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

Abstract

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). Prophylactic cranial radiation therapy (PCRT) was abolished except for CNS leukemia. Four-year event-free survival (4yr-EFS) and 4-year overall survival (4yr-OS) rates for all patients were 85.4% ± 1.1% and 91.2% ± 0.9%, respectively. Risk-adjusted therapy resulted in 4yr-EFS rates of 90.4% ± 1.4% for SR, 84.9% ± 1.6% for HR, and 66.5% ± 4.0% for ER. Based on NCI risk classification, 4yr-EFS rates were 88.2% in NCI-SR and 76.4% in NCI-HR patients, respectively. Compared to previous trial ALL-97, 4yr-EFS of NCI-SR patients was significantly improved (88.2% vs 81.2%, log rank p = 0.0004). The 4-year cumulative incidence of isolated (0.9%) and total (1.5%) CNS relapse were significantly lower than those reported previously. In conclusion, improved EFS in NCI-SR patients and abolish of PCRT was achieved in ALL-02.

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

“…The blast immunophenotypes reported in these publications were similar to those of our patients, except for positivity [23][24][25] By contrast, the standard treatment for ALL is long-term chemotherapy that comprises three phases: induction, consolidation, and maintenance. 26 Treatment intensity categories are classified according to the original risk group to which treatment protocols were applied as follows: JACLS ALL-02 SR and CCLSG ALL2004 SR are categorized as standard-risk ALL-type chemotherapy 5,8 ; whereas JACLS ALL-02 HR, JACLS ALL-02 ER, JACLS ALL-02 F, TCCSG L99-15 HR, TCCSG L99-1502 HEX, TCCSG L0416 HEX, and CCLSG ALL2004 salvage 1 are classified as high-risk ALL-type chemotherapy. 5,8,27,28 A standard chemotherapeutic regimen for BCP-ALL with 8q24/MYC-r has yet to be established, whereas the outcomes of children and adolescents with preBLL described by Herbrueggen et al appeared to be favorable when treated with regimens used for mature B-cell NHL, rather than ALL, despite the biological similarities to BCP-ALL.…”

“…26 Treatment intensity categories are classified according to the original risk group to which treatment protocols were applied as follows: JACLS ALL-02 SR and CCLSG ALL2004 SR are categorized as standard-risk ALL-type chemotherapy 5,8 ; whereas JACLS ALL-02 HR, JACLS ALL-02 ER, JACLS ALL-02 F, TCCSG L99-15 HR, TCCSG L99-1502 HEX, TCCSG L0416 HEX, and CCLSG ALL2004 salvage 1 are classified as high-risk ALL-type chemotherapy. 5,8,27,28 A standard chemotherapeutic regimen for BCP-ALL with 8q24/MYC-r has yet to be established, whereas the outcomes of children and adolescents with preBLL described by Herbrueggen et al appeared to be favorable when treated with regimens used for mature B-cell NHL, rather than ALL, despite the biological similarities to BCP-ALL. 12 In this study, all four patients treated with BL-type chemotherapy, and three of five patients treated with high-risk ALL-type chemotherapy, are alive without disease (Table 1; Figure 1; Supporting Information Table S2).…”

“…Patients with 8q24/ MYC ‐r BCP‐ALL were primarily from among the 4043 patients enrolled in the Japan Association of Childhood Leukemia Study (JACLS) ALL‐02 study ( n = 1252) 5 ; the Tokyo Children's Cancer Study Group (TCCSG) L99‐15 ( n = 770), L04‐16 ( n = 150), L06‐16 ( n = 194), L07‐16 ( n = 274), and L09‐16 ( n = 607) studies 6,7 ; 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 Table S1), which are based on the European Group for the Immunological Characterization of Leukemias criteria 11 .…”

“…Patients with 8q24/MYC-r BCP-ALL were primarily from among the 4043 patients enrolled in the Japan Association of Childhood Leukemia Study (JACLS) ALL-02 study (n = 1252) 5 ; the Tokyo Children's Cancer Study Group (TCCSG) L99-15 (n = 770), L04-16 (n = 150), L06-16 (n = 194), L07-16 (n = 274), and L09-16 (n = 607) studies 6,7 ;…”

Monitoring Ponatinib in a Child with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

“…She responded poorly to prednisolone. Therefore, we started induction chemotherapy based on the Japan Association of Childhood Leukemia Study (JACLS) HR-02 concurrent with dasatinib 60 mg/m 2 /day [5]. Her parents provided consent for treatment.…”