Seminars in Oncology
Volume 36, Issue 3 , Pages 213-226 , June 2009

Acute Leukemia in Adolescents and Young Adults

  • Anjali S. Advani

      Affiliations

    • The Cleveland Clinic Lerner College of Medicine and Department of Hematologic Oncology and Blood Disorders, The Cleveland Clinic, Cleveland, OH
    • ,
  • Stephen P. Hunger

      Affiliations

    • The Children's Hospital and the Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, CO
    • ,
  • Alan K. Burnett

      Affiliations

    • Department of Haematology, School of Medicine, Cardiff University, Cardiff, United Kingdom
    • Corresponding Author InformationAddress correspondence to Alan K. Burnett, MBChB, MD, Professor of Haematology, School of Medicine, Cardiff University, Heat Park, Cardiff CF4 14XN, UK

References 

  1. Bleyer A, Montello M, Budd T. Young adults with leukemia in the United States: lack of clinical trial participation and mortality reduction during the last decade [abstract]. J Clin Oncol 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2004;22(Suppl 14):6623
  2. Larson S, Stock W. Progress in the treatment of adults with acute lymphoblastic leukemia. Curr Opin Hematol. 2008;14:400–407
  3. Usvasalo A, Raty R, Knuutila S, Vettenranta K, Harila-Saari A, Jantunen E, et al. Acute lymphoblastic leukemia in adolescents and young adults in Finland. Haematologica. 2008;93:1161–1168
  4. DeAngelo DJ. The treatment of adolescents and young adults with acute lymphoblastic leukaemia. Am Soc Hematol Educ Book. 2005;123–130
  5. Secker-Walker LM, Craig JM, Hawkins JM, Hoffbrand AV. Philadelphia chromosome positive acute lymphoblastic leukemia in adults: age distribution, BCR breakpoint and prognostic significance. Leukemia. 1991;5:196–199
  6. Aguiar RC, Sohal J, van Rhee F, Carapeti M, Franklin IM, Goldstone AH, et al. TEL-AML1 fusion in acute lymphoblastic leukaemia of adults (MRC Adult Leukaemia Working Party). Br J Haematol. 1996;95:673–677
  7. Borkhardt A, Cazzaniga G, Viehmann S, Valsecchi MG, Ludwig WD, Burci L, 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 Ematologica Oncologia Pediatrica and the Berlin-Frankfurt-Munster Study Group). Blood. 1997;90:571–576
  8. Jeha S. Who should be treating adolescents and young adults with acute lymphoblastic leukaemia?. Eur J Cancer. 2003;39:2579–2583
  9. Whitehead VM, Vuchich MJ, Lauer SJ, Mahoney D, Carroll AJ, Shuster JJ, et al. Accumulation of high levels of methotrexate polyglutamates in lymphoblasts from children with hyperdiploid (greater than 50 chromosomes) B-lineage acute lymphoblastic leukaemia: a Pediatric Oncology Group study. Blood. 1992;80:1316–1323
  10. Nachman J, Masera G, Bleyer A. Acute Lymphoblastic leukemia. In:  Bleyer WA,  Barr RE editor. Cancer in adolescents and young adults. Heidelberg: Springer; 2007;p. 83–98
  11. Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, Raimondi SC, et al. Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell. 2002;1:75–87
  12. Weng AP, Ferrando AA, Lee W, Morris JP, Silverman LB, Sanchez-Irizarry C, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 2004;306:269–271
  13. Nachman J. Clinical characteristics, biologic features and outcome for young adult patients with acute lymphoblastic leukaemia. Br J Haematol. 2005;130:166–173
  14. Kaspers GJ, Veerman AJ, Pieters R, Van Zantwijk CH, Smets LA, Van Wering ER, et al. In vitro cellular drug resistance and prognosis in newly diagnosed childhood acute lymphoblastic leukemia. Blood. 1997;90:2723–2729
  15. Roman-Gomez J, Jimenez-Velasco A, Castillejo JA, Agirre X, Barrios M, Navarro G, et al. Promoter hypermethylation of cancer-related genes: a strong independent prognostic factor in acute lymphoblastic leukemia. Blood. 2004;104:2492–2496
