Total body irradiation, etoposide, cyclophosphamide, and autologous peripheral blood stem-cell transplantation followed by randomization to therapy with interleukin-2 versus observation for patients with non-Hodgkin lymphoma: results of a phase 3 randomized trial by the Southwest Oncology Group (SWOG 9438).

Diffuse large B-cell lymphoma (DLBCL) can be cured in about 60% of cases with immuno-chemotherapy. However, a large subset of patients with DLBCL do not go into remission, or relapse after first-line therapy. Further therapy options are therefore needed. Phospholipase Cγ2 (PLCγ2) is one of the key regulators of the B cell receptor signaling pathway, which targets several pro-proliferative factors, such as nuclear factor κB (NFκB), Ras and Akt. Using immunohistochemistry, we found that PLCγ2 was strongly expressed in 63% of cases of DLBCL. The PLC inhibitor U73122 had an inhibitory effect on cell proliferation and induced apoptosis and G0/G1 cell cycle arrest. Co-treatment with enzastaurin or the Src inhibitor pp2 together with U73122 had an additive effect on cell proliferation compared to U73122 alone. Unexpectedly, strong PLCγ2 expression was associated with better overall survival. In conclusion, PLCγ2 is strongly expressed in a significant number of DLBCLs and has prognostic implications. Inhibition of PLCγ2 could be a new target for lymphoma treatment.

Expression and pro-survival function of phospholipase Cγ2 in diffuse large B-cell lymphoma

While rituximab-based chemo-immunotherapy has improved response and long-term survival rates in diffuse large B-cell non-Hodgkin lymphoma (DLBCL), relapse and death from recurrent disease is still the eventual outcome in a significant proportion of patients, especially those with high-risk disease. Autologous hematopoietic stem cell transplant (AHSCT) in first remission, which was studied mainly before the advent of rituximab, has lost its appeal due to several small negative trials. However, definitive data do not exist to determine the role of AHSCT in first remission. In this review, we critically evaluate studies investigating AHSCT in DLBCL in first remission. Most available studies have shortcomings that limit the applicability of their findings. AHSCT in first remission may have a role in selected patients with high-risk DLBCL, but a carefully designed prospective study is required to appropriately evaluate this concept.

Diffuse large B-cell lymphoma: Is there a place for autologous hematopoietic stem cell transplant in first remission in the era of chemo-immunotherapy?

LI Wen-yu

Papers

Review on Randomized Study to Evaluate the Use of High-Dose Therapy as Part of Primary Treatment for "Aggressive" Lymphoma