Adolescents and young adults with acute lymphoblastic leukemia and acute myeloid leukemia

Characteristics and treatment outcome
  • Mirella Ampatzidou
  • Charikleia Kelaidi
  • Michael N. Dworzak
  • Sophia Polychronopoulou


At the therapeutic intersection between children and older adults, the treatment of adolescent and young adults (AYAs) with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) poses unique challenges due to their dismal outcome. In this brief review, we report on the biological features, clinical characteristics and treatment results of a pediatric and AYAs cohort of ALL and AML, treated in our department over a 15-year period. Additionally, we review the recent insights into disease biology, clinical, cytogenetic and molecular characteristics and differences between pediatric patients and AYAs with ALL and AML. In AYAs with ALL, most retrospective trials demonstrated a benefit of pediatric inspired regimens versus adult protocols. Translating the promising pediatric results to the AYAs subgroup, these patients can be successfully treated with risk-adjusted and minimal residual disease (MRD)-guided intensified chemotherapy, with survival rates that can surpass 70%. In AYAs the AML disease is genetically positioned more on the side of adult AML than on that of younger children, but also carries its own specific abnormalities, such as NUP98-NSD1. Toxicity may complicate all phases of treatment (induction and post-induction chemotherapy, hematopoietic stem cell transplantation-HSCT) and accounts for increased mortality, which counterbalances reduced cumulative incidence of relapse (CIR), in comparison with younger children. Intensification of supportive care while maintaining treatment intensity could further improve outcomes of AYAs with leukemia. Cooperative efforts between pediatric and adult hematologists are needed in order to further improve survival of AYAs with ALL and AML.


Adolescents and young adults (AYAs) Acute lymphoblastic leukemia (ALL) Acute myeloid leukemia (AML) Pediatric hematology-oncology 


