Tetsuya Takimoto

Recurrent childhood anaplastic large cell lymphoma: a retrospective analysis of registered cases in Japan

This report presents a retrospective study of 26 Japanese children with recurrent anaplastic large cell lymphoma. The first relapses were documented at a median of 10·5 months after the initial diagnosis. Twenty‐four patients achieved a second remission. After a median follow‐up period of 47 months, 18 patients are still alive: 15 patients are in second complete remission (CR), three patients are in third CR or later. The 5 year overall and relapse‐free survival rates were 61 ± 12% and 51 ± 12% respectively. The patients who received allogeneic haematopoietic stem cell transplantation during second CR showed a superior outcome to other patients.

Improved treatment results of children with B‐cell non‐Hodgkin lymphoma: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group B‐NHL03 study

Previous Japanese studies of childhood B‐cell non‐Hodgkin lymphoma (B‐NHL) have shown a favorable outcome, though the study size was too small to effectively assess the efficacy and safety of treatment for childhood B‐NHL.

Prognostic model for predicting overall survival in children and adolescents with rhabdomyosarcoma

BackgroundThe purpose of this study was to develop a prognostic model for the survival of pediatric patients with rhabdomyosarcoma (RMS) using parameters that are measured during routine clinical management.MethodsDemographic and clinical variables were evaluated in 1679 pediatric patients with RMS registered in the Surveillance, Epidemiology, and End Results (SEER) program from 1990 to 2010. A multivariate Cox proportional hazards model was developed to predict median, 5-year and 10-year overall survival (OS). The Akaike information criterion technique was used for model selection. A nomogram was constructed using the reduced model after model selection, and was internally validated.ResultsOf the total 1679 patients, 543 died. The 5-year OS rate was 64.5% (95% confidence interval (CI), 62.1-67.1%) and the 10-year OS was 61.8% (95%CI, 59.2-64.5%) for the entire cohort. Multivariate analysis identified age at diagnosis, tumor size, histological type, tumor stage, surgery and radiotherapy as significantly associated with survival (p < 0.05). The bootstrap-corrected c-index for the model was 0.74. The calibration curve suggested that the model was well calibrated for all predictions.ConclusionsThis study provided an objective analysis of all currently available data for pediatric RMS from the SEER cancer registry. A nomogram based on parameters that are measured on a routine basis was developed. The nomogram can be used to predict 5- and 10-year OS with reasonable accuracy. This information will be useful for estimating prognosis and in guiding treatment selection.

Critical infantile hepatic hemangioma: results of a nationwide survey by the Japanese Infantile Hepatic Hemangioma Study Group

BACKGROUND The current survey aimed to describe the clinical features of critical infantile hepatic hemangioma (IHH) and the implications of recent treatments. MATERIALS AND METHODS A nationwide survey of critical IHH patients treated between 2005 and 2010 was performed in all 117 registered pediatric surgical hospitals in Japan. As a result, 19 patients were identified and reviewed using a statistical analysis. RESULTS Abdominal distention (47.4%), high-output cardiac failure (47.4%), coagulopathy (42.1%), and respiratory distress (31.6%) were the major symptoms. Three patients died (1 of coagulopathy, 1 of cardiac failure, and 1 of both). An accompanying portovenous shunt was also highlighted. Infantile hepatic hemangioma was totally insensitive to steroid treatment in 3 (23.1%) of the 13 patients, and 9 (47.4%) of the 19 patients required other treatments. Surgical resection and β-blocker improved the hematologic data, whereas hepatic arterial ligation and embolization seemed to produce a limited effect. Among the dead patients, several hematologic parameters were significantly worse: the thrombocyte count (pretherapeutic: 73,000 vs 300,000/mm(3), dead vs survivor, respectively [P < .03]; posttherapeutic: 66,000 vs 388,700/mm(3) [P < .003]) and the prothrombin time (posttherapeutic, 35.0 vs 12.1 seconds [P < .0001], dead vs survivor, respectively). CONCLUSION For critical IHH cases with steroid-insensitive hematologic disorders, alternative treatments including β-blocker therapy, surgery, and liver transplantation should be considered.

Features and outcome of neonatal leukemia in Japan: Experience of the Japan Infant Leukemia Study Group

Neonatal leukemia characterized by early stem cell origin and extramedullary infiltration in the first 4 weeks of life is rare. We analyzed the features and outcome of neonatal leukemia in Japan to establish an appropriate treatment strategy for this rare disorder.

