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Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. Chronic lymphocytic leukemia CLL is the most common leukemia of adults in western countries.

Therapy is indicated in symptomatic and advanced stages and has changed fundamentally since when rituximab, an anti-CD20 antibody, has been approved for treatment of CLL. Until then therapy had been based on chemotherapy drugs. This study investigates whether survival in CLL patients improved at the population level after the introduction of combined chemoimmunotherapy.

Data from the cancer registry North-Rhine Westphalia was used to calculate relative survival Men meet men date Bochum by applying period analyses. These findings show marked improvements in the survival of CLL patients at the population level subsequently to the approval of anti-CD 20 antibodies like rituximab, ofatumumab or obinutuzumab for CLL treatment. Chronic lymphocytic leukemia CLL is the most common leukemic disease in western countries.

The age-standardized incidence rate is four to five cases perperson-years [ 12 ] and about patients in Germany are newly diagnosed with CLL annually. Men are more often affected than women. CLL is a disease of the elderly with a median age at diagnosis of 70 years. While age-standardized rates remained constant over the last 15 years, the absolute of cases increased [ 1 ].

Hence, healthcare needs will rise further during the next years. CLL is basically diagnosed after routine Men meet men date Bochum analyses. The clinical presentation of CLL is diverse and varies between an indolent and a highly aggressive course. Phase 3 trials investigating treatment in early and asymptomatic stages, could not demonstrate an advantage for overall survival [ 45 ]. Standard of care for these patients remains a watch-and-wait strategy. Therapy of CLL has changed fundamentally during the last decade. Until antineoplastic treatment was based on chemotherapeutic drugs, like chlorambucil or fluradabine as single-agents or fluradabine in combination with cyclophosphamide FC.

of the CLL8 study showed a marked improvement of progression-free and overall survival in patients treated with a combination of FC and rituximab, a monoclonal anti-CD20 antibody, in comparison to FC alone [ 6 ]. The CLL11 protocol [ 7 ] corroborated the notion that survival benefits could be obtained even for older and less-fit patients with marked comorbidities by adding an anti-CDantibody rituximab or obinutuzumab to chemotherapy with chlorambucil.

The combined chemoimmunotherapy has then rapidly become a standard regime in first-line therapy of CLL patients [ 8 ] from its introduction until recently when novel non-cytostatic, targeted agents have led to another paradigm shift in the treatment of CLL, and chemoimmunotherapy has been replaced as standard of care for many but so far not all patients with CLL.

Although controlled clinical trials have shown an improvement in survival achieved by chemoimmunotherapy, firm evidence is still lacking at a population-based level. Until now, there are only two representative population-based studies from Denmark and Sweden that analyzed survival for CLL patients in relation to the introduction of chemoimmunotherapy [ 910 ].

The aim of the work presented here was to investigate survival in CLL before and after the introduction of chemoimmunotherapy in a population of 2. Cancer reporting in NRW is mandatory since The database of the LKR NRW includes information on patient demographics, tumor diagnosis, tumor characteristics and mortality follow-up. Because of the high proportion of DCO-cases among people aged 80 years or more, we excluded CLL cases aged 80 years or more from the analyses. Mortality follow-up for cancer patients was routinely assessed by the LKR NRW through record linkage with electronic reports on all deceased individuals in NRW obtained from population registration offices.

To estimate cancer specific net- survival we calculated 5-year relative survival RS. RS for a calendar period is defined as the ratio of the observed survival of cancer patients and the expected survival of the general population of the same age, sex and calendar period [ 12 ]. Survival time per patient was calculated by the difference between date of diagnosis and death or right censoring whatever came first.

RS was calculated using the period approach [ 13 ]. Period analysis provides more up-to date survival estimates than the traditional cohort approach, since it exclusively reflects the survival experience of patients within a most recent calendar period, for which mortality follow-up is available. This is achieved by left truncation of observations at the beginning of this period, in addition to right censoring at its end [ 14 ].

Therefore, with the period approach changes in the prognosis of cancer patients can be detected timely. Expected survival was estimated by the Ederer II method [ 1516 ]. RS was estimated Men meet men date Bochum the calendar periods —, —, — and — We also computed age-specific RS for the age-groups 15—69 years and 70—79 years. All calculations were done with SAS, version 9. RS was estimated by Men meet men date Bochum the period macro published by Brenner et al.

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The median age at diagnosis was 69 for men and 73 for women. After restricting the analyses to patients aged 15—79 years and exclusion of DCO-cases, cases men, women remained for relative survival analyses. The proportion of DCO-cases that Men meet men date Bochum to be excluded was 7. The age-standardized incidence rate for to was 5.

For men, age-standardized 5-year RS was For women age-standardized 5-year RS also increased continuously over time from Correspondingly, age-specific trends in relative survival showed distinctly increasing rates of 5-year RS. For men aged 15—69 years 5-year RS raised about 7 percentage points from Women aged 15—69 years showed an increase in RS almost 10 percentage points over time from In the older age-group 70—79 years the observed RS increase was even stronger for both, men and women.

