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.

  • Original Article
  • Published:

Acute Leukemias

Outcome of treatment after first relapse in adults with acute lymphoblastic leukemia initially treated by the LALA-94 trial

Leukemia volume 21, pages 1907–1914 (2007)Cite this article

Abstract

Fifty-four percent of adults with acute lymphoblastic leukemia (ALL) who entered the LALA-94 trial experienced a first relapse. We examined the outcome of these 421 adult patients. One hundred and eighty-seven patients (44%) achieved a second complete remission (CR). The median disease-free survival (DFS) was 5.2 months with a 5-year DFS at 12%. Factors predicting a better outcome after relapse were any transplant performed in second CR (P<0.0001), a first CR duration >1 year (P=0.04) and platelet level >100 × 109/l at relapse (P=0.04). Risk groups defined at diagnosis and treatment received in first CR did not influence the outcome after relapse. The best results were obtained in a subset of patients who were eligible for allogeneic stem cell transplantation (SCT). Geno-identical allogeneic SCT was performed in 55 patients, and 3 patients received donor lymphocyte infusions. Forty-four transplantations were performed from an unrelated donor (of which four were cord blood). We conclude that most adult patients with recurring ALL could not be rescued using current available therapies, although allogeneic SCT remains the best therapeutic option.

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

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
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Durrant IJ, Prentice HG, Richards SM . Intensification of treatment for adults with acute lymphoblastic leukaemia: results of UK medical research council randomized trial UKALL XA. medical research council working party on leukaemia in adults. Br J Haematol 1997; 99: 84–92.

    Article  CAS  Google Scholar 

  2. Fiere D, Lepage E, Sebban C, Boucheix C, Gisselbrecht C, Vernant JP et al. Adult acute lymphoblastic leukemia: a multicentric randomized trial testing bone marrow transplantation as postremission therapy. J Clin Oncol 1993; 11: 1990–2001.

    Article  CAS  Google Scholar 

  3. Hoelzer D, Thiel E, Ludwig WD, Löffler H, Büchner T, Freund M et al. Follow-up of the first two successive German multicentre trials for adult ALL (01/81 and 02/84). Leukemia 1993; 7 (Suppl 2): S130–S134.

    PubMed  Google Scholar 

  4. Larson RA, Dodge RK, Burns CP, Lee EJ, Stone RM, Schulman P et al. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood 1995; 85: 2025–2037.

    CAS  PubMed  Google Scholar 

  5. Mandelli F, Annino L, Rotoli B, for the GIMEMA Cooperative Group. The GIMEMA ALL 0183 trial, analysis of 10-year follow-up. Br J Haematol 1996; 92: 663–672.

    Article  Google Scholar 

  6. Kantarjian HM, O'Brien S, Smith TL, Cortes J, Giles FJ, Beran M et al. Results of treatment with Hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol 2000; 18: 547–561.

    Article  CAS  Google Scholar 

  7. Hoelzer D . Acute lymphoblastic leukemia: progress in children, less in adults. N Engl J Med 1993; 329: 1343–1344.

    Article  CAS  Google Scholar 

  8. Bassan R, Lerede T, Barbui T . Strategies for the treatment of recurrent acute lymphoblastic leukemia in adults. Haematologica 1996; 81: 20–36.

    CAS  PubMed  Google Scholar 

  9. Weiss MA . Treatment of adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL). Leukemia 1997; 11 (Suppl 4): S28–S30.

    PubMed  Google Scholar 

  10. Welborn J . Impact of re-induction regimens for relapsed and refractory acute lymphoblastic leukemia in adults. Am J Hematol 1994; 45: 341–344.

    Article  CAS  Google Scholar 

  11. Garcia-Manero G, Thomas DA . Salvage therapy for refractory or relapsed acute lymphocytic leukemia. Hematol Oncol Clin North Am 2001; 15: 163–205.

    Article  CAS  Google Scholar 

  12. Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of LALA-94 trial. J Clin Oncol 2004; 22: 4075–4086.

    Article  CAS  Google Scholar 

  13. Dombret H, Gabert J, Boiron JM, Rigal-Huguet F, Blaise D, Thomas X et al. Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia – results of the prospective multicenter LALA-94 trial. Blood 2002; 100: 2357–2366.

    Article  CAS  Google Scholar 

  14. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR et al. Proposals for the classification of the acute leukaemias. French–American–British (FAB) co-operative group. Br J Haematol 1976; 33: 451–458.

    Article  CAS  Google Scholar 

  15. Kantarjian HM, Walters RS, Keating MJ, Barlogie B, McCredie KB, Freireich EJ . Experience with vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy in adults with refractory acute lymphoblastic leukemia. Cancer 1989; 64: 16–22.

