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 pediatric oncology group studies for childhood acute lymphoblastic leukemia 1984–2001: a report from the children's oncology group

Leukemia volume 24, pages 355–370 (2010)Cite this article

Abstract

From 1984 to 2001, the Pediatric Oncology Group (POG) conducted 12 acute lymphoblastic leukemia (ALL) studies. Ten-year event-free survival (EFS) for patients >12 months of age with B-precursor ALL on acute leukemia in children 14, 15 and 16 series were 66.7±1.2%, 68.1±1.4% and 73.2±2.1%, respectively. Intermediate dose methotrexate (ID MTX; 1 g/m2) improved outcomes for standard risk patients (10-year EFS 77.5±2.7% vs 66.3±3.1% for oral MTX). Neither MTX intensification (2.5 g/m2) nor addition of cytosine arabinoside/daunomycin/teniposide improved outcomes for higher risk patients. Intermediate dose mercaptopurine (1 g/m2) failed to improve outcomes for either group. Ten-year EFS for patients with T-cell ALL, POG 8704 and 9404 were 49.1±3.1% and 72.2±4.7%, respectively. Intensive asparaginase (10-year EFS 61.8 vs 42.7%) and high-dose MTX (5 g/m2) (10-year EFS 78.0 vs 65.8%) improved outcomes. There was a non-significant improvement in EFS for infants (10-year EFS 17.7±7.2–31.9±8.3%). Prognostic indicators for B-precursor ALL were age and WBC at diagnosis, gender, central nervous system disease, DNA index and cytogenetic abnormalities. Only gender was prognostic in T-cell ALL. In infants, WBC and MLL translocation were linked to inferior outcome.

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
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Fast Stats. An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute http://seer.cancer.gov/faststats. (Accessed on 25 August 2009).

  2. Pulte D, Gondos A, Brenner H . Trends in 5- and 10-year survival after diagnosis with childhood hematologic malignancies in the United States, 1990–2004. J Natl Cancer Inst 2008; 100: 1301–1309.

    Article  Google Scholar 

  3. Hunger S, Devidas M, Camitta B, Gaynon P, Winick N, Reaman G et al. Improved Survival For Children With Acute Lymphoblastic Leukemia (ALL) From 1990–2005: A Report From The Childrens Oncology Group (COG). SIOP 3–6 Oct 2008 Wiley-Liss Inc.: Berlin, Germany. p. 31.

  4. Harris MB, Shuster JJ, Pullen DJ, Borowitz MJ, Carroll AJ, Behm FG et al. Consolidation therapy with antimetabolite-based therapy in standard-risk acute lymphocytic leukemia of childhood: a Pediatric Oncology Group Study. J Clin Oncol 1998; 16: 2840–2847.

    Article  CAS  Google Scholar 

  5. Harris MB, Shuster JJ, Pullen J, Borowitz MJ, Carroll AJ, Behm FG et al. Treatment of children with early pre-B and pre-B acute lymphocytic leukemia with antimetabolite-based intensification regimens: a Pediatric Oncology Group Study. Leukemia 2000; 14: 1570–1576.

    Article  CAS  Google Scholar 

  6. Land VJ, Shuster JJ, Crist WM, Ravindranath Y, Harris MB, Krance RA et al. Comparison of two schedules of intermediate-dose methotrexate and cytarabine consolidation therapy for childhood B-precursor cell acute lymphoblastic leukemia: a Pediatric Oncology Group Study. J Clin Oncol 1994; 12: 1939–1945.

    Article  CAS  Google Scholar 

  7. Mahoney DH, Shuster J, Nitschke R, Lauer SJ, Winick N, Steuber CP et al. Intermediate-dose intravenous methotrexate with intravenous mercaptopurine is superior to repetitive low-dose oral methotrexate with intravenous mercaptopurine for children with lower-risk B-lineage acute lymphoblastic leukemia: a Pediatric Oncology Group phase III trial. J Clin Oncol 1998; 16: 246–254.

    Article  CAS  Google Scholar 

  8. Lauer SJ, Shuster JJ, Mahoney Jr DH, Winick N, Toledano S, Munoz L et al. A comparison of early intensive methotrexate/mercaptopurine with early intensive alternating combination chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group phase III randomized trial. Leukemia 2001; 15: 1038–1045.

    Article  CAS  Google Scholar 

  9. Chauvenet AR, Martin PL, Devidas M, Linda SB, Bell BA, Kurtzberg J et al. Antimetabolite therapy for lesser-risk B-lineage acute lymphoblastic leukemia of childhood: a report from Children′s Oncology Group Study P9201. Blood 2007; 110: 1105–1111.

