Failure to undergo activation-induced cell death due to global dysregulation of apoptosis is the pathogenic hallmark of large granular lymphocyte (LGL) leukemia. Consequently, immunosuppressive agents are rational choices for treatment. This first prospective trial in LGL leukemia was a multicenter, phase 2 clinical trial evaluating methotrexate at 10 mg/m2 orally weekly as initial therapy (Step 1). Patients failing methotrexate were eligible for treatment with cyclophosphamide at 100 mg orally daily (Step 2). The overall response in Step 1 was 38% with 95% confidence interval (CI): 26%, 53%. The overall response in Step 2 was 64% with 95% CI: 35%, 87%. The median overall survival for patients with anemia was 69 months with a 95% CI lower bound of 46 months and an upper bound not yet reached. The median overall survival for patients with neutropenia has not been reached 13 years from study activation. Serum biomarker studies confirmed the inflammatory milieu of LGL but were not a priori predictive of response. We identify a gene expression signature that correlates with response and may be STAT3 mutation driven. Immunosuppressive therapies have efficacy in LGL leukemia. Gene signature and mutational profiling may be an effective tool in determining whether methotrexate is appropriate therapy.
International audienceLetter to the Editor. Large granular lymphocyte (LGL) leukemia is a T or NK clonal disorder characterized by the tissue invasion of marrow, spleen and liver..
Wiring photoelectrodes: Vertically aligned silicon nanowires were chemically synthesized and tested for solar‐energy harnessing. Growth experiments reveal that such nanowire arrays can be obtained when the growth is slow. Photoelectrochemical studies validate that silicon nanowires are promising candidates for efficient solar cells.
T-cell prolymphocytic leukemia (T-PLL) is a rare, mature T-cell neoplasm with distinct features and an aggressive clinical course. Early relapse and short overall survival are commonplace. Use of the monoclonal anti-CD52 antibody alemtuzumab has improved the rate of complete remission and duration of response to over 50% and between 6–12 months, respectively. Despite this advance, without an allogeneic transplant, resistant relapse is inevitable. We report complete (7) and partial (1) remissions in eight patients receiving alemtuzumab and cladribine with or without an HDAC inhibitor. These data show that administration of epigenetic agents overcomes alemtuzumab resistance. We report epigenetically induced expression of the surface receptor protein CD30 in T-PLL. Subsequent treatment with the anti-CD30 antibody drug conjugate brentuximab vedotin overcame organ specific (skin) resistance to alemtuzumab. Our findings demonstrate activity of combination epigenetic and immunotherapy in the incurable illness T-PLL, particularly in the setting of prior alemtuzumab therapy.
Photoelektroden aus Drähtchen: Parallele Siliciumnanodrähte wurden chemisch synthetisiert und auf die Umwandlung von Sonnenenergie hin geprüft. Experimente belegen, dass solche Nanodrahtanordnungen durch langsames Wachstum aufgebaut werden können. In photoelektrochemischen Untersuchungen erwiesen sich die Nanodrähte als vielversprechende Kandidaten für effiziente Solarzellen.
Summary
Altered DNA methylation and histone acetylation in lymphoma provided the rationale for using vorinostat (SAHA), cladribine and rituximab (SCR) in non‐Hodgkin lymphomas (NHL) in this phase 1–2 study (NCT00764517). Treatment included cladribine 5 mg/m2 intravenously (IV) (days 1–5), rituximab 375 mg/m2 IV (weekly 4× for cycle 1 and 1×/month) and vorinostat orally once daily (days 1–14) every 28 days for up to six cycles. Phase 1 included relapsed patients (n = 10) in a standard 3 + 3 dose escalation design (vorinostat: 200, 300 and 400 mg). No dose‐limiting toxicities were seen. The phase 2 dose for vorinostat was 400 mg po (days 1–14). The majority of phase 2 patients had mantle cell lymphoma (MCL) (n = 57; 39 previously untreated, 10 relapsed). The primary objective was objective response rate [complete response (CR) + partial response] which was 39% (7/18) in relapsed patients and 97% (38/39) with 80% (31/39) attaining a CR in previously untreated MCL. At a median follow‐up of 42 months, median progression‐free survival (PFS) and overall survival (OS) for relapsed NHL were 19·5 [95% confidence interval (CI): 2·0–33·0] and 25·0 (95% CI: 12·0–45·0) months respectively. Median PFS for previously untreated MCL was 84·0 months; OS could not be estimated. Toxicities were primarily haematological.
Si nanowire growth kinetics was studied, and the growth rate was shown to be highly sensitive to SiH4
precursor pressures, changing from a second-order dependence at low pressures to first-order and then
independent at high pressures. Molecular collisions of SiH4 with He carrier gas account for this finding. The
second- and first-order correlation was explained by the unimolecular reaction model and the saturated growth
rate was due to the Langmuir adsorption limit. Our results suggest that precursor pressures must be controlled
carefully for desired growth kinetics.
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