[Background] The prognosis of children with acute lymphoblastic leukemia (ALL), who relapsed after a long period from the cessation of the initial treatment, is uncertain, and no treatment strategy has been fully established. [Methods] We analyzed the prognosis of patients who relapsed more than 24 months after the discontinuation of the treatment (very late relapse, VLR) in the KYCCSG protocols, ALL-96 and ALL-02. [Results] A total of 357 patients were enrolled in the two studies and 70 patients (19.6%) relapsed. Eight patients (2.2%) developed VLR with a median remission duration of 37.5 (range, 26–42) months after the cessation of the treatment. At the time of initial diagnosis, six patients were classified into the standard-risk group and two patients into the high-risk group. The sites of relapse were isolated bone marrow (BM) in six patients, isolated testis in one, and a combination of both BM and central nervous system in one. All the eight patients achieved a second complete remission (CR) after reinduction chemotherapy. Three of the eight patients received allogeneic stem cell transplantation (allo SCT). However, one of the three patients had another hematological relapse 11 months after the allo SCT and died. Five patients were successfully treated with chemotherapy only, and therefore, seven patients are alive in CR with a median follow-up duration of 57 (range, 32–92) months after their relapse. [Discussion] Our study indicated that the incidence of VLR is approximately 2%, which is similar to those of previous reports. All patients achieved a second CR after reinduction chemotherapy and seven of the eight patients are alive in CR without a second relapse. Our data suggests that the prognosis of patients with VLR of childhood ALL is favorable.

We retrospectively analyzed the clinical outcome of 12 pediatric patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT) using a myeloablative conditioning regimen consisting of granulocyte colony-stimulating factor (G-CSF), cytarabine, cyclophosphamide, and total-body irradiation in our hospital between 1995 and 2014. Eleven patients were in complete remission (CR; 6 in CR1, 5 in CR2) and one patient was not in remission. Both the 5-year overall survival and disease-free survival rates in patients undergoing HSCT in CR were 62.3±15.0% and 63.6±14.5%, respectively. One patient experienced primary engraftment failure, and two patients experienced post-HSCT relapse. Grades II–IV acute and chronic GVHD were observed in 7/11 and 2/9 patients, respectively. Five patients died due to bacterial infection (n=1), disease progression (n=1), and complications after the second HSCT (n=3). In this study, no marked beneficial effect of the regimen was observed in pediatric patients, unlike in adult patients with AML. Considering the high incidence of late adverse effects, reduced-toxicity regimens, such as G-CSF-combined reduced-intensity conditioning regimen, would be feasible for pediatric patients with AML.

High-dose intravenous methotrexate (HD-MTX) and intrathecal MTX, a necessary component for chemotherapy of childhood acute lymphoblastic leukemia (ALL), can cause long-term neurotoxicity, including leukoencephalopathy, which adversely impacts intellectual function. We report the results of a prospective longitudinal examination of cognitive function in a 4-year-old girl at diagnosis treated with HD-MTX intravenous chemotherapy. She achieved normal developmental milestones before her diagnosis of ALL. She lives with her parents who have average socio-economic status. After the diagnosis, she received treatment according to the JACLS ALL-02 SR protocol, which included HD-MTX 3 g/m²×2 courses and IT MTX×12 times. She underwent WISC-IV testing before and three times after the completion of standard-risk ALL therapy over a period of three years. Testing results demonstrated the preservation of fluid (reasoning) ability and crystalized (knowledge) ability, although the scores of working memory declined. General intellectual ability remained within the average range over time. Thus, no neurocognitive deficits were detected in this case within three years after HD-MTX. A prospective study of additional cases is planned to confirm these results.

A 14-year-old girl with FLT3-ITD-positive acute myeloid leukemia underwent HLA-haploidentical stem cell transplantation (SCT) from her father using a myeloablative conditioning regimen. Despite acyclovir (ACV) prophylaxis, the patient developed severe gingivostomatitis on day 56 after SCT, and herpes simplex virus type (HSV)-1 was detected in the oral mucosal membrane and blood. Increasing the dose of ACV did not improve her symptoms. A genetic drug resistance test revealed a mutation in the viral thymidine kinase gene. Furthermore, an antiviral susceptibility test confirmed the ACV resistance of HSV-1. Subsequent switching of antiviral therapy from ACV to foscarnet led to a prompt improvement. The incidence of ACV-resistant HSV infection will likely increase owing to the prevalence of HLA-mismatched SCT. Therefore, it is desirable to develop an examination system for drug-resistance-associated tests to insure the adaptation of antiviral drugs effective against ACV-resistant HSV-1.

