[in Japanese]

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[in Japanese]

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[in Japanese]

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[in Japanese]

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[in Japanese]

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[Purpose] Multiagent chemotherapy including a moderately emetogenic anticancer drug for brain tumors decreases the quality of life of children owing to frequent episodes of sudden nausea and vomiting. The standard antiemetic regimen is a steroid combined with a 5-HT₃ receptor antagonist. Recently, aprepitant, an NK-1 receptor antagonist, has been approved in Japan, and combination therapy with 3 drugs including aprepitant is recommended according to many guidelines. However, the safety and efficacy of aprepitant use in pediatric patients have not been established. Accordingly, we examined whether the concomitant use of aprepitant affects the efficacy and safety of the standard antiemetic regimen for chemotherapy in pediatric patients with brain tumors. [Methods] We retrospectively compared the outcomes of 10 pediatric patients with brain tumors concomitantly treated with aprepitant and 21 patients treated with a standard regimen, by reviewing the medical records of these patients. The 31 patients ranged in age from 7 to 18 years. The chemotherapy regimens were cyclophosphamide-carboplatin-etoposide and cisplatin-etoposide. [Results] No major adverse events were encountered. The frequencies of vomiting, nausea and particularly acute phase emesis were lower among patients receiving aprepitant (27.2%, 16.7%, and 41.9%, respectively) than among patients receiving the standard regimen. [Conclusion] Aprepitant use in pediatric patients, at the same dose as that used in adults, may be superior to the standard antiemetic regimen for moderately emetogenic anticancer therapy. Further studies are warranted to determine the optimal dosage.

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[Introduction] To date, few chemotherapeutic drugs have improved the survival rate of patients with diffuse intrinsic pontine glioma (DIPG). However, in some studies, metronomic chemotherapy with oral etoposide has been shown to improve the symptoms of patients with recurrent DIPG after radiotherapy, leading to a better quality of life.
[Methods] We reviewed the records of patients with DIPG, who were treated at our institution between April 2007 and January 2013, and verified the effectiveness of oral etoposide therapy in these patients.
[Results] One boy and 10 girls were included in this study. The median age at diagnosis was 5 years (range, 3–10 years). All the patients were diagnosed by magnetic resonance imaging except for one patient who underwent biopsy and was diagnosed as having glioblastoma. The median time from diagnosis to the administration of oral etoposide was 7 months (range, 2–10 months). Clinical improvement was seen in 8 of the 11 patients who had received treatment, whereas radiological improvement was observed in 3 of the 9 patients who underwent imaging studies. Among 8 patients taking steroids, 2 discontinued treatment, and another 2 had a dose reduction after starting oral etoposide. The median duration of oral etoposide administration was 6 months, with a maximum duration of 24 months. All adverse events were acceptable, except for severe myelosuppression in one patient who concomitantly received oral etoposide and whole spinal irradiation for spinal dissemination.
[Conclusion] We observed clear treatment benefits with oral etoposide therapy in some patients with recurrent DIPG. Therefore, we suggest that oral etoposide be considered as a form of palliative chemotherapy for these patients.

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Here, we report our experience of sperm banking for adolescent male patients in our institute (as a children’s hospital) for the last twenty-four years. There were no nationwide guidelines of sperm banking even for adult male patients before 2003. However, we informed them and their parents about therapy-related infertility and sperm banking since 1990. Moreover, we carried it out under written informed consent since then. To date, there have been fifteen patients who qualified for sperm banking. Eleven patients were sufficiently informed; however, two patients were uninformed because of treatment emergency, and we failed to inform the other two. Four of the eleven patients refused sperm banking. Eventually, seven patients banked their sperm and two of them got married. One fathered a child with assisted reproductive technology and the other got his wife pregnant naturally. One unmarried patient recovered spermatogenesis because he underwent reduced intensity conditioning. At present, only two patients have continued to bank their sperm. We consider that the purpose of sperm banking is not only to preserve fertility but also to encourage patients and to contribute to improving their quality of life. Sperm should be cryopreserved before the initiation of treatment to obtain good-quality sperm. Hemato-oncologists need to keep this in mind and to inform every patient and enlighten other medical staff members about it. In the near future, we have to discuss and cope with the many problems of sperm banking, such as the applicable criteria for it, lack of information about fertility preservation, poor communication with patients, high percentage of unmarried patients, and its high cost.

