Trends in incidence and medical resource utilisation in patients with chronic lymphocytic leukaemia: insights from the UK Clinical Practice Research Datalink (CPRD).

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in European adults. We aimed to evaluate time trends in CLL incidence and medical resource utilisation of CLL patients in the UK. We conducted a retrospective, observational cohort analysis using the UK Clinical Practice Research Datalink (CPRD) comprising mainly primary care data. We included adult patients with newly diagnosed CLL between January 2000 and June 2012. Descriptive and trend analyses of CLL incidence and medical resource utilisation were performed. A total of 2576 patients with CLL met the eligibility criteria. At diagnosis, the majority of patients (71.7 %) were above 65 years of age. The European age-standardised CLL incidence rate in the CPRD was 6.2/100,000 (95 % confidence interval [CI] 6.0, 6.5/100,000) person-years. There was no statistically significant increase over time. The CLL patients had on average 74.6 general practitioner visits during a median follow-up of 3.3 years. Between 2000 and 2012, the average number of recorded hospitalisations and referrals per year corrected for duration of follow-up significantly (p < 0.001) increased by 8.1 % (95 % CI 6.8 %, 9.3 %) and 16.4 % (95 % CI 15.4 %, 17.3 %), respectively. Referrals and hospitalisations in the second year compared to the first year following the CLL diagnosis significantly decreased. CLL incidence rates in the CPRD were stable over the period from 2000 to 2012. Medical resource utilisation in UK primary care was well documented, but further research is needed to describe secondary and tertiary care medical resource utilisation e.g. chemotherapy administration, which is inadequately captured in the CPRD.

Impact of genetic variability and treatment-related factors on outcome in early breast cancer patients receiving (neo-) adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide, and docetaxel.

To assess the impact of patient-related factors, including genetic variability in genes involved in the metabolism of chemotherapeutic agents, on breast cancer-specific survival (BCSS) and recurrence-free interval (RFI). We selected early breast cancer patients treated between 2000 and 2010 with 4-6 cycles of (neo-)adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) or 3 cycles FEC followed by 3 cycles docetaxel. Tumor stage/subtype; febrile neutropenia and patient-related factors such as selected single nucleotide polymorphisms and baseline laboratory parameters were evaluated. Multivariable Cox regression was performed. Of 991 patients with a mean follow-up of 5.2 years, 152 (15.3 %) patients relapsed and 63 (6.4 %) patients died. Advanced stage and more aggressive subtype were associated with poorer BCSS and RFI in multivariable analysis (p < 0.0001). Associations with worse BCSS in multivariable analysis were: homozygous carriers of the rs1057910 variant C-allele in CYP2C9 (hazard ratio [HR] 30.4; 95 % confidence interval [CI] 6.1-151.5; p < 0.001) and higher white blood cell count (WBC) (HR 1.2; 95 % CI 1.0-1.3; p = 0.014). The GT genotype of the ABCB1 variant rs2032582 was associated with better BCSS (HR 0.5; 95 % CI 0.3-0.9, p = 0.021). Following associations with worse RFI were observed: higher WBC (HR 1.1; 95 % CI 1.0-1.2; p = 0.026), homozygous carriers of the rs1057910 variant C-allele in CYP2C9 (HR 10.9; 95 % CI 2.5-47.9; p = 0.002), CT genotype of the CYBA variant rs4673 (HR 1.8; 95 % CI 1.2-2.7; p = 0.006), and G-allele homozygosity for the UGT2B7 variant rs3924194 (HR 3.4; 95 % CI 1.2-9.7, p = 0.023). Patient-related factors including genetic variability and baseline white blood cell count, impacted on outcome in early breast cancer.

Identification of two independent MHC class II antigens in a bovine lymphoblastoid cell line.

Bovine major histocompatibility complex (MHC) class II antigens were investigated using monoclonal antibodies (MoAbs) with known MHC class II specificities in other species. Thirty-four MoAbs were tested for reactivity with bovine peripheral blood mononuclear (PBM) cells and the bovine lymphoblastoid cell line, BL3, by flow cytometry. Twenty-seven of 31 MoAbs tested, reacted with BL3 cells, and 22 of 25 MoAbs tested with PBM cells were reactive. MoAbs that reacted with BL3 cells were used to immunoprecipitate class II molecules from BL3 lysate labeled with [35S]methionine. Using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography, many MoAbs were found to immunoprecipitate a single band of approximately 31,000 relative mass (Mr). MoAbs yielding successful immunoprecipitations and with known antigen specificity in other species were then used in sequential immunoprecipitations and two dimensional (2-D) non-equilibrium pH gradient electrophoresis (NEPHGE). The HLA-DR specific MoAb H4 and the predominantly HLA-DQ specific MoAb CC11.23 were used to identify the presence of two independent antigens in BL3 cell lysate. These class II molecules consist of alpha and beta chains.