390 Enhanced suppression of Raf-1 activity by K vitamins mediates their synergy with Sorafenib to inhibit HCC cell growth in vitro and in vivo
EJC SUPPLEMENTS(2010)
摘要
Anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-negative (ALCL-ALK−) is a provisional entity in the WHO 2008 Classification that represents 2–3% of NHL and 12% of T-cell NHL. No particular risk factor has been clearly identified for ALCL, but a recent study showed an odds ratio of 18 for ALCL associated with breast implants. Usually, the architecture of involved organs is eroded by solid, cohesive sheets of neoplastic cells, with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) and classical Hodgkin lymphoma being the main differential diagnoses. In this regard, staining for PAX5 and CD30 is useful. Translocations involving ALK are absent, TCR genes are clonally rearranged. CGH and GEP studies suggest a tendency of ALCL-ALK− to differ both from PTCL-NOS and from ALCL-ALK+.Patients with ALCL-ALK− are usually adults with a median age of 54–61 years, and a male-to-female ratio of 0.9. At presentation, ALCL-ALK− is often in III–IV stage, with B symptoms, high International Prognostic Index score, high lactate dehydrogenase serum levels, and an aggressive course. ALCL-ALK− presents with lymph node involvement in ∼50% of cases; extranodal spread (20%) is less common. Staging work-up for ALCL-ALK− is similar to that routinely used for nodal NHL. Overall prognosis is poor, with a 5-year OS of 30–49%, which is significantly worse when compared to OS reported in patients with ALCL-ALK+ (5-year: 70–86%). Patients with systemic ALCL exhibit a significantly better survival compared with patients with PTCL-NOS, with a 5-year OS of 51% and 32%, respectively. Age, PIT scoring system, β2-microglobulin, and bone marrow infiltration are the main prognostic factors. The expression of proteins involved in the regulation of apoptosis (caspase 3, Bcl-2, PI9) and of CD56 is related to clinical outcome.ALCL-ALK− is generally responsive to doxorubicin-containing chemotherapy, but relapses are frequent. CHOP is the most commonly used regimen to treat systemic ALCL with complete remission rates of 56%, and a 10-year DFS of 28%. Encouraging results have been reported with more intensive chemotherapy regimens. The addition of etoposide improved outcome. Alemtuxumab-CHOP regimen was associated with excellent remission rate but increased toxicity. The role of high-dose chemotherapy supported by ASCT has not been investigated in a trial of exclusively ALCL patients. When used in first remission, it was associated with a 5-year PFS of 64%. High-dose chemotherapy with ASCT is the standard therapeutic option for patients with relapsed or refractory disease. The role of allogeneic transplantation in patients with relapsed/refractory ALCL remains to be defined but there are data to support the contention that a graft-versus-lymphoma effect does exist. Myeloablative conditioning has been associated with 5-year PFS and OS of 40% and 41%, respectively, but a 5-year TRM of 33% was reported. Allo-SCT can be an option for relapsed/refractory ALCL in younger patients, preferably in the setting of a clinical trial.Pralatrexate, anti-CD30 monoclonal antibodies, brentuximab vedotin (SGN-35) in particular, 131I-anti-CD45 radioantibody, yttrium-anti-CD25 radioimmunoconjugates, histone deacetylase inhibitors, bortezomib, gemcitabine, vorinostat, lenalidomide, and their combinations represent the most appealing chemotherapy and/or targeted agents to be investigated in future trials.
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