Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Educational Report
  • Published:

Acute Leukemias

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

Leukemia volume 24, pages 335–344 (2010)Cite this article

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Pui CH, Evans WE . Acute lymphoblastic leukemia. N Engl J Med 1998; 339: 605–615.

    Article  CAS  Google Scholar 

  2. Pui CH, Relling MV, Downing JR . Acute lymphoblastic leukemia. N Engl J Med 2004; 350: 1535–1548.

    Article  CAS  Google Scholar 

  3. Schrappe M . Evolution of BFM trials for childhood ALL. Ann Hematol 2004; 83: 121–123.

    Google Scholar 

  4. Chessells J . Recent advances in management of acute leukaemia. Arch Dis Child 2000; 82: 438–442.

    Article  CAS  Google Scholar 

  5. Fujimoto T, Hasegawa K, Take H, Miyazaki S, Kishida H, Shin H et al. Maintenance therapy and pharmacokinetics of intermittent high-dose methotrexate in acute childhood leukemia. Acta Haematol Jpn 1977; 40: 119–132.

    CAS  Google Scholar 

  6. Hiyoshi Y, Fujimoto T, Kuriya N, Otani Y, Nibu K, Yanai M et al. Prognostic factors in children with acute lymphoblastic leukemia: II. Multivariate analysis. Jpn J Clin Oncol 1985; 15: 13–23.

    Article  CAS  Google Scholar 

  7. Koizumi S, Fujimoto T, Takeda T, Yatabe M, Utsumi J, Mimaya J et al. Comparison of intermittent or continuous methotrexate plus 6-mercaptopurine in regimens for standard-risk acute lymphoblastic leukemia in childhood (JCCLSG-S811). Cancer 1988; 61: 1292–1300.

    Article  CAS  Google Scholar 

  8. Koizumi S, Fujimoto T . Improvement in treatment of childhood acute lymphoblastic leukemia: a 10-year study by the Children’s Cancer and Leukemia Study Group. Int J Hematol 1994; 59: 99–112.

    CAS  Google Scholar 

  9. Koizumi S, Fujimoto T, Oka T, Watanabe S, Kikuta A, Tsuchiya T et al. Overview of clinical studies of childhood acute lymphoblastic leukemia for more than ten years by the Japanese Children’s Cancer and Leukemia Study Group. Pediatr Hematol Oncol 1997; 14: 17–28.

    Article  CAS  Google Scholar 

  10. Tsurusawa M, Katano N, Yamamoto Y, Hirota T, Koizumi S, Watanabe A et al. Improvement in CNS protective treatment in non-high-risk childhood acute lymphoblastic leukemia: report from the Japanese Children’s Cancer and Leukemia Study Group. Med Pediatr Oncol 1999; 32: 259–266.

    Article  CAS  Google Scholar 

  11. Okamoto T, Yokota S, Katano N, Seriu T, Nakao M, Taniwaki M et al. Minimal residual disease in early phase of chemotherapy reflects poor outcome in children with acute lymphoblastic leukemia—A retrospective study by the Children’s Cancer and Leukemia Study Group in Japan. Leuk Lymph 2002; 43: 1001–1006.

    Article  Google Scholar 

  12. Hori T, Yamaji K, Yokota S, Okamoto T, Watanabe A, Kikuta A et al. Augmented therapy for MRD-positive patients with acute lymphoblastic leukemia can reduce the MRD levels and the risk of relapse: a report from the Japanese Childhood Cancer and Leukemia Study Group ALL 2000 MRD pilot study. Blood 2008; 112: 117 (abstract 301).

    Google Scholar 

  13. 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: 4–6.

    Article  Google Scholar 

  14. Childhood ALL Collaborative Group. Duration and intensity of maintenance chemotherapy in acute lymphoblastic leukaemia: overview of 42 trials involving 12000 randomised children. Lancet 1996; 347: 1783–1788.

    Article  Google Scholar 

  15. Tubergen DG, Gilchrist GS, O’Brien RT, Coccia PF, Sather NH, Waskerwitz MJ et al. Prevention of CNS disease in intermediate-risk acute lymphoblastic leukemia: comparison of cranial radiation and intrathecal methotrexate and importance of systemic therapy: a Children’s Cancer Group report. J Clin Oncol 1993; 11: 520–526.

    Article  CAS  Google Scholar 

  16. Sullivan MP, Chen T, Dyment PG, Hvizdala E, Steuber CP . Equivalence of intrathecal chemotherapy and radiotherapy as central nervous system prophylaxis in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study. Blood 1982; 60: 948–958.

    CAS  Google Scholar 

  17. Pullen J, Boyett J, Shuster J, Crist W, Land V, Frankel L et al. Extended triple intrathecal chemotherapy trial for prevention of CNS relapse in good-risk and poor-risk patients with B-progenitor acute lymphoblastic leukemia: a Pediatric Oncology Group study. J Clin Oncol 1993; 11: 839–849.

    Article  CAS  Google Scholar 

  18. Pui CH, Simone JV, Hancock ML, Evans WE, Williams DL, Bowman WP et al. Impact of three methods of treatment intensification on acute lymphoblastic leukemia in children: long-term results of St Jude total therapy X. Leukemia 1992; 6: 150–157.

    CAS  Google Scholar 

  19. Buhrer C, Henze G, Hofmann J, Reiter A, Schellonq G, Riehm H . Central nervous system relapse prevention in 1165 standard-risk children with acute lymphoblastic leukemia in five BFM trials. Hematol Blood Transfus 1990; 33: 500–503.

    CAS  Google Scholar 

  20. Reiter A, Schrappe M, Ludwig WD, Hiddemann W, Sauter S, Henze G et al. Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86. Blood 1994; 84: 3122–3133.

