Skip to main content
SpringerLink
Log in

Acute Lymphoblastic Leukaemia in Elderly Patients

Biological Characteristics and Therapeutic Approaches

  • Review Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Acute lymphoblastic leukaemia (ALL) is a rare disease in the elderly. The prevalence of ALL in patients >60 years of age is reported to be between 16% and 31% of all adult cases. The biology of ALL in older patients seems to be significantly different from that in younger patients and may, at least in part, explain poor treatment outcome. Immunophenotyping and cytogenetic characteristics are among the most important biological differences in comparison with younger adults. The frequency of pre B-cell ALL and common ALL is higher and T-cell ALL subtype is under-represented in elderly populations compared with younger patients. The frequency of the Philadelphia chromosome also seems to increase with age and adversely influences complete remission rate and survival. Few reports on the effectiveness and toxicity of therapeutic programmes concerning exclusively older patients with ALL have been published so far and only some of them were prospective studies.

In some of the studies age-adapted approaches have been applied in which protocols processed earlier for younger patients have been adopted for older patients. In such modified protocols chemotherapy was usually less aggressive, especially if it was given for patients with comorbidities and poor performance status. Consequently, in several studies elderly patients received suboptimal treatment. Death during induction chemotherapy was observed in 7–42% of the patients in particular reports. The overall response rate varied from 12% to 85%. The median overall survival (OS) durations in patients who received a curative approach ranged from 3 to 14 months and from 1 to 14 months in patients treated palliatively. Poor performance status, comorbidities and high early mortality during intensive chemotherapy are the main reasons for poor treatment results and short OS time. New therapeutic approaches are necessary to improve the outcome in this age group of patients with ALL.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I

Similar content being viewed by others

References

  1. Kebriaei P, Anastasi J, Larson RA. Acute lymphoblastic leukemia: diagnosis and classification. Best Pract Res Clin Haematol 2002; 15: 597–621

    Article  PubMed  CAS  Google Scholar 

  2. Cartwright RA. Epidemiology. In: Whittaker JA, editor. Leukemia. Oxford: Blackwell, 1992

    Google Scholar 

  3. Sandler DP, Ross JA. Epidemiology of acute leukemia in children and adults. Semin Oncol 1997; 24: 3–16

    PubMed  CAS  Google Scholar 

  4. Hoelzer D, Gokbuget N. New approaches in acute lymphoblastic leukemia in adults: where do we go? Semin Oncol 2000; 27: 540–59

    PubMed  CAS  Google Scholar 

  5. Farhi DC, Rosenthal NS. Acute lymphoblastic leukemia. Clin Lab Med 2000; 20: 17–28

    PubMed  CAS  Google Scholar 

  6. Kebriaei P, Larson RA. Progress and challenges in the therapy of adult acute lymphoblastic leukemia. Curr Opin Hematol 2003; 10: 284–9

    Article  PubMed  Google Scholar 

  7. Laport GF, Larson RA. Treatment of adult acute lymphoblastic leukemia. Semin Oncol 1997; 24: 70–82

    PubMed  CAS  Google Scholar 

  8. Taylor PR, Reid MM, Proctor SJ. Acute lymphoblastic leukemia in the elderly. Leuk Lymphoma 1994; 13: 373–80

    Article  PubMed  CAS  Google Scholar 

  9. Sorensen JT, Gerald K, Bodensteiner D, et al. Effect of age on survival in acute leukemia: 1950–1990. Cancer 1993; 72: 1602–6

    Article  PubMed  CAS  Google Scholar 

  10. Taylor PR, Reid MM, Bown N, et al. Acute lymphoblastic leukemia in patients aged 60 years and over: a population-based study of incidence and outcome. Blood 1992; 80:1813–7

    PubMed  CAS  Google Scholar 

  11. Annino L, Goekbuget N, Delannoy A. Acute lymphoblastic leukemia in the elderly. Hematology J 2002; 3: 219–23

    Article  Google Scholar 

  12. Hussein KK, Dahrberg S, Head D, et al. Treatment of acute lymphoblastic leukemia in adults with intensive induction, consolidation, and maintenance chemotherapy. Blood 1989; 73: 57–63

    PubMed  CAS  Google Scholar 

  13. Kantarjian HM, O’Brien S, Smith T, et al. Acute lymphocytic leukaemia in the elderly: characteristics and outcome with the vincristine-adriamycin dexamethasone (VAD) regimen. Br J Haematol 1994; 88: 94–100

    Article  PubMed  CAS  Google Scholar 

  14. Bassan R, Di Bona E, Lerede T, et al. Age-adapted moderatedose induction and flexible outpatient postremission therapy for elderly patients with acute lymphoblastic leukemia. Leuk Lymphoma 1996; 22: 295–301

