Contributions
Abstract: EP628
Type: E-Poster Presentation
Session title: Chronic lymphocytic leukemia and related disorders - Biology & Translational Research
Background
CLL is the most common B-lymphoid malignancy in the Caucasian population, principally affecting the elderly and displaying marked genetic and clinical heterogeneity. Targeted treatments have proved successful in extending the life-expectancy of those with ultra-high risk CLL. The poor outcomes of this subgroup have been mostly attributed to TP53 mutations. However, SF3B1 and NOTCH1 gene mutations are also significant driver mutations contributing to this ultra-high-risk group.
Flow cytometry has enabled the identification of further high-risk subgroups through the detection of surface pro-tumour microenvironment modulators - including CD49d, CD62L and ROR1. The most prognostically significant is CD49d which is associated with bulky lymphadenopathy and shortened overall and treatment-free survivals. Blocking these surface modulators has proved promising in inducing CLL apoptosis and clinical trials in this area are ongoing.
The National Cancer Registry of Ireland (NCRI) collects cancer incidence data from hospital in-patient enquiry (HIPE) data and laboratory reports. However, there is a potential for national incidence figures to underestimate real-world data.
Aims
We have performed an in-depth study of consecutive newly diagnosed CLL patients captured directly from the flow cytometry laboratory and compared our incidence figures to registry data from the NCRI. Including a second cohort of previously diagnosed CLL patients who required therapy during the study time period, we performed extended immunophenotyping (CD62L, CD49d and ROR1) and mutational analysis of TP53 and NOTCH1 genes in order to characterize disease biology in a representative Irish population.
Methods
Two patient groups were recruited from three institutions (St. James’s Hospital, University Hospital Limerick and the Midlands Regional Hospital) from October 2017 - September 2018. Group 1 included consecutive patients with newly diagnosed CLL and group 2 included previously-diagnosed patients who required treatment during the study time period. Ethics approval was granted and written informed consent was sought for biobanking, immunophenotypic and molecular analysis (extended flow panel, TP35 and NOTCH1 mutational status). If consent was not provided, the patients were included for epidemiological purposes only.
Results
148 patients were included: 111 newly-diagnosed (1) and 38 known cases of known CLL pre-treatment (2). An incidence of 5 per 100,000 (females) and 11 per 100,000 (males) was established. The median age was 67.5 years with 58 patients (39%) aged ≥ 70 years . The male to female ratio was 2.2:1. Immunophenotyping and mutational analysis of groups 1 and 2 revealed: CD62L (1-63.5%; 2- 64%), CD49d (1- 27.1%; 2- 34.6%), ROR1 (1- 85.9%; 2- 88.5%), mutated TP53 (1- 9.2%; 2- 11.8%) and mutated NOTCH1 (1- 9.4%; 2 16.7%).The association between CD49d expression and lymphadenopathy was demonstrated. In cases where expression levels fell between 10-30%; CD62L had two (11.7%) and CD49d had nine (90%) cases of bimodal distribution patterns.
Conclusion
We have established in-depth epidemiological and molecular analysis of an Irish patient cohort in an effort to redress the paucity of published Irish data. We have established that our CLL cohort and biobank benchmarks from a clinical and laboratory perspective to other international cohorts. A longitudinal study of the patient cohort will establish whether CD49d expression ≥10% is prognostically useful and whether cases of CD62L with bimodal patterns of expression have clinical relevance.
Keyword(s): Chronic lymphocytic leukemia, Flow cytometry, Mutation analysis, Notch
Abstract: EP628
Type: E-Poster Presentation
Session title: Chronic lymphocytic leukemia and related disorders - Biology & Translational Research
Background
CLL is the most common B-lymphoid malignancy in the Caucasian population, principally affecting the elderly and displaying marked genetic and clinical heterogeneity. Targeted treatments have proved successful in extending the life-expectancy of those with ultra-high risk CLL. The poor outcomes of this subgroup have been mostly attributed to TP53 mutations. However, SF3B1 and NOTCH1 gene mutations are also significant driver mutations contributing to this ultra-high-risk group.
Flow cytometry has enabled the identification of further high-risk subgroups through the detection of surface pro-tumour microenvironment modulators - including CD49d, CD62L and ROR1. The most prognostically significant is CD49d which is associated with bulky lymphadenopathy and shortened overall and treatment-free survivals. Blocking these surface modulators has proved promising in inducing CLL apoptosis and clinical trials in this area are ongoing.
The National Cancer Registry of Ireland (NCRI) collects cancer incidence data from hospital in-patient enquiry (HIPE) data and laboratory reports. However, there is a potential for national incidence figures to underestimate real-world data.
Aims
We have performed an in-depth study of consecutive newly diagnosed CLL patients captured directly from the flow cytometry laboratory and compared our incidence figures to registry data from the NCRI. Including a second cohort of previously diagnosed CLL patients who required therapy during the study time period, we performed extended immunophenotyping (CD62L, CD49d and ROR1) and mutational analysis of TP53 and NOTCH1 genes in order to characterize disease biology in a representative Irish population.
Methods
Two patient groups were recruited from three institutions (St. James’s Hospital, University Hospital Limerick and the Midlands Regional Hospital) from October 2017 - September 2018. Group 1 included consecutive patients with newly diagnosed CLL and group 2 included previously-diagnosed patients who required treatment during the study time period. Ethics approval was granted and written informed consent was sought for biobanking, immunophenotypic and molecular analysis (extended flow panel, TP35 and NOTCH1 mutational status). If consent was not provided, the patients were included for epidemiological purposes only.
Results
148 patients were included: 111 newly-diagnosed (1) and 38 known cases of known CLL pre-treatment (2). An incidence of 5 per 100,000 (females) and 11 per 100,000 (males) was established. The median age was 67.5 years with 58 patients (39%) aged ≥ 70 years . The male to female ratio was 2.2:1. Immunophenotyping and mutational analysis of groups 1 and 2 revealed: CD62L (1-63.5%; 2- 64%), CD49d (1- 27.1%; 2- 34.6%), ROR1 (1- 85.9%; 2- 88.5%), mutated TP53 (1- 9.2%; 2- 11.8%) and mutated NOTCH1 (1- 9.4%; 2 16.7%).The association between CD49d expression and lymphadenopathy was demonstrated. In cases where expression levels fell between 10-30%; CD62L had two (11.7%) and CD49d had nine (90%) cases of bimodal distribution patterns.
Conclusion
We have established in-depth epidemiological and molecular analysis of an Irish patient cohort in an effort to redress the paucity of published Irish data. We have established that our CLL cohort and biobank benchmarks from a clinical and laboratory perspective to other international cohorts. A longitudinal study of the patient cohort will establish whether CD49d expression ≥10% is prognostically useful and whether cases of CD62L with bimodal patterns of expression have clinical relevance.
Keyword(s): Chronic lymphocytic leukemia, Flow cytometry, Mutation analysis, Notch