Display options
Cite
Hewamana S, Dearden C. Treatment options for high-risk chronic lymphocytic leukaemia. Ther Adv Hematol. 2011;2(3):147-59doi: 10.1177/2040620711404469.
Hewamana, S., & Dearden, C. (2011). Treatment options for high-risk chronic lymphocytic leukaemia. Therapeutic advances in hematology, 2(3), 147-59. https://doi.org/10.1177/2040620711404469
Hewamana, Saman, and Dearden, Claire. "Treatment options for high-risk chronic lymphocytic leukaemia." Therapeutic advances in hematology vol. 2,3 (2011): 147-59. doi: https://doi.org/10.1177/2040620711404469
Hewamana S, Dearden C. Treatment options for high-risk chronic lymphocytic leukaemia. Ther Adv Hematol. 2011 Jun;2(3):147-59. doi: 10.1177/2040620711404469. PMID: 23556086; PMCID: PMC3573406.
Copy Download .nbib Format: NLM
Share it on

Ther Adv Hematol. 2011 Jun;2(3):147-59. doi: 10.1177/2040620711404469.

Treatment options for high-risk chronic lymphocytic leukaemia.

Therapeutic advances in hematology

Saman Hewamana, Claire Dearden

Affiliations

  1. Department of Haemato-Oncology, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, UK.

PMID: 23556086 PMCID: PMC3573406 DOI: 10.1177/2040620711404469

Abstract

Chronic lymphocytic leukaemia (CLL) is the most common form of leukaemia in the Western world. The natural history of CLL is extremely variable with a survival time from initial diagnosis that ranges from 2 to more than 20 years. Understanding the clinical diversity and allowing the subclassification of CLL into various prognostic groups not only assists in predicting future outcome for patients, but also helps to direct treatment decisions. Chlorambucil and fludarabine were the standard therapy for CLL for decades. Randomized studies have reported superior overall response and progression-free survival (PFS) for fludarabine compared with alkylator-based therapy and for the fludarabine-cyclophospamide (FC) combination over fludarabine alone. More recently the addition of rituximab to the FC regimen (R-FC) has shown significant improvement in overall response, PFS and overall survival compared with FC alone. However, there are patients for whom this regimen still provides less satisfactory results. Within the above studies CLL patients who have some of the poorer prognostic markers, such as unmutated IgVH genes and/or high beta-2 microglobulin (B2M), and those who fail to achieve a minimal residual disease (MRD) negative remission are likely to have a shorter PFS compared with those without these features. Various strategies have been explored to improve the outcome for such patients. These include the addition of agents to a frontline R-FC regimen, use of consolidation and consideration of maintenance. The only group that can be clearly identified pretreatment for whom conventional fludarabine-based therapies produce significantly inferior response rates, PFS and overall survival are the patients who harbour a genetic fault; deletion or mutation or a combination of deletion and mutation of tumour protein p53 (TP53). TP53 inactivation is a less common finding at first treatment but becomes much more common in fludarabine-refractory patients. Alemtuzumab and high-dose corticosteroids have been shown to be effective in this group of CLL patients. Trials combining these two agents have shown improved responses, particularly for those patients with bulky nodal disease for whom alemtuzumab alone may be insufficient. Since the duration of responses remains relatively short, suitable patients should be considered for allogeneic stem cell transplantation according to the European Group for Blood and Marrow Transplantation (EBMT) guidelines. Furthermore, there are a number of other new treatments on the horizon, including humanized antibodies directed against novel targets and small-molecule inhibitors.

