Prognostic markers in chronic lymphocytic leukemia

Česká verzia

Authors: M. Motyčková ¹; P. Žák ¹; V. Vroblová ²; C. Andrýs ² ; D. Belada ¹; J. Malý ¹; L. Smolej ¹
Authors place of work: Oddělení klinické hematologie II. interní kliniky Lékařské fakulty UK a FN Hradec Králové, přednosta prof. MUDr. Jaroslav Malý, CSc. ¹; Ústav klinické imunologie a alergologie Lékařské fakulty UK a FN Hradec Králové, přednosta prof. RNDr. Jan Krejsek, CSc. ²
Published in the journal: Vnitř Lék 2011; 57(10): 847-857
Category: Přehledné referáty

Summary

Chronic lymphocytic leukemia is the most common leukemia type in Western countries. Even incidence of chronic lymphocytic leukemia is high, this disease remained beyond interest for a very long time. However, in the last few years the view of this disease fundamentally changed and due to intensive study, new knowledge especially on pathogenesis, prognostic factors and therapy based on intensive therapeutic procedures were made. Today we know that usage of classical prognostic factors is insufficient for prognosis evaluation in the individuals. However modern (IgVH mutation status, cytogenetic abberations) and new markers (LPL/ADAM29 ratio, microRNA, markers of angiogenesis etc) have potential to distinguish patients in early stages to groups with significantly different prognosis and predict clinical course of the disease.

Key words:
chronic lymphocytic leukemia – prognostic factors – prognosis – IgVH mutation status – cytogenetic aberrations

Zdroje

1. Vroblová V, Smolej L, Vrbacký F et al. Biological prognostic markers in chronic lymphocytic leukemia. Acta Medica (Hradec Kralove) 2009; 52: 3–8.

2. Kluin PM, Ko YH, Kovrigina AM et al. World Health Organisation Classification of Tumors of Haematopoietic and Lymphoid Tissue. 4th ed. Lyon: Agency for Research on Cancer 2008.

3. Zent CS, Polliack A. Staging chronic lymphocytic leukemia (CLL) for prognosis at diagnosis. Leuk Lymphoma 2006; 47: 2433–2434.

4. Klabusay M, Hrabčáková V, Stehlíková O et al. Role průtokové cytometrie v diagnostice a sledování pacientů s chronickou lymfocytární leukemií. Transfuze Hematol Dnes 2010; 16: 45–51.

5. Norin S, Kimby E, Lundin J. Tumor burden status evaluated by computed tomography scan is of prognostic importance in patients with chronic lymphocytic leukemia. Med Oncol 2010; 27: 820–825.

6. Goldin LR, Landgren O, Marti GE et al. Familial Aspects of Chronic Lymphocytic Leukemia, Monoclonal B-Cell Lymphocytosis (MBL), and Related Lymphomas. European J Clin Med Oncol 2010; 2: 119–126.

7. Paneesha S, Milligan DW. Stem cell transplantion for chronic lymphocytic leukaemia. Br J Haematol 2005; 128: 145–152.

8. Smolej L. Modern concept in the treatment of chronic lymphocytic leukemia. Hematology 2009; 14: 249–254.

9. Krejčí M, Adam Z, Pour L et al. Chronická B lymfatická leukemie a jí podobné stavy. Vnitř Lék 2009; 55: 746–765.

10. Moreno C, Montserrat E. New prognostic markers in chronic lymphocytic leukemia. Blood Rev 2008; 22: 211–219.

11. Gine E, Martinez A, Villamor N et al. Retraction: Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia (“accelerated” chronic lymphocytic leukemia) with aggressive clinical behavior. Haematologica 2010; 95: 1620.

12. Gentile M, Mauro FR, Guarini A et al. New developments in the diagnosis, prognosis and treatment of chronic lymphocytic leukemia. Curr Opin Oncol 2005; 17: 597–604.

13. Montserrat E. New prognostic markers in CLL. Hematology Am Soc Hematol Educ Program 2006: 279–284.

14. Wagner SD, Cwynarski K. Chronic lymphocytic leukaemia: new biological markers for assessing prognosis. Hematol J 2004; 5: 197–201.

