Changes in the Natural History, Treatment Modalities, and Survival Patterns in Patients with Chronic Lymphocytic Leukemia (CLL) from 1980 to 2008. The Hospital Clinic of Barcelona Experience
Authors: Abrisqueta Pau , Bosch Francesc , Aymerich Marta , Gine Eva , Moreno Carol , Rozman Maria , Villamor Neus , Campo Elias , Rozman Ciril , Montserrat Emili 
Published: April 2020

Abstract
Whether recent advances in the understanding and treatment of CLL are changing referral patterns of patients with this disease to specialized centers and their outcome is largely unknown. We analyzed demographics, disease characteristics, treatments administered, and survival over a period of 28 years in a series of 900 patients with CLL separated in three different cohorts based on the year of referral (table). As shown in the table, one of the main differences observed over the years relies on the stage of the disease, with most patients being currently seen in early phase of the disease, reflecting an earlier diagnosis because of analyses performed for routine reasons. In contrast, no differences were observed in patients’ age over the years, in agreement with the stable incidence of CLL in different age groups (SEER). No differences were detected in the proportion of patients developing autoimmune cytopenias, Richter’s syndrome or second neoplasias (data not shown). Not unexpectedly, since 1990 most patients receive purine analogs-based therapies. Importantly, the increasing proportion of patients who remain alive in each time period not only reflects an earlier diagnosis but also improvement in clinical management. Thus, median survivals of patients &lt; 65 with Binet B or C disease are 3.9 yrs (1980–1989), 7.5 yrs (1990–1999) and not reached (2000 onwards), and the proportion of patients alive at 5 years in the same periods of time are 43%, 63% and 72% (figure). Unfortunately survival of patients &gt; 65 yrs has not improved (median survival around 5.5 years across the three groups). Also, survival of patients in early stage (Binet A) has remained basically unchanged. From this large, single-institution study it can be concluded that the outcome of patients with CLL has been steadily improving since 1980. Nevertheless, the most significant progress has been made in younger patients with advanced disease, which constitute a small proportion of subjects with CLL. Besides to improving the outcome of these patients, future efforts should be aimed at prolonging survival of all patients, irrespectively of their age, and seeking the cure for the disease.
1980–1989 1990–1999 &gt; 2000 P Number 254 388 258 Age (yrs). 67 (24–88) 66 (28–96) 67 (34–94) NS &lt; 65 yrs (%) 43 46 45 &gt; 65 yrs (%) 57 54 55 Males (%) 55 55 60 NS Binet A (%) 65 75 85 &lt;0.001 Binet B (%) 22 16 10 Binet C (%) 13 9 5 Blood lymphocyte count (per μL) 46 (37–54) 30 (24–33) 19 (16–22) &lt;0.001 Hb (g/dL) 14 (13–15) 14 (13–15) 15 (14–16) NS Platelets (per μL) 190 (181–199) 183 (177–190) 202 (194–211) 0.002 LDH increased (%) 22 12 9 &lt;0.001 ECOG &gt; 2 (%) 1.2 1.9 0 NS Treatment No treated (%) 59 37 60 &lt;0.001 No PA (%) 84 44 26 &lt;0.001 PA (%) 10 19 11 PA + other cytotoxics (%) 5 34 33 Rit.+ PA in comb. (%) 1 3 30 Alive (%) 21 37 81 Alive at 5-yrs (%) 65 (59–71) 70 (65–75) 77 (70–84) Overall median s. (yrs) 8.3 (7–10) 8.3 (8–9) &gt; 8 NS PA = Purine analogs; Rit. = Rituximab