International Journal of Hematology

, Volume 110, Issue 3, pp 295–305 | Cite as

Outcomes of adult acute lymphoblastic leukemia in the era of pediatric-inspired regimens: a single-center experience

  • Adisak Tantiworawit
  • Thanawat RattanathammetheeEmail author
  • Chatree Chai-Adisaksopha
  • Ekarat Rattarittamrong
  • Lalita Norasetthada
Original Article


Recent data on acute lymphoblastic leukemia (ALL) treatment with multi-agent chemotherapy showed excellent response in pediatric patients in terms of long-term survival; however, the clinical needs for adult patients are still unmet. Adolescent and young adults’ (AYA) ALL could benefit from a pediatric-inspired regimen with a higher rate of long-term remission. This retrospective study sought to investigate the efficacy of treatment of adult ALL in a single center over the past decade. We analyzed 107 ALL patients with a median age of 26 years (range 15–63 years). Of these, 67.3% received adult regimen and 32.7% received pediatric-inspired regimen. The median follow-up time was 11.6 months (range 1–120). Complete remission (CR) was similarly achieved in over 80% in both schemes. Relapse and refractory rates were higher in the adult group (75%) than in the pediatric (45.7%) group. Two-year disease-free survival in the pediatric group was significantly superior to the adult group (47.1% vs 24.7%, hazard ratio [HR], 1.73, 95% CI 1.22–3.03). Two-year overall survival was higher in pediatric group as compared to adult group (50.8% versus 31.2%, HR 1.52, 95% CI 0.83–2.78). Thus, these findings show that the pediatric-inspired regimen should be considered for the treatment of adult ALL.


Adult ALL Adolescence and young adults’ (AYA) ALL Treatment outcomes Pediatric-inspired regimen 



The authors would like to thank all medical staff, nurses and paramedic team in Chiang Mai University (CMU) Hospital, Chiang Mai, Thailand for their participation in the care of all patients.

Author contributions

TR and AT were responsible for design of the study, data collection, interpretation of the data and writing the manuscript. TR and CC analyzed the data. All authors contributed to the revision of manuscript and approved the final version.

Compliance with ethical standards

Conflict of interest

All of the authors have no conflict of interest.

Supplementary material

12185_2019_2678_MOESM1_ESM.docx (22 kb)
Supplementary material 1 (DOCX 22 kb)