15. Kozák T. Prognostické faktory chronické lymfocytární leukemie. Transfuze Hematol Dnes 2010; 16: 56–61.

16. Muntañola A, Bosch F, Arguis P et al. Abdominal computed tomography predicts progression in patients with Rai stage 0 chronic lymphocytic leukemia. J Clin Oncol 2007; 25: 1576–1580.

17. Eichhorst BF, Busch R, Hopfinger G et al. German CLL Study Group. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood 2006; 107: 885–891.

18. Blum KA, Young D, Broering S et al. Computed tomography scans do not improve the predictive power of 1996 national cancer institute sponsored working group chronic lymphocytic leukemia response criteria. J Clin Oncol 2007; 25: 5624–5629.

19. Hallek M, Cheson BD, Catovsky D et al. International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008; 111: 5446–5456.

20. Hamblin TJ. Prognostic markers in chronic lymphocytic leukaemia. Best Pract Res Clin Haematol 2007; 20: 455–468.

21. Zent CS, Ding W, Schwager SM et al. The prognostic significance of cytopenia in chronic lymphocytic leukaemia/small lymphocytic lymphoma. Br J Haematol 2008; 141: 615–621.

22. Kyasa MJ, Parrish RS, Schichman SA et al. Autoimmune cytopenia does not predict poor prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma. Am J Hematol 2003; 74: 1–8.

23. Montillo M, Hamblin T, Hallek M et al. Chronic lymphocytic leukemia: novel prognostic factors and their relevance for risk-adapted therapeutic strategies. Haematologica 2005; 90: 391–399.

24. Hus I, Podhorecka M, Bojarska-Junak A et al. The clinical significance of ZAP-70 and CD38 expression in B-cell chronic lymphocytic leukaemia. Ann Oncol 2006; 17: 683–690.

25. Wierda W. New prognostic factors in chronic lymphocytic leukemia. Clin Adv Hematol Oncol 2009; 7: 32–33.

26. Molica S. Sex differences in incidence and outcome of chronic lymphocytic leukemia patients. Leuk Lymphoma 2006; 47: 1477–1480.

27. Molica S, Brugiatelli M, Callea V et al. Comparison of younger versus older B-cell chronic lymphocytic leukemia patients for clinical presentation and prognosis. A retrospective study of 53 cases. Eur J Haematol 1994; 52: 216–221.

28. Montserrat E, Sanchez-Bisono J, Viñolas N et al. Lymphocyte doubling time in chronic lymphocytic leukaemia: analysis of its prognostic significance. Br J Haematol 1986; 62: 567–575.

29. Van Bockstaele F, Verhasselt B, Philippé J. Prognostic markers in chronic lymphocytic leukemia: a comprehensive review. Blood Rev 2009; 23: 25–47.

30. Gentile M, Cutrona G, Neri A et al. Predictive value of beta2-microglobulin (beta2-m) levels in chronic lymphocytic leukemia since Binet A stages. Haematologica 2009; 94: 887–888.

31. Molica S, Levato D, Cascavilla N et al. Clinico-prognostic implications of simultaneous increased serum levels of soluble CD 23 and beta2-microglobulin in B-cell chronic lymphocytic leukemia. Eur J Haematol 1999; 62: 117–122.

32. Hallek M, Langenmayer I, Nerl C et al. Elevated serum thymidine kinase levels identify a subgroup at high risk of disease progression in early, nonsmoldering chronic lymphocytic leukemia. Blood 1999; 93: 1732–1737.

33. Hallek M, Wanders L, Ostwald M et al. Serum beta(2)-microglobulin and serum thymidine kinase are independent predictors of progression-free survival in chronic lymphocytic leukemia and immunocytoma. Leuk Lymphoma 1996; 22: 439–447.

34. Rozman C, Montserrat E, Rodríguez--Fernández JM et al. Bone marrow histologic pattern-the best single prognostic parameter in chronic lymphocytic leukemia: a multivariate survival analysis of 329 cases. Blood 1984; 64: 642–648.

35. Berková A, Michalová K. Cytogenetické nálezy u chronické lymfocytární leukemie (CLL). Transfuze Hematol Dnes 2010; 16: 52–55.