  16. Stock W, La M, Sanford B, Bloomfield CD, Vardiman JW, Gaynon P, 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;112:1646–1654
  17. Boissel N, Auclerc MF, Lheritier V. 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
  18. de Bont JM, Holt B, Dekker AW, van der Does-van den Berg, Sonneveld P, Pieters R. Significant difference in outcome for adolescents with acute lymphoblastic leukemia treated on pediatric vs. adult protocols in the Netherlands. Leukemia. 2004;18:2032–2035
  19. Nachman J, Sather HN, Buckley JD, Gaynon PS, Steinherz PG, Tubergen DG, et al. Young adults 16-21 years of age at diagnosis entered on Children's Cancer Group acute lymphoblastic leukemia and acute myeloblastic leukemia protocols (Results of treatment). Cancer. 1993;71:3377–3385
  20. Ribera JM, Oriol A, Sanz MA, Tormo M, Fernandez-Abellan P, del Potro E, et al. Comparison of the results of the treatment of adolescents and young adults with standard-risk acute lymphoblastic leukemia with the Program Espanol de Tratamiento en Hematologia pediatric-based protocol ALL-96. J Clin Oncol. 2008;26:1843–1849
  21. DeAngelo D, Dahlberg S, Silverman LB. A multicenter phase II study using a dose intensified pediatric regimen in adults with untreated acute lymphoblastic leukaemia [abstract]. Blood. 2007;110:587
  22. Huget F, Pigneux A, Thomas XP, Chevallier A, Buzyn Y, Chalandon E, et al. For the Group for Research on Adult ALL (GRAALL) (Outcome of a pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL): final results of the GRAALL-2003 study [abstract]). J Clin Oncol ASCO Annual Meeting Proceedings. 2008;26:7005
  23. Goldstone AH, Richards SM, Fielding AK, Rowe JM. Chemotherapy or allografting for young adults with high-risk ALL? Response. Blood. 2008;111:5755
  24. Rubnitz JE, Lensing S, Zhou Y, Sandlund JT, Razzouk BI, Ribeiro RC, et al. Death during induction therapy and first remission of acute leukemia in childhood. Cancer. 2004;101:1677–1684
  25. Mattano LA, Sather HN, Trigg ME, Nachman JB. Osteonecrosis as a complication of treating acute lymphoblastic leukemia in children: a report from the Children's Cancer Group. J Clin Oncol. 2000;18:3262–3272
  26. Barry E, DeAngelo DJ, Neuberg D, Stevenson K, Loh ML, Asselin BL, 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
  27. Kern W, Haferlach T, Schoch C, Loffler H, Gassmann W, Heinecke A, et al. Early blast clearance by remission induction therapy is a major independent prognostic factor for both achievement of complete remission and long-term outcome in acute myeloid leukemia: data from the German AML Cooperative Group (AMLCF) 1992 trial. Blood. 2002;101:64–70
  28. Wheatley K, Burnett AK, Goldstone AH, Gray RG, Hann IM, Harrison CJ, et al. A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial (United Kingdom Medical Research Council's Adult and Childhood Leukaemia Working Parties). Br J Haematol. 1999;107:69–79
  29. Slovak M, Kopecky K, Cassileth PA, Harrington DH, Theil K, Mohamed A, et al. Karyotypic analysis predicts outcome of pre-remission and post-remission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study. Blood. 2000;96:4075–4083
  30. Grimwade D, Walker H, Oliver F, Wheatley K, Harrision C, Harrison G, et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. Blood. 1998;92:2322–2333
  31. Grimwade D, Walker H, Harrison G, Oliver F, Chatters S, Harrison C, et al. The predictive value of hierarchical cytogenetic classification in older adults with AML: analysis of 1,065 patients entered into the MRC AML11 Trial. Blood. 2001;98:1312–1320