    Article  CAS  Google Scholar 

  10. Rodes S, Bell BA, Abish SB, Pullen J, Chauvenet A, Kurtzberg J et al. A Report of the Event-Free Survival (EFS) and Neurotoxicity for Children with Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia (ALL) on Pediatric Oncology Group (POG) Protocol 9405. ASH Annual Meeting Abstracts 2005; 106: 882–888.

    Google Scholar 

  11. Bell BA, Abish SB, Chauvenet A, Kurtzberg J, Pullen J, Devidas M et al. A Report of the Event Free Survival (EFS) for Children with Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia (ALL) Treated on Pediatric Oncology Group (POG) Protocol 9605. ASH Annual Meeting Abstracts 2005; 106: 875–887.

    Google Scholar 

  12. Carson TY, Bell BA, Erdmann G, Bostrom B, Camitta BM, Devidas M . Possible advantage of twice-daily 6-mercaptopurine dosing in children with Acute Lymphoblastic Leukemia (ALL). ASH Annual Meeting Abstracts 2007; 110: 851–885.

    Google Scholar 

  13. Smith M, Arthur D, Camitta B, Carroll A, 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.

    Article  CAS  Google Scholar 

  14. Winick N, Shuster JJ, Bowman WP, Borowitz M, Farrow A, Jacaruso D et al. Intensive oral methotrexate protects against lymphoid marrow relapse in childhood B-precursor acute lymphoblastic leukemia. J Clin Oncol 1996; 14: 2803–2811.

    Article  CAS  Google Scholar 

  15. Winick NJ, McKenna RW, Shuster JJ, Schneider NR, Borowitz MJ, Bowman WP et al. Secondary acute myeloid leukemia in children with acute lymphoblastic leukemia treated with etoposide. J Clin Oncol 1993; 11: 209–217.

    Article  CAS  Google Scholar 

  16. Amylon MD, Shuster J, Pullen J, Berard C, Link MP, Wharam M et al. Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group Study. Leukemia 1999; 13: 335–342.

    Article  CAS  Google Scholar 

  17. Asselin B, Shuster J, Amylon M, Halperin E, Hutchinson R, Lipshultz S et al. Improved Event-Free Survival (EFS) with High Dose Methotrexate (HDM) in T-Cell Lymphoblastic Leukemia (T-ALL) and Advanced Lymphoblastic Lymphoma (T-NHL): a Pediatric Oncology Group (POG) Study. J Clin Oncol (Meeting Abstracts) 2001; 20: 1464.

    Google Scholar 

  18. Clavell LA, Gelber RD, Cohen HJ, Hitchcock-Bryan S, Cassady JR, Tarbell NJ et al. Four-agent induction and intensive asparaginase therapy for treatment of childhood acute lymphoblastic leukemia. N Engl J Med 1986; 315: 657–663.

    Article  CAS  Google Scholar 

  19. Silverman LB, Declerck L, Gelber RD, Dalton VK, Asselin BL, Barr RD et al. Results of Dana-Farber Cancer Institute Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981–1995). Leukemia 2000; 14: 2247–2256.

    Article  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. Jones RL . Utility of dexrazoxane for the reduction of anthracycline-induced cardiotoxicity. Exp Rev Cardiovascular Ther 2008; 6: 1311–1317.

    Article  CAS  Google Scholar 

  22. Lauer SJ, Camitta BM, Leventhal BG, Mahoney D, Shuster JJ, Kiefer G et al. Intensive alternating drug pairs after remission induction for treatment of infants with acute lymphoblastic leukemia: a Pediatric Oncology Group Pilot Study. J Pediatr Hematol Oncol 1998; 20: 229–233.

    Article  CAS  Google Scholar 

  23. Frankel LS, Ochs J, Shuster JJ, Dubowy R, Bowman WP, Hockenberry-Eaton M et al. Therapeutic trial for infant acute lymphoblastic leukemia: the Pediatric Oncology Group experience (POG 8493). J Pediatr Hematol Oncol 1997; 19: 35–42.

    Article  CAS  Google Scholar 

  24. Kaplan E, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  25. Gray R . A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988; 16: 1141–1154.

    Article  Google Scholar 

  26. Mahoney Jr DH, Shuster JJ, Nitschke R, Lauer SJ, Steuber CP, Winick N et al. Acute neurotoxicity in children with B-precursor acute lymphoid leukemia: an association with intermediate-dose intravenous methotrexate and intrathecal triple therapy--a Pediatric Oncology Group Study. J Clin Oncol 1998; 16: 1712–1722.

