Abstract
As past studies of adolescent and young adults (AYA) with acute myeloid leukemia (AML) reported conflicting results, we conducted a retrospective analysis using data from three Japanese pediatric AML studies. Among the 782 patients with de novo AML, 44 were classified as AYA (age ≥15 years at diagnosis), 164 as infants (0–1 year), 413 as younger children (2–11 years), and 161 as older children (12–14 years). While the 5-year event-free survival rate of AYA was not different among the groups, the five-year survival rate (54.7 %) was significantly lower than that of the other three groups (P = 0.019): 68.7 % for infants, 73.2 % for younger children, and 75.5 % for older children. No difference in the 5-year cumulative incidence of relapse was observed, but treatment-related death (TRD) of AYA was significantly higher (29.4 %) than that in infants (14.8 %), younger children (10.2 %), and older children (13.8 %). Multivariate analysis showed age ≥15 years old at diagnosis was associated with both poor survival rate and high TRD. Adolescents with AML had inferior survival due to a higher incidence of TRD, especially after failure of initial frontline treatment.
Similar content being viewed by others
References
Tsukimoto I, Tawa A, Horibe K, Tabuchi K, Kigasawa H, Tsuchida M, et al. Risk-stratified therapy and the intensive use of cytarabine improves the outcome in childhood acute myeloid leukemia: the AML99 trial from the Japanese Childhood AML Cooperative Study Group. J Clin Oncol. 2009;27:4007–13.
Rubnitz JE, Inaba H, Dahl G, Ribeiro RC, Bowman WP, Taub J, et al. Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial. Lancet Oncol. 2010;11:543–52.
Creutzig U, Zimmermann M, Bourquin J-P, Dworzak MN, Fleischhack G, Graf N, et al. Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004. Blood. 2013;122:37–43.
Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, et al. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group Trial AAML0531. J Clin Oncol. 2014;32:3021–32.
Abrahamsson J, Forestier E, Heldrup J, Jahnukainen K, Jónsson OG, Lausen B, et al. Response-guided induction therapy in pediatric acute myeloid leukemia with excellent remission rate. J Clin Oncol. 2011;29:310–5.
Gibson BES, Webb DKH, Howman AJ, de Graaf SSN, Harrison CJ, Wheatley K, et al. Results of a randomized trial in children with acute myeloid leukaemia: medical research council AML12 trial. Br J Haematol. 2011;155:366–76.
Chessells JM, Hall E, Prentice HG, Durrant J, Bailey CC, Richards SM. 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;12:463–73.
Boissel N, Auclerc M-F, Lhéritier V, Perel Y, Thomas X, LeBlanc T, 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;21:774–80.
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;112:1646–54.
Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children’s oncology group. J Clin Oncol. 2012;30:1663–9.
Nachman JB, La MK, Hunger SP, Heerema NA, Gaynon PS, Hastings C, et al. Young adults with acute lymphoblastic leukemia have an excellent outcome with chemotherapy alone and benefit from intensive postinduction treatment: a report from the children’s oncology group. J Clin Oncol. 2009;27:5189–94.
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;25:813–9.
Pui C-H, Pei D, Campana D, Bowman WP, Sandlund JT, Kaste SC, et al. Improved prognosis for older adolescents with acute lymphoblastic leukemia. J Clin Oncol. 2011;29:386–91.
Hayakawa F, Sakura T, Yujiri T, Kondo E, Fujimaki K, Sasaki O, et al. Markedly improved outcomes and acceptable toxicity in adolescents and young adults with acute lymphoblastic leukemia following treatment with a pediatric protocol: a phase II study by the Japan Adult Leukemia Study Group. Blood Cancer J. 2014;4:e252.
Kato M, Manabe A, Koh K, Inukai T, Kiyokawa N, Fukushima T, et al. Treatment outcomes of adolescent acute lymphoblastic leukemia treated on Tokyo Children’s Cancer Study Group (TCCSG) clinical trials. Int J Hematol. 2014;100:180–7.
Creutzig U, Büchner T, Sauerland MC, Zimmermann M, Reinhardt D, Döhner H, 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;112:562–71.
Rubnitz JE, Pounds S, Cao X, Jenkins L, Dahl G, Bowman WP, et al. Treatment outcome in older patients with childhood acute myeloid leukemia. Cancer. 2012;118:6253–9.
Canner J, Alonzo TA, Franklin J, Freyer DR, Gamis A, Gerbing RB, 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;119:4162–9.