Results of the Japan Association of Childhood Leukemia Study (JACLS) NHL-98 protocol for the treatment of B-cell non-Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia in childhood

The Japan Association of Childhood Leukemia Study (JACLS) NHL-98 is a multicenter study designed to evaluate treatment outcomes in Japanese children with B-cell non-Hodgkin lymphoma (B-NHL) and mature B-cell acute lymphoblastic leukemia (B-ALL). The study was supported by a central pathology review system and used a new, standardized protocol with short, intensive treatment regimens. From April 1998 to May 2002, 69 patients with B-NHL and B-ALL up to 16 years of age were enrolled in the NHL-98 study. Treatment was stratified by risk group; patients with limited disease were in groups A and B, and those with extensive disease were in groups C and D. Patients in groups B, C, and D received consolidation phases with high-dose methotrexate (HDMTX) followed by other multi-agent chemotherapy. Patients in group A did not receive either MTX or etoposide. Only patients in group D received etoposide. The event-free survival rates were 100% in groups A and B, 75.1% in group C, and 66.2% in group D. Overall, patients with limited disease had favorable results. For patients with extensive disease, additional treatment options such as increased doses of anticancer drugs warrant further investigation.

Prognostic Impact of Intensified Maintenance Therapy on Children With Advanced Lymphoblastic Lymphoma: A Report From the Japanese Pediatric Leukemia/Lymphoma Study Group ALB-NHL03 Study.

Childhood advanced lymphoblastic lymphoma (LBL) has a favorable outcome with an event‐free survival (EFS) rate of over 80% in response to treatment strategies for acute lymphoblastic leukemia (ALL). However, no progress has been made in this outcome over the past 10 years.

Critical hepatic hemangioma in infants: Recent nationwide survey in Japan

The International Society for the Study of Vascular Anomalies (ISSVA) classification divides vascular lesions into two major entities: neoplasms originating from the vascular endothelium and vascular malformations. Although this concept has been widely accepted, little has been established regarding vascular lesions in deep organs, such as infantile hepatic hemangioma (IHH). The current nationwide survey identified 19 critical infantile hemangiomas during the most recent 5 years. On histopathology all the lesions examined were neoplastic, but portovenos shunt was found histologically or clinically in some cases. High‐output cardiac failure, consumption coagulopathy, and respiratory distress were the major symptoms, and treatment‐resistant coagulopathy seemed to be the most reliable predictor of fatal outcome. Although steroid has been the gold standard treatment for these lesions, 25% of the patients were totally insensitive to steroids, whereas propranolol had a prompt effect in one case. For critical IHH with steroid‐insensitive thrombocytopenia and prothrombin time prolongation, novel therapeutic options including beta‐blocker therapy, surgery, and liver transplantation should be urgently considered as alterative treatment. The present review summarizes the results of the survey.

Prognostic impact of cytogenetic abnormalities in children and adolescents with mature B-cell non-Hodgkin lymphoma: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG)

Little information is available on cytogenetic abnormalities and their prognostic importance in childhood mature B‐cell non‐Hodgkin lymphoma (B‐NHL). We performed a review of 79 abnormal karyotypes in childhood B‐NHL treated by a uniform protocol. Del(17p) was independently associated with significantly inferior event‐free survival in Burkitt or Burkitt‐like lymphoma. The adverse prognosis of MYC/8q24 rearrangement, +7q or del(13q), was not observed, which had been suggested as risk factors in FAB/LMB96. Our results imply the possible existence of a biological difference among ethnicities and should be useful to narrow down the gene causing poor prognosis in childhood B‐NHL. Pediatr Blood Cancer 2015;62:1294–1296.

Management of pediatric renal tumor: Past and future trials of the Japan Wilms Tumor Study Group.

The Japan Wilms Tumor Study group (JWiTS) was founded in 1996 to improve outcomes for children with renal tumor in Japan, and a nationwide multicenter cooperative study was initiated thereafter. JWiTS‐1 (1996–2005) was analyzed, and JWiTS‐2 (2005–2014) is now under analysis; the following problems have been identified and used to decide future study protocol: (i) there has been a decline in survival rate for patients with rhabdoid tumor of the kidney (RTK) and new treatment strategies are required; (ii) the survival rate for bilateral Wilms tumors (BWT) has improved, but results for renal preservation are unsatisfactory; (iii) the prognosis of stage IV favorable nephroblastoma is very good, suggesting that the current protocols provide overtreatment, particularly for patients with lung metastasis; and (iv) no effective biological risk factors exist for predicting the outcome of Wilms tumor, and a study of the genetic changes of these tumors is necessary to determine biological markers for use in risk classification. To solve these issues, the development of a new risk classification of pediatric renal tumors is required. In addition, different study protocols should be developed according to the risk‐based classification of the patients. Further, a new study protocol for BWT began in 2015, and new study protocols are being prepared for RTK, and for Wilms tumor with lung metastasis. In addition, an analysis of biological markers with regard to risk classification is to be performed. Furthermore, to create new protocols for patients with rare renal tumors, international collaboration with Childrens Oncology Group and International Society of Pediatric Oncology is necessary.