Top

Published in:

01-07-2018 | Original Article

Treatment outcome of children with acute lymphoblastic leukemia: the Tokyo Children’s Cancer Study Group (TCCSG) Study L04-16

Authors: Hiroyuki Takahashi, Ryosuke Kajiwara, Motohiro Kato, Daisuke Hasegawa, Daisuke Tomizawa, Yasushi Noguchi, Kazutoshi Koike, Daisuke Toyama, Hiromasa Yabe, Michiko Kajiwara, Junya Fujimura, Manabu Sotomatsu, Setsuo Ota, Miho Maeda, Hiroaki Goto, Yoko Kato, Tetsuya Mori, Takeshi Inukai, Hiroyuki Shimada, Keitaro Fukushima, Chitose Ogawa, Atsushi Makimoto, Takashi Fukushima, Kentaro Ohki, Katsuyoshi Koh, Nobutaka Kiyokawa, Atsushi Manabe, Akira Ohara

Published in: International Journal of Hematology | Issue 1/2018

Abstract

The survival rate of children with acute lymphoblastic leukemia (ALL) has increased to approximately 90% after substantial progress in risk-oriented treatment strategies. Between 2005 and 2013, the Tokyo Children’s Cancer Study Group (TCCSG) conducted a risk-oriented, non-randomized study, L04-16. The principal aim of this study was to assemble background characteristics and treatment outcomes, and gather genetic information on leukemic cells under central diagnosis. This report outlines the background characteristics and treatment outcomes of 1033 children with ALL treated according to a TCCSG platform. The 5-year event-free and overall survival (OS) rates for all children were 78.1 ± 1.3 and 89.6 ± 1.0%, respectively. The OS rate was significantly higher in children with B-cell precursor (BCP)-ALL (91.9 ± 1.0%, n = 916) than in those with T-ALL (71.9 ± 4.3%, n = 117, p < 0.001). In univariate analysis for BCP-ALL, children aged 1–6 years (5y-OS: 94.2 ± 1.0%), with an initial white blood cell count of < 20,000/μL (94.0 ± 1.0%), high hyperdiploidy (95.4 ± 1.6%), ETV6-RUNX1 (97.4 ± 1.2%) or TCF3-PBX1 (96.9 ± 2.1%), and “Day8NoBlasts” (96.4 ± 1.1%) had the best outcomes. Genetic investigation revealed two novel fusion genes within this cohort: ETV6-ZNF385A and ZNF362-TCF4. Our study highlighted the clinical aspects of genomic features of ALL in Japanese children. We provide fundamental information for the further molecular investigation of this disease.

Available only for authorised users

Pui CH, Carroll WL, Meshinchi S, Arceci RJ. Biology, risk stratification, and therapy of pediatric acute leukemias: an update. J Clin Oncol. 2011;29:551–65.CrossRefPubMed

Pui CH, Mullighan CG, Evans WE, Relling MV. Pediatric acute lymphoblastic leukemia: where are we going and how do we get there? Blood. 2012;120:1165–74.CrossRefPubMedPubMedCentral

Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015;373:1541–52.CrossRefPubMed

Inaba H, Greaves M, Mullighan CG. Acute lymphoblastic leukaemia. Lancet. 2013;381:1943–55.CrossRefPubMed

Locatelli F, Schrappe M, Bernardo ME, Rutella S. How I treat relapsed childhood acute lymphoblastic leukemia. Blood. 2012;120:2807–16.CrossRefPubMed

Bhojwani D, Pui CH. Relapsed childhood acute lymphoblastic leukaemia. Lancet Oncol. 2013;14:e205–17.CrossRefPubMed

Manabe A, Ohara A, Hasegawa D, Koh K, Saito T, Kiyokawa N, et al. Tokyo Children’s Cancer Study Group. Significance of the complete clearance of peripheral blasts after 7 days of prednisolone treatment in children with acute lymphoblastic leukemia: the Tokyo Children’s Cancer Study Group Study L99-15. Haematologica. 2008;93:1155–60.CrossRefPubMed

