Front-line fludarabine-cyclophosphamide-rituximab (FCR) in 110 patients with chronic lymphocytic leukaemia (CLL): real-life experience with long-term outcomes, toxicities and responses to second-line therapies.

Fludarabine-cyclophosphamide-rituximab (FCR) has been the gold standard front-line treatment for fit CLL patients until novel agent's introduction. Decision between either time-limited FCR or "endless" Bruton's tyrosine kinase inhibitor (BTKi) therapy may be difficult in fit IGHV-mutated-non-TP53 cases. We describe the outcomes after front-line FCR in 110 CLL patients from 5 centres in Catalonia, Spain, over a period of more than 10 years. ORR was 96.3% and CR 74.5%. Median second-treatment free survival (TFS1) was 6.2 years and median OS was 10.8 years. 50 (45.5%) patients required a subsequent therapy. Median third-treatment free survival was better for BTKi than for chemotherapy ± antiCD20 strategies (not reached vs 3.1 years, p = 0.003). Only 50 (45.5%) patients completed 6 cycles of FCR, and the main reason for discontinuation was cytopenia 29 (26.4%). 15 (13.6%) patients developed a second cancer, and 5 (4.5%) patients experienced a Richter's transformation (RT). At the end of follow-up, 50 (45.5%) patients remained in CR. Response rates, TFS1, OS, RT, and second cancers did not differ between patients treated with 6 vs 4 cycles of FCR. In conclusion, front-line FCR treatment leads to very long CR in almost half of patients, and BTKi yields excellent outcomes in relapsed patients.

Comorbidities at Diagnosis, Survival, and Cause of Death in Patients with Chronic Lymphocytic Leukemia: A Population-Based Study.

This study aimed to examine the prevalence of comorbidities in patients diagnosed with chronic lymphocytic leukemia (CLL), and to assess its influence on survival and cause-specific mortality at a population-based level. Incident CLL cases diagnosed in the Girona province (Spain) during 2008-2016 were extracted from the Girona Cancer Registry. Rai stage and presence of comorbidities at diagnosis, further categorized using the Charlson comorbidity index (CCI), were obtained from clinical records. Observed (OS) and relative survival (RS) were estimated and Cox's proportional hazard models were used to explore the impact of comorbidity on mortality. Among the 400 cases included in the study, 380 (99.5%) presented at least one comorbidity at CLL diagnosis, with diabetes without end organ damage (21%) being the most common disease. 5-year OS and RS were 68.8 (95% CI: 64.4-73.6) and 99.5 (95% CI 3.13-106.0), respectively, which decreased markedly with increasing CCI, particularly in patients with CCI ≥ 3. Multivariate analysis identified no statistically significant association between the CCI and overall CLL-related or CLL-unrelated mortality. In conclusion, a high CCI score negatively influenced the OS and RS of CLL patients, yet its effect on mortality was statistically non-significant when also considering age and the Rai stage.

Population-based survival of lymphoid neoplasms: Twenty years of epidemiological data in the Girona province, Spain.

BACKGROUND: The aim of this study was to describe survival of lymphoid neoplasms (LNs) in the Girona province (Spain) during 1996-2015. METHODS: Data were extracted from the Girona cancer registry. LN incident cases were registered using the ICD-O-3, following the 2008 WHO classification scheme and HAEMACARE grouping. Follow-up was available until the 31/12/2015. Observed and relative survival (RS) were estimated with Kaplan-Meier and Pohar Perme methods, respectively. RESULTS: 4294 LNs diagnosed over a 20-year period were included in the survival analyses. 5-year RS was 62.3 % (95 % confidence interval (CI): 60.4-64.4), and ranged from 88.5%-41.1% according to subtype. Findings were similar between men and women, while survival decreased markedly with age. RS for all LNs improved during the first two periods of study, being 56.5 % (95 % CI: 53.1-60.0) in 1996-2002, 64.8 % (95 % CI: 61.7-68.2) in 2003-2008, and 65.6 % (95 % CI: 62.0-69.5) in 2009-2015. This pattern was mostly attributed to an improved survival of mature B-cell neoplasms, yet only statistically significant differences were reported for follicular lymphoma and mantle cell lymphoma subtypes. CONCLUSIONS: Our study provides estimates of survival in LNs and its subtypes, allowing comparisons between countries. Survival for overall cases improved across the period of study, yet rates are still poor for most subtypes, evidencing the need of therapeutic research programs.