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Background. Mercaptopurine (6-MP) and methotrexate (MTX) form the backbone of maintenance therapy for childhood acute lymphoblastic leukemia (ALL). It is widely noted that the inter- and intrapatient variations in the clinical efficacy and adverse effects of 6-MP and MTX are enormous, and optimal dosage varies considerably. The aim of this study was to elucidate the factors that affect the optimal dosage setting of 6-MP/MTX in the maintenance phase of treatment. Methods. Fifty children (aged 1 to 15) who were diagnosed as having ALL in our institution between April 1995 to March 2010 and who finished maintenance therapy were enrolled in this study. We investigated the 6-MP/MTX dosages from the beginning (6-MP/MTX: 40 mg/m² / 25 mg/m²) and compared patients’ characteristics (sex, white blood cell count, age, immunophenotype, body surface area, prednisolone response, risk classification, obesity index) and relapse rates across each category. Results. Thirty-four patients needed to change their 6-MP dosage (increase, n=20; decrease, n=14), whereas 18 patients needed to change their MTX dosage (increase, n=3; decrease, n=15). The patients’ characteristics were not significantly different in each category of dosage changes; on the other hand, it was shown that 4 of 7 relapse patients experienced an increase in 6-MP dosage of more than 50% within the first 6 months after the start of maintenance treatment. Conclusions. In this study, we conclude that the patients’ characteristics are not related to the 6-MP/MTX dosage change in maintenance therapy, and it is suggested that the major increase in 6-MP dosage may predict the occurrence of relapse.

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Several combination therapies have been employed as palliative chemotherapies for refractory solid tumors. Although irinotecan (IRT) plus temozolomide (TMZ) (IT therapy) has been demonstrated to be tolerable and active in children with relapsed solid tumors, this combination chemotherapy has not been reported in Japanese patients. We retrospectively reviewed the toxicity and efficacy of IT therapy in eight patients with refractory solid tumors. Three patients had Ewing sarcoma/PNET, and five had undifferentiated sarcoma, hepatoblastoma, infantile fibrosarcoma, neuroblastoma, or Wilms tumor. All the patients received various therapies for their disease, including chemotherapy, radiotherapy, tumor resection, autologous peripheral blood stem cell transplantation or cord blood transplantation. All eight patients received a total of 27 courses, with a median of three courses per patient. Seven patients received oral TMZ (150 mg/m²/day) plus intravenous IRT (50 mg/m²/day) on days 1–5, and one received oral TMZ (100 mg/m²/day) on days 1–5 plus IRT (20 mg/m²/day) on days 1–5 and 8–12. We observed partial responses in three patients, stable disease in four patients, and progressive disease in one patient, with a median of three courses of IT therapy. Four patients died of progressive disease, one patient is currently disease-free, and three survived with stable disease. Toxicities included grade 3 diarrhea (three courses, 11.1%), grades 3–4 neutropenia (nine courses, 33.3%), and grades 3–4 thrombocytopenia (two courses, 7.4%). IT therapy was tolerable and effective for Japanese children with refractory solid tumors and who had completed other various chemotherapies.

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Background: Central venous catheters (CVCs) are essential for improving the quality of life of pediatric cancer patients during treatment. Catheter colonization is one of the most frequent complications, and CVC removal is a standard approach to treating catheter colonization. Some studies showed that antibiotic lock therapy (ALT) could rescue colonized CVCs, but the evidence supporting the efficacy of ALT is still unclear. Thus, here, we report our experience with ALT in the treatment of catheter colonization in pediatric cancer patients.
Methods: A retrospective chart review was performed for 113 pediatric cancer patients with CVCs (tunneled cuffed catheters) at the University of Tokyo Hospital from April 2008 to August 2013. This study involved 28942 total catheter days. There were 172 episodes of catheter colonization during this period, 15 of which were treated with ALT for about 7 days, mainly with vancomycin (n=13). ALT success was defined as negative blood culture after the ALT.
Results: ALT succeeded in 13 episodes (86.7%). The incidence of catheter colonization was 5.70 per 1000 CVC days in the ALT-rescued CVC group, whereas it was 5.95 per 1000 CVC days in the newly inserted CVC group. The cumulative incidence rate of catheter colonization and the duration of use were almost identical between the two groups (p=0.399 and 0.267, respectively). Two episodes were treated with ALT alone and required the removal of the catheters.
Conclusion: ALT with systemic antibiotics for the treatment of catheter colonization is effective in pediatric cancer patients.