  1. 1.
    Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017;7(6):e577.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med. 2006;354(2):166–78.CrossRefPubMedGoogle Scholar
  3. 3.
    Thanawut P, Chansung K, Limwattananon C. Cost analysis for treatment of adult patients with acute leukemia in Thailand 2006. Available from: Accessed 10 Dec 2018
  4. 4.
    Brandwein JM. Treatment of acute lymphoblastic leukemia in adolescents and young adults. Curr Oncol Rep. 2011;13(5):371–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Boissel N, Baruchel A. Acute lymphoblastic leukemia in adolescent and young adults: treat as adults or as children? Blood. 2018;132(4):351–61.CrossRefPubMedGoogle Scholar
  6. 6.
    Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Seksarn P, Wiangnon S, Veerakul G, Chotsampancharoen T, Kanjanapongkul S, Chainansamit SO. Outcome of childhood acute lymphoblastic leukemia treated using the thai national protocols. Asian Pac J Cancer Prev. 2015;16(11):4609–14.CrossRefPubMedGoogle Scholar
  8. 8.
    Kantarjian H, Thomas D, O’Brien S, Cortes J, Giles F, Jeha S, et al. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer. 2004;101(12):2788–801.CrossRefPubMedGoogle Scholar
  9. 9.
    Ravandi F, O’Brien SM, Cortes JE, Thomas DM, Garris R, Faderl S, et al. Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2015;121(23):4158–64.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Gökbuget N, Kneba M, Raff T, Trautmann H, Bartram CR, Arnold R, et al. Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood. 2012;120(9):1868–76.CrossRefPubMedGoogle Scholar
  11. 11.
    Gleissner B, Gokbuget N, Bartram CR, Janssen B, Rieder H, Janssen JW, et al. Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood. 2002;99(5):1536–43.CrossRefPubMedGoogle Scholar
  12. 12.
    Boissel N, Auclerc MF, Lheritier 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(5):774–80.CrossRefPubMedGoogle Scholar
  13. 13.
    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(5):1646–54.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    de Bont JM, Holt B, Dekker AW, 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(12):2032–5.CrossRefPubMedGoogle Scholar
  15. 15.
    Hallbook H, Gustafsson G, Smedmyr B, Soderhall S, Heyman M, Swedish Adult Acute Lymphocytic Leukemia G, et al. 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(7):1551–61.CrossRefPubMedGoogle Scholar
  16. 16.
    Ramanujachar R, Richards S, Hann I, Goldstone A, Mitchell C, Vora A, et al. Adolescents with acute lymphoblastic leukaemia: outcome on UK national paediatric (ALL97) and adult (UKALLXII/E2993) trials. Pediatr Blood Cancer. 2007;48(3):254–61.CrossRefPubMedGoogle Scholar
  17. 17.
    Rytting ME, Jabbour EJ, Jorgensen JL, Ravandi F, Franklin AR, Kadia TM, 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(8):819–23.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    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(8):1161–8.CrossRefPubMedGoogle Scholar
  20. 20.
    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(31):5189–94.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    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(7):813–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Hough R, Rowntree C, Goulden N, Mitchell C, Moorman A, Wade R, et al. Efficacy and toxicity of a paediatric protocol in teenagers and young adults with Philadelphia chromosome negative acute lymphoblastic leukaemia: results from UKALL 2003. Br J Haematol. 2016;172(3):439–51.CrossRefPubMedGoogle Scholar
  23. 23.
    Pui CH, 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(4):386–91.CrossRefPubMedGoogle Scholar
  24. 24.
    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 Programa Espanol de Tratamiento en Hematologia pediatric-based protocol ALL-96. J Clin Oncol. 2008;26(11):1843–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Rijneveld AW, van der Holt B, Daenen SM, Biemond BJ, de Weerdt O, Muus P, et al. Intensified chemotherapy inspired by a pediatric regimen combined with allogeneic transplantation in adult patients with acute lymphoblastic leukemia up to the age of 40. Leukemia. 2011;25(11):1697–703.CrossRefPubMedGoogle Scholar
  26. 26.
    Toft N, Birgens H, Abrahamsson J, Griskevicius L, Hallbook H, Heyman M, et al. Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia. Leukemia. 2018;32(3):606–15.CrossRefPubMedGoogle Scholar
  27. 27.
    DeAngelo DJ, Stevenson KE, Dahlberg SE, Silverman LB, Couban S, Supko JG, et al. Long-term outcome of a pediatric-inspired regimen used for adults aged 18-50 years with newly diagnosed acute lymphoblastic leukemia. Leukemia. 2015;29(3):526–34.CrossRefPubMedGoogle Scholar
  28. 28.
    Storring JM, Minden MD, Kao S, Gupta V, Schuh AC, Schimmer AD, et al. Treatment of adults with BCR-ABL negative acute lymphoblastic leukaemia with a modified paediatric regimen. Br J Haematol. 2009;146(1):76–85.CrossRefPubMedGoogle Scholar
  29. 29.
    Dombret H, Cluzeau T, Huguet F, Boissel N. Pediatric-like therapy for adults with ALL. Curr Hematol Malig Rep. 2014;9(2):158–64.CrossRefPubMedGoogle Scholar
