Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Intensive chemotherapy to improve outcome in patients with acute lymphoblastic leukemia over the age of 40: a phase II study for efficacy and feasibility by HOVON

Leukemia volume 26, pages 1726–1729 (2012)Cite this article

Subjects

Recently, it has been shown that outcome of acute lymphoblastic leukemia (ALL) in younger adults can be improved by intensified pediatric-based chemotherapy.1, 2, 3 However, toxicity of these schedules seems prohibitive above the age of 40.2 To improve the current dismal outlook for older patients, intensification of chemotherapy, although less stringent as in younger patients, may still be an option. A relatively intensive chemotherapeutic regimen that had already been applied successfully in both younger and older patients in a single center4, 5 seemed a promising approach for older patients. Cornerstone of that treatment was a ‘pre-induction’ course with non-cross-reactive drugs for rapid tumor load reduction before regular induction, consolidation and maintenance courses. High-risk ALL patients, who had received the pre-induction course with cytarabine and etoposide appeared to have a better survival than lower-risk patients who had not.4 After addition of methotrexate (MTX), the regimen was therefore given to all patients regardless of risk assessment.5 It resulted in a 5-year overall survival (OS) of 60% in patients with a median age of 39 years.5 As the regimen seemed tolerable for older patients, the Dutch–Belgian cooperative group HOVON investigated whether it was feasible and effective in a multicenter setting in patients over 40 years.

From October 2005 until January 2008, 60 consecutive, unselected, newly diagnosed ALL patients between 40 and 70 years of age were treated according to the schedule depicted in Table 1a, unless intensive chemotherapy was unfeasible because of severe comorbidity. Patients with an HLA-identical sibling were offered a non-myeloablative allogeneic stem cell transplantation (allo-SCT) in first complete remission (CR). Patients with high-risk disease without sibling donor were eligible for unrelated donor SCT.

Table 1a Chemotherapy schedule
Full size table

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Barry EV, 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: 813–819.

    Article  CAS  Google Scholar 

  2. Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E et al. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol 2009; 27: 911–918.

    Article  CAS  Google Scholar 

  3. Rijneveld AW, van der Holt B, Daenen SMGJ, 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: 1697–1703.

    Article  CAS  Google Scholar 

  4. Daenen S, van Imhoff GW, van den Berg E, de Kam PJ, Haaxma-Reiche H, Vellenga E et al. Improved outcome of adult acute lymphoblastic leukaemia by moderately intensified chemotherapy which includes a ‘pre-induction’ course for rapid tumour reduction: preliminary results on 66 patients. Br J Haematol 1998; 100: 273–282.

    Article  CAS  Google Scholar 

  5. Daenen S, van Imhoff GW, de Wolf JT, Vellenga E, van den Berg-de Ruiter E, Kluin-Nelemans HC . A ‘pre-induction course’ with non-cross-reacting cytostatic drugs for rapid tumour load reduction improves outcome in adult acute lymphoblastic leukaemia. Br J Haematol 2007; 138: 275–277.

    Article  CAS  Google Scholar 

  6. Jaffe ES, Harris NL, Stein H, Vardiman JW (eds). WHO Classification of Tumours of the Haematopoietic and Lymphoid Tissues. IARC Press: Lyon, pp 106–117.

  7. Rowe JM . Optimal management of adults with ALL. Br J Haematol 2009; 144: 468–483.

    Article  Google Scholar 

  8. Pulte D, Gondos A, Brenner H . Improvement in survival in younger patients with acute lymphoblastic leukemia from the 1980 s to the early 21st century. Blood 2009; 113: 1408–1411.

    Article  CAS  Google Scholar 

  9. O’Brien S, Thomas DA, Ravandi F, Faderl S, Pierce S, Kantarjian H . Results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimen in elderly patients with acute lymphocytic leukemia. Cancer 2008; 113: 2097–2101.

    Article  Google Scholar 

  10. Sancho JM, Ribera JM, Xicoy B, Morgades M, Oriol A, Tormo M et al. Results of the PETHEMA ALL-06 trial in elderly patients with Philadelphia chromosome-negative acute lymphoblastic leukemia. Eur J Haematol 2007; 78: 102–110.

    CAS  PubMed  Google Scholar 

  11. Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood 2008; 111: 1827–1833.

    Article  CAS  Google Scholar 

  12. Cornelissen JJ, van der Holt B, Verhoef GE, van ‘t Veer MB, van Oers MH, Schouten HC et al. Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison. Blood 2009; 113: 1375–1382.

    Article  CAS  Google Scholar 

  13. Mohty M, Labopin M, Tabrizzi R, Theorin N, Fauser AA, Rambaldi A et al. Reduced intensity conditioning allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a retrospective study from the European group for Blood and Marrow transplantation. Haematologica 2008; 93: 303–306.

    Article  Google Scholar 

  14. Marks DI, Wang T, Perez WS, Antin JH, Copelan E, Gale RP et al. The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first and second complete remission. Blood 2010; 116: 366–374.

    Article  CAS  Google Scholar 

  15. Yanada M, Ohno R, Naoe T . Recent advances in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Int J Hematol 2009; 89: 3–13.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The study was registered at www.isrctn.org as ISRCTN00446029. It was approved by the ethics committees of the participating institutions and was conducted in accordance to the Declaration of Helsinki. All patients gave written informed consent.

Author information

Authors and Affiliations

  1. University Medical Centre Groningen, Groningen, The Netherlands

    S Daenen

  2. HOVON Data Center, Erasmus MC—Daniel den Hoed, Rotterdam, The Netherlands

    B van der Holt & E W de Klerk

  3. University Medical Center Utrecht, Utrecht, The Netherlands

    A W Dekker

  4. Leiden University Medical Center, Leiden, The Netherlands

    R Willemze

  5. Erasmus MC, Rotterdam, The Netherlands

    A W Rijneveld & J J Cornelissen

  6. Academic Medical Center, Amsterdam, The Netherlands

    B J Biemond

  7. Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    P Muus

  8. VU University Medical Center, Amsterdam, The Netherlands

    A A van de Loosdrecht

  9. Academic Hospital Maastricht, Maastricht, The Netherlands

    H C Schouten

  10. Isala Clinic-Sophia, Zwolle, The Netherlands

    M van Marwijk Kooy

  11. ZNA Stuivenberg, Antwerpen, Belgium

    D A Breems

  12. H. Hart Ziekenhuis, Roeselare, Belgium

    H Demuynck

  13. University Hospital Gasthuisberg, Leuven, Belgium

    J Maertens

  14. Haga Hospital, The Hague, The Netherlands

    P W Wijermans

  15. Meander Medical Center, Amersfoort, The Netherlands

    S Wittebol

Authors
  1. S Daenen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B van der Holt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A W Dekker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R Willemze
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A W Rijneveld
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B J Biemond
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P Muus
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A A van de Loosdrecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. H C Schouten
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M van Marwijk Kooy
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. D A Breems
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. H Demuynck
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. J Maertens
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. P W Wijermans
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. S Wittebol
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. E W de Klerk
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. J J Cornelissen
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of HOVON, the Dutch-Belgian Cooperative Group for Hematological Oncology

Corresponding author

Correspondence to S Daenen.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Daenen, S., van der Holt, B., Dekker, A. et al. Intensive chemotherapy to improve outcome in patients with acute lymphoblastic leukemia over the age of 40: a phase II study for efficacy and feasibility by HOVON. Leukemia 26, 1726–1729 (2012). https://doi.org/10.1038/leu.2012.53

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2012.53

This article is cited by

Search

Advanced search

Quick links