Tomizawa D, Tawa A, Watanabe T, Saito AM, Kudo K, Taga T, et al. Excess treatment reduction including anthracyclines results in higher incidence of relapse in core binding factor acute myeloid leukemia in children. Leukemia. 2013;27:2413–6.
Tomizawa D, Tawa A, Watanabe T, Saito AM, Kudo K, Taga T, et al. Appropriate dose reduction in induction therapy is essential for the treatment of infants with acute myeloid leukemia: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group. Int J Hematol. 2013;98:578–88.
Imaizumi M, Tawa A, Hanada R, Tsuchida M, Tabuchi K, Kigasawa H, et al. Prospective study of a therapeutic regimen with all-trans retinoic acid and anthracyclines in combination of cytarabine in children with acute promyelocytic leukaemia: the Japanese childhood acute myeloid leukaemia cooperative study. Br J Haematol. 2010;152:89–98.
Kudo K, Kojima S, Tabuchi K, Yabe H, Tawa A, Imaizumi M, et al. Prospective study of a pirarubicin, intermediate-dose cytarabine, and etoposide regimen in children with Down syndrome and acute myeloid leukemia: the Japanese Childhood AML Cooperative Study Group. J Clin Oncol. 2007;25:5442–7.
Taga T, Shimomura Y, Horikoshi Y, Ogawa A, Itoh M, Okada M, et al. Continuous and high-dose cytarabine combined chemotherapy in children with down syndrome and acute myeloid leukemia: report from the Japanese children’s cancer and leukemia study group (JCCLSG) AML 9805 down study. Pediatr Blood Cancer. 2011;57:36–40.
Creutzig U, van den Heuvel-Eibrink MM, Gibson B, Dworzak MN, Adachi S, de Bont E, et al. Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel. Blood. 2012;120:3187–205.
Woods WG, Franklin ARK, Alonzo TA, Gerbing RB, Donohue KA, Othus M, et al. Outcome of adolescents and young adults with acute myeloid leukemia treated on COG trials compared to CALGB and SWOG trials. Cancer. 2013;119:4170–9.
Pichler H, Reismüller B, Steiner M, Dworzak MN, Pötschger U, Urban C, et al. The inferior prognosis of adolescents with acute lymphoblastic leukaemia (ALL) is caused by a higher rate of treatment-related mortality and not an increased relapse rate–a population-based analysis of 25 years of the Austrian ALL-BFM (Berlin-Frankfurt-Münster) Study Group. Br J Haematol. 2013;161:556–65.
Majhail NS, Brazauskas R, Hassebroek A, Bredeson CN, Hahn T, Hale GA, 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;18:861–73.
Burke MJ, Gossai N, Cao Q, Macmillan ML, Warlick E, Verneris MR. Similar outcomes between adolescent/young adults and children with AML following allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2014;49:174–8.
Bitan M, He W, Zhang M-J, Abdel-Azim H, Ayas MF, Bielorai B, et al. Transplantation for children with acute myeloid leukemia: a comparison of outcomes with reduced intensity and myeloablative regimens. Blood. 2014;123:1615–20.
Zwaan CM, Meshinchi S, Radich JP, Veerman AJP, Huismans DR, Munske L, et al. FLT3 internal tandem duplication in 234 children with acute myeloid leukemia: prognostic significance and relation to cellular drug resistance. Blood. 2003;102:2387–94.
Brown P, McIntyre E, Rau R, Meshinchi S, Lacayo N, Dahl G, et al. The incidence and clinical significance of nucleophosmin mutations in childhood AML. Blood. 2007;110:979–85.
Ho PA, Alonzo TA, Gerbing RB, Pollard J, Stirewalt DL, Hurwitz C, et al. Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children’s Oncology Group. Blood. 2009;113:6558–66.
Acknowledgments
The authors thank all the investigators, coworkers, and members of participating hospitals in the AML studies conducted by the CCLSG, TCCSG, JACLS, KYCCSG, and JPLSG. The authors also thank Dr. Julian Tang of the Department of Education for Clinical Research, National Center for Child Health and Development, for critical comments and editorial assistance. This work was supported by a Grant for Innovative Cancer Medicine Research from the Ministry of Health, Labour, and Welfare of Japan (H26-KakushintekiGan-Ippan-061).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The authors declare that they have no conflicts of interest.
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
Cite this article
Tomizawa, D., Watanabe, T., Hanada, R. et al. Outcome of adolescent patients with acute myeloid leukemia treated with pediatric protocols. Int J Hematol 102, 318–326 (2015). https://doi.org/10.1007/s12185-015-1825-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12185-015-1825-x