Keywords: CLL; high risk; prognosis; treatment

References

  1. Leukemia. 2009 Jan;23(1):212-4 - PubMed
  2. Blood. 2008 Jun 15;111(12):5446-56 - PubMed
  3. J Clin Oncol. 2007 Mar 1;25(7):793-8 - PubMed
  4. J Clin Oncol. 2009 Feb 1;27(4):498-503 - PubMed
  5. Blood. 2008 Aug 15;112(4):975-80 - PubMed
  6. Cancer. 2011 Jan 1;117(1):116-24 - PubMed
  7. Leuk Lymphoma. 2003 Feb;44(2):337-42 - PubMed
  8. Cancer. 1985 Nov 15;56(10):2369-75 - PubMed
  9. Lancet. 2010 Oct 2;376(9747):1164-74 - PubMed
  10. Nouv Rev Fr Hematol. 1988;30(5-6):433-6 - PubMed
  11. N Engl J Med. 2000 Dec 14;343(24):1750-7 - PubMed
  12. J Clin Oncol. 2005 May 1;23(13):2971-9 - PubMed
  13. J Clin Oncol. 2009 Sep 20;27(27):4578-84 - PubMed
  14. Clin Cancer Res. 2009 Jul 15;15(14):4759-68 - PubMed
  15. Leukemia. 2008 Nov;22(11):2048-53 - PubMed
  16. Leuk Lymphoma. 1999 Jun;34(1-2):167-70 - PubMed
  17. Leukemia. 2008 Jul;22(7):1377-86 - PubMed
  18. Leukemia. 2007 Jan;21(1):12-7 - PubMed
  19. Br J Haematol. 2009 Jan;144(1):95-8 - PubMed
  20. Leuk Lymphoma. 2008 Nov;49(11):2108-15 - PubMed
  21. Leukemia. 2003 May;17(5):841-8 - PubMed
  22. J Clin Oncol. 2010 Apr 1;28(10):1749-55 - PubMed
  23. Blood. 2007 Jun 1;109(11):4679-85 - PubMed
  24. Leuk Lymphoma. 2007 Dec;48(12):2412-7 - PubMed
  25. N Engl J Med. 2000 Dec 28;343(26):1910-6 - PubMed
  26. J Clin Oncol. 2003 Jul 15;21(14):2747-53 - PubMed
  27. Blood. 2010 Jun 3;115(22):4393-402 - PubMed
  28. J Clin Oncol. 1991 Jan;9(1):44-9 - PubMed
  29. J Clin Oncol. 2009 Sep 10;27(26):4378-84 - PubMed
  30. Clin Cancer Res. 2008 Nov 1;14(21):6907-15 - PubMed
  31. J Clin Oncol. 2007 Mar 1;25(7):799-804 - PubMed
  32. Blood. 2008 Jun 1;111(11):5291-7 - PubMed
  33. Blood. 2002 Aug 15;100(4):1177-84 - PubMed
  34. Leukemia. 2009 Dec;23(12):2281-9 - PubMed
  35. Leukemia. 2009 Nov;23(11):2027-33 - PubMed
  36. Haematologica. 2008 Mar;93(3):475-6 - PubMed
  37. Blood. 2002 Aug 15;100(4):1410-6 - PubMed
  38. J Clin Oncol. 2009 Dec 10;27(35):6012-8 - PubMed
  39. Eur J Cancer. 2010 Aug;46(12):2145-9 - PubMed
  40. J Clin Oncol. 2010 Apr 1;28(10):1756-65 - PubMed
  41. Blood. 2008 May 15;111(10):4916-21 - PubMed
  42. Ann Oncol. 2009 Dec;20(12):2007-12 - PubMed
  43. Blood. 2006 Feb 1;107(3):885-91 - PubMed
  44. Cancer. 2010 May 15;116(10):2360-5 - PubMed
  45. Leukemia. 2009 Oct;23(10):1779-89 - PubMed
  46. J Clin Oncol. 2005 May 20;23(15):3433-8 - PubMed
  47. Haematologica. 2010 Jul;95(7):1136-43 - PubMed
  48. Blood. 2009 Apr 2;113(14):3168-71 - PubMed
  49. Leukemia. 2002 Jun;16(6):993-1007 - PubMed
  50. J Clin Oncol. 2006 Jan 20;24(3):437-43 - PubMed
  51. Blood. 2008 Sep 1;112(5):1923-30 - PubMed
  52. Lancet. 1996 May 25;347(9013):1432-8 - PubMed
  53. Haematologica. 2010 Oct;95(10):1705-12 - PubMed
  54. Blood. 2000 Oct 15;96(8):2723-9 - PubMed
  55. Blood. 2010 Oct 7;116(14):2438-47 - PubMed
  56. Clin Cancer Res. 2005 Nov 1;11(21):7757-63 - PubMed
  57. Blood. 1998 Nov 15;92(10):3804-16 - PubMed
  58. Leukemia. 2007 Sep;21(9):1885-91 - PubMed
  59. J Clin Oncol. 2009 Aug 20;27(24):3994-4001 - PubMed
  60. Cell Death Differ. 2003 Apr;10(4):477-84 - PubMed
  61. Leukemia. 2009 Nov;23(11):1980-8 - PubMed
  62. Leuk Lymphoma. 2010 Jan;51(1):85-8 - PubMed
  63. Blood. 2009 Jul 30;114(5):957-64 - PubMed
  64. J Clin Oncol. 2006 Dec 1;24(34):5343-9 - PubMed
  65. Lancet. 2007 Jul 21;370(9583):230-239 - PubMed
  66. Blood. 2007 Jan 15;109(2):399-404 - PubMed
  67. Br J Haematol. 2007 May;137(4):355-63 - PubMed
  68. J Clin Oncol. 2006 May 20;24(15):2337-42 - PubMed
  69. J Clin Oncol. 1995 Mar;13(3):570-4 - PubMed
  70. Br J Haematol. 2001 Jul;114(1):70-7 - PubMed
  71. Blood. 2009 Oct 15;114(16):3382-91 - PubMed
  72. Blood. 2010 Sep 23;116(12):2078-88 - PubMed
  73. Haematologica. 2005 Oct;90(10):1435-6 - PubMed
  74. Blood. 1998 Jun 1;91(11):4342-9 - PubMed
  75. Leukemia. 2005 Jun;19(6):1029-33 - PubMed
  76. J Clin Oncol. 2007 Dec 10;25(35):5616-23 - PubMed
  77. Blood. 2008 Feb 1;111(3):1094-100 - PubMed
  78. Br J Haematol. 2004 May;125(3):294-317 - PubMed
  79. Ann Hematol. 2003 Dec;82(12):759-65 - PubMed
  80. Lancet Oncol. 2006 Jun;7(6):480-8 - PubMed
  81. Curr Opin Investig Drugs. 2009 Jun;10(6):588-96 - PubMed
  82. J Clin Oncol. 2008 Nov 1;26(31):5094-100 - PubMed
  83. Blood. 2008 Oct 15;112(8):3322-9 - PubMed
  84. Blood. 2004 May 1;103(9):3278-81 - PubMed
  85. N Engl J Med. 2002 Aug 8;347(6):452-3 - PubMed

Publication Types