Population-based incidence of lymphoid neoplasms: Twenty years of epidemiological data in the Girona province, Spain.

BACKGROUND: The aim of this study was to describe incidence patterns of lymphoid neoplasms in the Girona province (Spain) (1996-2015), and to predict the number of cases in Spain during 2020. METHODS: Data were extracted from the Girona cancer registry. Incident cases were classified using the ICD-O-3, third revision, and grouped according to the WHO 2008 classification scheme. Age-adjusted incidence rates to the European standard population (ASRE) were estimated and incidence trends were modeled using Joinpoint. RESULTS: 4367 lymphoid neoplasms were diagnosed in the Girona province. The ASRE for overall lymphoma was 37.1 (95% CI: 36.0; 38.2), with a marked male predominance in almost all subtypes. During 1996-2015, incidence trends remained stable for broader lymphoma categories. According to our predictions, 17,950 new cases of LNs will be diagnosed in Spain in 2020. CONCLUSIONS: This 'real-world' data will provide valuable information to better inform etiological hypotheses and plan future health-care services.

Challenges in assessing the real incidence of chronic lymphocytic leukemia: 16 years of epidemiological data from the province of Girona, Spain.

Determining chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) incidence is challenging for two reasons: cancer registries tend to underreport CLL cases and its diagnostic criteria changed markedly in 2008. No studies have reported incidence rates dealing with both difficulties, and thus CLL/SLL burden in Europe is currently uncertain. Herein, we present accurate CLL/SLL incidence in a Spanish region during 1998-2013, using the population-based Girona Cancer Registry (GCR). We detected an 18.2% under-reporting of CLL/SLL cases when combining records from the GCR and additional information sources (i.e., records of flow cytometry laboratories, hospital registries and hematologists' databases). In addition, age-adjusted rates (using the 2013 European population) changed from 7.57 (95% CI 6.87; 8.30) in 1998-2008 to 6.35 (95% CI 5.51; 7.30) in 2009-2013. Overall, completeness of CLL/SLL data requires accurate diagnosis and reporting of cases. Revision of cancer registry operations to include CLL/SLL-specific surveillance is likely to ensure that the monitoring of this malignancy is entirely accurate.

Anemia associated with impaired erythropoietin secretion after allogeneic stem cell transplantation: incidence, risk factors, and response to treatment.

After allogeneic stem cell transplantation (allo-SCT) some patients develop persistent anemia in association with an inadequate erythropoietin (Epo) secretion. We determined the frequency and risk factors for this complication and the response to treatment with erythropoiesis stimulating proteins (ESP). Of 83 evaluable allo-SCT patients, 63 (76%) developed persistent anemia at a median of 34 (range: 30-244) days after allo-SCT. Forty-one (49%) patients had anemia considered as primary, and in all of them inadequate serum Epo levels (median 43.3, range: 2.5-134, mU/mL) were found. A high creatinine level during the first month after allo-SCT was associated with primary anemia (relative risk [RR] 2.5, P = .01). Of the 41 patients, 35 received ESP. Transfusion independence and an Hb level higher than 10 g/dL was achieved in 29 of 30 (97%) evaluable patients. Median ferritin levels at the beginning and at the end of the ESP treatment was 1628 (range: 168-5208) and 805 (range: 14-7443) ng/mL, respectively (P = .04). In conclusion, anemia associated with impaired Epo secretion after allo-SCT is more frequent than usually recognized and it is associated to early postransplantation renal damage. This complication easily reverts with ESP, which seems to contribute to reduce iron overload.