Conflict of interest

M. Ampatzidou, C. Kelaidi, M.N. Dworzak and S. Polychronopoulou declare that they have no competing interests.


  1. 1.
    Stock W. Adolescents and young adults with acute lymphoblastic leukemia. Ash Educ Book. 2010;21–9. doi: 10.1182/asheducation-2010.1.21
  2. 2.
    Levine SR, McNeer JS, Isakoff MS. Chalenges faced in the treatment of acute lymphoblastic leukemia in adolescents and young adults. Clin Oncol Adolesc Young Adults. 2016;6:11–20.Google Scholar
  3. 3.
    Ribera JM, Ribera J, Genesca E. Treatment of adolescents and young adults with acute lymphoblastic leukemia. Mediterr J Hematol Infect Dis. 2014;6(1):e2014052. doi: 10.4084/MJHID.2014.052.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Curran E, Stock W. How I treat acute lymphoblastic leukemia in older adolescents and young adults. Blood. 2015;125(24):3702–10.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Ampatzidou M, Panagiotou JP, Paterakis G, et al. Childhood acute lymphoblastic leukemia: 12 years of experience, using a Berlin-Frankfurt-Munster approach, in a Greek center. Leuk Lymphoma. 2014;27:1–5, Jun.Google Scholar
  6. 6.
    Möricke A, Reiter A, Zimmermann M, et al. 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.CrossRefPubMedGoogle Scholar
  7. 7.
    Ibrahim A, Ali A, Mohammed MM. Outcome of adolescents with acute lymphoblastic leukemia treated by pediatrics versus adults protocols. Adv Hematol. 2014;1–7. doi: 10.1155/2014/697675
  8. 8.
    Rizzari C, Putti MC, Colombini A, et al. Rationale for a pediatric-inspired approach in the adolescent and young adult population with acute lymphoblastic leukemia, with a focus on asparaginase treatment. Hematol Rep. 2014;6:5554.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    De Angelo DJ. The treatment of adolescents and young adults with acute lymphoblastic leukemia. Ash Educ Book. 2005;123–30. doi: 10.1182/asheducation-2005.1.123
  10. 10.
    Advani AS. Biology and treatment of acute lymphoblastic leukemia in adolescents and young adults. Asco Educ Book. 2013;285–9. doi: 10.1053/j.seminoncol.2009.03.007
  11. 11.
    Ram R, Wolach O, Vidal L, et al. Adolescents and young adults with acute lymphoblastic leukemia have a better outcome when treated with pediatric inspired regimens: Systematic review and meta-analysis. Am J Hematol. 2012;87:472–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Hallbook H, Gustafsson G, Smedmyr B, Swedish Adult Acute Lymphocytic Leukemia Group, Swedish Childhood Leukemia Group. Treatment outcome in young adults and children 〉10 years of age with acute lymphoblastic leukemia in Sweden: a comparison between a pediatric protocol and an adult protocol. Cancer. 2006;107:1551–61.CrossRefPubMedGoogle Scholar
  13. 13.
    Usvasalo A, Räty R, Knuutila S, et al. Acute lymphoblastic leukemia in adolescents and young adults in Finland. Haematologica. 2008;93:1161–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Rytting ME, Jabbour EJ, Jorgensen JL, et al. Final results of a single institution experience with a pediatric-based regimen, the augmented Berlin-Frankfurt-Munster, in adolescents and young adults with acute lymphoblastic leukemia, and comparison to the hyper-CVAD regimen. Am J Hematol. 2016;91:819–23.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Boissel N, Sender LS. Best practices in adolescent and young adult patients with acute lymphoblastic leukemia: A focus on asparaginase. J Adolesc Young Adult Oncol. 2015;4(3):118–28.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Creutzig U, Zimmermann M, Ritter J, et al. Treatment strategies and long-term results in paediatric patients treated in four consecutive AML-BFM trials. Leukemia. 2005;19(12):2030–42.CrossRefPubMedGoogle Scholar
  17. 17.
    Creutzig U, Zimmermann M, Reinhardt D, et al. Changes in cytogenetics and molecular genetics in acute myeloid leukemia from childhood to adult age groups. Cancer. 2016;122(24):3821–30.CrossRefPubMedGoogle Scholar
  18. 18.
    Rubnitz JE, Onciu M, Pounds S, et al. Acute mixed lineage leukemia in children: The experience of St Jude Children’s Research Hospital. Blood. 2009;113(21):5083–9.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Grimwade D, Walker H, Oliver F, et al. The importance of diagnostic cytogenetics on outcome in AML: Analysis of 1,612 patients entered into the MRC AML 10 trial. The medical research council adult and children’s leukaemia working parties. Blood. 1998;92(7):2322–33.PubMedGoogle Scholar
  20. 20.
    Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the world health organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.CrossRefPubMedGoogle Scholar
  21. 21.
    Ostronoff F, Othus M, Gerbing RB, et al. NUP98/NSD1 and FLT3/ITD coexpression is more prevalent in younger AML patients and leads to induction failure: A COG and SWOG report. Blood. 2014;124(15):2400–7.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    August KJ, Aplenc R, Sung L, et al. Adolescents and young adults (AYA) with acute myeloid leukemia (AML) have increased treatment-related mortality with similar outcomes – a report from the children’s oncology group trials AAML03P1 and AAML0531. Blood. 2014;124(21):3672.Google Scholar
  23. 23.
    Creutzig U, Buechner T, Sauerland MC, et al. Significance of age in acute myeloid leukemia patients younger than 30 years: A common analysis of the pediatric trials AML-BFM 93/98 and the adult trials AMLCG 92/99 and AMLSG HD93/98A. Cancer. 2008;112(3):562–71.CrossRefPubMedGoogle Scholar
  24. 24.
    Creutzig U, Zimmermann M, Reinhardt D, Dworzak M, Stary J, Lehrnbecher T. Early deaths and treatment-related mortality in children undergoing therapy for acute myeloid leukemia: Analysis of the multicenter clinical trials AML-BFM 93 and AML-BFM 98. J Clin Oncol. 2004;22(21):4384–93.CrossRefPubMedGoogle Scholar
  25. 25.
    Canner J, Alonzo TA, Franklin J, et al. Differences in outcomes of newly diagnosed acute myeloid leukemia for adolescent/young adult and younger patients: A report from the children’s oncology group. Cancer. 2013;119(23):4162–9.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Hann IM, Stevens RF, Goldstone AH, et al. Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia. Results of the medical research council’s 10th AML trial (MRC AML10). Blood. 1997;89(7):2311–8.PubMedGoogle Scholar
  27. 27.
    Tomizawa D, Watanabe T, Hanada R, et al. Outcome of adolescent patients with acute myeloid leukemia treated with pediatric protocols. Int J Hematol. 2015;102(3):318–26.CrossRefPubMedGoogle Scholar
  28. 28.
    Woods WG, Franklin AR, Alonzo TA, et al. Outcome of adolescents and young adults with acute myeloid leukemia treated on COG trials compared to CALGB and SWOG trials. Cancer. 2013;119(23):4170–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Majhail NS, Brazauskas R, Hassebroek A, et al. Outcomes of allogeneic hematopoietic cell transplantation for adolescent and young adults compared with children and older adults with acute myeloid leukemia. Biol Blood Marrow Transplant. 2012;18(6):861–73.CrossRefPubMedGoogle Scholar
  30. 30.
    Vignon M, Andreoli A, Dhédin N, et al. Graft-Versus-Host disease in adolescents and young adults (15–24 years old) after allogeneic hematopoietic stem cell transplantation for acute leukemia in first complete remission. J Adolesc Young Adult Oncol. 2017;6(2):299–306. doi: 10.1089/jayao.2016.0060

Copyright information

© Springer-Verlag GmbH Austria 2017

Authors and Affiliations

  • Mirella Ampatzidou
    • 1
  • Charikleia Kelaidi
    • 1
  • Michael N. Dworzak
    • 2
  • Sophia Polychronopoulou
    • 1
  1. 1.Department of Pediatric Hematology-Oncology, Oncology Unit “Marianna Vardinogianni-ELPIDA”Aghia Sophia Children’s Hospital GoudiAthensGreece
  2. 2.Children’s Cancer Research Institute and St. Anna Children’s Hospital, Department of PediatricsMedical University of ViennaViennaAustria

Personalised recommendations