İmmünsüpresyon Zemininde Gelişen Lenfoproliferatif Hastalik Özellikleri Ve Sağkalimi Etkileyen Parametreler

Yıl 2024, Cilt: 34 Sayı: 5, 671 - 679, 31.10.2024

Sabin Goktas Aydın , Meliha Nalçacı , İpek Yönal Hindilerden , Sevgi Kalayoğlu Beşışık , Mustafa Nuri Yenerel , Ahmet Aydin

https://doi.org/10.54005/geneltip.1493721

Öz

Amaç: Lenfoid hücre maligniteleri, en yavaş seyirliden en agresife kadar değişen, diferansiasyonun farklı seyrindeki immun sistem hücrelerinden ortaya çıkan malignitelerdir. İmmün yetersizlik zemininde gelişen lenfoma ise, primer lenfomaya kıyasla daha nadir gözlenen, prognozu ve tedaviye yanıtı kötü, mortalitesi yüksek bir hastalıktır. Biz bu çalışmada immün yetersizlik zemininde gelişen lenfoma hastalarının klinik ve laboratuvar özelliklerini değerlendirmeyi, bu hastalarda sağkalım oranlarını, tedavi yanıtlarını ve mortalite-sağkalım üzerine etkili olabilecek faktörleri değerlendirmeyi amaçladık.
Yöntem: Çalışmaya, Ocak 2013 ile Ocak 2023 tarihleri arasında başvuran, 15 immün yetersizlik zemininde gelişen lenfoma hastası ve aynı tarihte başvuran 49 primer yeni tanı lenfoma hastası dahil edildi. İmmünsüpresyon nedenleri, immünsüpresyon tedavileri ve süreleri, lenfoma evre ve tedavileri, tedaviye verilen yanıtları, mortalite oranları, sağkalım süreleri, laboratuvar değerleri poliklinik dosyaları ve yatış epikrizleri kullanılarak değerlendirildi.
Bulgular: Tedavi sonrası remisyon/kısmi remisyon gelişimi immünsüpresyon zemininde lenfoma gelişen olgularda anlamlı olarak daha düşüktü (p=0,025 OR 5,6 (1,4-22 %95CI)). Primer lenfomalı hastalarda international prognostic index (IPI) değeri anlamlı olarak daha düşük bulunmakla birlikte; her iki grup birlikte değerlendirildiğinde, IPI skoru yükseldikçe tedaviye verilen yanıt kötüydü (p<0,001). B2 mikroglobulin düzeyleri eksitus olan hastalarda daha yüksek olarak bulundu (3,4±1,8mg/l vs 5,2±1,8 mg/l p<0,01). İmmünsüpresyon zemininde gelişen lenfoma hastalarından, eksitus gözlenenlerde Epstein-Barr Virus (EBV) DNA pozitiflik oranı anlamlı olarak daha yüksekti . Takip süresi sonunda, primer lenfoma olan hastaların 5’inde (%10,2) mortalite gözlenirken, immünsüpresyon zemininde gelişen lenfomalı hastaların 7’sinde (%46,7) mortalite gözlendi (p<0,01 OR7,7). Her iki grup birlikte değerlendirildiğinde, progresyonsuz ortalama sağkalım süresi 30,8±1,8 ay bulundu. İmmünsüpresyon zemininde gelişen lenfoma hastalarında, ortalama progresyonsuz sağkalım süresi 22,4±4,2 ay (14,1-90,6 %95CI) iken; primer lenfoma olanlarda ortalama progresyonsuz sağkalım süresi 32,2±1,5 ay (29,1-35,3 %95CI) olarak saptandı ve gruplar arasında anlamlı fark bulundu (p=0,004).
Sonuç: İmmünsüpresyon zemininde gelişen lenfoproliferatif hastalıkların, primer lenfomaya kıyasla prognozu kötü, sağkalımı kısa, mortalitesi yüksek bir hastalık olduğu çalışmamızda da gösterilmiştir. Ayrıca bu hastalarda sağkalım ve prognozu belirlemede IPI değeri, B2 mikroglobulin değeri ve EBV serolojisi önemlidir.