Hasegawa D, Manabe A, Ohara A, Kikuchi A, Koh K, Kiyokawa N, et al. Tokyo Children’s Cancer Study Group. The utility of performing the initial lumbar puncture on day 8 in remission induction therapy for childhood acute lymphoblastic leukemia: TCCSG L99-15 study. Pediatr Blood Cancer. 2012;58:23–30.CrossRefPubMed

Kato M, Koh K, Manabe A, Saito T, Hasegawa D, Isoyama K, et al. No impact of high-dose cytarabine and asparaginase as early intensification with intermediate-risk paediatric acute lymphoblastic leukaemia: results of randomized trial TCCSG study L99-15. Br J Haematol. 2014;164:376–83.CrossRefPubMed

10.

Koh K, Tomizawa D, Saito AM, Watanabe T, Miyamura T, Hirayama M, et al. Early use of allogeneic hematopoietic stem cell transplantation for infants with MLL gene-rearrangement-positive acute lymphoblastic leukemia. Leukemia. 2015;29:290–6.CrossRefPubMed

11.

Manabe A, Kawasaki H, Shimada H, Kato I, Kodama Y, Sato A, et al. Imatinib use immediately before stem cell transplantation in children with Philadelphia chromosome-positive acute lymphoblastic leukemia: results from Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) Study Ph(+) ALL04. Cancer Med. 2015;4:682–9.CrossRefPubMedPubMedCentral

12.

Tsurusawa M, Mori T, Kikuchi A, Mitsui T, Sunami S, Kobayashi R, et al. Lymphoma committee of Japanese Pediatric Leukemia/Lymphoma Study Group. Improved treatment results of children with B-cell non-Hodgkin lymphoma: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group B-NHL03 study. Pediatr Blood Cancer. 2014;61:1215–21.CrossRefPubMed

13.

Gocho Y, Kiyokawa N, Ichikawa H, Nakabayashi K, Osumi T, Ishibashi T, et al. A novel recurrent EP300-ZNF384 gene fusion in B-cell precursor acute lymphoblastic leukemia. Leukemia. 2015;29:2445–8.CrossRefPubMed

14.

Hirabayashi S, Ohki K, Nakabayashi K, Ichikawa H, Momozawa Y, Okamura K, et al. Tokyo Children’s Cancer Study Group (TCCSG). ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype. Haematologica. 2017;102:118–29.CrossRefPubMedPubMedCentral

15.

Imamura T, Kiyokawa N, Kato M, Imai C, Okamoto Y, Yano M, et al. Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan. Blood Cancer J. 2016;6:e419.CrossRefPubMedPubMedCentral

16.

Möricke A, Reiter A, Zimmermann M, Gadner H, Stanulla M, Dördelmann M, et al. German-Austrian-Swiss ALL-BFM Study Group. Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95. Blood. 2008;111:4477–89.CrossRefPubMed

17.

Smith M, Arthur D, Camitta B, Carroll AJ, Crist W, Gaynon P, et al. Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. J Clin Oncol. 1996;14:18–24.CrossRefPubMed

18.

Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–8.CrossRefPubMed

19.

Kato M, Ishimaru S, Seki M, Yoshida K, Shiraishi Y, Chiba K, et al. Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic leukemia in children. Leukemia. 2017;31:580–4.CrossRefPubMed

20.

Vora A, Andreano A, Pui CH, Hunger SP, Schrappe M, Möricke A, et al. J Clin Oncol. 2016;34:919–26.CrossRefPubMedPubMedCentral

21.

Campana D, Pui CH. Minimal residual disease-guided therapy in childhood acute lymphoblastic leukemia. Blood. 2017;129:1913–8.CrossRefPubMedPubMedCentral

22.

Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer-Grümayer R, Möricke A, et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood. 2010;115:3206–14.CrossRefPubMed

23.

Vora A, Goulden N, Mitchell C, Hancock J, Hough R, Rowntree C, et al. Augmented post-remission therapy for a minimal residual disease-defined high-risk subgroup of children and young people with clinical standard-risk and intermediate-risk acute lymphoblastic leukaemia (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2014;15:809–18.CrossRefPubMed

24.

