KRONİK LENFOSİTİK LÖSEMİ’DE TANI ANINDA HİPOGAMMAGLOBULİNEMİ SAĞKALIM VE ENFEKSİYON RİSKİ ÜZERİNDE ETKİLİ MİDİR?

Year 2018, , 294 - 299, 30.12.2018

Erden Atilla , Fulya Özel Pınar Ataca Atilla Pervin Topçuoğlu Hamdi Akan Meral Beksaç Osman İlhan Muhit Özcan Önder Arslan Günhan Gürman Selami Koçak Toprak

https://doi.org/10.24938/kutfd.439565

Abstract

Amaç:
Kronik Lenfositik Lösemi (KLL) en sık görülen lösemi alt tipidir. KLL’de en
önemli mortalite ve morbidite nedenlerinden biri enfeksiyonlardır.
Hipogammaglobulinemi, enfeksiyon riskini arttıran durumlar arasındadır. Bu
çalışmada, merkezimizde KLL tanısı alan ve tanı anında hipogammaglobulinemisi
tespit edilen hastaların enfeksiyon gelişimi ve sağkalım verileriyle
değerlendirilmesi amaçlanmıştır.

Gereç ve Yöntem:
Bu çalışmaya 2000-2014 yılları arasında Ankara Üniversitesi Tıp Fakültesi
Hematoloji Bilim Dalında KLL tanısı almış 75 hasta dahil edilmiştir. Hastaların
özellikleri, geçirdikleri enfeksiyonlar, tedavileri ve sağkalım bilgilerine
geriye dönük olarak hasta dosyalarından ulaşılmıştır. Kategorik veriler,
Ki-kare testiyle karşılaştırılmıştır. p<0.05 değeri anlamlı kabul
edilmiştir. Genel sağkalım, Kaplan-Meier metoduyla belirlenmiştir.

Bulgular:
Tanı anında 75 hastanın ortanca yaşı 59’dur (aralık: 32-85). En az 1 immunoglobulin
alt tipi düzeyinde düşüklük 32 hastada (%43) tespit edilmiştir. Herhangi bir
immunoglobulin düzeyinde düşüklük saptanan hastaların yaş ortalaması,
hipogamaglobulinemi saptanmayanlardan istatistiksel olarak anlamlı yüksektir
(62 ile 57, p=0.03). Tanı anından itibaren birinci yılda orta-ağır enfeksiyon
geçiren 26 hasta (%35) mevcuttur. En az 1 immunoglobulin alt tipi düzeyinde
düşüklük tespit edilen hastaların orta-ağır enfeksiyon riskinde
hipogamaglobulinemisi olmayan hastalara göre anlamlı bir fark saptanmamıştır
(10 (%38) ile 16 (%62), p=0.63). 5 yıllık genel sağkalım, normal ve düşük
immunoglobulin olan hastalarda sırasıyla %93 ve %83’tür (p=0.15)

Sonuç:
KLL’de tanı anında herhangi bir immunoglobulin düzeyinde düşüklük tespit edilen
hastalarda enfeksiyon riski açısından anlamlı bir artış gözlenmemiştir. Genel
sağkalım immunoglobulin düzeyleri normal olan hastalarla benzerdir.

Keywords

Kronik Lenfositer Lösemi, hipogammaglobulinemi, enfeksiyon

Is Hypogammaglobulinemia Present at Diagnosis of Chronic Lymphocytic Leukemia effective on Survival and Risks of Infection?

Abstract

Objective: Chronic
lymphocytic leukemia (CLL) is the most common subtype of leukemia. One of the
most important causes of mortality and morbidity in CLL is infections.
Hypogammaglobulinemia is among the conditions that increase the risk of
infection. In this study, it was aimed to evaluate the patients with CLL who
had hypogammaglobulinemia at the time of diagnosis, development of infections
and survival data.

 Material and Methods: Seventy-five
patients with CLL who admittted between 2000 and 2014 at the Department of
Hematology, Ankara University School of Medicine were included in this study.
Patient characteristics, infections, treatment and survival data were obtained
retrospectively from patient files. Categorical data were compared with
Chi-square test. p value <0.05 was considered significant. Overall survival
(GS) was determined by the Kaplan-Meier method.

Results:
At the time of diagnosis, the median age of 75 patients was 59 (range: 32-85).
At least 1 immunoglobulin subtype level was detected as low in 32 patients
(43%). The mean age of patients with low immunoglobulin levels was
statistically significantly higher than those without hypogammaglobulinemia (62
to 57, p=0.03). There were 26 patients (35%) who had a moderate to severe
infection in the first year after diagnosis. Patients with low levels of at
least 1 immunoglobulin subtype had no significant difference in the risk of
moderate to severe infections compared to patients without
hypogammaglobulinemia (10 (38%) and 16 (62%), p=0.63). The 5-year overall
survivals were 93% and 83% (p=0.15) in patients with normal and low
immunoglobulin, respectively.