Anahtar Kelimeler

Uzun kodlamayan RNA, lncRNA, Laringeal kanser, miRNA, UCA1, miR138, CDK6

Immunosuppression-Based Lymphoproliferative Disease Features and Parameters Affecting Survival

Öz

Aim: Lymphoid cell malignancies originate from the immune cells at various stages of differentiation, ranging from the slowest progressing ones to the most aggressive types. The immune deficiency-associated lymphomas are less frequently seen with worse prognoses, poor treatment responses, and high mortality rates than the primary lymphomas. In this study, we aim to evaluate the clinical and laboratory findings and to determine the survival rates, treatment responses, and the factors that may influence the mortality and survival rates in patients with immunodeficiency-associated lymphomas.
Methods: The study included 15 patients with immunodeficiency-associated lymphomas and 49 patients with newly diagnosed primary lymphomas between January 2013 and January 2023. Patient characteristics, treatments, and mortality rates were retrospectively analyzed using data charts.
Results: The remission and partial remission rates after the treatment were significantly lower in the patients with immunodeficiency-associated lymphomas [p=0.025; OR=5.6 (1.4-22, 95%CI)]. The IPI values of the primary lymphoma patients were significantly lower. Upon evaluating all patients in both groups collectively, a discernible trend indicated a deterioration in treatment responses correlating with escalating International Prognostic Index (IPI) values (p < 0.001). The levels of β-2 microglobulin were higher in the deceased patients (3.4±1.8mg/l vs 5.2±1.8mg/l; p<0.01). The EBV DNA positivity rates were significantly higher in the deceased patients in the patient group with immunodeficiency-based lymphomas (p<0.05). Mortalities were observed in 5 (10.2%) patients with primary lymphomas and in 7 (46.7%) patients with immunodeficiency-associated lymphomas at the end of the follow-up period (p<0.01; OR=7.7). The mean progression-free survival rate was 30.8±1.8. The mean progression-free survival rate of the patients with immunodeficiency-associated lymphomas was 22.4±4.2 months (14.1-90.6 95%CI), whereas, in the primary lymphoma patients, it was 32.2±1.5 months (29.1-35.3 95%CI), leading to a significant difference between the two groups (p=0.004).
Conclusion: Our study demonstrated that immunodeficiency-associated lymphoma has a poorer prognosis, shorter survival rates, and higher mortality. In addition, IPI values, levels of β-2 microglobulin, and the outcomes of EBV serology tests are essential factors in determining this group of patients' prognoses and survival rates.

Anahtar Kelimeler

Non-Hodgkin lymphoma, immunosuppression-related lymphoma survival, prognosis

Etik Beyan

E-10840098-202.3.02-3213 numarası ile onaylanmıştır.