  30. 30.
    Testi A, Valsecchi M, Conter V, Vignetti M, Paoloni F, Giona F, et al. Difference in outcome of adolescents with acute lymphoblastic leukemia (ALL) enrolled in pediatric (AIEOP) and adult (GIMEMA) protocols [abstract]. Blood. 2004;104(11):Abstract 1954.Google Scholar
  31. 31.
    Alves M, Daudt L, Mazzucco K, Taniguchi A, Nava T, Moreno F, et al. Is it better to treat adolescents with acute lymphoblastic leukemia as old children or as young adults? Blood. 2008;112:Abstract 3968.Google Scholar
  32. 32.
    Schroder H, Kjeldahl M, Boesen AM, Nielsen OJ, Schmidt K, Johnsen HE, et al. Acute lymphoblastic leukemia in adolescents between 10 and 19 years of age in Denmark–secondary publication. Dan Med Bull. 2006;53(1):76–9.PubMedGoogle Scholar
  33. 33.
    Cluzeau T, Dhedin N, Huguet F, Raffoux E, Maury S, Mannone L, et al. Dose- intensity impacts on survival of adolescents and young adults with acute lymphoblastic leukemia treated in adult departments by a pediatric protocol (FRALLE 2000BT) [abstract]. Blood. 2012;120(21):Abstract 3561.Google Scholar
  34. 34.
    Stock W, Luger SM, Advani AS, Geyer S, Harvey RC, Mullighan CG, et al. Favorable outcomes for older adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL): early results of US intergroup trial C10403 [abstract]. Blood. 2014;124(21):Abstract 796.Google Scholar
  35. 35.
    Gökbuget N, Beck J, Brandt K, Brüggemann M, Burmeister T, Diedrich H, et al. Significant improvement of outcome in adolescents and young adults (AYAs) aged 15-35 years with acute lymphoblastic leukemia (ALL) with a pediatric derived adult ALL protocol: results of 1529 AYAs in 2 consecutive trials of the German Multicenter Study Group for Adult ALL (GMALL) [abstract]. Blood. 2013;122(21):Abstract 839.Google Scholar
  36. 36.
    Albritton K, Caligiuri M, Anderson B, Nichols C, Ulman D, Adams H, et al. Closing the gap: research and care imperatives for adolescents and young adults with cancer: NIH; 2006. Publication no. 06-6067: available from: Accessed 25 Nov 2018
  37. 37.
    Muffly L, Alvarez E, Lichtensztajn D, Abrahao R, Gomez SL, Keegan T. Patterns of care and outcomes in adolescent and young adult acute lymphoblastic leukemia: a population-based study. Blood Adv. 2018;2(8):895–903.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Nagura E, Kimura K, Yamada K, Ota K, Maekawa T, Takaku F, et al. Nation-wide randomized comparative study of doxorubicin, vincristine and prednisolone combination therapy with and without L-asparaginase for adult acute lymphoblastic leukemia. Cancer Chemother Pharmacol. 1994;33(5):359–65.CrossRefPubMedGoogle Scholar
  39. 39.
    Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005;106(12):3760–7.CrossRefPubMedGoogle Scholar
  40. 40.
    Short NJ, Jabbour E, Sasaki K, Patel K, O’Brien SM, Cortes JE, et al. Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2016;128(4):504–7.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Moorman AV, Harrison CJ, Buck GA, Richards SM, Secker-Walker LM, Martineau M, et al. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood. 2007;109(8):3189–97.CrossRefPubMedGoogle Scholar
  42. 42.
    Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, et al. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009;113(19):4489–96.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Thomas DA, Faderl S, Cortes J, O’Brien S, Giles FJ, Kornblau SM, et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004;103(12):4396–407.CrossRefPubMedGoogle Scholar
  44. 44.
    Porkka K, Koskenvesa P, Lundan T, Rimpilainen J, Mustjoki S, Smykla R, et al. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia. Blood. 2008;112(4):1005–12.CrossRefPubMedGoogle Scholar
  45. 45.
    Short NJ, Kantarjian H, Jabbour E, Ravandi F. Which tyrosine kinase inhibitor should we use to treat Philadelphia chromosome-positive acute lymphoblastic leukemia? Best Pract Res Clin Haematol. 2017;30(3):193–200.CrossRefPubMedGoogle Scholar
  46. 46.
    Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, et al. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014;123(6):843–50.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Kim DY, Joo YD, Lim SN, Kim SD, Lee JH, Lee JH, et al. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood. 2015;126(6):746–56.CrossRefPubMedGoogle Scholar
  48. 48.
    Jabbour E, Kantarjian H, Ravandi F, Thomas D, Huang X, Faderl S, et al. Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a single-centre, phase 2 study. Lancet Oncol. 2015;16(15):1547–55.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Sasaki K, Jabbour EJ, Ravandi F, Short NJ, Thomas DA, Garcia-Manero G, et al. Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a propensity score analysis. Cancer. 2016;122(23):3650–6.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Japanese Society of Hematology 2019

Authors and Affiliations

  1. 1.Division of Hematology, Department of Internal Medicine, Faculty of MedicineMaharaj Nakorn Chiang Mai Hospital, Chiang Mai UniversityChiang MaiThailand

Personalised recommendations