Pui CH, Pei D, Coustan-Smith E, Jeha S, Cheng C, Bowman WP, et al. Clinical utility of sequential minimal residual disease measurements in the context of risk-based therapy in childhood acute lymphoblastic leukaemia: a prospective study. Lancet Oncol. 2015;16:465–74.CrossRefPubMedPubMedCentral

25.

Larsen EC, Devidas M, Chen S, Salzer WL, Raetz EA, Loh ML, et al. Dexamethasone and high-dose methotrexate improve outcome for children and young adults with high-risk B-acute lymphoblastic leukemia: a report from Children’s Oncology Group Study AALL0232. J Clin Oncol. 2016;34:2380–8.CrossRefPubMedPubMedCentral

26.

Pieters R, de Groot-Kruseman H, Van der Velden V, Fiocco M, van den Berg H, de Bont E, et al. Successful therapy reduction and intensification for childhood acute lymphoblastic leukemia based on minimal residual disease monitoring: study ALL10 from the Dutch Childhood Oncology Group. J Clin Oncol. 2016;34:2591–601.CrossRefPubMed

27.

Wood BL, Winter SS, Dunsmore KP, Devidas M, Chen S, Asselin B, et al. T-lymphoblastic leukemia (T-ALL) shows excellent outcome, lack of significance of the early thymic precursor (ETP) immunophenotype, and validation of the prognostic value of end-induction minimal residual disease (MRD) in Children’s Oncology Group (COG) Study AALL0434. Blood. 2014;124:1 (abstract).CrossRef

28.

Kobayashi K, Mitsui K, Ichikawa H, Nakabayashi K, Matsuoka M, Kojima Y, et al. ATF7IP as a novel PDGFRB fusion partner in acute lymphoblastic leukaemia in children. Br J Haematol. 2014;165:836–41.CrossRefPubMed

29.

Tanaka Y, Kato M, Hasegawa D, Urayama KY, Nakadate H, Kondoh K, et al. Susceptibility to 6-MP toxicity conferred by a NUDT15 variant in Japanese children with acute lymphoblastic leukaemia. Br J Haematol. 2015;171:109–15.CrossRefPubMed

Title: Treatment outcome of children with acute lymphoblastic leukemia: the Tokyo Children’s Cancer Study Group (TCCSG) Study L04-16
Authors: Hiroyuki Takahashi
Ryosuke Kajiwara
Motohiro Kato
Daisuke Hasegawa
Daisuke Tomizawa
Yasushi Noguchi
Kazutoshi Koike
Daisuke Toyama
Hiromasa Yabe
Michiko Kajiwara
Junya Fujimura
Manabu Sotomatsu
Setsuo Ota
Miho Maeda
Hiroaki Goto
Yoko Kato
Tetsuya Mori
Takeshi Inukai
Hiroyuki Shimada
Keitaro Fukushima
Chitose Ogawa
Atsushi Makimoto
Takashi Fukushima
Kentaro Ohki
Katsuyoshi Koh
Nobutaka Kiyokawa
Atsushi Manabe
Akira Ohara
Publication date: 01-07-2018
Publisher: Springer Japan
Published in: International Journal of Hematology / Issue 1/2018
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-018-2440-4

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2018

Nationwide survey of therapy-related leukemia in childhood in Japan

PAS positivity of erythroid precursor cells is associated with a poor prognosis in newly diagnosed myelodysplastic syndrome patients

A low birth weight infant with no malformations delivered by a primary immune thrombocytopenia patient treated with eltrombopag

Systemic Epstein–Barr virus-positive T-cell lymphoproliferative disorders of childhood with fulminant leukocytosis and tumor lysis: a case report with autopsy findings

IgM k multiple myeloma with monoclonal surface immunoglobulin expression

Perioperative safety and hemostatic efficacy of Advate® in patients with hemophilia A in a postmarketing surveillance in Japan

Keynote webinar | Spotlight on antibody–drug conjugates in cancer