Conclusion:
There was no significant increase in risk of infection in patients with low
immunoglobulin levels at the time of diagnosis in CLL. Overall survival is
similar to that of patients with normal immunoglobulin levels.

Keywords

Chronic Lymphocytic Leukemia, hypogammaglobulinemia, infection

References

• 1. Parker TL, Strout MP. Chronic lymphocytic leukemia: prognostic factors and impact on treatment. Discov Med. 2011;11(57):115-23.
• 2. Morrison VA. Infectious complications of chronic lymphocytic leukemia: pathogenesis, spectrum of infection, preventive approaches. Best Pract Res Clin Haematol. 2010;23(1):145-53.
• 3. Wadhwa PD, Morrison VA. Infectious complications of chronic lymphocytic leukemia. Semin Oncol. 2006;33(2):240-9.
• 4. Thurmes P, Call T, Slager S, Zent C, Jenkins G, Schwager S et al. Comorbid conditions and survival in unselected, newly diagnosed patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2008;49(1):49-56.
• 5. Andersen MA, Vojdeman FJ, Andersen MK, Brown PDN, Geisler CH, Weis Bjerrum O et al. Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia is a predictor of early death. Leuk Lymphoma. 2016;57(7):1592-9.
• 6. Foa R, Catovsky D, Brozovic M, Marsh G, Ooyirilangkumaran T, Cherchi M et al. Clinical staging and immunological findings in chronic lymphocytic leukemia. Cancer. 1979;44(2):483-7.
• 7. Davey FR, Kurec AS, Tomar RH, Smith JR. Serum immunoglobulins and lymphocyte subsets in chronic lymphocytic leukemia. Am J Clin Pathol. 1987;87(1):60-5.
• 8. Rozman C, Montserrat E, Vinolas N. Serum immunoglobulins in B-chronic lymphocytic leukemia. Natural history and prognostic significance. Cancer. 1988;61(2):279-83.
• 9. Kay NE, Perri RT. Evidence that large granular lymphocytes from B-CLL patients with hypogammaglobulinemia down-regulate B-cell immunoglobulin synthesis. Blood. 1989:73(8):1016.
• 10. Hersey P, Wotherspoon J, Reid G, Gunz FW. Hypogammaglobulinaemia associated with abnormalities of both B and T lymphocytes in patients with chronic lymphatic leukaemia. Clin Exp Immunol. 1980;39(3):698-707.
• 11. Kay NE. Abnormal T-cell subpopulation function in CLL: excessive suppressor (T gamma) and deficient helper (T mu) activity with respect to B-cell proliferation. Blood. 1981;57(3):418-20.
• 12. Griffiths H, Lea J, Bunch C, Lee M, Chapel H. Predictors of infection in chronic lymphocytic leukaemia (CLL). Clin Exp Immunol. 1992;89(3):374-7.
• 13. Weeks JC, Tierney MR, Weinstein MC. Cost effectiveness of prophylactic intravenous immune globulin in chronic lymphocytic leukemia. N Engl J Med. 1991;325(2):81-6.
• 14. Colovic NBA, Martinovic-Cemerikic V, Jankovic G. Prognostic significance of serum immunoglobulins in B-chronic lymphocytic leukemia. Arch Oncolog. 2001;9(2):79-82.
• 15. Shvidel L, Tadmor T, Braester A, Bairey O, Rahimi-Levene N, Herishanu Y et al. 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.
• 16. Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H et al. 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(12):5446-56.
• 17. The NCI Common Terminology Criteria for Adverse Events v3.0 is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. U.S. Department of Health and Human Services: 2009.
• 18. Itala M, Helenius H, Nikoskelainen J, Remes K. Infections and serum IgG levels in patients with chronic lymphocytic leukemia. Eur J Haematol. 1992;48(5):266-70.
• 19. Molica S, Levato D, Levato L. Infections in chronic lymphocytic leukemia. Analysis of incidence as a function of length of follow-up. Haematologica. 1993;78(6):374-7.
• 20. Aittoniemi J, Miettinen A, Laine S, Sinisalo M, Laippala P, Vilpo L et al. Opsonising immunoglobulins and mannan-binding lectin inchronic lymphocytic leukemia. Leuk Lymphoma. 1999;34(3-4):381-5.
• 21. Svensson T, Hoglund 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.
• 22. Sinisalo M, Aittoniemi J, Koski T, Tobin G, Thunberg U, Sundstrom C et al. Similar humoral immunity parameters in chronic lymphocytic leukemia patients independent of VH gene mutation status. Leuk Lymphoma. 2004;45(12):2451-4.
• 23. Parikh SA, Leis JF, Chaffee KG, Call TG, Hanson CA, Ding W et al. Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia: natural history, clinical correlates, and outcomes. Cancer. 2015;121(17):2883-91.
• 24. Rizzo D, Chauzeix J, Trimoreau F, Woillard JB, Genevieve F, Bouvier A et al. Ig M peak independently predicts treatment-free survival in chronic lymphocytic leukemia and correlates with accumulation of adverse oncogenetic events. Leukemia. 2015;29(2):337-45.