Research Article
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The effect of prognostic features of patients with chronic lymphocytic leukemia on overall survival and treatment-free survival: A single-center experience

Year 2024, Volume: 41 Issue: 1, 125 - 131, 29.03.2024

Abstract

Chronic lymphocytic leukemia (CLL) is a disease with a highly variable clinical spectrum and prognosis, and is more common in the elderly population. The identification of high-risk patients according to prognostic factors and the application of new treatment regimens have improved survival in CLL. The purpose of our study was to examine the effects of important prognostic factors on survival in patients with CLL in our patient population. Treatment-free survival (TFS) and overall survival (OS) analyses were performed in patients diagnosed with CLL between January 2000 and June 2013 according to clinical characteristics at the time of diagnosis, bone marrow infiltration pattern, lactate dehydrogenase (LDH) and beta 2-Microglobulin levels, CD38 expression and fluorescent insitu hybridization (FISH) findings. Two hundred and forty-five patients were evaluated. Presence of initial B symptom, Rai stage>I, Binet stage B and C, diffuse infiltration of bone marrow by lymphocytes, LDH, and beta 2-Microglobulin levels above upper limit of normal (ULN), and CD38 positivity shortened both TFS and OS (p<0.05). Also, age over 65 years, performance score of 2 and above, and del17p positivity shortened OS (p<0.05) but did not make a statistically significant difference in TFS. In multivariate analysis, it was determined that advanced age was an independent poor prognostic factor affecting OS, and Rai stage was an independent risk factor affecting TFS (p<0.05). When Rai stage was excluded, beta 2-Microglobulin and LDH were found to be negative prognostic risk factors affecting TFS independent of other factors. LDH level, which is not included in the international prognostic scoring system, was found to be a marker affecting TFS and OS in our study.

References

  • The Surveillance E, and End Results (SEER) Program of the National Cancer Institute. Cancer Stat Facts: Leukemia—Chronic Lymphocytic Leukemia (CLL). [Internet]. Available from: https://seer.cancer.gov/statfacts/html/clyl.html;2023
  • Hallek M, Al-Sawaf O. Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures. Am J Hematol [Internet]. 2021 Dec 1;96(12):1679–705. Available from: https://doi.org/10.1002/ajh.26367
  • Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS. Clinical staging of chronic lymphocytic leukemia. Blood [Internet]. 1975;46(2):219–34. Available from: http://europepmc.org/abstract/MED/1139039
  • Binet JL, Leporrier M, Dighiero G, Charron D, Vaugier G, Beral HM, et al. A clinical staging system for chronic lymphocytic leukemia. Prognostic significance. Cancer [Internet]. 1977 Aug 1;40(2):855–64. Available from: https://doi.org/10.1002/1097-0142(197708)40:2%3C855::AID-CNCR2820400239%3E3.0.CO
  • An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol. 2016 Jun;17(6):779–90.
  • Rassenti LZ, Jain S, Keating MJ, Wierda WG, Grever MR, Byrd JC, et al. Relative value of ZAP-70, CD38, and immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic leukemia. Blood. 2008 Sep;112(5):1923–30.
  • Shen Q-D, Xu W, Yu H, Li L, Zhang S-J, Li J-Y. [Prognostic significance of lactate dehydrogenase and beta2-microglobulin in chronic lymphocytic leukemia]. Zhongguo shi yan xue ye xue za zhi. 2007 Dec;15(6):1305–8.
  • Autore F, Strati P, Innocenti I, Corrente F, Trentin L, Cortelezzi A, et al. Elevated Lactate Dehydrogenase Has Prognostic Relevance in Treatment-Naïve Patients Affected by Chronic Lymphocytic Leukemia with Trisomy 12. Cancers (Basel) [Internet]. 2019 Jun 26;11(7):896. Available from: https://pubmed.ncbi.nlm.nih.gov/31248056
  • Oscier DG, Rose-Zerilli MJJ, Winkelmann N, Gonzalez de Castro D, Gomez B, Forster J, et al. The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial. Blood. 2013 Jan;121(3):468–75.
  • Puente XS, Pinyol M, Quesada V, Conde L, Ordóñez GR, Villamor N, et al. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature. 2011 Jun;475(7354):101–5.
  • Hallek M, Wanders L, Ostwald M, Busch R, Senekowitsch R, Stern S, 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 Aug;22(5–6):439–47.
  • Wierda WG, Brown JR, Stilgenbauer S, Coutre S, Byrd JC, Mato AR, et al. Prognostic role of beta-2 microglobulin (B2M) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) patients (pts) treated with ibrutinib (ibr). J Clin Oncol [Internet]. 2018 May 20;36(15_suppl):7521. Available from: https://doi.org/10.1200/JCO.2018.36.15_suppl.7521
  • Delgado J, Pratt G, Phillips N, Briones J, Fegan C, Nomdedeu J, et al. Beta2-microglobulin is a better predictor of treatment-free survival in patients with chronic lymphocytic leukaemia if adjusted according to glomerular filtration rate. Br J Haematol. 2009 Jun;145(6):801–5.
  • Gentile M, Cutrona G, Neri A, Molica S, Ferrarini M, Morabito F. Predictive value of beta2-microglobulin (beta2-m) levels in chronic lymphocytic leukemia since Binet A stages. Haematologica [Internet]. 2009 Jun;94(6):887–8. Available from: https://pubmed.ncbi.nlm.nih.gov/19483161
  • Pratt G, Thomas P, Marden N, Alexander D, Davis Z, Hussey D, et al. Evaluation of serum markers in the LRF CLL4 trial: β2-microglobulin but not serum free light chains, is an independent marker of overall survival. Leuk Lymphoma [Internet]. 2016 Oct 2;57(10):2342–50. Available from: https://doi.org/10.3109/10428194.2015.1137291
  • Li H, Xiong W, Liu H, Yi S, Yu Z, Liu W, et al. Serum LDH level may predict outcome of chronic lymphocytic leukemia patients with a 17p deletion: a retrospective analysis of prognostic factors in China. Chin J Cancer Res [Internet]. 2017 Apr;29(2):156–65. Available from: https://pubmed.ncbi.nlm.nih.gov/28536495
  • Rozman C, Hernandez-Nieto L, Montserrat E, Brugues R. Prognostic significance of bone-marrow patterns in chronic lymphocytic leukaemia. Br J Haematol. 1981 Apr;47(4):529–37.
  • Pangalis GA, Roussou PA, Kittas C, Mitsoulis-Mentzikoff C, Matsouka-Alexandridis P, Anagnostopoulos N, et al. Patterns of bone marrow involvement in chronic lymphocytic leukemia and small lymphocytic (well differentiated) non-Hodgkin’s lymphoma. Its clinical significance in relation to their differential diagnosis and prognosis. Cancer. 1984 Aug;54(4):702–8.
Year 2024, Volume: 41 Issue: 1, 125 - 131, 29.03.2024