36. Zenz T, Döhner H, Stilgenbauer S. Genetics and risk-stratified approach to therapy in chronic lymphocytic leukemia. Best Pract Res Clin Haematol 2007; 20: 439–453.

37. Döhner H, Stilgenbauer S, Benner A et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000; 343: 1910–1916.

38. Jankovičová K, Krejsek J, Kopecký O et al. Hodnocení apoptózy buněk akutní myeloidní leukemie a B-lymfocytární chronické lymfatické leukemie po kultivaci s cytostatiky a její vztah k mnohočetné rezistenci. Vnitř Lék 2005; 51: 175–182.

39. Tam CS, Otero-Palacios J, Abruzzo LV et al. Chronic lymphocytic leukaemia CD20 expression is dependent on the genetic subtype: a study of quantitative flow cytometry and fluorescent in-situ hybridization in 510 patients. Br J Haematol 2008; 141: 36–40.

40. Malčíková J, Pospíšilová Š, Mayer J et al. Význam nádorového supresoru p53 u chronické lymfocytární leukemie. Transfuze Hematol Dnes 2010; 16 (Suppl): 29–32.

41. Hallek M, Fischer K, Fingerle-Rowson G et al. International Group of Investigators; German Chronic Lymphocytic Leukaemia Study Group. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 2010; 376: 1164–1174.

42. Rossi D, Cerri M, Deambrogi C et al. The prognostic value of TP53 mutations in chronic lymphocytic leukemia is independent of Del17p13: implications for overall survival and chemorefractoriness. Clin Cancer Res 2009; 15: 995–1004.

43. Lin TS, Ruppert AS, Johnson AJ et al. Phase II study of flavopiridol in relapsed chronic lymphocytic leukemia demonstrating high response rates in genetically high-risk disease. J Clin Oncol 2009; 27: 6012–6018.

44. Doubek M, Jungová A, Brejcha M et al. Alemtuzumab v terapii chronické lymfocytární leukemie: retrospektivní analýza a hodnocení léčebné odpovědi podle cytogenetického rizika. Vnitř Lék 2009; 55: 549–554.

45. Schetelig J, van Biezen A, Brand R et al. Allogeneic hematopoietic stem-cell transplantation for chronic lymphocytic leukemia with 17p deletion: a retrospective European Group for Blood and Marrow Transplantation analysis. J Clin Oncol 2008; 26: 5094–5100.

46. Rosenwald A, Alizadeh AA, Widhopf G et al. Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med 2001; 194: 1639–1647.

47. Smolej, L. Saudková, M. Špaček et al. ZAP-70 u chronické B-lymfocytární leukemie: klinický význam a metody detekce. Vnitř Lék 2006; 52: 1194–1199.

48. Hamblin TJ, Davis Z, Gardiner A et al. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 1999; 94: 1848–1854.

49. Damle RN, Wasil T, Fais F et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 1999; 94: 1840–1847.

50. Vasconcelos Y, Davi F, Levy V et al. Binet’s staging system and VH genes are independent but complementary prognostic indicators in chronic lymphocytic leukemia. J Clin Oncol 2003; 21: 3928–3932.

51. Kröber A, Seiler T, Benner A et al. V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood 2002; 100: 1410–1416.

52. Kröber A, Bloehdorn J, Hafner S et al. Additional genetic high-risk features such as 11q deletion, 17p deletion, and V3-21 usage characterize discordance of ZAP-70 and VH mutation status in chronic lymphocytic leukemia. J Clin Oncol 2006; 24: 969–975.

53. Del Principe MI, Del Poeta G, Buccisano F et al. Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia. Blood 2006; 108: 853–861.

54. Vroblova V, Vrbacky F, Hrudkova M et al. Significant change in ZAP-70 expression during the course of chronic lymphocytic leukemia. Eur J Haematol 2010; 84: 513–517.

55. Nückel H, Hüttmann A, Klein-Hitpass L et al. Lipoprotein lipase expression is a novel prognostic factor in B-cell chronic lymphocytic leukemia. Leuk Lymphoma 2006; 47: 1053–1061.

56. Oppezzo P, Vasconcelos Y, Settegrana C et al. French Cooperative Group on CLL. The LPL/ADAM29 expression ratio is a novel prognosis indicator in chronic lymphocytic leukemia. Blood 2005; 106: 650–657.

