The Clinical Characteristics and Therapeutic Outcomes of Elderly Patients with Chronic Lymphocytic Leukemia: A Retrospective Multicenter Study
Authors: Tombak Anil , Tiftik Naci , Dogu Mehmet Hilmi , Sari Ismail , Akay Meltem Olga , Karagulle Mustafa , Kaya Emin , Korkmaz Serdal , Sencan Mehmet , Akyol Gulsah , Kaynar Leylagul , Comert Melda , Saydam Guray , Dal Sinan Mehmet , Ayyildiz Orhan M. , Yildirim Rahsan , Kiki Ilhami , Kara Erdal , Esen Ramazan , Sungur Mehmet Ali , Erkurt Mehmet Ali , Altuntas Fevzi , Unal Ali , Ilhan Osman 
Published: October 2019

Abstract
Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in Western countries, predominates in the elderly. In this retrospective multicenter study, we investigated the clinical, biological features, outcomes and prognosis in 418 patients with CLL (269 men, 149 women with median age 73.8 years, range from 65 to 91years), who were diagnosed in 10 university hospitals in Turkey from January 2002 to December 2012. Three groups of patients were distinguished: 65-69 years-old (n=121), 70-79 years-old (n=210) and ≥80 years-old (n=87). There were B symptoms in 32.9% of all patients and the rate of B symptoms increased with the increasing age (rate of B symptoms in 3 age groups: 28.9%, 31.9%, 40.7%, respectively) (p=0.189). Bulky disease was seen in 5% of all patients. However, the rate of bulky disease decreased with the increasing age (rate of bulky disease in 3 age groups: 6.7%, 5.2%, 2.3%, respectively) (p=0.189). There was no organomegaly in 49.2% of the patients. However, rates of isolated hepatomegaly, isolated splenomegaly and hepatosplenomegaly were 7.7%, 22.9%, 20.2%, respectively. There were co-morbid diseases in 50.4% of all patients (hypertension 34.6%, type 2 diabetes mellitus 14.3%, coronary heart disease 10%, carcinoma 4%, thyroid disease 0.4%, and other diseases 23.6%). However, co-morbidity rates did not differ in 3 age groups (p=0.517). The infection rate was 16.6% and infections were seen mostly in ≥80 years-old patient group (rates were as 16.7%, 16.2%, and 17.4%, respectively) (p=0.966). The most common infection was lower respiratory tract infection in elderly patients (12.4%). The other common infections were urinary tract (1.9%), skin (1.4%), upper respiratory tract (0.5%) and sepsis (0.2%). The mean hemoglobin level was 11.9 ± 2.5 gr/dL and decreased with increasing age (12.7 gr/dL, 12.1 gr/dL, 11.2 gr/dL in 3 age groups, respectively) and this was statistically significant (p=0.008). The mean platelet count was 158300/mcL, leukocyte count was 41.9 x109/L, and lymphocyte count was 32.3 x 109/L, and these values were similar in 3 age groups. Bone marrow infiltration was mostly in diffuse pattern (33.7%) instead of interstitial (9.5%) or nodular pattern (9.8%) in all ages (p=0.575). Mean LDH, ß2-microglobulin levels and sedimentation/h were similar in 3 age groups. There was autoimmune hemolytic anemia in 13.8% of the patients. No biological differences (17p del, 13q del by fluorescent in situ hybridization, CD38, ZAP-70) were found across age groups (p=0.994). ECOG score was 0, 1, 2, 3, 4 in 35.5%, 40.1%, 20.5%, 3.4%, and 0.5% of the patients, respectively and the score increased with increasing age with a statistically significant difference (p=0.001). Most of the patients presented with early stage of CLL (Rai 0-I-II: 66.7%, Rai III-IV: 33.3%), however, stage of the disease increased with the increasing age (Rai 0-I-II: 66.3%, Rai III-IV: 33.7% in first group; Rai 0-I-II: 70.2%, Rai III-IV: 29.8% in second group; Rai 0-I-II: 58.4%, Rai III-IV: 41.7% in third group; p<0.099). 47.4% of the patients had to be treated and the indications for treatment were stage III-IV disease (50.7%), B symptoms (30.5%), increased doubling time (7.7%), frequent infections (4.8%), bulky disease (3.7%), and immune cytopenias (2.6%). Patients were treated mostly with chlorambucil + methylprednisolone (26.3%) and chlorambucil (25.8%) alone. Rates of complete remission (CR), partial remission (PR), stabile and progressive disease after treatment are 43.3%, 39.8%, 4.1%, and 12.9%, respectively. In the advanced age group, CR rate was found to be less than the younger patients (CR rates in 3 age groups: 62.5%, 36.1%, and 28.1%, respectively). Remission time was 0-12 months in 39.5%, 13-24 months in 23.6%, and >24 months in 36.9% of the patients. However, the remission times did not differ according to the 3 age group (p=0.412). In addition, remission time after therapy did not differ according to the co-morbidity rates (p=0.709). 20.9% of the patients died and 76.4% of the deaths were CLL related sepsis and pneumonia. The cause of deaths did not differ according to the 3 age groups (p=0.612). In conclusion, patients with CLL in advanced ages present with higher ECOG score, higher stages, and more co-morbidities and infections are the most important mortality reason. This study highlights the importance of a comprehensive medical care, achieving specific management strategies for elderly patients with CLL.

Disclosures
Saydam: Novartis Pharmaceuticals Corporation, Turkey: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees.