Secondary Immunodeficiency Frequency in Patients with Chronic Lymphocytic Leukemia: The Relationship with Stage and Treatment
Abstract
Background: Chronic lymphocytic leukemia (CLL) is one of the most common hematological malignancies. In patients with CLL, serum immunoglobulin levels decrease over time due to both the disease itself and the chemo-immunotherapeutic agents used. It was aimed to reveal the relationship between hypogammaglobulinemia and disease stage, and chemo-immunotherapies.
Materials and Methods: Data were obtained by retrospectively examining 74 patients who were followed-up between 2008-2019. The relationship between all parameters (demographic characteristics, RAI stages or therapy subtypes) and serum IgG levels was analyzed.
Results: Thirty-two of 74 patients received a therapy. Twenty-two patients were on combined therapy with rituximab or only rituximab and 10 were treated with chemotherapeutic agents only. The frequency of hypogammaglobulinemia was 5.4% at the diagnosis, this rate was 55% in patients receiving a therapy. Hypogammaglobulinemia was higher in advanced stages. In patients with rituximab, higher levels of IgG decrease were observed.
Conclusion: Serum IgG level was significantly lower in patients with advanced-stage, received chemotherapy, especially rituximab. In addition to basal IgG, immunoglobulin levels should be checked during treatment, and follow-up period. Early replacement intravenous immunoglobulins will be important to reduce severe infection attacks due to secondary immunodeficiency.
1. Dhalla F, Lucas M, Schuh A, et al. Antibody deficiency secondary to chronic lymphocytic leukemia: Should patients be treated with prophylactic replacement immunoglobulin? J Clin Immunol. 2014;34(3):277-82.
2. Forconi F, Moss P. Perturbation of the normal immune system in patients with CLL. Blood. 2015;126(5):573‐81.
3. Tsai HT, Caporaso NE, Kyle RA, et al. Evidence of serum immunoglobulin abnormalities up to 9.8 years before diagnosis of chronic lymphocytic leukemia: a prospective study. Blood. 2009;114(24):4928-32.
4. Vanura K, Rieder F, Kastner MT, et al. Chronic lymphocytic leukemia patients have a preserved cytomegalovirus-specific antibody response despite progressive hypogammaglobulinemia. PLoS One. 2013;8(10):e78925.
5. Sun C, Tian X, Lee YS, et al. Partial reconstitution of humoral immunity and fewer infections in patients with chronic lymphocytic leukemia treated with ibrutinib. Blood. 2015;126(19):2213-9.
6. Parikh SA, Leis JF, Chaffee KG, et al. Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia: Natural history, clinical correlates, and outcomes. Cancer. 2015;121(17):2883-91.
7. Günther G, Dreger B. Post-marketing observational study on 5% intravenous immunoglobulin therapy in patients with secondary immunodeficiency and recurrent serious bacterial infections. Microbiol Immunol. 2013;57(7):527-35.
8. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-90.
9. Tadmor T, Welslau M, Hus I. A review of the infection pathogenesis and prophylaxis recommendations in patients with chronic lymphocytic leukemia. Expert Rev Hematol. 2018;11(1):57-70.
10. Mauro FR, Morabito F, Vincelli ID, et al. Clinical relevance of hypogammaglobulinemia, clinical and biologic variables on the infection risk and outcome of patients with stage A chronic lymphocytic leukemia. Leuk Res. 2017;57:65-71.
11. Crassini KR, Zhang E, Balendran S, et al. Humoral immune failure defined by immunoglobulin class and immunoglobulin G subclass deficiency is associated with shorter treatment-free and overall survival in Chronic Lymphocytic Leukaemia. Br J Haematol. 2018;181(1):97-101.
12. Andersen MA, Vojdeman FJ, Andersen MK, et al. Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia is a predictor of early death. Leuk Lymphoma. 2016;57(7):1592-9.
13. Lachance S, Christofides AL, Lee JK, et al. A Canadian perspective on the use of immunoglobulin therapy to reduce infectious complications in chronic lymphocytic leukemia. Curr Oncol. 2016;23(1):42-51.
14. Freeman JA, Crassini KR, Best OG, et al. Immunoglobulin G subclass deficiency and infection risk in 150 patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2013;54(1):99-104.
