JACLS ALL-02 SR protocol reduced-intensity chemotherapy produces excellent outcomes in patients with low-risk childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. As overall cure rates of childhood ALL have improved, reduction of overall treatment intensity while still ensuring excellent outcomes is imperative for low-risk patients. We report the outcomes of patients treated following the standard-risk protocol from the prospective Japan Association of Childhood Leukemia Study (JACLS) ALL-02 study, which was conducted between 2002 and 2008 for patients with newly diagnosed ALL aged 1-18 years.

The incidence of symptomatic osteonecrosis is similar between Japanese children and children in Western countries with acute lymphoblastic leukaemia treated with a Berlin-Frankfurt-Münster (BFM)95-based protocol.

In this study, we performed a retrospective analysis of a cohort of Japanese paediatric patients with B-cell precursor (BCP)-acute lymphoblastic leukaemia (ALL) treated with a Berlin-Frankfurt-Münster (BFM)95-based protocol, to clarify the incidence, clinical characteristics, and risk factors of osteonecrosis (ON) in comparison to the ALL-02 protocol. We identified a high frequency of ON with the BFM95-based protocol compared to the ALL-02 protocol. The incidence of symptomatic ON with the BFM95-based protocol is comparable to previous studies in Western countries.

Combination of clofarabine, etoposide, and cyclophosphamide in adult relapsed/refractory acute lymphoblastic leukemia: a phase 1/2 dose-escalation study by the Japan Adult Leukemia Study Group.

This phase 1/2 study aimed to identify the maximum tolerated dose, the recommended phase 2 dose (RP2D), and efficacy of the clofarabine, etoposide, and cyclophosphamide combination regimen in adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL). Patients aged ≥ 15 years with relapsed/refractory ALL were enrolled. Escalating doses of clofarabine (20-30 mg/m/day × 5 days), etoposide (50-100 mg/m/day × 5 days), and cyclophosphamide (200-440 mg/m/day × 5 days) were administered.

Alectinib for relapsed or refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma: An open-label phase II trial.

Anaplastic lymphoma kinase (ALK) inhibition is expected to be a promising therapeutic strategy for ALK-positive malignancies. We aimed to examine the efficacy and safety of alectinib, a second-generation ALK inhibitor, in patients with relapsed or refractory ALK-positive anaplastic large cell lymphoma (ALCL). This open-label, phase II trial included patients (aged 6 years or older) with relapsed or refractory ALK-positive ALCL.

Attempts to optimize postinduction treatment in childhood acute myeloid leukemia without core-binding factors: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG).

We previously reported that risk-stratified therapy and intensive postremission chemotherapy (PRC) contributed to the improved survival of childhood acute myeloid leukemia (AML) in the AML99 study, which led us to consider a reduction in the number of PRC courses with more restrictive indications for stem cell transplantation (SCT) in the successor AML-05 study. We here report the outcome of AML patients without core-binding factor mutation (non-CBF AML) in the AML-05 study. Two-hundred eighty-nine children (age < 18 years old) with non-CBF AML were eligible.

A risk-stratified therapy for infants with acute lymphoblastic leukemia: a report from the JPLSG MLL-10 trial.

The prognosis for infants with acute lymphoblastic leukemia (ALL), particularly those with KMT2A gene rearrangement (KMT2A-r), is dismal. Continuous efforts have been made in Japan to investigate the role of hematopoietic stem cell transplantation (HSCT) for infants with KMT2A-r ALL, but improvement in outcome was modest. In the Japanese Pediatric Leukemia/Lymphoma Study Group MLL-10 trial, infants with ALL were stratified into 3 risk groups (low risk [LR], intermediate risk [IR], and high risk [HR]) according to KMT2A status, age, and presence of central nervous system leukemia.

Risk-adjusted therapy for pediatric non-T cell ALL improves outcomes for standard risk patients: results of JACLS ALL-02.

This study was a second multicenter trial on childhood ALL by the Japan Childhood Leukemia Study Group (JACLS) to improve outcomes in non-T ALL. Between April 2002 and March 2008, 1138 children with non-T ALL were enrolled in the JACLS ALL-02 trial. Patients were stratified into three groups using age, white blood cell count, unfavorable genetic abnormalities, and treatment response: standard risk (SR), high risk (HR), and extremely high risk (ER).

Negative CD19 expression is associated with inferior relapse-free survival in children with RUNX1-RUNX1T1-positive acute myeloid leukaemia: results from the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 study.

