Treating adolescents and young adults (AYAs) diagnosed with cancer is a challenge. Acute myeloid leukemia (AML) which is usually diagnosed in a previously healthy kid, requiring immediate aggressive chemotherapy, brings difficulties and conflicts associated with severe illness to extremes. The incidence of AML in adolescents aged 15-19 years approaches 8.5 per million. Only in recent years has it become evident that the prognosis of AYAs diagnosed with AML is poorer compared to younger children diagnosed with AML with similar characteristics. No specific genetic aberration or other known poor risk factor was found to explain the inferior prognosis of AYAs. In acute lymphoblastic leukemia the contribution of differences between adult and pediatric protocols to AYA outcome is established. It has been suggested that pediatric protocols should also apply to AYAs with AML; however, data supporting this are vague. Herein, existing evidence regarding special considerations in treating AYAs with AML is discussed. Mental and psychological age-specific aspects important to consider when treating AYAs with AML are overviewed. Awareness for adolescent special needs, adherence to protocols and intensive supportive care are important. Multidisciplinary adolescent-oriented staff should be involved in the therapy of any AYA with AML escorting this special patient population on the road to cure.

Juliusson G, Lazarevic V, Horstedt AS, Hagberg O, Hoglund M: Acute myeloid leukemia in the real world: why population-based registries are needed. Blood 2012;119:3890-3899.
Horibe K, Saito AM, Takimoto T, Tsuchida M, Manabe A, Shima M, Ohara A, Mizutani S: Incidence and survival rates of hematological malignancies in Japanese children and adolescents (2006-2010): based on registry data from the Japanese Society of Pediatric Hematology. Int J Hematol 2013;98:74-88.
Bleyer A, O'Leary M, Barr R, Ries LAG (eds): Cancer Epidemiology in older adolescents and Young Adults 15 to 29 Years of Age, Including SEER Incidence and Survival: 1975-2000. NIH publ No 06-5767. Bethesda, National Cancer Institute, 2006.
Boissel N, Auclerc MF, Lheritier V, Perel Y, Thomas X, Leblanc T, Rousselot P, Cayuela JM, Gabert J, Fegueux N, Piguet C, Huguet-Rigal F, Berthou C, Boiron JM, Pautas C, Michel G, Fiere D, Leverger G, Dombret H, Baruchel A: 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.
De Bont JM, Holt B, Dekker AW, van der Does-van den Berg A, 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.
Rubnitz JE, Inaba H: Childhood acute myeloid leukaemia. Br J Haematol 2012;159:259-276.
Creutzig U, van den Heuvel-Eibrink MM, Gibson B, Dworzak MN, Adachi S, de Bont E, Harbott J, Hasle H, Johnston D, Kinoshita A, Lehrnbecher T, Leverger G, Mejstrikova E, Meshinchi S, Pession A, Raimondi SC, Sung L, Stary J, Zwaan CM, Kaspers GJ, Reinhardt D: Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel. Blood 2012;120:3187-3205.
Creutzig U, Zimmermann M, Ritter J, Reinhardt D, Hermann J, Henze G, Jurgens H, Kabisch H, Reiter A, Riehm H, Gadner H, Schellong G: Treatment strategies and long-term results in paediatric patients treated in four consecutive AML-BFM trials. Leukemia 2005;19:2030-2042.
Webb DK, Harrison G, Stevens RF, Gibson BG, Hann IM, Wheatley K: Relationships between age at diagnosis, clinical features, and outcome of therapy in children treated in the Medical Research Council AML 10 and 12 trials for acute myeloid leukemia. Blood 2001;98:1714-1720.
Johnston DL, Alonzo TA, Gerbing RB, Lange BJ, Woods WG: The presence of central nervous system disease at diagnosis in pediatric acute myeloid leukemia does not affect survival: a Children's Oncology Group study. Pediatr Blood Cancer 2010;55:414-420.