    Article  PubMed  CAS  Google Scholar 

  15. Legrand O, Marie JP, Marjanovic Z, et al. Prognostic factors in elderly acute lymphoblastic leukaemia. Br J Haematol 1997; 97: 596–602

    Article  PubMed  CAS  Google Scholar 

  16. Thomas X, Olteanu N, Charrin C, et al. Acute lymphoblastic leukemia in the elderly: the Edouard Herriot Hospital experience. Am J Hematol 2001; 67: 73–83

    Article  PubMed  CAS  Google Scholar 

  17. Pagano L, Mele L, Casorelli I. Acute lymphoblastic leukemia in the elderly: a twelve year retrospective, single center study. Haematologica 2000; 85: 1327–9

    PubMed  CAS  Google Scholar 

  18. Gokbuget N, Hoelzer D, Arnold R, et al. Subtypes and treatment outcome in adult acute lymphoblastic leukemia (ALL) >55 years [abstract]. Hematol J 2001; 1Suppl. 1: 186

    Google Scholar 

  19. Ferrari A, Annino L, Crescenzi S, et al. Acute lymphoblastic leukemia in the elderly: results of two different treatment approaches in 49 patients during a 25-year period. Leukemia 1995; 9: 1643–7

    PubMed  CAS  Google Scholar 

  20. Mandelli F, Annino L, Vegna ML, et al. Treatment of acute lymphoblastic leukemia in the elderly result of the GIMEMAA ALL 0288 >60 years trial. In: Buchner T, Hiddeman W, Wormann B, et al., editors. Acute leukemias VI: prognostic factors and treatment strategies. Berlin: Springer-Verlag, 1997: 688–94

    Google Scholar 

  21. Robak T. Compared to traditional protocols, newer induction schedules have limited benefits for older people with acute myeloid leukemia. Evid Based Oncol 2002; 3: 77–80

    Article  Google Scholar 

  22. Pui CH, Evans WE. Acute lymphoblastic leukemia. N Engl J Med 1998; 339: 605–14

    Article  PubMed  CAS  Google Scholar 

  23. Nagura E, Minami S, Nagata K, et al. Analysis of elderly patients aged 60 years old or over with acute lymphoblastic leukemia. Nippon Ronen Igakkai Zasshi 1999; 36: 52–8

    Article  PubMed  CAS  Google Scholar 

  24. Kantarjian HM, O’Brien S, Smith TL, et al. Results of treatment with hyper-CVAD a dose-intensive regimen in adult acute lymphocytic leukemia. J Clin Oncol 2000; 18: 547–61

    PubMed  CAS  Google Scholar 

  25. Robak T, Szmigielska-Kap A, Wrzesień-Kuś A, et al. Acute lymphoblastic leukemia in elderly: the Polish Adult Leukemia Group (PALG) experience. Ann Hematol 2003; 83: 225–31

    Article  PubMed  Google Scholar 

  26. Spath-Schwalbe E, Heil G, Heimpel H. Acute lymphoblastic leukemia in patients over 59 years of age: experience in a single center over a 10 year period. Ann Hematol 1994; 69: 291–6

    Article  PubMed  CAS  Google Scholar 

  27. Yenerel MN, Atamer T, Yavuz AS, et al. Myeloid antigen expression provides favorable outcome in patients with adult acute lymphoblastic leukemia: a single center study. Ann Hematol 2002; 81: 498–503

    Article  PubMed  CAS  Google Scholar 

  28. Dombret H, Gabert J, Boiron JM, 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: 2357–66

    Article  PubMed  CAS  Google Scholar 

  29. Faderl S, Kantarjian HM, Thomas DA, et al. Outcome of Philadelphia chromosome positive adult acute lymphoblastic leukemia. Leuk Lymphoma 2000; 36: 263–73

    Article  PubMed  CAS  Google Scholar 

  30. Secker-Walker LM, Prentice HG, Durrant J. Cytogenetics adds independent prognostic information in adults with acute lymphoblastic leukaemia on MRC trial UKALL XA. MRC Adult Leukemia Working Party. Br J Hematol 1997; 96: 601–10

    Article  CAS  Google Scholar 

  31. Weztler M, Dodge RK, Mrozek K, et al. Prospective karyotype analysis in adult acute lymphoblastic leukemia: the Cancer and Leukaemia Group B experience. Blood 1999; 93: 3983–93

    Google Scholar 

  32. Gleissner B, Gokbuget N, Bartram CR, 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: 1536–43

    Article  PubMed  CAS  Google Scholar 

  33. The Groupe Francais de Cytogenetique Hematologique. Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings outcome. A Collaborative Study of the Group Francais de Cytogenetique Hematologique. Blood 1996; 87: 3135–42

