(Background) To improve the prognosis of high-risk neuroblastoma, we intensified the treatment by cord blood transplantation (CBT) with reduced-intensity conditioning (RIC).
(Patients and Methods) Fifteen consecutive patients with high-risk neuroblastoma, who were treated between 2005 and 2012 in our institution, were retrospectively reviewed.
(Results) Induction chemotherapy followed by high dose chemotherapy (HDC) was administered to all the patients. After HDC, primary tumor surgical resection was performed, and radiotherapy was administered to the primary site and residual metastases. The median patient age was 2.9 years. The chemotherapy responses were as follows: 2 patients showed a very good partial response, 11 showed a partial response, and 2 showed a mixed response. Five patients had no evidence of disease after treatment, but 8 patients experienced recurrences and 2 patients died from complications of HDC. The probabilities of event-free survival and overall survival at 5 years were 33.3±12.2% and 26.7±12.6%, respectively. Six patients were treated by CBT after local therapy. Either busulfan/fludarabine or melphalan/fludarabine was used for preconditioning for CBT. Grade I/II acute graft-versus-host disease was observed in 3 patients. No treatment-related death was observed. The relapse-free survival was not significantly different between groups (17.8 months with CBT vs 22.7 months without CBT, p=0.23).
(Conclusion) RIC-CBT for high-risk neuroblastoma was safely performed. However, patient prognosis did not improve.

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Crizotinib, an inhibitor of ALK, is expected to improve the outcome of advanced neuroblastoma; however, treatment experience with crizotinib is extremely limited in Japan. Here, we report the case of a patient treated with crizotinib against ALK amplified refractory stage 4 neuroblastoma. Our patient was a girl aged one year and 4 months and diagnosed as having neuroblastoma arising from the left adrenal gland with multiple metastases. She received three courses of the 05A1/05A3 regimen and high-dose chemotherapy, and surgery was subsequently performed. Headache, hypalgesia of the lower limb, movement disorders, and dysuria occurred 17 days after surgery, and spinal cord metastasis was observed by magnetic resonance imaging. Since fluorescence in situ hybridization analysis showed amplified ALK in cells in the cerebrospinal fluid, she received radiotherapy and crizotinib. After 26 days of crizotinib administration, she showed a partial response, but treatment was discontinued as a result of grade 3 vomiting. To confirm the safety and efficacy of crizotinib, further accumulation of experience in the use of crizotinib is important.

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Diencephalic syndrome, a rare cause of failure to thrive in infants and young children, is characterized by severe emaciation and hyperactivity and is often associated with hypothalamic tumor. In infants and young children, the diagnosis of brain tumor is frequently delayed because of the difficulty in performing a detailed neurological assessment and obscured symptoms of increased intracranial pressure due to unclosed cranial sutures. Here, we report the case of a 2-year-old girl who was diagnosed as having pilocytic astrocytoma of the hypothalamus and diencephalic syndrome presenting with a history of failure to thrive since 7 months of age. This observation suggests the importance of considering a brain tumor as a possible cause of unexplained failure to thrive in infants and young children.

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Introduction: Preoperative chemotherapy, based on cisplatin (CDDP), is essential to hepatoblastoma. Although the standard chemotherapy consists of CDDP and pirarubicin (hereafter, CITA) in Japan, we report here a case of intermediate-risk hepatoblastoma in a patient receiving CDDP monotherapy because of complication caused by initial CITA. Representative case: The representative case is that of a 1-year-old girl with PRETEXT III intermediate-risk hepatoblastoma. On the eighth day after open biopsy, we started CITA therapy. On the fourth day after initial CITA, she suffered from diffuse peritonitis caused by intestinal perforation. After the operation was performed, her myelosuppression and wound dehiscence were prolonged. We started CDDP monotherapy from Day 38 after the initiation of CITA. Subsequently, the therapy was completed on schedule with mild myelosuppression, and we were able to perform radical surgery. Conclusion: CDDP monotherapy may be one of the options for intermediate-risk hepatoblastoma with severe complications to avoid the prolongation of the interval of chemotherapy.

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Unrelated cord blood transplantation (UCBT) and mismatched related donor stem cell transplantation (MMRD-SCT) have been considered as alternative therapeutic options for patients with very severe aplastic anemia (VSAA) and severe infection when an HLA-matched donor is not available. However, a high rate of graft failure and severe graft-versus-host disease (GVHD) are the major problems in SCT from these alternative donors. Here, we report the case of a 2-year-old boy with VSAA complicated by repeated infection who was successfully treated by UCBT (HLA 5/6 antigen-matched). Cord blood with a sufficient number of total nucleated and CD34-positive cells was used, and a conditioning regimen including low-dose TBI was employed. Iron-chelating therapy was performed before UCBT. Engraftment was achieved on day 20 without severe acute GVHD. Although CMV antigenemia persisted for 5 months, which might have resulted from ATG use in the conditioning regimen, UCBT may become a good alternative therapeutic option for VSAA.

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