Cancer Chemotherapy and Pharmacology

, Volume 81, Issue 2, pp 393–398 | Cite as

A pilot study of daunorubicin-augmented hyper-CVAD induction chemotherapy for adults with acute lymphoblastic leukemia

  • Sung-Yong KimEmail author
  • Ji Hyun Park
  • So Young Yoon
  • Yo-Han Cho
  • Mark Hong Lee
Original Article


Induction of complete remission (CR) is imperative for long-term survival in adult acute lymphoblastic leukemia (ALL) patients regardless of transplantation eligibility. Hyper-CVAD chemotherapy is a widely-used frontline remission induction regimen for these patients. We conducted a pilot trial of frontline remission induction using daunorubicin-augmented hyper-CVAD regimen (hyper-CVDD) in adult ALL patients (n = 15). The CR rate after this modified regimen was 100% (n = 15). Twelve patients were able to proceed to allogeneic hematopoietic cell transplantation, two patients died before transplantation due to infection, and the remaining one who was ineligible for transplant due to her age received an additional five courses of consolidation chemotherapy. Overall survival (OS) and event-free survival (EFS) of the study patients was 61.0 and 47.5% at 3 years. OS and relapse-free survival of transplanted patients was 66.8 and 55.0% at 3 years. This pilot trial demonstrates the favorable efficacy of the hyper-CVDD chemotherapy as a frontline remission induction regimen. Further clinical trials using this regimen are warranted.


Acute lymphoblastic leukemia Adult Remission induction Chemotherapy Daunorubicin Hyper-CVAD 



The authors gratefully thank all the patients who participated in the trial.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all the individual participants included in the study.