Abstract

References

  • The Surveillance E, and End Results (SEER) Program of the National Cancer Institute. Cancer Stat Facts: Leukemia—Chronic Lymphocytic Leukemia (CLL). [Internet]. Available from: https://seer.cancer.gov/statfacts/html/clyl.html;2023
  • Hallek M, Al-Sawaf O. Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures. Am J Hematol [Internet]. 2021 Dec 1;96(12):1679–705. Available from: https://doi.org/10.1002/ajh.26367
  • Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS. Clinical staging of chronic lymphocytic leukemia. Blood [Internet]. 1975;46(2):219–34. Available from: http://europepmc.org/abstract/MED/1139039
  • Binet JL, Leporrier M, Dighiero G, Charron D, Vaugier G, Beral HM, et al. A clinical staging system for chronic lymphocytic leukemia. Prognostic significance. Cancer [Internet]. 1977 Aug 1;40(2):855–64. Available from: https://doi.org/10.1002/1097-0142(197708)40:2%3C855::AID-CNCR2820400239%3E3.0.CO
  • An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol. 2016 Jun;17(6):779–90.
  • Rassenti LZ, Jain S, Keating MJ, Wierda WG, Grever MR, Byrd JC, et al. Relative value of ZAP-70, CD38, and immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic leukemia. Blood. 2008 Sep;112(5):1923–30.
  • Shen Q-D, Xu W, Yu H, Li L, Zhang S-J, Li J-Y. [Prognostic significance of lactate dehydrogenase and beta2-microglobulin in chronic lymphocytic leukemia]. Zhongguo shi yan xue ye xue za zhi. 2007 Dec;15(6):1305–8.
  • Autore F, Strati P, Innocenti I, Corrente F, Trentin L, Cortelezzi A, et al. Elevated Lactate Dehydrogenase Has Prognostic Relevance in Treatment-Naïve Patients Affected by Chronic Lymphocytic Leukemia with Trisomy 12. Cancers (Basel) [Internet]. 2019 Jun 26;11(7):896. Available from: https://pubmed.ncbi.nlm.nih.gov/31248056
  • Oscier DG, Rose-Zerilli MJJ, Winkelmann N, Gonzalez de Castro D, Gomez B, Forster J, et al. The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial. Blood. 2013 Jan;121(3):468–75.
  • Puente XS, Pinyol M, Quesada V, Conde L, Ordóñez GR, Villamor N, et al. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature. 2011 Jun;475(7354):101–5.
  • Hallek M, Wanders L, Ostwald M, Busch R, Senekowitsch R, Stern S, 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 Aug;22(5–6):439–47.
  • Wierda WG, Brown JR, Stilgenbauer S, Coutre S, Byrd JC, Mato AR, et al. Prognostic role of beta-2 microglobulin (B2M) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) patients (pts) treated with ibrutinib (ibr). J Clin Oncol [Internet]. 2018 May 20;36(15_suppl):7521. Available from: https://doi.org/10.1200/JCO.2018.36.15_suppl.7521
  • Delgado J, Pratt G, Phillips N, Briones J, Fegan C, Nomdedeu J, et al. Beta2-microglobulin is a better predictor of treatment-free survival in patients with chronic lymphocytic leukaemia if adjusted according to glomerular filtration rate. Br J Haematol. 2009 Jun;145(6):801–5.
  • Gentile M, Cutrona G, Neri A, Molica S, Ferrarini M, Morabito F. Predictive value of beta2-microglobulin (beta2-m) levels in chronic lymphocytic leukemia since Binet A stages. Haematologica [Internet]. 2009 Jun;94(6):887–8. Available from: https://pubmed.ncbi.nlm.nih.gov/19483161
  • Pratt G, Thomas P, Marden N, Alexander D, Davis Z, Hussey D, et al. Evaluation of serum markers in the LRF CLL4 trial: β2-microglobulin but not serum free light chains, is an independent marker of overall survival. Leuk Lymphoma [Internet]. 2016 Oct 2;57(10):2342–50. Available from: https://doi.org/10.3109/10428194.2015.1137291
  • Li H, Xiong W, Liu H, Yi S, Yu Z, Liu W, et al. Serum LDH level may predict outcome of chronic lymphocytic leukemia patients with a 17p deletion: a retrospective analysis of prognostic factors in China. Chin J Cancer Res [Internet]. 2017 Apr;29(2):156–65. Available from: https://pubmed.ncbi.nlm.nih.gov/28536495
  • Rozman C, Hernandez-Nieto L, Montserrat E, Brugues R. Prognostic significance of bone-marrow patterns in chronic lymphocytic leukaemia. Br J Haematol. 1981 Apr;47(4):529–37.
  • Pangalis GA, Roussou PA, Kittas C, Mitsoulis-Mentzikoff C, Matsouka-Alexandridis P, Anagnostopoulos N, et al. Patterns of bone marrow involvement in chronic lymphocytic leukemia and small lymphocytic (well differentiated) non-Hodgkin’s lymphoma. Its clinical significance in relation to their differential diagnosis and prognosis. Cancer. 1984 Aug;54(4):702–8.
There are 18 citations in total.

