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<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<0.0001), IGVH mutational status (13% vs. 6%, respectively, P<0.0001) and karyotype (16% vs. 2%, respectively, P<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<0.0001), and anti-CD20 monoclonal antibodies (28% vs. 78%, P<0.0001). Overall survival at 6 years was significantly worse in public than in private hospitals (72% vs. 93%, respectively, P<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.
Human herpesvirus 6 (HHV-6) may cause severe complications after haematopoietic stem cell transplantation (HSCT). Monitoring this virus and providing precise, rapid and early diagnosis of related clinical diseases, constitute essential measures to improve outcomes. A prospective survey on the incidence and clinical features of HHV-6 infections after HSCT has not yet been conducted in Brazilian patients and the impact of this infection on HSCT outcome remains unclear. A rapid test based on real-time quantitative polymerase chain reaction (qPCR) has been optimised to screen and quantify clinical samples for HHV-6. The detection step was based on reaction with TaqMan® hydrolysis probes. A set of previously described primers and probes have been tested to evaluate efficiency, sensitivity and reproducibility. The target efficiency range was 91.4% with linearity ranging from 10-106 copies/reaction and a limit of detection of five copies/reaction or 250 copies/mL of plasma. The qPCR assay developed in the present study was simple, rapid and sensitive, allowing the detection of a wide range of HHV-6 loads. In conclusion, this test may be useful as a practical tool to help elucidate the clinical relevance of HHV-6 infection and reactivation in different scenarios and to determine the need for surveillance.
Introduction: Some patients with CLL will require treatment at diagnosis, but many other will remain untreated under observation for several years. In 2008, the International Workshop on Chronic Lymphocytic Leukemia(IWCLL) defined the criteria for treatment indications, which have been widely used in daily practice and in clinical trials. We have observed that many patients tolerate several of these clinical manifestations without treatment need, especially in public hospitals were resources and treatment options are scarce. We identified 5 reference centers for CLL that share the same profile of being more conservative in indicating treatment for CLL patients. We decided to analyze if more conservative local criteria for treatment indication impacts on patients' outcomes. Objective: To describe the outcomes of a series of CLL patients treated according to locally defined more conservative criteria for initiating treatment. Methods: The Brazilian Registry of CLL was started in 2004 as a prospective observational data collection tool. Inclusion criteria for enrollment followed the IWCLL guidelines. We retrospectively evaluated all patients with CLL in the Brazilian Registry of CLL who were followed between January 2013 and April 2020 at the 5 reference centers (3 public and 2 private). The following local criteria were used for treatment indications to all patients included: 1) persistent and progressive symptomatic cytopenias (no predefined minimum levels), 2) Massive or symptomatic lymphadenopathy, 3) Massive or symptomatic splenomegaly, 4) Disease-related symptoms, only if persistent and if other causes were excluded, and 5) Autoimmune complications including anemia or thrombocytopenia non-responsive to steroids. Progressive lymphocytosis and extranodal manifestations were not considered for treatment indication. Results: A total of 581 patients were followed during the observation period of 7 years (median follow-up was 40 months (range: 3-86). Median age was 65 years (range: 32-98) and most patients were male (57%). Binet stage was A in 67%, B in 14% and C in 19% of cases. FISH, performed in only 199 patients (34%), was normal in 47%, and showed del13q in 22%, trisomy 12 in 17%, del11q in 8% and del17p in 7%. According to IWCLL criteria, 257 (44%) presented indication for treatment over the time: 140 (55%) at diagnosis and 117 (45%) during follow-up. Based on the local criteria, 148 (25%) patients met criteria for indication of treatment. Therefore, 109 patients with IWCLL indication were not treated to date according to the local criteria. The IWCLL indications for these untreated patients were: cytopenias in 50 patients (48%), constitutional symptoms in 37 patients (35%), progressive lymphocytosis in 9 (9%), and lymphadenopathy or splenomegaly in 8 (8%). The median observation time for these untreated patients from the time of indication of treatment by IWCLL until the analysis was closed was 39 months, ranging from 3 to 86 months. Of the 109 untreated patients, 12 (13%) died during follow-up: 4 from infections probably unrelated to CLL (all patients were elderly, Binet A, non-neutropenic and non-hypoglobulinemic), 2 from cardiac causes, 1 from a car accident and 5 of unknown causes (lost follow-up after at least 2 years). No deaths were attributable to LLC. Overall survival at 4 years was 90% for the patients who were treated versus 89% for the patients who were not treated (P=0.85). Conclusion: Our data suggest that it is feasible and safe to adopt more conservative criteria to indicate treatment in a CLL patient. A more restrict approach may not only reflect in a significant financial impact to the health care system but also avoid premature exposition to prolonged and/or potentially toxic treatments. This finding might be of special interest to low-income countries. Disclosures No relevant conflicts of interest to declare.
Infections was the most frequent etiology of death with 52,95% and the most lethal was pulmonary infection (29,42%). The range age [15-30 years[had the highest rate of lethaly (83,33%). The most lethal disease was ALL with 66,67%. The chemotherapy with poor survival was Bleomycin-CHOP with a lethality of 33,33%. Summary/Conclusion:The main associated factor to their lethality was infection and the worst prognosis's cancer was acute lymphoblastic leukemia. We hope that with a better partnership with developped countries and the sharing of experience we will improve our overall survival and the global prognosis of these diseases.
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