  32. Burnett AK, Goldstone AH, Wheatley K. Core binding factor leukaemias are a discrete group: experience from MRC AML 10, 11 and 12 trials. Br J Haematol. 1999;105:67
  33. Burnett AK, Hills RK, Wheatley K, Goldstone AH, Prentice AG, Milligan D. A sensitive risk score for directing treatment in younger patients with AML. Blood. 2006;108:10a
  34. Bowen DT, Frew ME, Hills R, Gale RE, Wheatley K, Groves MJ, et al. RAS mutation in acute myeloid leukemia is associated with distinct cytogenetic subgroups but does not influence outcome in patients younger than 60 years. Blood. 2005;106:2113–2119
  35. Kottaridis PD, Gale RE, Frew ME, Harrison G, Langabeer S, Belton AA, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukaemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001;98:1752–1759
  36. Levis , Small D. ITD does matter in leukemia?. Leukemia. 2003;17:1738–1752
  37. Frohling S, Schlenk RF, Breitruck J, Benner A, Kreitmeier S, Tobis K, et al. Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study group Ulm. Blood. 2002;100:4372–4380
  38. Mead AJ, Linch DC, Hills RK, Wheatley K, Burnett AK, Gale RE. FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia. Blood. 2007;110:1262–1270
  39. Dohner K, Schlenk RF, Habdank M, Scholl C, Rucker FG, Corbacioglu A, et al. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood. 2005;106:3740–3746
  40. Gale RE, Green C, Allen C, Mead AJ, Burnett AK, Hills RK, et al. The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood. 2008;111:2776–2784
  41. Frohling S, Schlenk RF, Stolze I. CEBPα mutations in younger adults with acute myeloid leukemia and normal cytogenetics: prognostic relevance and analysis of cooperating mutations. J Clin Oncol. 2004;22:624–633
  42. Preudhomme C, Sagot C, Boissel N, Cayuela JM, Tigaud I, de Botton S, et al. Favorable prognostic significance of CEBPα mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukaemia French Association (ALFA). Blood. 2002;100:2717–2723
  43. Cairoli R, Beghini A, Grillo G, bu-Duhier FM, Geertsma-Kleinekoort WM, Wilson GA, et al. Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study. Blood. 2006;107:3463–3468
  44. Care RS, Valk PJ, Goodeve AC, et al. Incidence and prognosis of c-KIT and FLT3 mutations in core binding factor (CBF) acute myeloid leukaemias. Br J Haematol. 2003;121:775–777
  45. Paschka P, Marcucci G, Ruppert AS, Mrozek K, Chen H, Kittles RA, et al. Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B study. J Clin Oncol. 2006;24:3904–3911
  46. Virappane P, Gale R, Hills R, Kakkas I, Summers K, Stevens J, et al. Mutation of the Wilms' tumor 1 gene is a poor prognostic factor associated with chemotherapy resistance in normal karyotype acute myeloid leukemia. J Clin Oncol. 2008;26:5429–5435
  47. Barjesteh van Waalwijk S, van Doorn-Khosrovani S, Erpelinck C, van Putten WL, Valk PJ, van der Poel-van de Luytgaarde , et al High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients. Blood. 2003;101:837–845
  48. Venditti A, Buccisano F, Del Poeta C, Maurillo L, Tamburini A, Cox C, et al. Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia. Blood. 2000;96:3948–3952
  49. San Miguel JF, Martinez A, Macedo A, Vidriates MB, Lopez-Berges C, Gonzalez M, et al. Immunophenotyping investigation of minimal residual disease is a useful approach for predicting relapse in acute myeloid leukemia patients. Blood. 1997;90:2465–2470
  50. Sievers EL, Lange BJ, Alonzo TA, Gerhing RB, Smith Haferlach ID. Determination of relapse risk based on assessment of minimal residual disease during complete remission by multiparameter flow cytometry in unselected patients with acute myeloid leukemia. Blood. 2004;104:3078–3085
