DOI QR코드

DOI QR Code

Chronic Lymphocytic Leukemia and Prognostic Factors

  • Published : 2012.07.31

Abstract

Background: The clinical course of individual chronic lymphocytic leukemia (CLL) is highly variable and clinical staging systems do not help us to predict if and at what rate there will be disease progression in an individual patient diagnosed with early stage disease. Recently, several important observations related to other prognostic factors including lymphocyte doubling time (LDT), ${\beta}_2$-microglobulin (${\beta}_2$-MG), and percent of smudge cell in peripheral blood smears, cytogenetic and molecular analysis have been made. The aim of this study was to evaluate a range of prognostic factors in our CLL patients. Design and methods: Seventy patients with CLL were enrolled. Prognostic factors of disease including Binet staging, LDT, ${\beta}_2$-MG, ESR, LDH, percent of smudge cell in peripheral blood smear, absolute lymphocyte count, and conventional cytogenetic (CC) analysis were evaluated at diagnosis, and the patients were followed up to determine their outcome. We compared factors with each other and with Binet staging and prognosis. Results: Enrolled patients aged 37-85 years at diagnosis or during follow up. There was no relationship between serum LDH level (P=0.3), ESR (P=0.11), percent of smudge cells in peripheral blood smear (P=0.94), and absolute lymphocyte count (P=0.18) with the stage of disease and prognosis, but the ${\beta}_2$ macroglobulin level (p<0.0001), LDT (p<0.001) had direct and significant relation with staging and outcome. In 19% of patients cytogenetic alteration were seen. Conclusion: The detection of cytogenetic alteration only using the CC method is not sufficient and we need to use FISH, but because FISH study is an expensive method not available in all areas, instead we believe that ${\beta}_2$ MG can be applied in its place as a good prognostic factor for CLL at diagnosis and during follow up. We suggest to add it to Binet staging for prognostic subgrouping of CLL.