    Article  CAS  Google Scholar 

  16. Schrappe M, Reiter A, Ludwig WD, Harbott J, Zimmermann M, Hiddemann W et al. Inproved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. German–Austrian–Swiss ALL–BFM study group. Blood 2000; 95: 3310–3322.

    CAS  PubMed  Google Scholar 

  17. Schaison G, Auclerc MF, Baruchel A, Leblanc T, Leverger G . Prognosis of acute lymphoblastic leukemia in children. Results of the French protocol FRALLE 93. Bull Acad Natl Med 2001; 185: 149–160.

    CAS  PubMed  Google Scholar 

  18. Capizzi RL, Keeser LW, Sartorelli AC . Combination chemotherapy: theory and practice. Semin Oncol 1977; 4: 227–253.

    CAS  PubMed  Google Scholar 

  19. Milpied N, Gisselbrecht C, Harousseau JL, Sebban C, Witz F, Troussard X et al. Successful treatment of adult acute lymphoblastic leukemia after relapse with prednisone, intermediate-dose cytarabine, mitoxantrone, and etoposide (PAME) chemotherapy. Cancer 1990; 66: 627–631.

    Article  CAS  Google Scholar 

  20. Arcese W, Meloni G, Giona F, Vegna ML, Testi AM, Annino L et al. Idarubicin plus ARA-C followed by allogeneic or autologous bone marrow transplantation in advanced acute lymphoblastic leukemia. Bone Marrow Transplant 1991; 7 (Suppl 2): 38.

    PubMed  Google Scholar 

  21. Visani G, Tosi P, Zingani PL, Manfroi S, Ottaviani E, Cenacchi A et al. FLAG (fludarubicine, cytarabine, G-CSF) as a second line therapy for acute lymphoblastic leukemia with myeloid antigen expression: In vitro and in vivo effects. Eur J Haematol 1996; 56: 308–312.

    Article  CAS  Google Scholar 

  22. Reman O, Buzyn A, Lhéritier V, Huguet F, Kuentz M, Stamatoullas A et al. Rescue therapy combining intermediate-dose cytarabine with amsacrine and etoposide in relapsed adult acute lymphoblastic leukemia. Hematol J 2004; 5: 123–129.

    Article  CAS  Google Scholar 

  23. Arlin Z, Feldman E, Kempin S, Ahmed T, Mittelman A, Savona S et al. Amsacrine with high-dose cytarabine is highly effective therapy for refractory and relapsed acute lymphoblastic keukemia in adults. Blood 1988; 72: 433–435.

    CAS  PubMed  Google Scholar 

  24. Thomas X, Bauduer F, Thiebaut A, Brion A, Maloisel F, Fenaux P et al. Idarubicin and ifosfamide in the treatment of refractory and relapsed acute lymphoblastic leukemia. In: Hiddemann W, Büchner T, Wörmann B, Ritter J, Creutzig U, Keating M, Plunkett W (eds). Acute Leukemias VII. Experimental approaches and novel therapies. Springer-Verlag: Berlin Heidelberg, 1998, pp 766–770.

    Google Scholar 

  25. Klein JP, Rizzo JD, Zhang MJ, Keiding N . Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part I: Unadjusted analysis. Bone Marrow Transplant 2001; 28: 909–915.

    Article  CAS  Google Scholar 

  26. Keating MJ, Holmes R, Lerner S, Ho DH . L-Asparaginase and PEG asparaginase – past, present, and future. Leuk Lymphoma 1993; 10 (Suppl): 153–157.

    Article  Google Scholar 

  27. Kantarjian HM, Walters RS, Keating MJ, Barlogie B, McCredie KB, Freireich EJ . Experience with vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy in adults with refractory acute lymphocytic leukemia. Cancer 1989; 64: 16–22.

    Article  CAS  Google Scholar 

  28. Thomas DA, Kantarjian H, Smith TL, Koller C, Cortes J, O'Brien S et al. Primary refractory and relapsed adult acute lymphoblastic leukemia: characteristics, treatment results, and prognosis with salvage therapy. Cancer 1999; 86: 1216–1230.

    Article  CAS  Google Scholar 

  29. Butturini A, Gale RP . Chemotherapy versus transplantation in acute leukaemia. Br J Haematol 1989; 72: 1–8.

    Article  CAS  Google Scholar 

  30. Fielding AK, Richards SM, Chopra R, Lazarus HM, Litzow MR, Buck G et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL): an MRC UKALL12/ECOG 2993 study. Blood 2007; 109: 944–950.

    Article  CAS  Google Scholar 

  31. George SL, Ochs JJ, Mauer AM, Simone JV . The importance of an isolated central nervous system relapse in children with acute lymphoblastic leukemia. J Clin Oncol 1985; 3: 776–781.