Zuckerman T, Ganzel C, Tallman MS, Rowe JM: How I treat hematologic emergencies in adults with acute leukemia. Blood 2012;120:1993-2002.
Lass A, Akagbosu F, Abusheikha N, Hassouneh M, Blayney M, Avery S, Brinsden P: A programme of semen cryopreservation for patients with malignant disease in a tertiary infertility centre: lessons from 8 years' experience. Hum Reprod 1998;13:3256-3261.
Levine J, Canada A, Stern CJ: Fertility preservation in adolescents and young adults with cancer. J Clin Oncol 2010;28:4831-4841.
Rosendahl M, Andersen MT, Ralfkiaer E, Kjeldsen L, Andersen MK, Andersen CY: Evidence of residual disease in cryopreserved ovarian cortex from female patients with leukemia. Fertil Steril 2010;94:2186-2190.
Beck-Fruchter R, Weiss A, Shalev E: GnRH agonist therapy as ovarian protectants in female patients undergoing chemotherapy: a review of the clinical data. Hum Reprod Update 2008;14:553-561.
Blumenfeld Z, Avivi I, Eckman A, Epelbaum R, Rowe JM, Dann EJ: Gonadotropin-releasing hormone agonist decreases chemotherapy-induced gonadotoxicity and premature ovarian failure in young female patients with Hodgkin lymphoma. Fertil Steril 2008;89:166-173.
Epelman CL: The adolescent and young adult with cancer: state of the art - psychosocial aspects. Curr Oncol Rep 2013;15:325-331.
Zebrack BJ, Mills J, Weitzman TS: Health and supportive care needs of young adult cancer patients and survivors. J Cancer Surviv 2007;1:137-145.
Thiede C, Koch S, Creutzig E, Steudel C, Illmer T, Schaich M, Ehninger G: Prevalence and prognostic impact of NPM1 mutations in 1,485 adult patients with acute myeloid leukemia (AML). Blood 2006;107:4011-4020.
Brown P, McIntyre E, Rau R, Meshinchi S, Lacayo N, Dahl G, Alonzo TA, Chang M, Arceci RJ, Small D: The incidence and clinical significance of nucleophosmin mutations in childhood AML. Blood 2007;110:979-985.
Hollink IH, Zwaan CM, Zimmermann M, Arentsen-Peters TC, Pieters R, Cloos J, Kaspers GJ, de Graaf SS, Harbott J, Creutzig U, Reinhardt D, van den Heuvel-Eibrink MM, Thiede C: Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML. Leukemia 2009;23:262-270.
Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, Rees J, Hann I, Stevens R, Burnett A, Goldstone A: 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;92:2322-2333.
Park SH, Chi HS, Min SK, Park BG, Jang S, Park CJ: Prognostic impact of c-KIT mutations in core binding factor acute myeloid leukemia. Leuk Res 2011;35:1376-1383.
Pollard JA, Alonzo TA, Gerbing RB, Ho PA, Zeng R, Ravindranath Y, Dahl G, Lacayo NJ, Becton D, Chang M, Weinstein HJ, Hirsch B, Raimondi SC, Heerema NA, Woods WG, Lange BJ, Hurwitz C, Arceci RJ, Radich JP, Bernstein ID, Heinrich MC, Meshinchi S: Prevalence and prognostic significance of KIT mutations in pediatric patients with core binding factor AML enrolled on serial pediatric cooperative trials for de novo AML. Blood 2010;115:2372-2379.
Patel JP, Gonen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, Van Vlierberghe P, Dolgalev I, Thomas S, Aminova O, Huberman K, Cheng J, Viale A, Socci ND, Heguy A, Cherry A, Vance G, Higgins RR, Ketterling RP, Gallagher RE, Litzow M, van den Brink MR, Lazarus HM, Rowe JM, Luger S, Ferrando A, Paietta E, Tallman MS, Melnick A, Abdel-Wahab O, Levine RL: Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 2012;366:1079-1089.