    CAS  Google Scholar 

  21. Conter V, Arico M, Valsecchi MG, Rizzari C, Testi AM, Messina C et al. Extended intrathecal methotrexate may replace cranial irradiation for prevention of CNS relapse in children with intermediate-risk acute lymphoblastic leukemia treated with Berlin–Frankfurt–Munster-based intensive chemotherapy. J Clin Oncol 1995; 13: 2497–2502.

    Article  CAS  Google Scholar 

  22. Clarke M, Gaynon P, Hann I, Harrison G, Masera G, Peto R et al. CNS-directed therapy for childhood acute lymphoblastic leukemia: Childhood ALL Collaborative Group overview of 43 randomized trials. J Clin Oncol 2003; 21: 1798–1809.

    Article  CAS  Google Scholar 

  23. Steinherz PG . Radiotherapy vs intrathecal chemotherapy for CNS prophylaxis in childhood ALL. Oncology 1989; 3: 47–53.

    CAS  Google Scholar 

  24. Cherlow JM, Steinherz PG, Sather HN, Gaynon PS, Grossman NJ, Kersey JH et al. The role of radiation therapy in the treatment of acute lymphoblastic leukemia with lymphomatous presentation: a report from the Children’s Cancer Group. Int J Radiat Oncol Biol Phys 1993; 27: 1001–1009.

    Article  CAS  Google Scholar 

  25. Pui CH, Campana D, Deqing P, Bowman WP, Sandlund JT, Kaste SC et al. Treating childhood acute lymphoblastic leukaemia without cranial irradiation. N Engl J Med 2009; 360: 2730–2741.

    Article  CAS  Google Scholar 

  26. Chessells JM, Veys P, Kempski H, Henley P, Leiper A, Webb D et al. Long-term follow-up of relapsed childhood acute lymphoblastic leukaemia. Br J Haematol 2003; 123: 396–405.

    Article  Google Scholar 

  27. Davies SM . Subsequent malignant neoplasms in survivors of childhood cancer: Childhood Cancer Survivor Study (CCSS) studies. Pediatr Blood Cancer 2007; 48: 727–730.

    Article  Google Scholar 

  28. Steinherz LJ, Graham T, Hurwitz R, Sondheimer HM, Schaffer EM, Schwartz RG et al. Guidelines for monitoring of anthracycline cardiomyopathy: a rebuttal. Pediatrics 1994; 93: 433–437.

    Google Scholar 

  29. Dantchev D, Paintrand M, Hayat M, Bourut C, Mathe G . Low heart and skin toxicity of a tetrahydropyranyl derivative of adriamycin (THPADM) as observed by electron and light microscopy. J Antibiot (Tokyo) 1979; 32: 1085–1086.

    Article  CAS  Google Scholar 

  30. Chauvergne J, Fumoleau P, Cappelaere P, Metz R, Armand JP, Chevallier B et al. Phase II study of pirarubicin (THP) in patients with cervical, endometrial and ovarian cancer: study of the Clinical Screening Group of the European Organization for Research and Treatment of Cancer (EORTC). Eur J Cancer 1993; 29A: 350–354.

    Article  CAS  Google Scholar 

  31. Oeffinger KC, Eshelman DA, Tomlinson GE, Buchanan GR, Foster BM . Grading of late effects in young adult survivors of childhood cancer followed in an ambulatory adult setting. Cancer 2000; 88: 1687–1695.

    Article  CAS  Google Scholar 

  32. Landier W, Bhatia S, Eshelman DA, Forte KJ, Sweeney T, Hester AL et al. Development of risk-based guidelines for pediatric cancer survivors: the Children’s Oncology Group Long-Term Follow-up Guidelines from the Children’s Oncology Group Late Effects Committee and Nursing Discipline. J Clin Oncol 2004; 22: 4979–4990.

    Article  Google Scholar 

Download references

Acknowledgements

We thank the patients who enrolled in these studies and their families.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Aichi Medical University, Aichi, Japan

    M Tsurusawa & Y Shimomura

  2. Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, Japan

    K Asami

  3. Department of Pediatrics, Fukushima Medical School, Fukushima, Japan

    A Kikuta

  4. Department of Pediatrics, Nakadori Hospital, Akita, Japan

    A Watanabe

  5. Division of Hematology and Oncology, Shizuoka Children's Hospital, Shizuoka, Japan

    Y Horikoshi

  6. Department of Pediatrics, International Medical Center of Japan, Tokyo, Japan

    T Matsushita

  7. Department of Pediatrics, Toyama Medical and Pharmaceutical University, Toyama, Japan

    H Kanegane

  8. Department of Pediatrics, Shiga Medical School, Shiga, Japan

    S Ohta

  9. Division of Pediatrics, Kagawa National Children's Hospital, Kagawa, Japan

    A Iwai

  10. Department of Pediatrics, Nihon University, Itabashi Hospital, Tokyo, Japan

    H Mugishima

  11. Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan

    S Koizumi

Authors
  1. M Tsurusawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y Shimomura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K Asami
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A Kikuta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y Horikoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T Matsushita
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H Kanegane
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S Ohta
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A Iwai
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. H Mugishima
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. S Koizumi
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for the Japanese Childhood Cancer and Leukemia Study Group

Corresponding author

Correspondence to M Tsurusawa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tsurusawa, M., Shimomura, Y., Asami, K. et al. Long-term results of the Japanese Childhood Cancer and Leukemia Study Group studies 811, 841, 874 and 911 on childhood acute lymphoblastic leukemia. Leukemia 24, 335–344 (2010). https://doi.org/10.1038/leu.2009.259

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2009.259

Keywords

This article is cited by

Search

Advanced search

Quick links