57. Josefsson P, Geisler CH, Leffers H et al. CLLU1 expression analysis adds prognostic information to risk prediction in chronic lymphocytic leukemia. Blood 2007; 109: 4973–4979.

58. Buhl AM, Jurlander J, Geisler CH et al. CLLU1 expression levels predict time to initiation of therapy and overall survival in chronic lymphocytic leukemia. Eur J Haematol 2006; 76: 455–464.

59. Kotaskova J, Tichy B, Trbusek M et al. High expression of lymphocyte-activation gene 3 (LAG3) in chronic lymphocytic leukemia cells is associated with unmutated immunoglobulin variable heavy chain region (IGHV) gene and reduced treatment-free survival. J Mol Diagn 2010; 12: 328–334.

60. Nückel H, Rebmann V, Dürig J et al. HLA-G expression is associated with an unfavorable outcome and immunodeficiency in chronic lymphocytic leukemia. Blood 2005; 105: 1694–1698.

61. Perez-Chacon G, Rosado S, Rebolleda N et al. Prognostic irrelevance of HLA-G in B-cell chronic lymphocytic leukemia. Int J Lab Hematol 2009; 31: 327–337.

62. Majid A, Lin TT, Best G et al. CD49d is an independent prognostic marker that is associated with CXCR4 expression in CLL. Leuk Res 2010 Nov 17. [Epub ahead of print]

63. Nückel H, Switala M, Collins CH et al. High CD49d protein and mRNA expression predicts poor outcome in chronic lymphocytic leukemia. Clin Immunol 2009; 131: 472–480.

64. Mráz M, Pospíšilová Š, Mayer J. MicroRNA v patogenezi chronické lymfocytární leukemie a jejich prognostický význam. Transfuze Hematol Dnes 2010; 16: 33–35.

65. Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol 2002; 29 (6 Suppl 16): 15–18.

66. Smolej L, Andrýs C, Krejsek J et al. Bazický fibroblastový růstový faktor (bFGF) a cévní endotelový růstový faktor (VEGF) jsou zvýšeny v plazmě periferní krve nemocných s chronickou lymfocytární leukemií a klesají po intenzivní léčbě obsahující fludarabin. Vnitř Lék 2007; 53: 1171–1176.

67. Bairey O, Boycov O, Kaganovsky E. All three receptors for vascular endothelial growth factor (VEGF) are expressed on B-chronic lymphocytic leukemia (CLL) cells. Leuk Res 2004; 28: 243–248.

68. Smolej L. Význam mikroprostředí u chronické lymfocytární leukemie. Transfuze Hematol Dnes 2010; 16: 24–28.

69. Smolej L, Andrys C, Peková S et al. Plasma levels of basic fibroblast growth factor and vascular endothelial growth factor and their association with IgVH mutation status in patients with B-cell chronic lymphocytic leukemia. Haematologica 2006; 91: 1432–1433.

70. Molica S, Cutrona G, Vitelli G et al. Markers of increased angiogenesis and their correlation with biological parameters identifying high-risk patients in early B-cell chronic lymphocytic leukemia. Leuk Res 2007; 31: 1575–1578.

71. Hájek R, Kunická Z, Skleničková M et al. Stanovení aktivity telomerázy u mnohočetného myelomu. Klin Onkol 2005; 18: 80–83.

72. Brezinova J, Berkova A, Vcelikova S et al. Telomere length, molecular cytogenetic findings, and immunophenotypic features in previously untreated patients with B-chronic lymphocytic leukemia. Neoplasma 2010; 57: 215–221.

73. Zenz T, Hoth P, Busch R et al. TP53 Mutations and Outcome After Fludarabine and Cyclophosphamide (FC) or FC Plus Rituximab (FCR) in the CLL8 Trial of the GCLLSG. Blood (ASH Annual Meeting Abstracts) 2009; 114: Abstract 1267.

74. Malcikova J, Smardova J, Rocnova L et al. Monoallelic and biallelic inactivation of TP53 gene in chronic lymphocytic leukemia: selection, impact on survival, and response to DNA damage. Blood 2009; 114: 5307–5314.

75. Zenz T, Kröber A, Scherer K et al. Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up. Blood 2008; 112: 3322–3329.