    Article  CAS  Google Scholar 

  32. Herzig RH, Bortin MM, Barrett AJ, Blume KG, Gluckman E, Horowitz MM et al. Bone-marrow transplantation in high-risk acute lymphoblastic leukaemia in first and second remission. Lancet 1987; 1: 786–789.

    Article  CAS  Google Scholar 

  33. Fleming DR, Henslee-Downey PJ, Romond EH, Harder EJ, Marciniak E, Munn RK et al. Allogeneic bone marrow transplantation with T cell-depleted partially matched related donors for advanced acute lymphoblastic leukemia in children and adults: a comparative matched cohort study. Bone Marrow Transplant 1996; 17: 917–922.

    CAS  PubMed  Google Scholar 

  34. Davies SM, Ramsay NK, Weisdorf DJ . Feasibility and timing of unrelated donor identification for patients with ALL. Bone Marrow Transplant 1996; 17: 737–740.

    CAS  PubMed  Google Scholar 

  35. Gluckman E, Rocha V, Boyer-Chammard A, Locatelli F, Arcese W, Pasquini R et al. Outcome of cord-blood transplantation from related and unrelated donors: Eurocord Transplant Group and the European Blood and Marrow Transplantation Group. N Engl J Med 1997; 337: 373–381.

    Article  CAS  Google Scholar 

  36. Rubinstein P, Carrier C, Saradavou A, Kurtzberg J, Adamson J, Migliaccio AR et al. Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med 1998; 339: 1565–1577.

    Article  CAS  Google Scholar 

  37. Takeuchi J, Kyo T, Naito K, Sao H, Takahashi M, Miyawaki S et al. Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study. Leukemia 2002; 16: 1259–1266.

    Article  CAS  Google Scholar 

  38. Ribera JM, Oriol A, Bethencourt C, Parody R, Hernandez-Rivas JM, Moreno MJ et al. Comparison of intensive chemotherapy, allogeneic or autologous stem cell transplantation as post-remission treatment for adult patients with high-risk acute lymphoblastic leukemia. Results of the PETHEMA ALL-93 trial. Haematologica 2005; 90: 1346–1356.

    CAS  PubMed  Google Scholar 

  39. Labar B, Suciu S, Zittoun R, Muus P, Marie JP, Fillet G et al. Allogeneic stem cell transplantation in acute lymphoblastic leukemia and non Hodgkin's lymphoma for patents &lt; or=50 years old in first complete remission: results of the EORTC ALL-3 trial. Haematologica 2004; 89: 809–817.

    PubMed  Google Scholar 

  40. Sebban C, Lepage E, Vernant JP, Gluckman E, Attal M, Reiffers J et al. Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. J Clin Oncol 1994; 12: 2580–2587.

    Article  CAS  Google Scholar 

  41. Hunault M, Harousseau JL, Delain M, Truchan-Graczyk M, Cahn JY, Witz F et al. Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. Blood 2004; 104: 3028–3037.

    Article  CAS  Google Scholar 

  42. Rowe J, Richards S, Burnett A, Wiernik PH, Harrison G, Lazarus HM et al. Favorable results of allogeneic bone marrow transplantation (BMT) for adult with Philadelphia (Ph)-chromosome-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR): results from the International ALL trial (MRC UKALL XII/ECOG E2993). Blood 2001; 98 (Suppl 1): 2009.

    Google Scholar 

  43. Yanada M, Matsuo K, Suzuki T, Naoe T . Allogeneic hematopoietic stem cell transplantation as part of postremission therapy improves survival for adult patients with high-risk acute lymphoblastic leukemia. Cancer 2006; 106: 2657–2663.

    Article  Google Scholar 

Download references

Acknowledgements

We greatly thank Professor Charles Dumontet for proofreading this paper. This work was supported in part by PHRC no. 94-95-97.02, Ministère de l'Emploi et de la Solidarité, France.