Five-year RS for 70—year-old men rose from We found marked improvements in relative survival at population level subsequently to fundamental changes in first-line therapy of patients diagnosed with CLL. For both, men and women, the 5-year age-standardized RS increased about 13 percentage points after the approval of anti-CD 20 antibodies like rituximab, ofatumumab or obinutuzumab for the treatment of CLL.

of clinical studies have shown ly that CLL patients treated with chemoimmunotherapy achieved markedly longer progression-free survival, which also translated into prolonged overall survival [ 67 ]. The population-based registry data shown in this analysis confirm these findings. Two population-based studies from Denmark and Sweden also Men meet men date Bochum improvements in the survival of CLL patients following the introduction of chemoimmunotherapy. However, both studies analysed data up to and hence the time period studied in which chemoimmunotherapy was available was short.

Further Sylvan et al. With the selected method of relative survival, CLL-associated enhancements seem to be most probably associated with survival improvements shown in this work.

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Treatment for CLL probably is a main factor, because of the profound change of treatment options following the approval of monoclonal antibodies. Although rituximab was available prior toit was not approved for the treatment of CLL in Germany and therefore the effect on the survival of CLL patients in the earlier time periods is negligible. At this point, we cannot formally exclude that improvements in other measures such as supportive medication, or improved anti-infective therapies had a positive influence on survival.

However, there were no marked changes in this patient management with regard to these health problems during the reported time period. Unfortunately, we cannot analyse the according to the known prognostic factors in CLL, as this data is not reported to the registry. However, the distribution of factors such as deletion 17p, TP53 mutation, deletion 11q or an unmutated IGHV status is relatively constant over time, so that the influence of these factors on the present work can most likely be neglected.

Two points make the particularly relevant and demand further transfer of knowledge between clinical and epidemiological research and routine care. First, the improved survival rates of patients with CLL in routine care show Men meet men date Bochum the knowledge gained from clinical research and the advantages of newly approved drugs are also evident in Men meet men date Bochum care.

The presented here show a marked increase of the overall survival in the era with monoclonal anti-CD20 antibodies when compared to the era before, where these antibodies were not available for CLL therapy. It must therefore remain a goal to publish relevant study without delay and to update guidelines for routine care as quickly as possible. On the other hand, the work also in a gain of knowledge for the registry strategy.

In order to be able to do population-based research accompanying clinical studies, it should be discussed to expand and specify the collected data sets. While data on therapies and on the course of the cancer have recently been added to cancer registration and will be available for future analyses, data on genetic prognostic factors should furthermore be included in the registry data sets.

We recognize that our analysis has some limitations. First, some of our survival estimates are based on small s and consequently survival is imprecisely estimated especially when we stratify for age. Second, our time trend analysis of survival assumes that the stage distribution of CLL remained constant over time. Unfortunately, data on stage Binet were too incomplete for a meaningful analysis of stage shifts over time.

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Early stage and asymptomatic CLL cases are usually diagnosed and treated in the ambulatory setting including private practitioners and reporting of incident CLL cases by private practitioners may be less complete. As a consequence, our report may underrepresent cases with early stages of CLL.

Third, the high DCO among patients aged 80 years or more forced us to exclude this age group and therefore our may not be generalizable to CLL cases aged 80 years or more. Fourth, as data on therapy were too incomplete for the study period, we could not directly study the influence of the introduction of chemoimmunotherapy on survival. Our interpretations are based on an ecologic approach, which has independent confirmatory value nevertheless.

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Fifth, we realize that the same type of analysis now Men meet men date Bochum to be done after the introduction of targeted agents such as BTK inhibitors or venetoclax to test for the effect of these drugs on overall survival. This may take a few years until the registry data have matured enough for this analysis. Further information on experimental de is available in the Nature Research Reporting Summary linked to this article. Surveillance, Epidemiology, and End Program.

Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet Lond Engl. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. Engl J Med ;— Routine treatment of patients with chronic lymphocytic leukaemia by office-based haematologists in Germany-data from the Men meet men date Bochum Tumour Registry Lymphatic Neoplasms.

Hematol Oncol ;— Improved survival for patients diagnosed with chronic lymphocytic leukemia in the era of chemo-immunotherapy: a Danish population-based study of patients. Blood Cancer J ;6:e Article Google Scholar. First-line therapy in chronic lymphocytic leukemia: a Swedish nation-wide real-world study on consecutive patients treated between and Doll R, Cook P.

Summarizing indices for comparison of cancer incidence data. Int J Cancer. Berkson J, Gage RP. Calculation of survival rates for cancer. Proc Staff Meet Mayo Clin ;— Brenner H, Gefeller O. An alternative approach to monitoring cancer patient survival. A computer program for period analysis of cancer patient survival. Eur J Cancer Oxf Engl CAS Google Scholar. The relative survival rate: a statistical methodology.

Natl Cancer Inst Monogr ;— Choosing the relative survival method for cancer survival estimation. Google Scholar. Standard cancer patient population for age standardising survival ratios. Download references. You can also search for this author in PubMed Google Scholar. Fink received research support by Celgene, honoraria by Janssen and travel grants by AbbVie. The remaining authors declare no potential competing interests. Reprints and Permissions.

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Survival of patients with chronic lymphocytic leukemia before and after the introduction of chemoimmunotherapy in Germany. Blood Cancer J. Download citation. Received : 10 December Revised : 13 July Accepted : 08 September Published : 29 October

Men meet men date Bochum

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