Diffuse large B-cell lymphomas (DLBCL) represent the most common type of adult malignant lymphoma in western countries and are treated with high dose combination chemotherapy. Although initially the majority of patients respond to this therapy, many do not achieve complete remission and others experience an early relapse. Several studies have shown that prediction of the clinical response to chemotherapy is possible before the start of chemotherapy treatment. Apparently, DLBCL are intrinsically either resistant or sensitive to chemotherapy-induced cell death. Differences in functional integrity of the apoptosis cascade are an important factor predicting outcome in DLBCL. In this review we discuss the possible mechanisms leading to intrinsic resistance to apoptosis and provide an explanation why strong differences in apoptosis sensitivity between DLBCL are observed. Subsequently we will focus on how differences in this intrinsic apoptosis resistance provide an explanation for the variable response to combination chemotherapy and how this can be used for further therapy tailoring.
Copyright 2006 John Wiley & Sons, Ltd.