Effective VCR/DEX pulse maintenance therapy in the KYCCSG ALL-02 protocol for pediatric acute lymphoblastic leukemia

Abstract

In a previous study of childhood acute lymphoblastic leukemia (ALL) by the Kyushu-Yamaguchi Children's Cancer Study Group, ALL-96, we achieved a 72.1 % 5-year event-free survival (EFS) and an 84.8 % 5-year overall survival (OS). In a subsequent study, ALL-02, we adopted a vincristine dexamethasone (VCR/DEX) pulse regimen as maintenance therapy in the context of the ALL-96 study using the same risk classification and treatment schedule. A total of 156 pediatric cases of ALL were treated with ALL-02. All of the patients were classified as standard-risk or high-risk. Risk stratification was based on white cell counts, immunophenotype, the presence of central nervous system (CNS) disease at diagnosis, organomegaly, and early treatment response (day 14 bone marrow status). The 7-year EFS and OS rates were 77.7 % (95 % CI 70.6-84.8 %) and 89.5 % (95 % CI 84.6-94.4 %), respectively. CNS 3 status [hazard ratio (HR) = 5.0, p = 0.009] and high white blood cell count at diagnosis (HR = 2.6, p = 0.047) were risk factors for poor EFS in multivariate analysis. Our strategies to categorize patients into two risk groups, and to treat with a VCR/DEX pulse were feasible and reasonably effective treatments for pediatric ALL.

Nationwide study of pediatric B‐cell precursor acute lymphoblastic leukemia with chromosome 8q24/MYC rearrangement in Japan

“…the Japanese Childhood Cancer and Leukemia Study Group (CCLSG) ALL2000 MRD (n = 305) and ALL2004 studies (n = 326) 8 ; and the Kyushu-Yamaguchi Childhood Cancer Study Group ALL-02 study (n = 165). 9 Disease classification as either BCP-ALL or Burkitt-ALL was determined by flow-cytometric analysis, according to the Japanese Pediatric Leukemia/Lymphoma Study Group criteria 10 (Supporting Information…”

Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan

“…Diagnostic samples of bone marrow or peripheral blood were obtained from patients with pediatric BCP-ALL enrolled in and treated under clinical trial protocols of the Japan Association of Childhood Leukemia Study Group (JACLS)-ALL02 study ( n =1252), 11 , 12 Tokyo Children's Cancer Study Group (TCCSG)-L04-16 ( n =150), L06-16 ( n =194), L07-16 ( n =274) and L09-16 ( n =607) studies, 13 Childhood Cancer and Leukemia Study Group (CCLSG)-ALL2004 study ( n =325) 14 and Kyushu–Yamaguchi Childhood Cancer Study Group (KYCCSG)-ALL02 study ( n =156). 15 The diagnosis of BCP-ALL was based on morphological findings of bone marrow aspirates and immunophenotypic analyses of leukemic cells by flow cytometry. Conventional cytogenetic analyses and molecular studies were performed as part of the routine work-up in each protocol.…”

“…Conventional cytogenetic analyses and molecular studies were performed as part of the routine work-up in each protocol. 11 , 12 , 13 , 14 , 15 Patients with recurrent fusion transcripts, including ETV6-RUNX1 , E2A-PBX1 , MLL -related fusion and BCR-ABL , and those with high hyperdiploidy were excluded that defined as B-others ALL. Down syndrome-related BCP-ALL was also excluded from this study.…”

Nationwide survey of pediatric hypodiploid acute lymphoblastic leukemia in Japan

“…Treatment was heterogeneous and depended on the clinical trials of each study group, but all clinical trials achieved an EFS rate of 70-80% and an OS rate of 80-90%. 4,[7][8][9][10]12 In terms of the incidence of hypodiploid ALL, the Children's Cancer Group was the first to report that of 1,880 patients, 110 (5.8%) had hypodiploid karyotypes defined as ≤45 chromosomes. 14 In a clinical study by St Jude Children's Research Hospital, the incidence of hypodiploidy with ALL was similar: of 979 patients, 67 (6.8%) had hypodiploidy.…”

“…We retrospectively collected clinical data of patients with hypodiploid ALL from the registries of four clinical study groups in Japan: Tokyo Children's Cancer Study Group (TCCSG); [4][5][6][7] Japan Association of Childhood Leukemia Study (JACLS); 8,9 Japanese Children's Cancer and Leukemia Study Group; 10,11 and Kyushu-Yamaguchi Children's Cancer Study Group. 12 The study protocol was reviewed and approved by the ethics committees of the Institutional Review Boards of Tokyo Metropolitan Children's Medical Center and the four clinical study groups. Out of the 4,261 patients who were registered in the clinical trials between 1997 and 2012, 179 cases (4.2%) of hypodiploid ALL were identified.…”