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.
Here we present an atypical and aggressive case of extranodal NK/T cell lymphoma presenting in a 22 year old Caucasian female as orbital swelling without evidence of nasal mucosal involvement. It is important to distinguish NKTL from the more common benign lymphoproliferative lesions of the orbital adnexa as prognosis of these two clinical entities varies and timely diagnosis is key. The present case demonstrates that extranodal NKTL can occur in the orbit without evidence of the more common nasal mucosal presentations and should be included in the differential diagnosis of ocular adnexal lesions suspicious for a lymphoproliferative disorder and/or an inflammatory process.
The effect of early posthatch starvation on myonuclear apoptosis was examined in chickens. Male broiler chickens were or were not provided feed for the first 3-d posthatch. Subsequently, all chickens were provided feed for an additional 4-d posthatch. Chickens were killed at 3- and 7-d posthatch, and the pectoralis thoracicus was harvested, fixed and embedded in paraffin. Muscle sections were labeled with the terminal deoxynucleotidyl transferase histochemical staining technique to identify apoptotic nuclei. At 3- and 7-d posthatch, there was a significantly (P < 0.05) smaller myofiber cross-sectional area for the starved compared with the fed chickens. A larger proportion (P < 0.05) of apoptotic nuclei relative to total nuclei was observed in the starved compared to the fed chickens killed at 3-d posthatch, but the proportion of apoptotic nuclei relative to total nuclei did not differ (P > 0.05) between the starved and fed chickens killed at 7-d posthatch. It appears that apoptosis is a mechanism contributing to the smaller myofiber size observed when feed is not provided early posthatch.
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