Yasuto Shimomura

Minimal residual disease-based augmented therapy in childhood acute lymphoblastic leukemia: A report from the Japanese Childhood Cancer and Leukemia Study Group†

The majority of minimal residual disease (MRD)‐positive patients with acute lymphoblastic leukemia (ALL) have poor outcomes. The ALL2000 study was performed to evaluate the efficacy of augmented chemotherapy based on MRD‐restratification in childhood ALL.

Continuous and high-dose cytarabine combined chemotherapy in children with down syndrome and acute myeloid leukemia: Report from the Japanese children's cancer and leukemia study group (JCCLSG) AML 9805 down study.

The aim of the JCCLSG AML 9805 Down study was to evaluate the effect of continuous and high‐dose cytarabine combined chemotherapy on the survival outcome of acute myeloid leukemia (AML) with Down syndrome (DS).

Long-term results of the Japanese Childhood Cancer and Leukemia Study Group studies 811, 841, 874 and 911 on childhood acute lymphoblastic leukemia

We analyzed the long-term outcomes of 1021 patients with acute lymphoblastic leukemia (ALL), enrolled in four successive clinical trials (ALL811, ALL841, ALL874 and ALL911) between 1981 and 1993. All patients received risk-adopted therapy according to leukocyte count and age at the time of diagnosis. The median follow-up durations of the four studies were 17.8 years in ALL811, 15.5 years in ALL841, 11.9 years in ALL874 and 15.8 years in ALL911. Patients’ event-free survival (EFS) and overall survival (OS) rates at 12 years were 41.0 and 54.3% in ALL811, 50.2 and 60.2% in ALL841, 57.3 and 64.7% in ALL874, and 63.4 and 71.7% in ALL911, respectively. Thus, cure can become a reality for about 70% of children with ALL. There is, however, still a significant difference in survival outcomes according to risk group. Late effects were observed in 70 patients out of 834 (8.4%); hepatitis and short stature were most commonly reported. Reduction of late adverse effects for all patients and development of new treatment strategies for very-high-risk patients are major issues for upcoming trials to address.

Assessment of Corticosteroid-induced Osteonecrosis in Children Undergoing Chemotherapy for Acute Lymphoblastic Leukemia: A Report From the Japanese Childhood Cancer and Leukemia Study Group

Steroid-induced osteonecrosis (ON) is a challenging complication encountered during modern chemotherapy for childhood acute lymphoblastic leukemia (ALL). We retrospectively assessed the incidence of ON and its risk factors in a total of 1095 patients enrolled in 3 consecutive Japanese Children’s Cancer and Leukemia Study Group ALL studies (ALL941 [1994 to 2000], n=464; ALL2000 [2000 to 2004], n=305; and ALL2004 [2004 to 2010], n=326). ON was diagnosed in 16 patients, of whom 15 were symptomatic. The cumulative incidence of ON was 0.76% in ALL941, 0.35% in ALL2000, and 3.6% in ALL2004. The incidence of ON in ALL941/2000, in which only prednisolone was administered as a steroid, was significantly lower than that in ALL2004, in which dexamethasone was used as a partial substitute for prednisolone (P<0.01). In ALL2004, sex and age were significantly correlated with the incidence of ON (1.3% in boys vs. 6.7% in girls, P=0.0132; 0.42% for age <10 y vs. 15.6% for age ≥10 y, P<0.0001), suggesting that girls aged 10 years and above are at a greater risk of ON onset. These results indicate that the risk of ON should be considered when administering dexamethasone as part of ALL protocol treatment in girls aged 10 years and above.

Assessment of late cardiotoxicity of pirarubicin (THP) in children with acute lymphoblastic leukemia

Pirarubicin (tetrahydropyranyl‐adriamycin: THP) is a derivative of doxorubicin with reportedly less cardiotoxicity in adults. However no studies of cardiotoxicity in children treated with THP have been reported. This study was performed to assess the THP‐induced cardiotoxicity for children with acute lymphoblastic leukemia (ALL).

Favourable outcomes in children with diffuse large B-cell lymphoma treated by a short-term ALL-like regimen: A report on the NHL960 study from the Japanese Childhood Cancer and Leukemia Study Group

In the NHL960 non-LB study, we treated diffuse large B-cell lymphoma (DLBCL) using a short-term ALL-like protocol. Thirty children up to 16 years of age with DLBCL were stratified into group 1 with stage I/II disease, or group 2 with stage III/IV disease. Their ages ranged from 9 months to 16 years of age, with a median of 9 years of age. The Murphys stages were stage I in 7, stage II in 10, stage III in 6, and stage IV in 7 subjects. They received an ALL-like treatment without prophylactic cranial irradiation for 6 or 9 months. All children achieved a complete remission. Two patients with stage 3 disease experienced recurrences at 18 and 37 months after the start of chemotherapy. They responded to a short intensive regimen with Rituximab, followed by stem cell transplantation, and are alive without disease. The follow-up time ranged from 41 to 124 months with a median of 80 months. For all patients analyzed in this study, their overall survival and event-free survival (EFS) at 7-years was 100% and 93% ± 4%, respectively. The 7-year EFS according to the treatment group was 100% for group 1, and 83% ± 11% for group 2, respectively.

Bacteremia Caused by Raoultella ornithinolytica in Two Children.

We encountered 2 immunocompromised children complicated by Raoultella ornithinolytica bacteremia. One had received methylprednisolone pulse therapy for IgA nephropathy, and the other had leukopenia because of chemotherapy for leukemia. Both children had no specific symptoms, and R. ornithinolytica bacteremia was identified by routine blood culture. Both patients were successfully treated with antibiotic treatment.

Medulloblastoma with epithelioid features in the cerebellar vermis.

A 6‐year‐old girl was admitted with a mass lesion in the cerebellar vermis. She underwent subtotal tumor resection, and on immunohistopathology the tumor consisted of two different parts: typical medulloblastoma (MB) characteristics and atypical teratoid/rhabdoid tumor (AT/RT) features, despite positive integrase interactor 1 expression. The patient was diagnosed with MB with epithelioid features. Chemoradiation therapy was started because of tumor recurrence at the primary site and dissemination to the spinal cord, as determined on magnetic resonance imaging 2 weeks after surgery. The patient died due to tumor progression 13 months after initial diagnosis, although transient partial remission was achieved.