15. Visentin A, Compagno N, Cinetto F, et al. Clinical profile associated with infections in patients with chronic lymphocytic leukemia. Protective role of immunoglobulin replacement therapy. Haematologica. 2015;100(12):e515-8.
16. Rozman C, Montserrat E, Viñolas N. Serum immunoglobulins in B-chronic lymphocytic leukemia. Natural history and prognostic significance. Cancer. 1988 15;61(2):279-83.
17. Parikh SA, Leis JF, Chaffee KG, et al. Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia: Natural history, clinical correlates, and outcomes. Cancer. 2015;121(17):2883-91.
18. Shvidel L, Tadmor T, Braester A, et al. Israeli CLL Study Group. Serum immunoglobulin levels at diagnosis have no prognostic significance in stage A chronic lymphocytic leukemia: a study of 1113 cases from the Israeli CLL Study Group. Eur J Haematol. 2014;93(1):29-33.
19. Davey FR, Kurec AS, Tomar RH, et al. Serum immunoglobulins and lymphocyte subsets in chronic lymphocytic leukemia. Am J Clin Pathol. 1987;87(1):60‐5.
20. Fernández Romero DS, Torre MG, Larrauri BJ, et al. Rituximab e hipogammaglobulinemia [Rituximab and hypogammaglobulinemia]. Medicina (B Aires). 2015;75(5):319‐23.
21. Roberts DM, Jones RB, Smith RM, et al. Rituximab-associated hypogammaglobulinemia: incidence, predictors and outcomes in patients with multi-system autoimmune disease. J Autoimmun. 2015;57:60‐65.
22. Svensson T, Höglund M, Cherif H. Clinical significance of serum immunoglobulin G subclass deficiency in patients with chronic lymphocytic leukemia. Scand J Infect Dis. 2013;45(7):537-42.
23. Best OG, Crassini K, Freeman JA, et al. The clinical significance of hypogammaglobulinaemia and serum immunoglobulin G subclass deficiency in patients with chronic lymphocytic leukaemia (CLL). Scand J Infect Dis. 2013;45(9):729.
24. Raanani P, Gafter-Gvili A, Paul M, et al. Immunoglobulin prophylaxis in chronic lymphocytic leukemia and multiple myeloma: systematic review and meta-analysis. Leuk Lymphoma. 2009;50(5):764‐72.
25. Casulo C, Maragulia J, Zelenetz AD. Incidence of hypogammaglobulinemia in patients receiving rituximab and the use of intravenous immunoglobulin for recurrent infections. Clin Lymphoma Myeloma Leuk. 2013;13(2):106‐11.
26. Makatsori M, Kiani-Alikhan S, Manson AL, et al. Hypogammaglobulinaemia after rituximab treatment-incidence and outcomes. QJM. 2014;107(10):821-8.
2. Forconi F, Moss P. Perturbation of the normal immune system in patients with CLL. Blood. 2015;126(5):573‐81.
3. Tsai HT, Caporaso NE, Kyle RA, et al. Evidence of serum immunoglobulin abnormalities up to 9.8 years before diagnosis of chronic lymphocytic leukemia: a prospective study. Blood. 2009;114(24):4928-32.
4. Vanura K, Rieder F, Kastner MT, et al. Chronic lymphocytic leukemia patients have a preserved cytomegalovirus-specific antibody response despite progressive hypogammaglobulinemia. PLoS One. 2013;8(10):e78925.
5. Sun C, Tian X, Lee YS, et al. Partial reconstitution of humoral immunity and fewer infections in patients with chronic lymphocytic leukemia treated with ibrutinib. Blood. 2015;126(19):2213-9.
6. Parikh SA, Leis JF, Chaffee KG, et al. Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia: Natural history, clinical correlates, and outcomes. Cancer. 2015;121(17):2883-91.
7. Günther G, Dreger B. Post-marketing observational study on 5% intravenous immunoglobulin therapy in patients with secondary immunodeficiency and recurrent serious bacterial infections. Microbiol Immunol. 2013;57(7):527-35.
8. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-90.
9. Tadmor T, Welslau M, Hus I. A review of the infection pathogenesis and prophylaxis recommendations in patients with chronic lymphocytic leukemia. Expert Rev Hematol. 2018;11(1):57-70.
10. Mauro FR, Morabito F, Vincelli ID, et al. Clinical relevance of hypogammaglobulinemia, clinical and biologic variables on the infection risk and outcome of patients with stage A chronic lymphocytic leukemia. Leuk Res. 2017;57:65-71.