Author information

Authors and Affiliations

  1. Hôpital Nord, Saint-Etienne, France

    E Tavernier

  2. Hôpital du Haut Levêque, Pessac, France

    J-M Boiron

  3. Hôpital Purpan, Toulouse, France

    F Huguet

  4. Westmead Hospital, Westmead, Australia

    K Bradstock

  5. Institut Paoli Calmettes, Marseille, France

    N Vey & J Gabert

  6. Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

    T Kovacsovics

  7. Hôpital de Jolimont, Haine St Paul, Belgium

    A Delannoy

  8. Centre Hospitalier Lapeyronie, Montpellier, France

    N Fegueux

  9. Centre Hospitalier, Lille, France

    P Fenaux

  10. Centre Henri Becquerel, Rouen, France

    A Stamatoullas

  11. Hôtel-Dieu, Clermont-Ferrand, France

    O Tournilhac

  12. Hôpital Necker, Paris, France

    A Buzyn

  13. Centre Hospitalier, Caen, France

    O Reman

  14. Hôpital Edouard Herriot, Lyon, France

    C Charrin, V Lhéritier & X Thomas

  15. INSERM U268, Villejuif, France

    C Boucheix

  16. Hôpital Pitié-Salpétrière, Paris, France

    J-P Vernant

  17. Hôpital Saint-Louis, Paris, France

    H Dombret

Authors
  1. E Tavernier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J-M Boiron
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F Huguet
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K Bradstock
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N Vey
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T Kovacsovics
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A Delannoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. N Fegueux
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. P Fenaux
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A Stamatoullas
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. O Tournilhac
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A Buzyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. O Reman
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. C Charrin
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. C Boucheix
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. J Gabert
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. V Lhéritier
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. J-P Vernant
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. H Dombret
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. X Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for the GET-LALA Group, the Swiss Group for Clinical Cancer Research SAKK and the Australasian Leukaemia and Lymphoma Group

Corresponding author

Correspondence to X Thomas.

Appendix

Appendix

The following hospitals participated in the LALA-94 trial:

Groupe d'Etude et de Traitement de la Leucémie Aiguë Lymphoblastique de l'Adulte (GET-LALA Group) – Hôpital Edouard Herriot, Lyon; Hôpital Saint-Louis, Paris; Hôpital du Haut Levêque, Pessac; Hôpital Purpan, Toulouse; Hôpital Henri Mondor, Créteil; Hôpital Pitié-Salpétrière, Paris; Institut Paoli Calmettes, Marseille; Hôpital Cochin, Paris; Hôpital de Hautepierre, Strasbourg; Hôpital de l'Archet, Nice; Hôpital Necker, Paris; Hôpital Jean Bernard, Poitiers; Hôpital Michallon, Grenoble; Institut Gustave Roussy, Villejuif; Hôpital du Bocage, Dijon; Hôpital Saint-Antoine, Paris; Centre Hospitalier, Caen; Hôpital Pontchaillou, Rennes; Centre Hospitalier de la Côte Basque, Bayonne; Centre Hospitalier Lyon-Sud, Pierre Bénite; HIA Percy, Clamart; Centre Hospitalier, Chambéry; Hôpital Dupuytren, Limoges; Centre Hospitalier, Avignon; Hôpital Louis Pasteur, Colmar; Centre Henri Becquerel, Rouen; Centre Hospitalier, Lille; Hôtel Dieu, Clermont-Ferrand; Hôpital André Mignot, Versailles; Hôpital Beaujon, Clichy; Centre Hospitalier, Annecy; Centre Hospitalier Lapeyronie, Montpellier; Centre Hospitalier, Aix en Provence; Hôpital Jean Monod, Le Havre; Hôpital Lariboisière, Paris; Hôpital Victor Dupouy, Argenteuil; Centre Hospitalier Dr Schaffner, Lens; Centre Antoine Lacassagne, Nice; Centre Hospitalier, Meaux; Centre Hospitalier, Perpignan; Clinique St Vincent, Lille; Centre Hospitalier, Nîmes; Centre Hospitalier, Roubaix, France.

Cliniques St Luc, Bruxelles; Centre Hospitalier Notre Dame et Reine Fabiola, Charleroi; Cliniques de Mont Godinne, Yvoir; ASBL, Loverval; Hôpital Saint Joseph, Gilly; Hôpital de Jolimont, Haine St Paul; Hôpital St Joseph, Mons; Hôpital de la Citadelle, Liège; Laboratoire de Cytogénétique, Leuven, Belgium.

Swiss Group for Clinical Cancer Research (SAKK) – Centre Hospitalier Universitaire Vaudois, Lausanne; Kantonsspital, St Gallen; Universitätsspital, Zürich; Hôpital Cantonal Universitaire, Genève; Kantonsspital, Basel; Inselspital, Bern; Kantonsspital, Winterthur; Kantonsspital, Luzern, Switzerland.

Australasian Leukaemia and Lymphoma Group (ALLG) – Westmead Hospital, Westmead; Adelaide Hospital, Adelaide; Mater Misericordae Hospital, Newcastle; Alfred Hospital, Melbourne; Royal Adelaide Hospital, Adelaide; Peter Mac Callum Cancer Centre Institute, Melbourne; Monash Medical Centre, Melbourne; Liverpool Hospital, Sydney; St George Hospital, Sydney, Australia.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tavernier, E., Boiron, JM., Huguet, F. et al. Outcome of treatment after first relapse in adults with acute lymphoblastic leukemia initially treated by the LALA-94 trial. Leukemia 21, 1907–1914 (2007). https://doi.org/10.1038/sj.leu.2404824

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404824

Keywords

This article is cited by

Search

Advanced search

Quick links