  1. 1.
    Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH (2014) UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood 123(6):843–850. Scholar
  2. 2.
    de Labarthe A, Rousselot P, Huguet-Rigal F, Delabesse E, Witz F, Maury S, Rea D, Cayuela JM, Vekemans MC, Reman O, Buzyn A, Pigneux A, Escoffre M, Chalandon Y, MacIntyre E, Lheritier V, Vernant JP, Thomas X, Ifrah N, Dombret H, Group for Research on Adult Acute Lymphoblastic L (2007) Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study. Blood 109 (4):1408–1413. Scholar
  3. 3.
    Thomas DA, O’Brien S, Faderl S, Garcia-Manero G, Ferrajoli A, Wierda W, Ravandi F, Verstovsek S, Jorgensen JL, Bueso-Ramos C, Andreeff M, Pierce S, Garris R, Keating MJ, Cortes J, Kantarjian HM (2010) Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome-negative precursor B-lineage acute lymphoblastic leukemia. J Clin Oncol 28(24):3880–3889. Scholar
  4. 4.
    Kantarjian HM, O’Brien S, Smith TL, Cortes J, Giles FJ, Beran M, Pierce S, Huh Y, Andreeff M, Koller C, Ha CS, Keating MJ, Murphy S, Freireich EJ (2000) Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol 18(3):547–561. Scholar
  5. 5.
    Gilladoga AC, Manuel C, Tan CT, Wollner N, Sternberg SS, Murphy ML (1976) The cardiotoxicity of adriamycin and daunomycin in children. Cancer 37(2 Suppl):1070–1078CrossRefPubMedGoogle Scholar
  6. 6.
    Yates J, Glidewell O, Wiernik P, Cooper MR, Steinberg D, Dosik H, Levy R, Hoagland C, Henry P, Gottlieb A, Cornell C, Berenberg J, Hutchison JL, Raich P, Nissen N, Ellison RR, Frelick R, James GW, Falkson G, Silver RT, Haurani F, Green M, Henderson E, Leone L, Holland JF (1982) Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study. Blood 60(2):454–462PubMedGoogle Scholar
  7. 7.
    Todeschini G, Tecchio C, Meneghini V, Pizzolo G, Veneri D, Zanotti R, Ricetti MM, Solero P, April F, Perona G (1998) Estimated 6-year event-free survival of 55% in 60 consecutive adult acute lymphoblastic leukemia patients treated with an intensive phase II protocol based on high induction dose of daunorubicin. Leukemia 12(2):144–149CrossRefPubMedGoogle Scholar
  8. 8.
    Gottlieb AJ, Weinberg V, Ellison RR, Henderson ES, Terebelo H, Rafla S, Cuttner J, Silver RT, Carey RW, Levy RN et al (1984) Efficacy of daunorubicin in the therapy of adult acute lymphocytic leukemia: a prospective randomized trial by cancer and leukemia group B. Blood 64(1):267–274PubMedGoogle Scholar
  9. 9.
    Matloub Y, Lindemulder S, Gaynon PS, Sather H, La M, Broxson E, Yanofsky R, Hutchinson R, Heerema NA, Nachman J, Blake M, Wells LM, Sorrell AD, Masterson M, Kelleher JF, Stork LC, Children’s Oncology G (2006) Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate: results of the Children’s Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children’s Oncology Group. Blood 108(4):1165–1173. Scholar
  10. 10.
    Amadori S, Arcese W, Isacchi G, Meloni G, Petti MC, Monarca B, Testi AM, Mandelli F (1991) Mitoxantrone, etoposide, and intermediate-dose cytarabine: an effective and tolerable regimen for the treatment of refractory acute myeloid leukemia. J Clin Oncol 9(7):1210–1214. Scholar
  11. 11.
    Mazza JJ, Leong T, Rowe JM, Wiernik PH, Cassileth PA (1996) Treatment of adult patients with acute lymphocytic leukemia in relapse. Leuk Lymphoma 20(3–4):317–319. Scholar
  12. 12.
    Appelbaum FR, Rosenblum D, Arceci RJ, Carroll WL, Breitfeld PP, Forman SJ, Larson RA, Lee SJ, Murphy SB, O’Brien S, Radich J, Scher NS, Smith FO, Stone RM, Tallman MS (2007) End points to establish the efficacy of new agents in the treatment of acute leukemia. Blood 109(5):1810–1816. pii]CrossRefPubMedGoogle Scholar
  13. 13.
    Nachman JB, Sather HN, Sensel MG, Trigg ME, Cherlow JM, Lukens JN, Wolff L, Uckun FM, Gaynon PS (1998) Augmented post-induction therapy for children with high-risk acute lymphoblastic leukemia and a slow response to initial therapy. N Engl J Med 338(23):1663–1671. Scholar
  14. 14.
    Chang JE, Medlin SC, Kahl BS, Longo WL, Williams EC, Lionberger J, Kim K, Kim J, Esterberg E, Juckett MB (2008) Augmented and standard Berlin-Frankfurt-Munster chemotherapy for treatment of adult acute lymphoblastic leukemia. Leuk Lymphoma 49(12):2298–2307. Scholar
  15. 15.
    Linker CA, Levitt LJ, O’Donnell M, Ries CA, Link MP, Forman SJ, Farbstein MJ (1987) Improved results of treatment of adult acute lymphoblastic leukemia. Blood 69(4):1242–1248PubMedGoogle Scholar
  16. 16.
    Sive JI, Buck G, Fielding A, Lazarus HM, Litzow MR, Luger S, Marks DI, McMillan A, Moorman AV, Richards SM, Rowe JM, Tallman MS, Goldstone AH (2012) Outcomes in older adults with acute lymphoblastic leukaemia (ALL): results from the international MRC UKALL XII/ECOG2993 trial. Br J Haematol 157(4):463–471. Scholar
  17. 17.
    Jabbour E, O’Brien S, Konopleva M, Kantarjian H (2015) New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia. Cancer 121(15):2517–2528. Scholar
  18. 18.
    Kantarjian H, Thomas D, O’Brien S, Cortes J, Giles F, Jeha S, Bueso-Ramos CE, Pierce S, Shan J, Koller C, Beran M, Keating M, Freireich EJ (2004) Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer 101(12):2788–2801. Scholar
  19. 19.
    Thomas D, O’Brien S, Faderl S, Ravandi F, Jabbour E, Pierce S, Cortes J, Kantarjian H (2010) Anthracycline dose intensification in adult acute lymphoblastic leukemia: lack of benefit in the context of the fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimen. Cancer 116(19):4580–4589. Scholar
  20. 20.
    Stock W, Johnson JL, Stone RM, Kolitz JE, Powell BL, Wetzler M, Westervelt P, Marcucci G, DeAngelo DJ, Vardiman JW, McDonnell D, Mrozek K, Bloomfield CD, Larson RA (2013) Dose intensification of daunorubicin and cytarabine during treatment of adult acute lymphoblastic leukemia: results of Cancer and Leukemia Group B Study 19802. Cancer 119(1):90–98. Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Hematology/Oncology, Konkuk University School of MedicineKonkuk UniversitySeoulRepublic of Korea

Personalised recommendations