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Objective: We investigated the intellectual function of ten pediatric patients after treatment of medulloblastoma.
Methods: To evaluate the intellectual function, we retrospectively analyzed the scores of the participants in the Japanese version of the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV). The median age at the time of diagnosis was 5.0 years. The median duration from the end of treatment to an examination was 59.5 months. We compared the scores of 4 indexes in all the patients, and compared the test results at two points. We examined the effects of hydrocephalus or radiation exposure symptoms as complications on the scores of the 4 indexes.
Results: The processing speed index score was lower than the others (FSIQ, 92.0; VCI, 90.0; PRI, 97.5; WMI, 95.5; PSI, 84.5). There was no significant difference between those two periods in the WISC-IV quotients of five children. The effects of both the hydrocephalus and radiation exposure symptoms on the scores of 4 indexes of WISC-IV did not reveal a statistically significant difference.
Conclusion: We should evaluate not only the change in the intellectual function, but also the educational outcome, which indicates social reintegration.

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A 9-year-old girl was admitted to our hospital because of fever, facial erythema and lacy exanthema of her upper and lower limbs. On the basis of clinical and laboratory findings, she was diagnosed as having systemic lupus erythematodes (SLE) and was given oral prednisolone (PSL) therapy. After one month of hospitalization, however, she complained of severe headache in the left occipital region, and multiple thrombi in the superior sagittal venous sinus and sigmoid sinus were detected on magnetic resonance imaging. Neither coagulation nor anticoagulation factors showed any evidence of abnormalities. She was also negative for the lupus anticoagulant and an anti-cardiolipin antibody. She was positive only for anti-phosphatidylserine-prothrombin (aPS/PT) complex antibodies in her plasma. This suggests that her cerebral thrombosis was due to antiphospholipid syndrome (APS) associated with SLE. PSL might also be involved in the generation of thrombi in her brain. Here, we discuss these possibilities as well as the importance of the aPS/PT test as a new tool for diagnosing APS.

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We report the case of a 1-day-old boy admitted to our neonatal intensive care unit for initial vomiting with thrombocytopenia. His platelet count was reduced to 3.0×10⁴/μL. At first, neonatal alloimmune thrombocytopenia was suspected, but the corresponding antibody was not detected. His thrombocytopenia was persistent, and giant platelets were first observed when he was 17 months old. Since a genetic test revealed GPIX gene mutation, he was diagnosed as having Bernard-Soulier syndrome (BSS). He is a compound heterozygote for a known p.Cys89Tyr mutation and a novel p.Gly40fsX43 mutation of one base deletion resulting in a frameshift and premature termination. Because he is diagnosed in his early infancy, he will be provided guidance about lifestyle when he is old enough to understand and managed appropriately when he bleeds. Neonatal alloimmune thrombocytopenia is a relatively frequent cause of neonatal thrombocytopenia without complications, but some congenital thrombocytopenia syndromes such as BSS are rare. It is important to carefully observe the platelet morphology when diagnosing thrombocytopenia.

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We encountered the case of a 10-year-old girl presenting with multiple hepatic focal nodular hyperplasia (FNH)-like lesions, which were difficult to differentiate from hepatocellular carcinoma (HCC) because of their atypical presentation. She was referred to our institution for an incidentally detected multiple liver mass during the follow-up for thigh pain. Enhanced MRI with gadolinium ethoxybenzyl diethy­lenetriamine-pentaacetic acid (Gd-EOB-DTPA) showed compatible observation in most nodules. However, a mass in S3 showed hypointensity in the hepatocellular phase, which is characteristic of HCC. We performed laparoscopic tumorectomy to rule out malignancy. A histopathological study showed benign hyperplastic lesions, but further classification was difficult. Thus, our final diagnosis was FNH-like lesions.
FNH-like lesions are hyperplastic lesions caused by a vascular abnormality similar to a typical FNH, although their features are not compatible with those of FNH. This disease may be difficult to distinguish from FNH or HCC because the imaging findings as well as the histopathological findings are atypical. We have to consider this disease when we see an imaging study indicating HCC, despite a benign clinical picture.

