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The article presents a study on the effectiveness of cyclophosphamide as a first-line therapy in large granular lymphocyte (LGL) leukemia which could be an interesting alternative to methotrexate. It reveals that cyclophosphamide should be given to patients for at least 4 months before changing drug regimen. It also notes that cyclophosphamide is effective in T/NK-LGL leukemia, in both neutropenic and anemic patients, based on a series of study conducted.

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/m 2 intravenously (IV) (days 1-5), rituximab 375 mg/m 2 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., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Mantle cell lymphoma (MCL) is a rare, aggressive subtype of B cell NHL for which there is no standard of care. It is characterized by the t(11;14) translocation, implicating cyclin D1 (CCND1) in its pathogenesis. Cyclin D1 is one of a family of 3 unlinked D type cyclin genes, CCND1, 2, 3. CCND1 is not expressed in normal B cells. Deregulated expression occurs as a result of juxtaposition of cis IgH enhancer elements, Eμ and 3' Cα, to the cyclin D1 gene. These enhancer elements and regions upstream of the CCND1 gene are hypomethylated on the translocated allele. Histones surrounding the translocation have shown hyperacetylation as well, a hallmark of transcriptionally active chromatin. The t(11;14) translocation is an epigenetic event, leading to cyclin D1 deregulated transcription. These findings provide the rationale for the use of epigenetic and targeted cyclin D1 therapies to overcome resistance and induce durable remissions in MCL., (Copyright © 2012 Elsevier Ltd. All rights reserved.)