Description: The safety and efficacy of ibrutinib (420 mg) in chronic lymphocytic leukemia (CLL) were evaluated in a phase 2 study; 51 patients had TP53 aberration (TP53 cohort) and 35 were enrolled because of age 65 years or older (elderly cohort). Both cohorts included patients with treatment-naive (TN) and relapsed/refractory (RR) CLL. With the median follow-up of 4.8 years, 49 (57.0%) of 86 patients remain on study. Treatment was discontinued for progressive disease in 20 (23.3%) patients and for adverse events in 5 (5.8%). Atrial fibrillation occurred in 18 (20.9%) patients for a rate of 6.4 per 100 patient-years. No serious bleeding occurred. The overall response rate at 6 months, the primary study endpoint, was 95.8% for the TP53 cohort (95% confidence interval, 85.7%-99.5%) and 93.9% for the elderly cohort (95% confidence interval, 79.8%-99.3%). Depth of response improved with time: at best response, 14 (29.2%) of 48 patients in the TP53 cohort and 9 (27.3%) of 33 in the elderly cohort achieved a complete response. Median minimal residual disease (MRD) in peripheral blood was 3.8 x 10 –2 at 4 years, with MRD-negative (〈10 –4 ) remissions in 5 (10.2%) patients. In the TP53 cohort, the estimated 5-year progression-free survival (PFS) was 74.4% in TN-CLL compared with 19.4% in RR-CLL ( P = .0002), and overall survival (OS) was 85.3% vs 53.7%, respectively ( P = .023). In the elderly cohort, the estimated 5-year PFS and OS in RR-CLL were 64.8% and 71.6%, respectively, and no event occurred in TN-CLL. Long-term administration of ibrutinib was well tolerated and provided durable disease control for most patients. This trial was registered at www.clinicaltrials.gov as #NCT01500733.

Description: Circulating monoclonal B cells may be detected in healthy adults, a condition called monoclonal B-cell lymphocytosis (MBL). MBL has also been identified in donated blood, but no systematic study of blood donors has been reported. Using sensitive and specific laboratory methods, we detected MBL in 149 (7.1%; 95% confidence interval, 6.0% to 8.3%) of 2098 unique donors ages 45 years or older in a Midwestern US regional blood center between 2010 and 2011. Most of the 149 donors had low-count MBL, including 99 chronic lymphocytic leukemia–like (66.4%), 22 atypical (14.8%), and 19 CD5 – (12.8%) immunophenotypes. However, 5 donors (3.4%) had B-cell clonal counts above 500 cells per µL, including 3 with 1693 to 2887 cells per µL; the clone accounted for nearly all their circulating B cells. Four donors (2.7%) had 2 distinct MBL clones. Of 51 MBL samples in which immunoglobulin heavy chain (IGH)V-D-J genotypes could be determined, 71% and 29% used IGHV3- and IGHV4-family genes, respectively. Sequencing revealed 82% with somatic hypermutation, whereas 18% had 〉98% germ-line identity, including 5 with entirely germ-line sequences. In conclusion, MBL prevalence is much higher in blood donors than previously reported, and although uncommon, the presence of high-count MBL warrants further investigations to define the biological fate of the transfused cells in recipients.

Description: Chronic lymphocytic leukemia (CLL) is characterized by immune dysregulation, often including hypogammaglobulinemia, which contributes to a high rate of infections and morbidity. Ibrutinib, a covalent inhibitor of Bruton tyrosine kinase (BTK), inhibits B-cell receptor signaling and is an effective, US Food and Drug Administration (FDA)-approved treatment of CLL. Inactivating germline mutations in BTK cause a severe B-cell defect and agammaglobulinemia. Therefore, we assessed the impact of ibrutinib on immunoglobulin levels, normal B cells, and infection rate in patients with CLL treated with single-agent ibrutinib on a phase 2 investigator-initiated trial. Consistent with previous reports, immunoglobulin G (IgG) levels remained stable during the first 6 months on treatment, but decreased thereafter. In contrast, there were a transient increase in IgM and a sustained increase in IgA (median increase 45% at 12 months, P 〈 .0001). To distinguish the effects on clonal B cells from normal B cells, we measured serum free light chains (FLCs). In -clonal CLL cases, clonal () FLCs were elevated at baseline and normalized by 6 months. Nonclonal () FLCs, which were often depressed at baseline, increased, suggesting the recovery of normal B cells. Consistently, we observed normal B-cell precursors in the bone marrow and an increase in normal B-cell numbers in the peripheral blood. Patients with superior immune reconstitution, as defined by an increase in serum IgA of ≥50% from baseline to 12 months, had a significantly lower rate of infections ( P = .03). These data indicate that ibrutinib allows for a clinically meaningful recovery of humoral immune function in patients with CLL. This trial was registered at www.clinicaltrials.gov as #NCT015007330.

Description: The 2016 LoNNe (Loss of the Night Network) intercomparison campaign is the fourth of four campaigns planned during EU COST Action ES1204. The first campaign took place in 2013 in Lastovo, Croatia, the second in Madrid, Spain (Bará et al 2015), the third in Torniella and Florence, Italy (Kyba et al 2015a). The 2016 campaign took place at the Parc Astronòmic Montsec (PAM). The campaign was supported by the European Collective Awareness Platform for Social and Sustainable Innovation (CAPPSI) STARS4ALL, in which the activity is planned to become a continuous light pollution initiative (LPI). The financing of this campaign, which is listed as a milestone in the MoU of the COST Action ES1204, was unexpectedly waived by the EU-COST Office due to administrative complications and re-organization of the grant-periods. The campaign continued the strategy of taking measurements at multiple sites, this year with a main fixed site and then excursions to other sites. The goals of the campaigns included: ● Understanding the difference between extinction measurements made by DSLR photometry and classical astronomical (telescope) photometry, and also understanding the relation between extinction and sky brightness at these two sites. ● Examining the difference in radiance measured with the mosaic technique of the US National Parks Service camera compared to all-sky fisheye imagery ● Examining the relationships between all-sky and zenith radiance reported by different instruments ● Quantifying the sky brightness at the sites, including full zenith spectral radiance at selected locations ● Measuring the systematic uncertainty on handheld SQM observations due to unit-to-unit differences This report provides a brief synopsis of the campaign and its preliminary outcomes. Section 2 describes the measurement locations, the detailed activities of the participants, the instruments used, and the environmental conditions. Section 3 describes a meeting with local authorities that took place during the campaign. Section 4 provides some preliminary results, outlines the ongoing analyses, and presents research questions for the next campaign to address. Section 5 provides recommendations for future intercomparison campaigns. The Municipality of Balaguer coordinated with us regarding the time that architectural lamps were turned off, and the village of Àger allowed us to turn all street lighting off at a time of our choice.