    Google Scholar 

  34. Delannoy A, Cazin B, Thomas X, et al. Treatment of acute lymphoblastic leukemia in the elderly: an evaluation of vindesine during induction and of interferon alpha given as a single agent after complete remission. Leuk Lymphoma 2002; 43: 75–81

    Article  PubMed  CAS  Google Scholar 

  35. Offidani M, Corvatta L, Centurioni R, et al. High-dose daunorubicin as liposomal compound (Daunoxome) in elderly patients with acute lymphoblastic leukemia. Hematology J 2003; 4: 47–53

    Article  CAS  Google Scholar 

  36. Gokbuget N, Hoelzer D. Recent approaches in acute lymphoblastic leukemia in adults. Rev Clin Exp Hematol 2002; 6: 114–41

    Article  PubMed  Google Scholar 

  37. Delannoy A, Sebban C, Cony-Makhoul P, et al. Age-adapted induction treatment of acute lymphoblastic leukemia in the elderly and assessment of maintenance with interferon combined with chemotherapy: a multicentric prospective study in forty patients. Leukemia 1997; 11: 1429–34

    Article  PubMed  CAS  Google Scholar 

  38. Imbach P, Fuchs A, Berchtold W, et al. Boys but not girls with T-lineage acute lymphocytic leukemia (ALL) are different from children with B-progenitor ALL: population based data results of initial prognostic factors and long-term event-free survival. Swiss Pediatric Oncology Group. J Pediatr Hematol Oncol 1995; 17: 346–9

    Article  PubMed  CAS  Google Scholar 

  39. Faderl S, Jeha S, Kantarjian HM. The biology and therapy of adult acute lymphoblastic leukemia. Cancer 2003; 98: 1337–54

    Article  PubMed  Google Scholar 

  40. Delannoy A, Ferrant A, Bosly A. Acute lymphoblastic leukemia in the elderly. Eur J Haematol 1990; 45: 90–3

    Article  PubMed  CAS  Google Scholar 

  41. Pagano L, Mele L, Trage G, et al. The treatment of acute lymphoblastic leukemia in the elderly. Leuk Lymphoma 2004; 45: 117–23

    Article  PubMed  Google Scholar 

  42. Elison RR, Mick R, Cuttner J, et al. The effect of postinduction intensification treatment with cytarabine and daunorubicin in adult acute lymphocytic leukemia: a prospective randomized clinical trial by Cancer and Leukemia Group B. J Clin Oncol 1991; 9: 2002–15

    Google Scholar 

  43. Virgilio JF, Moscinski LC, Ballerter OF, et al. Acute lymphocytic leukemia ALL in elderly patients. Hematol Oncol 1993; 11: 121–6

    Article  PubMed  CAS  Google Scholar 

  44. Cohen J. Pharmacokinetic changes in aging. Am J Med 1986; 80Suppl. 5A: 31–8

    Article  PubMed  CAS  Google Scholar 

  45. Druker BJ. Perspectives on the development of a molecularly targeted agent. Cancer Cell 2002; 1: 31–6

    Article  PubMed  CAS  Google Scholar 

  46. Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001; 344: 1038–42

    Article  PubMed  CAS  Google Scholar 

  47. Ottmann OG, Druker BJ, Sawyers CL, et al. A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome positive acute lymphoid leukemias. Blood 2002; 100: 1965–71

    Article  PubMed  CAS  Google Scholar 

  48. Ottmann OG, Wassmann B. Imatinib in the treatment of Philadelphia chromosome positive acute lymphoblastic leukemia. Best Pract Res Clin Haematol 2002; 15: 757–69

    Article  PubMed  CAS  Google Scholar 

  49. Ottmann OG, Wassmann B, Gokbuget N, et al. A randomized trial of imatinib versus chemotherapy induction followed by concurrent imatinib and chemotherapy as first-line treatment in elderly patients with de novo Philadelphia-positive acute lymphoblastic leukemia [abstract no. 791]. Blood 2003; 102: 226a

    Google Scholar 

  50. Thomas DA, Cortes J, Kanarjian HM. New agents in the treatment of acute lymphocytic leukaemia. Best Pract Res Clin Haematol 2002; 15: 771–90

    Article  PubMed  CAS  Google Scholar 

  51. Krishna R, Webb MS, St Onge G, et al. Liposomal and nonliposomal drug pharmacokinetics after administration liposome: encapsulated vincristine and their contribution to drug tissue distribution properties. J Pharmacol Exp Ther 2001; 298: 1206–12

    PubMed  CAS  Google Scholar 

  52. Sarris AH, Hagemeister F, Romaguera J, et al. Liposomal vincristine in relapsed non-Hodgkin’s lymphomas: early results of an ongoing phase II trial. Ann Oncol 2000; 11: 69–72

