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.
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