British journal of haematology
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Randomized Controlled Trial Comparative Study
Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma.
We conducted a prospective randomized phase II study to evaluate two chemotherapy regimens: (i) rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (R-HCVAD) alternating with rituximab, high-dose methotrexate, and cytarabine (R-MA) and (ii) rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in diffuse large B-cell lymphoma (DLBCL). This study randomized patients aged ≤60 years with DLBCL and an age-adjusted international prognostic index ≥2 to R-HCVAD/R-MA or R-CHOP based on a Bayesian adaptive algorithm. Interim analysis of the first 26 eligible patients showed that the complete response rate (CRR) was higher with R-HCVAD/R-MA than R-CHOP (P = 0·03); thus, R-CHOP arm was closed. ⋯ In the R-HCVAD/R-MA arm, 3-year PFS rates in patients aged 46-60 years and ≤45 years were 70·3% and 87·1% respectively (P = 0·13), and the treatment-associated early mortality rate in patients >45 years was 12%. In conclusion, R-HCVAD/R-MA is associated with excellent outcome in patients ≤45 years old. However, in patients >45 years old, R-HCVAD/R-MA is associated with unacceptable mortality rates.
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Orally active small molecules that selectively and specifically inhibit coagulation serine proteases have been developed for clinical use. For some patients these oral direct inhibitors (ODIs) offer substantial benefits over oral vitamin K antagonists (VKA). However, for the majority of patients with good anticoagulant control with VKAs the advantages of the ODIs are primarily convenience and few drug interactions. ⋯ Consequently, the need to consider the balance of benefit and risk in each individual patient is no less important than with VKA therapy. Dabigatran and rivaroxaban have been chosen for this review as examples of a thrombin inhibitor and an inhibitor of factor Xa respectively. The clinical application of these drugs is the focus of the review.
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In a fraction of patients, chronic lymphocytic leukaemia (CLL) can transform to Richter syndrome (RS), usually a diffuse large B-cell lymphoma (DLBCL). We studied genome-wide promoter DNA methylation in RS and clonally related CLL-phases of transformed patients, alongside de novo DLBCL (of non-germinal centre B type), untransformed-CLL and normal B-cells. The greatest differences in global DNA methylation levels were observed between RS and DLBCL, indicating that these two diseases, although histologically similar, are epigenetically distinct. ⋯ Its transcriptional repression by DNA methylation was confirmed by 5-aza-2'deoxycytidine treatment of DLBCL cells, determining an increased OSM expression. Our results showed that methylation patterns in RS are largely different from de novo DLBCL. Stem cell-related genes and cell cycle regulation genes are targets of DNA methylation in RS.