Approaches to treatment for acute lymphoblastic leukemia in adolescents and young adults



Acute lymphoblastic leukemia affects infants, children, adolescents, and adults. Although most children have a high likelihood of cure, outcomes in adults have much room for improvement. In between lies the adolescent and young adult population, not only in terms of age but also in clinical success rates. This review describes biology, prognostic factors, and treatment approaches in adolescents and young adults with acute lymphoblastic leukemia. Assessing the outcomes in adult and pediatric clinical trials that enroll adolescents and young adults can be especially useful in determining how best to treat these patients. Current new treatment strategies are also discussed.

References and Recommended Reading

  1. 1.
    Pui CH, Relling MV, Downing JR: Acute lymphoblastic leukemia. N Engl J Med 2004, 350:1535–1548.PubMedCrossRefGoogle Scholar
  2. 2.
    Stock W, Tsai T, Golden C, et al.: Cell cycle regulatory gene abnormalities are important determinants of leukemogenesis and disease biology in adult acute lymphoblastic leukemia. Blood 2000, 95:2364–2371.PubMedGoogle Scholar
  3. 3.
    Jemal A, Siegel R, Ward E, et al.: Cancer statistics, 2007. CA Cancer J Clin 2007, 57:43–66.PubMedCrossRefGoogle Scholar
  4. 4.
    Pui CH, Evans WE: Acute lymphoblastic leukemia. N Engl J Med 1998, 339:605–615.PubMedCrossRefGoogle Scholar
  5. 5.
    Chen CS, Sorensen PH, Domer PH, et al.: Molecular rear-rangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome. Blood 1993, 81:2386–2393.PubMedGoogle Scholar
  6. 6.
    Barry E, DeAngelo DJ, Neuberg D, et al.: Favorable outcome for adolescents with acute lymphoblastic leukemia treated on Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium protocols. J Clin Oncol 2007, 25:813–819.PubMedCrossRefGoogle Scholar
  7. 7.
    Armstrong SA, Look AT: Molecular genetics of acute lymphoblastic leukemia. J Clin Oncol 2005, 23:6306–6315.PubMedCrossRefGoogle Scholar
  8. 8.
    Borkhardt A, Cazzaniga G, Viehmann S, et al.: Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in the German and Italian multicenter therapy trials. Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Munster Study Group. Blood 1997, 90:571–577.PubMedGoogle Scholar
  9. 9.
    de Labarthe A, Rousselot P, Huguet-Rigal F, et al.: Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study. Blood 2007, 109:1408–1413.PubMedCrossRefGoogle Scholar
  10. 10.
    Foa R, Vignetti M, Vitale A, et al.: Dasatinib as front-line monotherapy for the induction treatment of adult and elderly Ph+ acute lymphoblastic leukemia (ALL) patients: interim analysis of the GIMEMA prospective study LAL1205 [abstract 7]. Blood (ASH annual meeting abstracts) 2007, 110:7.Google Scholar
  11. 11.
    Wetzler M, Dodge RK, Mrozek K, et al.: Prospective karyotype analysis in adult acute lymphoblastic leukemia: the cancer and leukemia Group B experience. Blood 1999, 93:3983–3993.PubMedGoogle Scholar
  12. 12.
    Pui CH, Evans WE: Treatment of acute lymphoblastic leukemia. N Engl J Med 2006, 354:166–178.PubMedCrossRefGoogle Scholar
  13. 13.
    Goldstone AH, Richards SM, Lazarus HM, et al.: In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood 2008, 111:1827–1833.PubMedCrossRefGoogle Scholar
  14. 14.
    Bruggemann M, Raff T, Flohr T, et al.: Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood 2006, 107:1116–1123.PubMedCrossRefGoogle Scholar
  15. 15.
    Schrappe M, Reiter A, Ludwig WD, et al.: Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. German-Austrian-Swiss ALL-BFM Study Group. Blood 2000, 95:3310–3322.PubMedGoogle Scholar
  16. 16.
    Nachman J: Clinical characteristics, biologic features and outcome for young adult patients with acute lymphoblastic leukaemia. Br J Haematol 2005, 130:166–173.PubMedCrossRefGoogle Scholar
  17. 17.
    Reiter A, Schrappe M, Ludwig WD, 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.PubMedGoogle Scholar
  18. 18.
    Schrappe M, Reiter A, Zimmermann M, et al.: Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995. Berlin-Frankfurt-Munster. Leukemia 2000, 14:2205–2222.PubMedCrossRefGoogle Scholar
  19. 19.
    Kantarjian HM, O’Brien S, Smith TL, et al.: Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol 2000, 18:547–561.PubMedGoogle Scholar
  20. 20.
    Larson RA, Dodge RK, Burns CP, et al.: A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood 1995, 85:2025–2037.PubMedGoogle Scholar
  21. 21.
    Chessells JM, Hall E, Prentice HG, et al.: The impact of age on outcome in lymphoblastic leukaemia; MRC UKALL X and XA compared: a report from the MRC Paediatric and Adult Working Parties. Leukemia 1998, 12:463–473.PubMedCrossRefGoogle Scholar
  22. 22.