  51. Kern W, Voskova D, Schoch C, Hiddemann W, Schnittger S, Haferlach T. Determination of relapse risk based on assessment of minimal residual disease during complete remission by multiparameter flow cytometry in unselected patients with acute myeloid leukemia. Blood. 2004;104:3078–3085
  52. Coustan-Smith E, Ribeiro RC, Rubnitz JE, Razzouk BI, Pui CH, Pounds S, et al. Clinical significance of residual disease during treatment in childhood acute myeloid leukaemia. Br J Haematol. 2003;123:243–252
  53. Feller N, van der Pol MA, van Stijn A, Weijers GW, Westra AH, Evertse BW, et al. MRD parameters using immunophenotypic detection methods are highly reliable in predicting survival in acute myeloid leukaemia. Leukemia. 2004;18:1380–1390
  54. Langebrake C, Creutzig U, Dworzak M, Hrusak O, Mejstrikova E, Griesinger F, et al. Residual disease monitoring in childhood acute myeloid leukemia by multiparameter flow cytometry: the MRD-AML-BFM study group. J Clin Oncol. 2006;24:3686–3692
  55. Freeman SD, Jovanovic JV, Grimwade D. Development of minimal residual disease-directed therapy in acute myeloid leukemia. Semin Oncol. 2008;35:388–400
  56. Grimwade DJ, Jovanovic J, Hills R, Nugent E, Patel Y, Flora RD, et al. Evaluation of prospective detection of PML-RARA and RARA-PML fusion transcripts by real-time quantitative PCR (RQ-PCR) to direct pre-emptive therapy with arsenic trioxide (ATO) in acute promyelocytic leukemia (APL) patients treated in the UK MRC AML15 trial. Blood. 2007;110:166A–167A
  57. Hann IM, Stevens RF, Goldstone AH, Rees JK, Wheatley K, Gray RG, et al. Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukaemia (Results of the Medical Research Council's 10th AML Trial (MRC AML 10)). Blood. 1997;89:2311–2318
  58. Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised recommendations of the international Working Group for diagnosis, standardization of response criteria treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21:4642–4649
  59. Burnett AK, Kell WJ, Goldstone AH, Milligan D, Hunter A, Prentice AG, et al. The addition of gemtuzumab ozogamicin to induction chemotherapy for AML improves disease free survival without extra toxicity: preliminary analysis of 1115 patients in the MRC AML15 trial. Blood. 2006;108:8A
  60. Arceci RJ, Burnett AK, Estey E, Hills R, Woods WG. Acute myelogenous leukaemia in adolescent and young adults: what is the optimal therapy?. ASCO Educational Book. 2006;533–541
  61. Tallman MS, Nabhan C, Feusner JH, Rowe JM. Acute promyelocytic leukemia: evolving therapeutic strategies. Blood. 2002;99:759–767
  62. Sanz M, Martín G, González M, Leon A, Rayon C, Rivas C, et al. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004;103:1237–1243
  63. Sanz MA, Tallman MS, Lo-Coco F. Tricks of the trade for the appropriate management of newly diagnosed acute promyelocytic leukemia. Blood. 2005;105:3019–3025
  64. Ghavamzadeh A, Alimoghaddam K, Ghaffari SH, Rostami S, Jahani M, Hosseini R, et al. Treatment of acute promyelocytic leukemia with arsenic trioxide without ATRA and/or chemotherapy. Ann Oncol. 2006;17;:131–134
  65. Estey E, Garcia-Manero G, Ferrajoli A, Faderl S, Verstovsek S, Jones D, et al. Use of all-trans retinoic acid + arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood. 2006;107:3469–3473
  66. Sanz MA, Grimwade D, Tallman MS, Lowenberg B, Fenaux P, Estey EH, et al. Guidelines on the management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European Leukemia Net. Blood. 2009;113:1875–1891

PII: S0093-7754(09)00042-6

doi: 10.1053/j.seminoncol.2009.03.007

Seminars in Oncology
Volume 36, Issue 3 , Pages 213-226 , June 2009

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