoma was started. The tumor size immediately decreased, and the metastatic lesions also disappeared after the initial 10 weeks of chemotherapy. Although a residual tumor remained in the suprasellar region, no tumor regrowth was detected 13 months after finishing the chemotherapy. The patient showed no symptoms or developmental delay. Although surgical resection is the recommended therapy for symptomatic DIA, our experience suggests that VC chemotherapy might be a therapeutic option for DIA in infants with unresectable tumor or multiple metastasis.

Although gross total resection of low-risk neuroblastoma remains the current treatment recommendation, neoadjuvant chemotherapy would be administered when image-defined risk factors (IDRFs) were positive. However, in the case of low-risk tumor with IDRFs and resistant to chemotherapy, the treatment of choice is not clearly defined. We describe the case of a 5-year-old girl who presented with a localized 78×83 mm² mass located in the left suprarenal fossa. The tumor completely involved the left renal artery, which on biopsy proved to be intermixed ganglioneuroblastoma, with favorable histology without MYCN amplification. The patient was assigned to the category of low-risk neuroblastoma with IDRFs. Despite chemotherapy for 6 weeks, the tumor showed no response. Thus, we tried debulking surgery to preserve the left kidney. However, since the bleeding was difficult to control, we performed complete resection with left nephrectomy. Histopathological findings showed ganglioneuroblastoma nodules with unfavorable histology without MYCN amplification. No adjuvant therapy was administered.

We present the case of an 11-month-old boy who developed cytomegalovirus (CMV) antigenemia during chemotherapy for rhabdomyosarcoma. He started treatment with ganciclovir, but the antigenemia assay did not show a negative result. Despite changing the antiviral agent to forscarnet, the antigenemia remained positive. Concurrent chemotherapy had to be continued for the malignancy. Fundoscopy was repeated twice, which showed no abnormalities. After completing all chemotherapy courses, the antigenemia values increased. At this point, fundoscopy revealed exudative lesions with hemorrhage in both eyes, which led to a diagnosis of CMV retinitis. Ganciclovir was readministered, and the fundus lesions then resolved. The antigenemia became negative upon apparent normalization of his immune system. The retinitis caused loss of vision in the left eye. This experience shows that chemotherapy alone can cause CMV retinitis. During chemotherapy, meticulous attention should be paid to immunological status and retinal findings.

Osteosarcoma (OS) is the most common malignant bone tumor in children. Patients without metastasis are curable, whereas those with metastasis have a dismal prognosis. A recent clinical test has shown that bisphosphonate inhibits metastasis and improves the survival of osteosarcoma patients. We encountered the case of a 14-year-old male who suffered from OS of the left femur with multiple pulmonary nodules and treated with zoledronic acid (ZA) in addition to conventional chemotherapy. Histopathological examinations of the resected tumor revealed complete necrosis, suggesting a good response to preoperative chemotherapy. After the completion of chemotherapy, a few nodules disappeared, although most of the remaining pulmonary nodules showed no change in shape. Only hematological toxicity was observed during chemotherapy with ZA. The addition of ZA to conventional chemotherapy was safe in our patient. Evaluation of ZA efficacy was difficult, because the possibility that the pulmonary nodules were physiological intrapulmonary lymph nodes was high. Further experiences of treating Japanese patients will clarify the safety and efficacy of bisphosphonate for OS.