Ten Percent of Newly Diagnosed CLL Patients Are Treated within the First Year of Diagnosis: Results of a Canadian Retrospective Population-Based Study
Authors: Pardy Natasha , Conrad David , Doucette Steve , Robinson K. Sue , Couban Stephen , Shivakumar Sudeep 
Published: November 2019

Abstract
Introduction: Chronic lymphocytic leukemia (CLL) is the most common leukemia in North America and 2,000 Canadians are diagnosed with this disorder annually (Seftel, 2009; Canadian Cancer Society). The current standard of care is a watchful waiting approach, delaying intervention until disease-related complications develop. Perception amongst clinicians suggests that most patients are treated within the first year of diagnosis. While several studies have examined time to first treatment, no studies have reported the proportion of patients treated within the first year of diagnosis. In studies performed at referral centers, median time to first treatment was 4.8 years or not reached (Parikh, 2013; Wierda, 2011).
Since all flow cytometry for the province of Nova Scotia in Canada is performed at a single central laboratory and most patients with an established diagnosis of CLL are assessed, followed and treated at a single centre, we sought to use this population-based experience to determine incidence of CLL in our population and the proportion of patients treated within the first year of diagnosis.
Methods: A centralized flow cytometry database search was performed for all peripheral blood flow cytometry from January 1, 2010 to December 31, 2012 using a free text search for "CD5" in the flow cytometry report. Flow cytometry reports retrieved from this search were then reviewed and potential CLL cases extracted. For this study, CLL was defined based on the 2008 WHO Classification and patients with small lymphocytic lymphoma were excluded. A detailed chart review was performed for all extracted reports, with data censored to June 24, 2015 and then adjudicated by two study authors (NP, DC). Patients with immunophenotypes fitting the WHO definition of CLL were included, as were those with Monoclonal B-cell Lymphocytosis (MBL) having a CLL phenotype and those progressing from MBL to CLL during the study period. The following patients groups were excluded: CD5 negative not consistent with atypical CLL, non-CLL CD5 positive hematologic malignancies, those with original diagnostic flow cytometry performed outside the study period, and flow cytometry performed for non-residents of Nova Scotia.
Results: A total of 358 flow cytometry reports were reviewed and 172 were excluded based on the above exclusion criteria. A further 6 were excluded due to insufficient data available to interpret the flow cytometry report. Of the remaining 180 reports, 125 patients were diagnosed with CLL over the three-year study period, 37 with MBL, and 18 with MBL progressing to CLL during the study period. Based on these data, the standardized incidence rate of CLL in Nova Scotia is 2.46/100,000 (3.5/100,000 including MBL). Mean age at diagnosis was 67.3 (std. dev. 10.0), with most CLL patients for whom data were available presenting with Rai stage 0 disease (65.1%). Median time to first visit with a hematologist from date of flow cytometry for all included patients with available data was 1.5 months (range: 0 - 26.4 months), and median duration of follow-up was 28.4 months.
Of the 112 patients with CLL for whom data were available, only 13 (10.4%) were treated within the first year of diagnosis with a median time to treatment of 2.4 months (range: 0 - 8.9 months) from the date of flow cytometry. Nine (81.8%) of these patients were Rai stage 2 or higher at diagnosis.
For the entire study period, of the 121 patients with CLL or progressing to CLL from MBL for whom data were available, 33 (25.38%) patients were treated during the study follow-up period at a median of 15.2 months (range: 0 - 48.9 months).
Conclusion: This retrospective population-based study shows that only 10% of patients with a new diagnosis of CLL are treated within the first year of diagnosis. It would be of interest to know if this proportion varies in different healthcare jurisdictions and in different healthcare systems. Given that CLL is most commonly diagnosed in asymptomatic individuals and most treatments in CLL are non-curative, the low proportion of patients treated in the first year likely reflects a preference amongst clinicians to defer chemotherapeutics and the concomitant toxicities until symptoms of disease require treatment. As treatments for CLL become more effective and are associated with lower toxicities, the proportion of patients treated soon after diagnosis may increase.

Disclosures
No relevant conflicts of interest to declare.