    Article  CAS  Google Scholar 

  27. Harris MB, Shuster JJ, Carroll A, Look AT, Borowitz MJ, Crist WM et al. Trisomy of leukemic cell chromosomes 4 and 10 identifies children with B-progenitor cell acute lymphoblastic leukemia with a very low risk of treatment failure: a Pediatric Oncology Group Study. Blood 1992; 79: 3316–3324.

    CAS  Google Scholar 

  28. Schrappe M, Reiter A, Zimmermann M, Harbott J, Ludwig W-D, Henze G et al. Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981–1995. Leukemia 2000; 14: 2205–2222.

    Article  CAS  Google Scholar 

  29. Hann I, Vora A, Harrison G, Harrison C, Eden O, Hill F et al. Determinants of outcome after intensified therapy of childhood lymphoblastic leukaemia: results from Medical Research Council United Kingdom acute lymphoblastic leukaemia XI protocol. Br J Haematol 2001; 113: 103–114.

    Article  CAS  Google Scholar 

  30. Nguyen K, Devidas M, Cheng SC, La M, Raetz EA, Carroll WL et al. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children′s Oncology Group study. Leukemia 2008; 22: 2142–2150.

    Article  CAS  Google Scholar 

  31. Lauer SJ, Pinkel D, Buchanan GR, Sartain P, Cornet JM, Krance R et al. Cytosine arabinoside/cyclophosphamide pulses during continuation therapy for childhood acute lymphoblastic leukemia. Potential selective effect in T-cell leukemia. Cancer 1987; 60: 2366–2371.

    Article  CAS  Google Scholar 

  32. Steuber CP, Levy GJ, Nix WL, Shepherd DA, Starling KA, Fernbach DJ . Use of L-asparaginase and cytosine arabinoside for refractory acute lymphocytic leukemia with particular reference to T-cell leukemia. Med Pediatr Oncol 1978; 5: 33–38.

    Article  CAS  Google Scholar 

  33. Dahl GV, Rivera G, Pui CH, Mirro Jr J, Ochs J, Kalwinsky DK et al. A novel treatment of childhood lymphoblastic non-Hodgkin's lymphoma: early and intermittent use of teniposide plus cytarabine. Blood 1985; 66: 1110–1114.

    CAS  Google Scholar 

  34. Goldberg JM, Silverman LB, Levy DE, Dalton VK, Gelber RD, Lehmann L et al. Childhood T-Cell Acute Lymphoblastic Leukemia: the Dana–Farber cancer institute acute lymphoblastic leukemia consortium experience. J Clin Oncol 2003; 21: 3616–3622.

    Article  Google Scholar 

  35. Moghrabi A, Levy DE, Asselin B, Barr R, Clavell L, Hurwitz C et al. Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95–01 for children with acute lymphoblastic leukemia. Blood 2007; 109: 896–904.

    Article  CAS  Google Scholar 

  36. Pui CH, Relling MV, Behm FG, Hancock ML, Boyett JM, Raimondi SC et al. L-asparaginase may potentiate the leukemogenic effect of the epipodophyllotoxins. Leukemia 1995; 9: 1680–1684.

    CAS  Google Scholar 

  37. Felix CA . Secondary leukemias induced by topoisomerase-targeted drugs. Biochimica et Biophysica Acta 1998; 1400: 233–255.

    Article  CAS  Google Scholar 

  38. Hutchinson RJ, Gaynon PS, Sather H, Bertolone SJ, Cooper HA, Tannous R et al. Intensification of Therapy for Children With Lower-Risk Acute Lymphoblastic Leukemia: Long-Term Follow-Up of Patients Treated on Children's Cancer Group Trial 1881. J Clin Oncol 2003; 21: 1790–1797.

    Article  Google Scholar 

  39. Nachman JB, Sather HN, Sensel MG, Trigg ME, Cherlow JM, Lukens JN et al. Augmented post-induction therapy for children with high-risk acute lymphoblastic leukemia and a slow response to initial therapy. N Engl J Med 1998; 338: 1663–1671.

    Article  CAS  Google Scholar 

  40. Lange BJ, Bostrom BC, Cherlow JM, Sensel MG, La MKL, Rackoff W et al. Double-delayed intensification improves event-free survival for children with intermediate-risk acute lymphoblastic leukemia: a report from the Children′s Cancer Group. Blood 2002; 99: 825–833.

    Article  CAS  Google Scholar 

  41. Gaynon PS, Trigg ME, Heerema NA, Sensel MG, Sather HN, Hammond GD et al. Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983–1995. Leukemia 2000; 14: 2223–2233.

    Article  CAS  Google Scholar 

  42. Bostrom BC, Sensel MR, Sather HN, Gaynon PS, La MK, Johnston K et al. Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group. Blood 2003; 101: 3809–3817.