This is a case of primary non-Hodgkin lymphoma of bone, evaluated using ¹⁸F-FDG PET/CT (PET/CT). A 16-year-old male presented with right knee pain for eight months. PET-CT showed abnormal FDG uptake at the distal right femur, throughout the right tibia, and at the left middle skull base. The patient was diagnosed as having stage III B-cell lymphoblastic lymphoma. He received chemotherapy on the basis of the NHL-BFM95 protocol. After consolidation therapy, PET/CT showed no abnormal uptake in the tibia and the skull base. The remaining uptake levels at the distal femur, the biopsy site, gradually decreased. The patient has been in complete remission for eight months after the completion of chemotherapy. PET/CT is useful for staging, and seems more useful than MRI or CT for evaluating treatment response in primary bone lymphoma. However, it is necessary to confirm the effective timing and the frequency of evaluation, taking radiation exposure and false-positive findings into consideration.

We report the case of a 17-year-old female patient with a very small right adrenal pheochromocytoma. She had been suffering from 5- to 10-min spells of tremor, numbness of extremities, facial pallor, cyanosis, palpitation and headache for about one year. Her baseline urine catecholamine levels were often in the reference or sometimes diagnostic ranges, and the diameter of the adrenal tumor was about 1.5 cm on MR images. The clinical diagnosis of pheochromocytoma was, however, made on the basis of a significant increase in plasma adrenaline levels during the spells and the positive uptake of 131-MIBG in the tumor. All of the symptoms and biochemical abnormalities were resolved after right adrenalectomy. Pheochromocytoma should be considered in patients with short spells and adrenal tumor regardless of the tumor size.

An 8-year-old girl was referred to our hospital because of abdominal pain preceded by bruising. Abdominal computed tomography identified two tumors. Laparotomy was performed for biopsy, and the tumors were diagnosed as solid-pseudopapillary neoplasm (SPN) of the pancreas. Distal pancreatectomy and resection of the disseminated lesion were performed. Three subsequent resections were performed owing to recurrences. The initial diagnosis was made 10 years ago, and there have been no recurrences in the past 6 years. SPN with evidence of high-grade malignant transformation was not identified histopathologically in specimens from primary, recurrent, and disseminated lesions. On the basis of the current World Health Organization classification, the SPN in this patient is categorized as a low-grade malignant neoplasm. The histopathologic finding of a malignant component rather than metastasis or dissemination indicates a worse prognosis.

A 7-month-old male infant, who suffered from systemic infection following BCG vaccination, was diagnosed as having p67^phox-deficient chronic granulomatous disease. At the age of three, he underwent bone marrow transplantation from an HLA-8/8-matched unrelated donor following a conditioning regimen that consisted of intravenous busulfan, fludarabine, and rabbit anti-thymocyte globulin. A total of 18.8 mg of Bu per kg body weight was administered, which was closely adjusted to obtain the recommended total cumulative area under the curve (65–70 mg/L×hr). Hematological engraftment was prompt, and serial chimerism analyses showed sustained complete chimerism on and after day 69. The patient was alive and free from disease 1 year and 9 months after transplantation with no severe treatment-related toxicity. This conditioning regimen is feasible for hematopoietic stem cell transplantation against nonmalignant diseases with a high risk of graft rejection, although long-term follow-up will be required to check for late adverse effects, such as gonadal dysfunction.

Direct Coombs test (DAT)-negative autoimmune hemolytic anemia (AIHA) accounts for approximately 10% of AIHA cases. Low-affinity IgG may contribute to the negative test results. We report the case of a girl aged 4 years and 1 month with severe anemia [hemoglobin (Hb) level, 5.3 mg/dL], suspected of having DAT-negative AIHA owing to low-affinity IgG. Although suspected of having AIHA, her laboratory examinations by the DAT-tube method revealed a negative DAT result. Because her Hb level improved after steroid therapy, she was diagnosed as having DAT-negative AIHA. Her Hb level was dependent on the steroid dose. Rituximab was administered 6 months postadmission. Thereafter, she showed partial improvement and treatment was discontinued 5 years after diagnosis. Her test sample collected at diagnosis and stored under chilled conditions for several days showed DAT C3bC3d positivity. Five years after the disease onset, DAT by the column method revealed IgG positivity. This method did not require RBC washing; in fact, IgG level decreased after RBC washing, suggesting the presence of low-affinity autoantibodies.