Balgobind BV, Hollink IH, Arentsen-Peters ST, Zimmermann M, Harbott J, Beverloo HB, von Bergh AR, Cloos J, Kaspers GJ, de Haas V, Zemanova Z, Stary J, Cayuela JM, Baruchel A, Creutzig U, Reinhardt D, Pieters R, Zwaan CM, van den Heuvel-Eibrink MM: Integrative analysis of type-I and type-II aberrations underscores the genetic heterogeneity of pediatric acute myeloid leukemia. Haematologica 2011;96:1478-1487.
Hollink IH, van den Heuvel-Eibrink MM, Arentsen-Peters ST, Pratcorona M, Abbas S, Kuipers JE, van Galen JF, Beverloo HB, Sonneveld E, Kaspers GJ, Trka J, Baruchel A, Zimmermann M, Creutzig U, Reinhardt D, Pieters R, Valk PJ, Zwaan CM: NUP98/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern. Blood 2011;118:3645-3656.
Ostronoff F, Alonzo TA, Gerbing RB, Loken MR, Pardo L, Aplenc R, Sung L, Raimondi SC, Hirsch BA, Kahwash S, Heerema-McKenney A, Winter L, Glick K, Byron P, Lavey RS, Davies SM, Smith FO, Gamis AS, Meshinchi S: Cryptic NUP98/NSD1 translocations are highly prevalent in FLT3/ITD-positive acute myeloid leukemia and lead to high rate of induction failure. Report from Children's Oncology Group. Blood 2012;120:529a.
Creutzig U, Buchner T, Sauerland MC, Zimmermann M, Reinhardt D, Dohner H, Schlenk RF: 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;112:562-571.
Hann IM, Stevens RF, Goldstone AH, Rees JK, Wheatley K, Gray RG, Burnett AK: 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). Adult and childhood leukaemia working parties of the Medical Research Council. Blood 1997;89:2311-2318.
Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D: Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the Medical Research Council AML15 trial. J Clin Oncol 2013;31:3360-3368.
Woods WG, Franklin AR, Alonzo TA, Gerbing RB, Donohue KA, Othus M, Horan J, Appelbaum FR, Estey EH, Bloomfield CD, Larson RA: Outcome of adolescents and young adults with acute myeloid leukemia treated on COG trials compared to CALGB and SWOG trials. Cancer 2013;119:4170-4179.
Rubnitz JE, Pounds S, Cao X, Jenkins L, Dahl G, Bowman WP, Taub JW, Pui CH, Ribeiro RC, Campana D, Inaba H: Treatment outcome in older patients with childhood acute myeloid leukemia. Cancer 2012;118:6253-6259.
Woods WG, Kobrinsky N, Buckley JD, Lee JW, Sanders J, Neudorf S, Gold S, Barnard DR, DeSwarte J, Dusenbery K, Kalousek D, Arthur DC, Lange BJ: Timed-sequential induction therapy improves postremission outcome in acute myeloid leukemia: a report from the children's Cancer Group. Blood 1996;87:4979-4989.
Moore JO, George SL, Dodge RK, Amrein PC, Powell BL, Kolitz JE, Baer MR, Davey FR, Bloomfield CD, Larson RA, Schiffer CA: Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B study 9222. Blood 2005;105:3420-3427.
Boros L, Chuang C, Butler FO, Bennett JM: Leukemia in Rochester (NY). A 17-year experience with an analysis of the role of cooperative group (ECOG) participation. Cancer 1985;56:2161-2169.
Bleyer WA: Cancer in older adolescents and young adults: epidemiology, diagnosis, treatment, survival, and importance of clinical trials. Med Pediatr Oncol 2002;38:1-10.
Gatta G, Capocaccia R, De Angelis R, Stiller C, Coebergh JW: Cancer survival in European adolescents and young adults. Eur J Cancer 2003;39:2600-2610.
Butow P, Palmer S, Pai A, Goodenough B, Luckett T, King M: Review of adherence-related issues in adolescents and young adults with cancer. J Clin Oncol 2010;28:4800-4809.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.