    Article  CAS  Google Scholar 

  43. Seibel NL, Steinherz PG, Sather HN, Nachman JB, Delaat C, Ettinger LJ et al. Early postinduction intensification therapy improves survival for children and adolescents with high-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood 2008; 111: 2548–2555.

    Article  CAS  Google Scholar 

  44. Mullighan CG, Downing JR . Genome-wide profiling of genetic alterations in acute lymphoblastic leukemia: recent insights and future directions. Leukemia 2009; 23: 1209–1218.

    Article  CAS  Google Scholar 

  45. de Haas V, Dee R, Cheroutre G, van den Berg H, van der Schoot CE . Gene expression profile of slowly responding subclones might represent different profiles already at diagnosis and might be used for prediction of outcome. Leukemia 2008; 23: 816–819.

    Article  Google Scholar 

  46. Ratei R, Basso G, Dworzak M, Gaipa G, Veltroni M, Rhein P et al. Monitoring treatment response of childhood precursor B-cell acute lymphoblastic leukemia in the AIEOP-BFM-ALL 2000 protocol with multiparameter flow cytometry: predictive impact of early blast reduction on the remission status after induction. Leukemia 2008; 23: 528–534.

    Article  Google Scholar 

  47. Flohr T, Schrauder A, Cazzaniga G, Panzer-Grumayer R, van der Velden V, Fischer S et al. Minimal residual disease-directed risk stratification using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the international multicenter trial AIEOP-BFM ALL 2000 for childhood acute lymphoblastic leukemia. Leukemia 2008; 22: 771–782.

    Article  CAS  Google Scholar 

  48. Andersson A, Ritz C, Lindgren D, Eden P, Lassen C, Heldrup J et al. Microarray-based classification of a consecutive series of 121 childhood acute leukemias: prediction of leukemic and genetic subtype as well as of minimal residual disease status. Leukemia 2007; 21: 1198–1203.

    Article  CAS  Google Scholar 

  49. Real PJ, Ferrando AA . NOTCH inhibition and glucocorticoid therapy in T-cell acute lymphoblastic leukemia. Leukemia 2009; 23: 1374–1377.

    Article  CAS  Google Scholar 

  50. Larson Gedman A, Chen Q, Kugel Desmoulin S, Ge Y, LaFiura K, Haska CL et al. The impact of NOTCH1, FBW7 and PTEN mutations on prognosis and downstream signaling in pediatric T-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group. Leukemia 2009; 23: 1417–1425.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by NIH. The research is supported by POG Grants CA 30969 and CA 29139, as well as the Chair's Grant U10 CA98543 and the Statistics and Data Center Grant U10 CA98413 of the Children's Oncology Group from the National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. A complete listing of grant support for research conducted by CCG and POG before initiation of the COG grant in 2003 is available online at: http://www.childrensoncoogygroup.org/admin/grantinfo.htm. SPH is the Ergen Family Chair in Pediatric Cancer. The opinions and assertions contained herein are the private views of the author(s) and are not to be construed as the official policy or position of the US Government, the Department of Defense, or the Department of the Air Force.

Author information

Authors and Affiliations

  1. National Cancer Institute, Bethesda, MD, USA

    W L Salzer

  2. Department of Epidemiology and Health Policy Research, College of Medicine, University of Florida and the Children's Oncology Group, Gainesville, FL, USA

    M Devidas

  3. Department of Pediatrics, Division of Pediatric Hematology/Oncology, New York University Cancer Institute, New York, NY, USA

    W L Carroll

  4. Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Texas Southwestern School of Medicine, Dallas, TX, USA

    N Winick

  5. Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Mississippi School of Medicine, Jackson, MS, USA

    J Pullen

  6. Department of Pediatrics, University of Colorado Denver School of Medicine and the Children's Hospital, Aurora, CO, USA

    S P Hunger

  7. Department of Pediatrics of the Medical College of Wisconsin and Children's Hospital of Wisconsin, Center for Cancer and Blood Disorders, Milwaukee, WI, USA

    B A Camitta

Authors
  1. W L Salzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Devidas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W L Carroll
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N Winick
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Pullen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S P Hunger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B A Camitta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to W L Salzer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Salzer, W., Devidas, M., Carroll, W. et al. Long-term results of the pediatric oncology group studies for childhood acute lymphoblastic leukemia 1984–2001: a report from the children's oncology group. Leukemia 24, 355–370 (2010). https://doi.org/10.1038/leu.2009.261

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2009.261

Keywords

This article is cited by

Search

Advanced search

Quick links