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We report on the case of a two-month-old female with acute megakaryoblastic leukemia (AMKL), who had abdominal distension due to massive ascites. The patient was administered low-dose etoposide and cytarabine, followed by the JACLS AML 99 protocol consisting of etoposide, cytarabine, and mitoxantrone as induction therapy. She required intensive care, including mechanical ventilation for three months because of respiratory failure caused by uncontrollable massive ascites. The massive ascites was probably caused by portal hypertension due to liver fibrosis, which has been reported as one of the characteristics of OTT-MAL (or RBM15-MKL1)-positive AMKL. With hematopoietic recovery from myelosuppression, the ascites gradually improved, but we were unable to continue chemotherapy because of severe portal hypertension. However, she has maintained remission for over two years and nine months only by induction chemotherapy, and so far, her general status has been good.

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Gemtuzumab ozogamicin (Mylotarg^®, GO) was approved for the treatment of relapsed and refractory CD33+ acute myeloid leukemia (AML) in Japan in 2005. The optimal therapeutic regimen of GO for childhood AML, however, has not been established. Here, we present the cases of four patients with pediatric refractory AML treated with fractionated GO monotherapy (9 mg/m² divided into three doses). Two patients achieved complete remission. Two patients developed Grade 2 infusion reactions and no patient developed veno-occlusive disease (VOD) during the fractionated GO monotherapy. Although all four patients had Grade 3 infection, no patient had other severe nonhematological toxicities. All four patients underwent subsequent HSCT after the fractionated GO monotherapy and three patients relapsed. Although there was no treatment-related mortality, VOD occurred in two patients as a complication after HSCT. Even with fractionated GO monotherapy, which can lessen the toxicity of GO, we need to be cautious of infections and VOD after HSCT.

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There are many reports on the effective diagnosis of acute leukemia by MRI. Acute leukemia patients with the symptom of bone pain or joint pain frequently show abnormal MRI findings in the bone or bone marrow. Here, we report the case of a 7-year-old girl who presented to our hospital with leg pain and was diagnosed with precursor B-cell acute lymphoblastic leukemia (ALL). An abnormal MRI finding suggested leukemic infiltration in the left femur. Following induction therapy, complete bone marrow remission was confirmed and the MRI finding improved to some extent. After further therapy, MRI revealed a new abnormal finding in the femur bone marrow. Suspecting a relapse, we performed FDG-PET/CT, which revealed a normal finding. Because there were no relapse symptoms except for the MRI finding including the negative result of FDG-PET/CT, we assumed that this finding was bone marrow reconversion. The abnormal MRI finding improved gradually as therapy proceeded to completion. Sequential observation is important for distinguishing it from leukemia relapse, and an abnormal MRI finding in the bone marrow does not always indicate a relapse.

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Allogeneic hematopoietic stem cell transplantation (SCT) is a curative treatment for severe combined immunodeficiency (SCID). However, the outcome is poor when cytomegalovirus (CMV) infection arises as a complication before SCT. Here, we report a case of SCID with CMV infection that was successfully treated by allogeneic cord blood transplantation (CBT). A 3-month-old male was admitted with fever and dyspnea. He was diagnosed as having SCID with CMV pneumonia and enterocolitis. Combined treatment with ganciclovir, intravenous immunoglobulin, and methylprednisolone pulse did not improve the CMV infection; however, the addition of foscarnet proved successful. He received CBT with a conditioning regimen comprising busulfan (4 mg/kg) and fludarabine (180 mg/m²). Neutrophils engrafted 10 days after CBT and CMV infection did not recur after transplantation. At 15 months post-transplantation, the patient remains well with no complications. Antiviral therapy before CBT might be the key to the successful outcome in this case.

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We report the case of a 13-year-old girl with nasopharyngeal carcinoma (T3N3M0) who had complained of neck pain and hearing loss. A fiberscope revealed a mass of the nasopharynx, and endoscopic tumor biopsy was performed. The histopathological diagnosis was undifferentiated nasopharyngeal carcinoma associated with the Epstein-Barr virus. She received 3 courses of neoadjuvant chemotherapy (NAC) containing cisplatin, 5-fluorouracil and leucovorin, followed by IMRT and concurrent chemoradiotherapy (CCRT). Although the MR and PET-CT images showed a lesion remaining after the completion of NAC, the lesion was completely eliminated after CCRT. Furthermore, she was treated with IFN-β for 6 consecutive months. At present, 10 months after the treatment, she maintains complete remission. The adverse event can be relieved by administering IMRT. Furthermore, the levels of serum EBV-DNA reflected the effects of the treatment. To the best of our knowledge, this strategy for pediatric nasopharyngeal carcinoma was well tolerated and resulted in a very effective therapy.

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