    Plasschaert SL, Kamps WA, Vellenga E, et al.: Prognosis in childhood and adult acute lymphoblastic leukaemia: a question of maturation? Cancer Treat Rev 2004, 30:37–51.PubMedCrossRefGoogle Scholar
  23. 23.
    Kuchinskaya E, Heyman M, Grander D, et al.: Children and adults with acute lymphoblastic leukaemia have similar gene expression profiles. Eur J Haematol 2005, 74:466–480.PubMedCrossRefGoogle Scholar
  24. 24.
    Nachman J, Siebel N, Sather H, et al.: Outcome for adolescent and young adults 16–21 years of age (AYA) with acute lymphoblastic leukemia (ALL) treated on the Children’s Cancer Group (CCG) 1961 study [abstract 683]. Blood (ASH annual meeting abstracts) 2004, 104:683.Google Scholar
  25. 25.
    Thomas X, Boiron JM, Huguet F, et al.: Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol 2004, 22:4075–4086.PubMedCrossRefGoogle Scholar
  26. 26.
    Arico M, Valsecchi MG, Camitta B, et al.: Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia. N Engl J Med 2000, 342:998–1006.PubMedCrossRefGoogle Scholar
  27. 27.
    Schultz KR, Bowman WP, Slayton W, et al.: Improved early event free survival (EFS) in children with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) with intensive imatinib in combination with high dose chemotherapy: Children’s Oncology Group (COG) Study AALL0031 [abstract 4]. Blood (ASH annual meeting abstracts) 2007, 110:4.Google Scholar
  28. 28.
    Stock W, La M, Sanford B, et al.: What determines the outcomes for adolescents and young adults with acute lymphoblastic leukemia treated on cooperative group protocols? A comparison of Children’s Cancer Group and Cancer and Leukemia Group B Studies. Blood 2008 (in press).Google Scholar
  29. 29.
    Boissel N, Auclerc MF, Lheritier V, et al.: Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol 2003, 21:774–780.PubMedCrossRefGoogle Scholar
  30. 30.
    de Bont JM, Holt B, Dekker AW, et al.: Significant difference in outcome for adolescents with acute lymphoblastic leukemia treated on pediatric vs adult protocols in the Netherlands. Leukemia 2004, 18:2032–2035.PubMedCrossRefGoogle Scholar
  31. 31.
    Abromowitch M, Ochs J, Pui CH, et al.: High-dose methotrexate improves clinical outcome in children with acute lymphoblastic leukemia: St. Jude Total Therapy Study X. Med Pediatr Oncol 1988, 16:297–303.PubMedCrossRefGoogle Scholar
  32. 32.
    Testi AM, Valsecchi MG, Conter V, et al.: Difference in outcome of adolescents with acute lymphoblastic leukemia (ALL) enrolled in pediatric (AIEOP) and adult (GIMEMA) protocols [abstract 1954]. Blood (ASH annual meeting abstracts) 2004, 104:1954.Google Scholar
  33. 33.
    Ramanujachar R, Richards S, Hann I, et al.: Adolescents with acute lymphoblastic leukaemia: outcome on UK national paediatric (ALL97) and adult (UKALLXII/E2993) trials. Pediatr Blood Cancer 2007, 48:254–261.PubMedCrossRefGoogle Scholar
  34. 34.
    DeAngelo DJ: The treatment of adolescents and young adults with acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program 2005, 123–130.Google Scholar
  35. 35.
    Jeha S: Who should be treating adolescents and young adults with acute lymphoblastic leukaemia? Eur J Cancer 2003, 39:2579–2583.PubMedCrossRefGoogle Scholar
  36. 36.
    Schiffer CA: Differences in outcome in adolescents with acute lymphoblastic leukemia: a consequence of better regimens? Better doctors? Both? J Clin Oncol 2003, 21:760–761.PubMedCrossRefGoogle Scholar
  37. 37.
    Bleyer A: The adolescent and young adult gap in cancer care and outcome. Curr Probl Pediatr Adolesc Health Care 2005, 35:182–217.PubMedCrossRefGoogle Scholar
  38. 38.
    Nachman J, Sather HN, Buckley JD, et al.: Young adults 16–21 years of age at diagnosis entered on Childrens Cancer Group acute lymphoblastic leukemia and acute myeloblastic leukemia protocols. Results of treatment. Cancer 1993, 71:3377–3385.PubMedCrossRefGoogle Scholar
  39. 39.
    DeAngelo DJ, Dahlberg S, Silverman LB, et al.: A multicenter phase II study using a dose intensified pediatric regimen in adults with untreated acute lymphoblastic leukemia [abstract 587]. Blood (ASH annual meeting abstracts) 2007; 110:587.Google Scholar
  40. 40.
    Haiat S, Vekhoff A, Marzac C, et al.: Improved outcome of adult acute lymphoblastic leukemia treated with a pediatric protocol: results of a pilot study [abstract 2822]. Blood (ASH annual meeting abstracts) 2007; 110:2822.Google Scholar
  41. 41.
    Huguet F, Raffoux E, Thomas X, et al.: Towards a pediatric approach in adults with acute lymphoblastic leukemia (ALL): the GRAALL-2003 study [abstract 147]. Blood (ASH annual meeting abstracts) 2006, 108:147.Google Scholar

Copyright information

© Current Medicine Group LLC 2008

Authors and Affiliations

  1. 1.Section of Hematology-OncologyUniversity of Chicago Medical CenterChicagoUSA

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