Keywords

References

  1. Binet J, A Auquier, ONE AUTHOR, et al (1981). A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer, 48, 198-206. https://doi.org/10.1002/1097-0142(19810701)48:1<198::AID-CNCR2820480131>3.0.CO;2-V
  2. Byrd J C, S Stilgenbauer, ONE AUTHOR, et al (2004). Chronic lymphocytic leukemia. ASH Education Program Book, 2004, 163-83.
  3. Crespo M, F Bosch, ONE AUTHOR, et al (2003). ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. New England J Med, 3488, 1764-75.
  4. Dhodapkar M, A Tefferi, ONE AUTHOR, et al (1993). Prognostic features and survival in young adults with early/intermediate chronic lymphocytic leukemia (B-CLL): a single institution study. Leukemia: official journal of the Leukemia Society of America. Leukemia Res Fund, 7, 1232.
  5. Di Giovanni S, G Valentini, ONE AUTHOR, et al (1989). Beta-2-microglobulin is a reliable tumor marker in chronic lymphocytic leukemia. Acta haematologica, 81, 181-5. https://doi.org/10.1159/000205558
  6. Dighiero G, T Hamblin (2008). Chronic lymphocytic leukaemia. The Lancet, 371, 1017-29. https://doi.org/10.1016/S0140-6736(08)60456-0
  7. Dighiero G, K Maloum, ONE AUTHOR, et al (1998). Chlorambucil in indolent chronic lymphocytic leukemia. New England J Med, 338, 1506-14. https://doi.org/10.1056/NEJM199805213382104
  8. Doneda L, M Montillo, ONE AUTHOR, et al (2003). Interphase fluorescence in situ hybridization analysis of del (11)(q23) and del (17)(p13) in chronic lymphocytic leukemia: a study of 40 early-onset patients. Cancer genetics and cytogenetics, 140, 31-6. https://doi.org/10.1016/S0165-4608(02)00640-4
  9. Furman R R (2010). Prognostic markers and stratification of chronic lymphocytic leukemia. ASH Education Program Book, 2010, 77-81.
  10. Glassman A B, K J Hayes (2005). The value of fluorescence in situ hybridization in the diagnosis and prognosis of chronic lymphocytic leukemia. Cancer genetics and cytogenetics, 158, 88-91. https://doi.org/10.1016/j.cancergencyto.2004.08.012
  11. Gordon L I, J Andersen, ONE AUTHOR, et al (1995). Advanced diffuse non-Hodgkin's lymphoma. Analysis of prognostic factors by the international index and by lactic dehydrogenase in an intergroup study. Cancer, 75, 865-73. https://doi.org/10.1002/1097-0142(19950201)75:3<865::AID-CNCR2820750319>3.0.CO;2-Z
  12. Hallek M, I Langenmayer, ONE AUTHOR, et al (1999). Elevated serum thymidine kinase levels identify a subgroup at high risk of disease progression in early, nonsmoldering chronic lymphocytic leukemia. Blood, 93, 1732-7.
  13. Kay N, S O'brien, ONE AUTHOR, et al (2007). The role of prognostic factors in assessing 'high-risk'subgroups of patients with chronic lymphocytic leukemia. Leukemia, 21, 1885-91. https://doi.org/10.1038/sj.leu.2404802
  14. Krober A, T Seiler, ONE AUTHOR, et al (2002). $V_H$ mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood, 100, 1410-16.
  15. Lai R, S O'Brien, ONE AUTHOR, et al (2002). Prognostic value of plasma interleukin-6 levels in patients with chronic lymphocytic leukemia. Cancer, 95, 1071-5. https://doi.org/10.1002/cncr.10772
  16. Mainou-Fowler T, H M Dignum, ONE AUTHOR, et al (2004). The prognostic value of CD38 expression and its quantification in B cell chronic lymphocytic leukemia (B-CLL). Leukemia & lymphoma, 45, 455-62. https://doi.org/10.1080/1042819032000141275
  17. Molica S, A Alberti (1987). Prognostic value of the lymphocyte doubling time in chronic lymphocytic leukemia. Cancer, 60, 2712-6. https://doi.org/10.1002/1097-0142(19871201)60:11<2712::AID-CNCR2820601122>3.0.CO;2-1
  18. Molica S, D Levato, ONE AUTHOR, et al (1999). Clinicoprognostic implications of simultaneous increased serum levels of soluble CD23 and $\beta_2$-microglobulin in B-cell chronic lymphocytic leukemia. Eur J Haematol, 62, 117-22.
  19. Montserrat E (2002). Classical and new prognostic factors in chronic lymphocytic leukemia: where to now? The Hematology J, 3, 7-9. https://doi.org/10.1038/sj.thj.6200139
  20. Montserrat E, F Gomis, ONE AUTHOR, et al (1991). Presenting features and prognosis of chronic lymphocytic leukemia in younger adults [see comments]. Blood, 78, 1545-51.
  21. Moreno C, E Montserrat (2010). Genetic lesions in chronic lymphocytic leukemia: what's ready for prime time use? Haematologica, 95, 12-5. https://doi.org/10.3324/haematol.2009.016873
  22. Mozaheb Z, A Aledavood, ONE AUTHOR, et al (2011). Distributions of major sub-types of lymphoid malignancies among adults in Mashhad, Iran. Cancer epidemiol, 35, 26-9. https://doi.org/10.1016/j.canep.2010.09.009
  23. Omoti C, O Awodu, ONE AUTHOR, et al (2007). Chronic lymphoid leukaemia: clinico-haematological correlation and outcome in a single institution in Niger Delta region of Nigeria. Int J Laboratory Hematol, 29, 426-32. https://doi.org/10.1111/j.1751-553X.2007.00888.x
  24. Oscier D G, A C Gardiner, ONE AUTHOR, et al (2002). Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors. Blood, 100, 1177-84.
  25. Rai K R, A Sawitsky, ONE AUTHOR, et al (1975). Clinical staging of chronic lymphocytic leukemia. Blood, 46, 219-34.
  26. Ripolles L, M Ortega, ONE AUTHOR, et al (2006). Genetic abnormalities and clinical outcome in chronic lymphocytic leukemia. Cancer Genetics and Cytogenetics, 171, 57-64. https://doi.org/10.1016/j.cancergencyto.2006.07.006
  27. Rozman C, E Montserrat (1995). Chronic lymphocytic leukemia. New England J Med, 333, 1052-67. https://doi.org/10.1056/NEJM199510193331606
  28. Shanafelt T D, S M Geyer, ONE AUTHOR, et al (2004). Prognosis at diagnosis: integrating molecular biologic insights into clinical practice for patients with CLL. Blood, 103, 1202-10.

Cited by

  1. Lack of Association of the NPAS2 Gene Ala394Thr Polymorphism (rs2305160:G>A) with Risk of Chronic Lymphocytic Leukemia vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7169
  2. Serum 25-hydroxyvitamin D Insufficiency in B-Chronic Lymphoid Leukemia at the Time of Disease Presentation in Pakistan vol.16, pp.14, 2015, https://doi.org/10.7314/APJCP.2015.16.14.5983
  3. Direct Coombs Test Positivity in B-Chronic Lymphoid Leukemia: a Marker of Advanced Clinical Disease vol.16, pp.14, 2015, https://doi.org/10.7314/APJCP.2015.16.14.6007
  4. Clinico-Hematological Profile of Patients with B-Chronic Lymphoid Leukemia in Pakistan vol.16, pp.2, 2015, https://doi.org/10.7314/APJCP.2015.16.2.793
  5. ZAP-70 Protein Expression in B-cell Chronic Lymphoid Leukemia: a Single Center Experience from Pakistan vol.16, pp.4, 2015, https://doi.org/10.7314/APJCP.2015.16.4.1587
  6. Clinical Significance of Smudge Cells in Peripheral Blood Smears in Hematological Malignancies and Other Diseases vol.17, pp.4, 2016, https://doi.org/10.7314/APJCP.2016.17.4.1847