Comparison of Clinical and Laboratory Features, Drug Availability, and Outcomes of CLL Patients Treated in Public or in Private Hospitals in Brazil: A Retrospective Analysis of the Brazilian Registry of CLL
Authors: Pfister Verena , Marques Fernanda de Morais , Parra Flavia , Yamamoto Mihoko , Santucci Silva Rodrigo , Bellesso Marcelo , Silva Wellington F , Buccheri Valeria , Azevedo Alita , Novis Yana , Fortier Sérgio Costa , Silveira Talita , Fogliatto Laura Maria , Perobelli Leila Martins , Ribeiro Glaciano , Lopes Germison Silva , Figueiredo Vera Lucia de Piratininga , Vescovi Matheus , Chiattone Carlos Sérgio , Arrais Celso 
Published: February 2021

Introduction: Chronic lymphocytic leukemia (CLL) typically occurs in elderly patients and has a highly variable clinical course. It is important to understand the aspects that affect the outcomes of CLL in a real-world setting. Besides biological factors, other socioeconomic and health system factors may influence the clinical course of CLL. Hence, data from the Brazilian Registry of CLL was analyzed to compare clinical and treatment-related characteristics in patients with CLL treated in public or in private institutions in Brazil.
Objective: To describe the outcomes of a series of CLL patients followed in public or in private hospitals in Brazil.
Methods: The Brazilian Registry of CLL was started in 2004 as a prospective non-interventional data collection tool. Inclusion criteria for enrollment followed the IWCLL guidelines. For this analysis, we included all patients with minimum available data for analysis of patient and disease characteristics and survival.
Results/discussion: From January 2004 to July 2020, 2927 patients from 37 centers met eligibility criteria for this analysis: 2324 (79%) were followed at public hospitals and 603 (21%) at private hospitals. The majority were male (57%), with median age of 65 years (ranging from 23 to 106). Binet stage was A in 1618 (58%) patients, B in 628 (23%) and C in 525 (19%). FISH for del(17p) was performed in only 479 patients (16%), while FISH for the most common aberrations [del(13q), +12, del(11q), and del(17p)] was performed in only 445 patients (15%). IGVH mutational status was performed in only 211 patients (7%), and karyotype in only 140 patients (5%). Comparing public and private hospitals, we observed that patients in public hospital are slightly older (median age 66 years vs. 64 years for private hospitals, P=0.04), had more advanced diseases at diagnosis (frequency of Binet B or C was 44% in public vs. 32% in private hospital, P&lt;0.0001), and there were more patients with elevated creatinine levels (14% vs. 10%, P=0.03). All prognostic markers were significantly more available in private than in public hospitals: FISH for del17p (42% of cases vs. 10%, respectively, P&lt;0.0001), IGVH mutational status (13% vs. 6%, respectively, P&lt;0.0001) and karyotype (16% vs. 2%, respectively, P&lt;0.0001). The frequency of del(17p) was similar between public and private hospitals (10% vs. 11%, P=NS), while the frequency of unmutated IGHV status was more common in private hospitals, although not statistically different (60% vs. 48%, P=0.09). Analyzing 2102 diagnosed after 2010, we observed that 864 patients (41%) were treated after a median time of 7 months (range: 0-267) after diagnosis. First line treatment was predominantly based chlorambucil (45%) or fludarabine (40%). Anti-CD20 monoclonal antibody was used in only 39% of cases: (rituximab in 35% and obinutuzumab in 4%). Novel agents were used in first line in only 2% of patients, and in most cases in the context of a clinical trial. Of note, most patients (86%) with del(17p) detected by FISH were treated with chemoimmunotherapy. When comparing treatments between public or private hospitals we observed striking differences: in public hospitals there were significantly less patients receiving fludarabine-base regimens (36% vs. 54%, P&lt;0.0001), and anti-CD20 monoclonal antibodies (28% vs. 78%, P&lt;0.0001). Overall survival at 6 years was significantly worse in public than in private hospitals (72% vs. 93%, respectively, P&lt;0.0001). After a multivariate analysis, survival in patients from public hospitals remained significantly worse than in private hospitals (hazard ratio 3.4, 95% confidence interval 2.4 - 4.8), after correcting for age, Binet staging and renal function.
Conclusion: Our data indicate that are striking differences between patients treated in public or private hospitals in Brazil. The lack of accessibility to basic laboratory tests for prognostic factors and adequate therapies probably explains the worse outcome of patients treated in public institutions. In fact, prognostic testing rates were poor in both contexts and most high-risk patients received chemoimmunotherapy first-line. Urgent strategies are needed to increase accessibility to prognostic testing and to novel agents for quality improvement in health care in CLL patients in Brazil.

Disclosures
No relevant conflicts of interest to declare.