Kaynakça

• Tran H, Nourse J, Hall S et al. Immunodeficiency Associated Lymphomas. Blood Reviews; 2008;22:261-281.
• Yarbo JW. The Epstein Barr virus and the distinction between benign and malignant lymphoproliferative processes. Semin Oncol 1993; 20:658-661.
• Swerdlow S, Campo E, Harris N et al. WHO Classification of tumors of haematopoetic and lymphoid tissue. 4th ed. Bosman F, Jaffe E, Lakhani S, Ohgaki H. editors Lyon, France International Agency for Research on Cancer (IARC); 2008.
• Salavoura K, Kolialexi A, Tsangaris G et al.Development of cancer in patients with primary immunodeficiencies. Anticancer Res; 2008;28:1263-1269.
• Leechawengwongsa E, Shearerb WT. Lymphoma complicating primary immunodeficiency syndromes. Curr Opin Hematol 2012; 19:305-312.
• Kaplan LD. HİV-associated lymphoma. Best Practice & Research Clinical Haematology 2012;25:101-117.
• Morrison VA, Dunn DL, Maniel JC et al. Clinical characteristics of posttransplant lymphoproliferative disorders. Am J Med 1994;97:14-24
• Lebland V, Sutton L, Dorent R et al. Lymphoproliferative disorders after organ transplantation: A report of 24 cases observed in a single center. J Clin Oncol 1995; 13:961-968.
• Craig FE, Gulley ML, Banks PM. Posttransplantation lymphoproliferative disorders. Am J Clin Pathol 1993; 99:265-276
• Nalesnik MA, Starzl TE. Epstein-Barr virus, infectious mononucleosis, and post- transplant lymphoproliferative disorders. Transplantation Science 1994;4:61-79.
• Fararjeh FA, Mahmood S, Yallop D et al. A retrospective analysis of post-transplant lymphoproliferative disorder following liver transplantation. Eur J Haematol. 2018;100(1):98-103.
• Benkerrou M, Durandy A, Fischer A. Therapy for transplant-related lymphoproliferative diseases. Hematol Oncol Clin North Am 1993; 7:467-475.
• Hasserjian RP, Chen S, Perkins SL et al. Immunomodulatuar agent related lymphoproliferative disorders. Mod Pathol 2009;22:1532-1540.
• Shapiro RS. Malignancies in the setting of primary immunodeficiency. İmplications for hematologists/oncologists. Am J Hematol 2011;86:48-55.
• Wagner N, Bartlett N. Lymphoma. In: Govindan R, Arqueta M, editors. The Washington Manual of Clinical Oncology. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2004. p. 278-97,57.
• Cheung CY, Ma MKM, Chau KF et al. Posttransplant lymphoproliferative disorders in kidney transplant recipients: retrospective cohort analysis over twodecades in Hong Kong. Oncotarget. 2017;8(57):96903-96912.
• Ciftciler R, Ciftciler AE, Saglam EA et al. Follow-up of Patients with Atypical Lymphoproliferation in Bone Marrow or Lymph Node Biopsy. Acta Medica, 52(1), 37–42
• Longa J L, Engelsa E A, Moorea R D et al. Incidence and outcomes of malignancy in the HAART era in an urban cohort of HİV-infected individuals. AIDS 2008;22:489-496
• Kawano N, Ono N, Kawano S et al. New concepts in EBV-associated B, T, and NK cell lymphoproliferative disorders. Virchows Arch. 2023;482(1):227-244.
• Taj MM, Hadzic N, Height SE et al. Long term outcome for immune suppression and immunerelated lyphoprolifreative disorder prospective data from the United Kingdom Children's Leukaemia and Cancer Group registry 1994-2004. Leuk Lymphoma. 2012;53(5):842-8.
• Sanz J, Arango M, Senent L et al. EBV associated postransplant lymphoproliferative disorderafter umbilical cord blood transplantation in adults with hematological diseases. Bone Marrow Transplant. 2014;49 (3):397-402.
• Carbone A, Volpi CC, Gualeni AV et al. Epstein Barr virus associated lymphomas in people with HIV. Curr Opin HİV AIDS. 2017;12(1):39-46.
• Chougule D, Nadkar M, Rajadhyaksha A et al. Association of clinical and serological parameters of systemic lupus erythematosus patients with Epstein-Barr virus antibody profile. J Med Virol. 2018;90(3):559-563.
• Taborelli M, Piselli P, Ettorre GM et al. Italian Transplant and Cancer Cohort Study. Survival after the diagnosis of de novo malignancy in liver transplant recipients. Int J Cancer. 2019;144(2):232-239.
• Murray SL, O'Leary E, De Bhailís ÁM et al. Cancer survival in kidney transplant recipients in Ireland. Nephrol Dial Transplant. 2020;35(10):1802-1810.
• Mukthinuthalapati PK, Gotur R, Ghabril M . Incidence, risk factors and outcomes of de novo malignanciespost liver transplantation. World J Hepatol. 2016;8(12):533-44.
• Mounier N, Spina M, Gabarre J et al. AIDS-related non-Hodgkin lymphoma: final analysis of 485patients treated with risk-adapted intensive chemotherapy. Blood. 2006;107(10):3832-40
• Oriol A, Ribera JM, Esteve J et al. PETHEMA Group, Spanish Society of Hematology. Lack of influence of human immunodeficiency virus infection status in the response to therapy and survival of adult patients with mature B-cell lymphoma or leukemia. Results of the PETHEMA-LAL3/97 study. Haematologica. 2003;88(4):445-53
• Seidemann K, Tiemann M, Henze G et al. Therapy for non-Hodgkin lymphoma in children with primaryimmunodeficiency: analysis of 19 patients from the BFM trials. Med Pediatr Oncol. 1999;33(6):536-44
• Bernatsky S, Velásquez García HA, Spinelli JJ et al. Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma.
• Ozbalak M, Ar MC, Tuzuner N et al. Detailed analysis of diffuse large B cell lymphoma patients: a single center, retrospective study. ISRN Hematol. 2013;2013:908191.
• Yadav C, Ahmad A, D'Souza B et al. Serum Lactate Dehydrogenase in Non-Hodgkin's Lymphoma: A Prognostic Indicator. Indian J Clin Biochem. 2016;31(2):240-2
• Pamuk G.E, Harmandar F, Hrmandar O et al. Non-Hodgkin Lenfoma Vakalarımızın Klinik Özelliklerinin Değerlendirilmesi .International Journal of Hematology and Oncology 2006;16(4):185-94.
• Wu L, Wang T, Gui W et al. Prognostic Significance of Serum Beta-2 Microglobulin in Patients with Non-Hodgkin Lymphoma Oncology 2014;87:40-47
• Kanemasa Y, Shimoyama T, Sasaki Y et al. Beta-2 microglobulin as a significant prognostic factor and a new risk model for patients with diffuse large B-cell lymphoma. Hematol Oncol. 2017;35(4):440-446.