We performed a retrospective analysis of leukaemic surface antigen expression and genomic data from a total of 100 RUNX1-RUNX1T1-positive paediatric acute myeloid leukaemia (AML) patients enrolled in the Japanese Paediatric Leukaemia/Lymphoma Study Group (JPLSG) AML-05 protocol to determine risk factors for relapse. In univariate analysis, the KIT exon 17 mutation (n = 21) and CD19 negativity (n = 59) were significant risk factors for relapse (P = 0·01). In multivariate analysis, CD19 negativity was the sole significant risk factor for relapse (hazard ratio, 3·09; 95% confidence interval, 1·26-7·59; P < 0·01), suggesting that biological differences between CD19-positive and CD19-negative RUNX1-RUNX1T1 AML patients should be investigated.

Discontinuation of L-asparaginase and poor response to prednisolone are associated with poor outcome of ETV6-RUNX1-positive pediatric B-cell precursor acute lymphoblastic leukemia.

ETV6-RUNX1-positive B precursor acute lymphoblastic leukemia (B-ALL) is a common subtype of pediatric B-ALL that has shown excellent outcomes in contemporary clinical trials for pediatric B-ALL. Examinations of the possibility of reducing therapeutic intensity may thus be explored. This prospective study examined outcomes in 205 pediatric patients with ETV6-RUNX1-positive B-ALL uniformly treated following the Japan Association of Childhood Leukemia Study Group (JACLS) ALL-02 protocol.

Prognostic factors of Erdheim-Chester disease: a nationwide survey in Japan.

Erdheim-Chester disease is a rare histiocytosis with insufficient clinical data. To clarify the clinical features and prognostic factors of Erdheim-Chester disease, we conducted a nationwide survey to collect the detailed data of 44 patients with Erdheim-Chester disease in Japan. The median age of onset of the participants was 51 (range: 23-76) years, and the median number of involved organs per patient was 4 (range: 1-11).

Evaluation of high-dose cytarabine in induction therapy for children with de novo acute myeloid leukemia: a study protocol of the Japan Children's Cancer Group Multi-Center Seamless Phase II-III Randomized Trial (JPLSG AML-12).

The purpose of this study is to compare the efficacy and safety of combination therapy (HD-ECM) including high-dose cytarabine in initial induction therapy with that of combination therapy (ECM) involving the continuous administration of cytarabine for previously untreated, newly diagnosed patients with AML at <18 years of age. This is a seamless Phase II-III clinical trial, consisting of Phase II and III parts. In the Phase II part, the safety of the experimental treatment (HD-ECM) will be examined.

Risk-stratified therapy for children with FLT3-ITD-positive acute myeloid leukemia: results from the JPLSG AML-05 study.

Acute myeloid leukemia harboring internal tandem duplication of FMS-like tyrosine kinase 3 (AML) is associated with poor prognosis. We evaluated the results of the AML-05 study, in which all AML patients were assigned to receive hematopoietic stem cell transplantation (HSCT) in the first remission (1CR). We also investigated the effects of additional genetic alterations on FLT3-ITD.

Prognostic value of genetic mutations in adolescent and young adults with acute myeloid leukemia.

Clinical outcomes and the genetic background of acute myeloid leukemia (AML) in adolescent and young adults (AYAs) are known to differ in younger children and older adults. To clarify the impact of genetic mutations on clinical outcomes of AYAs with AML, we analyzed data from the JPLSG AML-05 and JALSG AML201 studies. AYAs aged 15-39 years (n = 103) were included.

Clinical Features and Prognosis According to Immunophenotypic Subtypes Including the Early T-Cell Precursor Subtype of T-Lymphoblastic Lymphoma in the Japanese Pediatric Leukemia/Lymphoma Study Group ALB-NHL03 Study.

We reviewed the immunophenotypic subtypes of pediatric T-cell lymphoblastic lymphoma in the Japanese Pediatric Leukemia/Lymphoma Study Group ALB-NHL03 study. Of the 104 patients, 40 patients each had sufficient data to evaluate the immunophenotypes and early T-cell precursor (ETP) subtype. Pro-T, pre-T, intermediate T, and mature T cells were observed in 1, 9, 21, and 9 cases, respectively.

CXCR4 Overexpression is a Poor Prognostic Factor in Pediatric Acute Myeloid Leukemia With Low Risk: A Report From the Japanese Pediatric Leukemia/Lymphoma Study Group.

Background: Overexpression of CXC chemokine receptor 4 (CXCR4+) is a poor prognostic factor in adult acute myeloid leukemia (AML); however, its prognostic significance in pediatric AML is unclear.

Procedure: This retrospective study examined the prognostic significance of CXCR4+ in pediatric AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 study.

Results: In the total cohort (n = 248), no significant differences were observed between CXCR4+ patients (n = 81) and CXCR4- patients (n = 167) in terms of 3-year overall survival (OS) (69.

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.

Background: 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.

Procedure: We conducted the first nationwide prospective study of childhood advanced LBL to assess the efficacy and safety of ALL-directed therapy with an intensified maintenance phase.