11. Crassini KR, Zhang E, Balendran S, et al. Humoral immune failure defined by immunoglobulin class and immunoglobulin G subclass deficiency is associated with shorter treatment-free and overall survival in Chronic Lymphocytic Leukaemia. Br J Haematol. 2018;181(1):97-101.
12. Andersen MA, Vojdeman FJ, Andersen MK, et al. Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia is a predictor of early death. Leuk Lymphoma. 2016;57(7):1592-9.
13. Lachance S, Christofides AL, Lee JK, et al. A Canadian perspective on the use of immunoglobulin therapy to reduce infectious complications in chronic lymphocytic leukemia. Curr Oncol. 2016;23(1):42-51.
14. Freeman JA, Crassini KR, Best OG, et al. Immunoglobulin G subclass deficiency and infection risk in 150 patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2013;54(1):99-104.
15. Visentin A, Compagno N, Cinetto F, et al. Clinical profile associated with infections in patients with chronic lymphocytic leukemia. Protective role of immunoglobulin replacement therapy. Haematologica. 2015;100(12):e515-8.
16. Rozman C, Montserrat E, Viñolas N. Serum immunoglobulins in B-chronic lymphocytic leukemia. Natural history and prognostic significance. Cancer. 1988 15;61(2):279-83.
17. Parikh SA, Leis JF, Chaffee KG, et al. Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia: Natural history, clinical correlates, and outcomes. Cancer. 2015;121(17):2883-91.
18. Shvidel L, Tadmor T, Braester A, et al. Israeli CLL Study Group. Serum immunoglobulin levels at diagnosis have no prognostic significance in stage A chronic lymphocytic leukemia: a study of 1113 cases from the Israeli CLL Study Group. Eur J Haematol. 2014;93(1):29-33.
19. Davey FR, Kurec AS, Tomar RH, et al. Serum immunoglobulins and lymphocyte subsets in chronic lymphocytic leukemia. Am J Clin Pathol. 1987;87(1):60‐5.
20. Fernández Romero DS, Torre MG, Larrauri BJ, et al. Rituximab e hipogammaglobulinemia [Rituximab and hypogammaglobulinemia]. Medicina (B Aires). 2015;75(5):319‐23.
21. Roberts DM, Jones RB, Smith RM, et al. Rituximab-associated hypogammaglobulinemia: incidence, predictors and outcomes in patients with multi-system autoimmune disease. J Autoimmun. 2015;57:60‐65.
22. Svensson T, Höglund M, Cherif H. Clinical significance of serum immunoglobulin G subclass deficiency in patients with chronic lymphocytic leukemia. Scand J Infect Dis. 2013;45(7):537-42.
23. Best OG, Crassini K, Freeman JA, et al. The clinical significance of hypogammaglobulinaemia and serum immunoglobulin G subclass deficiency in patients with chronic lymphocytic leukaemia (CLL). Scand J Infect Dis. 2013;45(9):729.
24. Raanani P, Gafter-Gvili A, Paul M, et al. Immunoglobulin prophylaxis in chronic lymphocytic leukemia and multiple myeloma: systematic review and meta-analysis. Leuk Lymphoma. 2009;50(5):764‐72.
25. Casulo C, Maragulia J, Zelenetz AD. Incidence of hypogammaglobulinemia in patients receiving rituximab and the use of intravenous immunoglobulin for recurrent infections. Clin Lymphoma Myeloma Leuk. 2013;13(2):106‐11.
26. Makatsori M, Kiani-Alikhan S, Manson AL, et al. Hypogammaglobulinaemia after rituximab treatment-incidence and outcomes. QJM. 2014;107(10):821-8.
| Files | ||
| Issue | Vol 16, No 1 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v16i1.8437 | |
| Keywords | ||
| Immunodeficiency; Chronic lymphocytic leukemia (CLL); Monoclonal antibody; Immunotherapy; Immunoglobulin G (IgG) | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Yokus O, Jafarli K, Sametoglu F, Goze H, Serin I. Secondary Immunodeficiency Frequency in Patients with Chronic Lymphocytic Leukemia: The Relationship with Stage and Treatment. Int J Hematol Oncol Stem Cell Res. 2022;16(1):14-21.