    Article  PubMed  CAS  Google Scholar 

  53. Cortes J, O’Brien S, Estey E, et al. Phase I study of liposomal daunorubicin in patients with acute leukemia. Invest New Drugs 1999; 17: 81–7

    Article  PubMed  CAS  Google Scholar 

  54. Asselin BL. The three asparaginases: comparative pharmacology and optimal use in childhood leukemia. Adv Exp Med Biol 1999; 457: 621–9

    Article  PubMed  CAS  Google Scholar 

  55. Robak T. Monoclonal antibodies in the treatment of lymphoid leukemias. Leuk Lymphoma 2004; 45: 205–19

    Article  PubMed  CAS  Google Scholar 

  56. Gokbuget N, Hoelzer D. Treatment with monoclonal antibodies in acute lymphoblastic leukemia: current knowledge and future prospects. Ann Hematol 2004; 82: 201–5

    Article  Google Scholar 

  57. Ozsahin H, Fluss J, McLin V, et al. Rituximab with interleu-kin-2 after autologous bone marrow transplantation for acute lymphocytic leukemia in second remission. Med Pediatr Oncol 2003; 38: 300–1

    Article  Google Scholar 

  58. Jandula BM, Nomdedeu J, Martin P, et al. Rituximab can be useful as treatment for minimal residual disease in bcr-abl-positive acute lymphoblastic leukemia. Bone Marrow Transplant 2001; 77: 225–7

    Article  Google Scholar 

  59. Kolitz JE, O’Mara V, Willemze R, et al. Treatment of acute lymphoblastic leukemia (ALL) with Campath-1H: initial observations [abstract]. Blood 1994; 84: 1191a

    Google Scholar 

  60. Dyer MJ, Hale G, Hayhoe FG, et al. Effect of Campath-1 antibodies in vivo in patients with lymphoid malignancies: influence of antibody isotype. Blood 1989; 73: 1431–9

    PubMed  CAS  Google Scholar 

  61. Avivi I, Rowe JM, Goldstone AH. Stem cell transplantation in adult ALL patients. Best Pract Res Clin Haematol 2002; 15: 653–74

    Article  PubMed  CAS  Google Scholar 

  62. Massenkeil G, Nagy M, Lawang M, et al. Reduced intensity conditioning and prophylactic DLS can cure patients with high risk acute leukemias if complete donor chimerism can be achieved. Bone Marrow Transplant 2003; 31: 339–45

    Article  PubMed  CAS  Google Scholar 

  63. Giralt S, Anagnastopoulos A, Shahjahanan M, et al. Nonablative stem cell transplantation for older patients with acute leukemias and myelodysplastic syndromes. Semin Hematol 2002; 39: 57–26

    Article  PubMed  Google Scholar 

  64. Saris AH, Phan A, Duvic M, et al. Trimetrexate in relapsed T-cell lymphoma with skin involvement. J Clin Oncol 2002; 20: 2876–80

    Article  Google Scholar 

  65. Jones RJ, Sharkis SJ, Miller CB, et al. Bryostatin I, a unique biological response modifier: antileukemic activity in vitro. Blood 1990; 75: 1319–23

    PubMed  CAS  Google Scholar 

  66. Wall NR, Mohammad RM, Reddy KB, et al. Bryostatin I induces ubiquitination and proteasome degradation of Bcl-2 in the human acute lymphoblastic cell line, Reh. Int J Mol Med 2000; 5: 165–71

    PubMed  CAS  Google Scholar 

  67. Thomas DA, Giles FJ, Cortes J, et al. Antiangiogenic therapy in leukemia. Acta Haematol 2001; 106: 190–207

    Article  PubMed  CAS  Google Scholar 

  68. Richardson PG, Berenson J, Irwin D, et al. Phase II study of PS-341, a novel proteasome inhibitor, alone or in combination with dexamethasone in patients with multiple myeloma who have relapsed following front-line therapy and are refractory to their most recent therapy [abstract no. 3223]. Blood 2001; 98: 774a

    Google Scholar 

  69. Waters JS, Webb A, Cunningham D, et al. Phase I clinical and pharmacokinetics study of bcl-2 antisense oligonucleotide therapy in patients with non-Hodgkin’s lymphoma. J Clin Oncol 2000; 18: 1812–23

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by a grant from the Medical University of Lodz No 503-106-2.

The authors have provided no information on conflicts of interest directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland

    Tadeusz Robak

Authors
  1. Tadeusz Robak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tadeusz Robak.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Robak, T. Acute Lymphoblastic Leukaemia in Elderly Patients. Drugs Aging 21, 779–791 (2004). https://doi.org/10.2165/00002512-200421120-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-200421120-00003

Keywords

Search

Navigation