Details

Primary Language English
Subjects Haematological Tumours, Predictive and Prognostic Markers
Journal Section Research Article
Authors

Nevin Alayvaz Aslan 0000-0003-3292-8519

Yahya Büyükaşık 0000-0002-4764-2348

Nilgün Saynalp 0000-0002-4782-896X

Publication Date March 29, 2024
Submission Date December 19, 2023
Acceptance Date March 14, 2024
Published in Issue Year 2024 Volume: 41 Issue: 1

Cite

APA Alayvaz Aslan, N., Büyükaşık, Y., & Saynalp, N. (2024). The effect of prognostic features of patients with chronic lymphocytic leukemia on overall survival and treatment-free survival: A single-center experience. Journal of Experimental and Clinical Medicine, 41(1), 125-131.
AMA Alayvaz Aslan N, Büyükaşık Y, Saynalp N. The effect of prognostic features of patients with chronic lymphocytic leukemia on overall survival and treatment-free survival: A single-center experience. J. Exp. Clin. Med. March 2024;41(1):125-131.
Chicago Alayvaz Aslan, Nevin, Yahya Büyükaşık, and Nilgün Saynalp. “The Effect of Prognostic Features of Patients With Chronic Lymphocytic Leukemia on Overall Survival and Treatment-Free Survival: A Single-Center Experience”. Journal of Experimental and Clinical Medicine 41, no. 1 (March 2024): 125-31.
EndNote Alayvaz Aslan N, Büyükaşık Y, Saynalp N (March 1, 2024) The effect of prognostic features of patients with chronic lymphocytic leukemia on overall survival and treatment-free survival: A single-center experience. Journal of Experimental and Clinical Medicine 41 1 125–131.
IEEE N. Alayvaz Aslan, Y. Büyükaşık, and N. Saynalp, “The effect of prognostic features of patients with chronic lymphocytic leukemia on overall survival and treatment-free survival: A single-center experience”, J. Exp. Clin. Med., vol. 41, no. 1, pp. 125–131, 2024.
ISNAD Alayvaz Aslan, Nevin et al. “The Effect of Prognostic Features of Patients With Chronic Lymphocytic Leukemia on Overall Survival and Treatment-Free Survival: A Single-Center Experience”. Journal of Experimental and Clinical Medicine 41/1 (March 2024), 125-131.
JAMA Alayvaz Aslan N, Büyükaşık Y, Saynalp N. The effect of prognostic features of patients with chronic lymphocytic leukemia on overall survival and treatment-free survival: A single-center experience. J. Exp. Clin. Med. 2024;41:125–131.
MLA Alayvaz Aslan, Nevin et al. “The Effect of Prognostic Features of Patients With Chronic Lymphocytic Leukemia on Overall Survival and Treatment-Free Survival: A Single-Center Experience”. Journal of Experimental and Clinical Medicine, vol. 41, no. 1, 2024, pp. 125-31.
Vancouver Alayvaz Aslan N, Büyükaşık Y, Saynalp N. The effect of prognostic features of patients with chronic lymphocytic leukemia on overall survival and treatment-free survival: A single-center experience. J. Exp. Clin. Med. 2024;41(1):125-31.