Ibrutinib added to 10-day decitabine for older patients with AML and higher risk MDS

The treatment of older, unfit patients with acute myeloid leukemia (AML) is challenging. Based on preclinical data of Bruton tyrosine kinase expression/phosphorylation and ibrutinib cytotoxicity in AML blasts, we conducted a randomized phase 2 multicenter study to assess the tolerability and efficacy of the addition of ibrutinib to 10-day decitabine in unfit (ie, Hematopoietic Cell Transplantation Comorbidity Index ≥3) AML patients and higher risk myelodysplasia patients (HOVON135/SAKK30/15 trial). In total, 144 eligible patients were randomly (1:1) assigned to either 10-day decitabine combined with ibrutinib (560 mg; sequentially given, starting the day after the last dose of decitabine) (n = 72) or to 10-day decitabine (n = 72). The addition of ibrutinib was well tolerated, and the number of adverse events was comparable for both arms. In the decitabine plus ibrutinib arm, 41% reached complete remission/complete remission with incomplete hematologic recovery (CR/CRi), the median overall survival (OS) was 11 months, and 2-year OS was 27%; these findings compared with 50% CR/CRi, median OS of 11.5 months, and 2-year OS of 21% for the decitabine group (not significant). Extensive molecular profiling at diagnosis revealed that patients with STAG2, IDH2, and ASXL1 mutations had significantly lower CR/CRi rates, whereas patients with mutations in TP53 had significantly higher CR/CRi rates. Furthermore, multicolor flow cytometry revealed that after 3 cycles of treatment, 28 (49%) of 57 patients with available bone marrow samples had no measurable residual disease. In this limited number of cases, measurable residual disease revealed no apparent impact on event-free survival and OS. In conclusion, the addition of ibrutinib does not improve the therapeutic efficacy of decitabine. This trial was registered at the Netherlands Trial Register (NL5751 [NTR6017]) and has EudraCT number 2015-002855-85

Inferior outcome of addition of the aminopeptidase inhibitor tosedostat to standard intensive treatment for elderly patients with aml and high risk mds

Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66–81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1–21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60–77%) vs 64% (55–73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation w

Occurrence, distribution and abundance of cetaceans in Onslow Bay, North Carolina, USA

In this paper the occurrence, distribution and abundance of cetaceans in offshore waters of Onslow Bay, North Carolina, USA is described. Between June 2007 and June 2010 monthly aerial and shipboard line-transect surveys were conducted along ten 74km transects placed perpendicular to the shelf break. In total 42,676km of aerial trackline (218 sightings) and 5,209km of vessel trackline (100 sightings) were observed. Seven species of cetaceans were observed, but the fauna was dominated strongly by common bottlenose and Atlantic spotted dolphins. Both species were present year-round in the study area. Using photo-identification techniques, five bottlenose dolphins and one spotted dolphin were resighted during the three-year period. In general, the abundance of cetaceans in Onslow Bay was low and too few sightings were made to estimate monthly abundances for species other than bottlenose and spotted dolphins. Maximum monthly abundances of bottlenose and spotted dolphins were 4,100 (95% CI: 1,300–9,400) in May 2010 and 6,000 (95% CI: 2,500–17,400) in March 2009, respectively. Bottlenose dolphins were found throughout the study area, although they were encountered most frequently just off the shelf break. In contrast, spotted dolphins exhibited a strong preference for waters over the continental shelf and were not encountered beyond the shelf break.Publisher PDFPeer reviewe

Pollination of Habenaria pleiophylla Hoehne & Schlechter (Orchidaceae) by Heliconius erato phyllis Fabricius (Lepidoptera, Nymphalidae)

For the first time the pollination of a poorly known, terrestrial orchid, Habenaria pleiophylla Hoehne & Schlechter, 1921 (Orchidaceae) by a passion vine butterfly, Heliconius erato phyllis (Fabricius, 1775) (Lepidoptera, Nymphalidae) is reported. Number of pollinia-carrying individuals was determined on a population of H. erato phyllis in Horto Florestal Barba Negra, Barra do Ribeiro County, Rio Grande do Sul State. The pollination mechanism was described under laboratory conditions, in association with the butterfly feeding habit and the orchid flower morphology. Habenaria pleiophylla pollinia are cemented during nectar feeding on the ventral portion of the compound eyes near H. erato phyllis proboscis base. The pollinia are transferred to the stigma of other flowers during subsequent visits. Both males and females of H. eralo phyllis frequently visit H. pleiophylla flowers in the Barba Negra Forest. About forty percent of field collected adults had attached pollinia, ranging in number from one to 19 per individual. Thus, H. eralo phyllis may play an important role in the reproductive biology of this H. pleiophylla population