The addition of rituximab to CHOP or other chemotherapy regimens has reportedly led to a significant improvement in the prognosis of DLBL patients. Interestingly, it was suggested from preclinical models that rituximab chemosensitized drug-resistant B-lymphoma cells through down-regulation of anti-apoptotic factors and endogenous IL-10 expression [17, 18], suggesting that rituximab is likely to have a significant therapeutic effect by augmenting the effect of anticancer agents in CHOP in a synergistic fashion and thereby compensating for a low CHOP RDI. However, from our results, it was clear that maintaining a high RDI remained crucial in the use of

R-CHOP for DLBL patients, in a similar fashion to CHOP alone. We identified advanced age as the only factor that reduced RDI. A nationwide Rapamycin study of RDI in CHOP-like chemotherapies in patients with non-Hodgkin’s lymphoma (NHL) in https://www.selleckchem.com/products/abt-199.html the United States also showed that older age was a risk factors for reduced RDI, in addition to lack of use of prophylactic

colony stimulating factor (CSF), advanced disease stage, poor PS and a lower serum albumin level [19]. Moreover, the study indicated that prophylactic CSF use is important in maintaining a high RDI, particularly in elderly patients. The American Society of Clinical Oncology update guideline for the use of CSF, also recommends use of prophylactic CSF during curative and intensive chemotherapy for elderly patients with DLCL, to reduce the incidence of febrile neutropenia and infections [14]. In addition, according to the European Organization for Research and Treatment of Cancer guideline on the use of G-CSF, when dose-dense or dose-intense chemotherapy has a survival benefit, prophylactic G-CSF use is recommended, especially in elderly patients [20]. Indeed, in a prospective study on prediction of febrile neutropenia in the first cycle of chemotherapy

for NHL, elderly patients were identified as candidates for primary CSF prophylaxis [21]. Taking into account these reports as well as our results, prophylactic use of CSF could be recommend, at least in elderly patients with DLBL who are scheduled to receive R-CHOP chemotherapy in order to maintain RDI. As our study was a retrospective cohort study with a small study population and/or short median follow-up periods, it was inevitable that treatment DNA Methyltransferas inhibitor bias due to physician discretion in making treatment decisions would arise. Therefore, prospective randomized trials will be required to confirm the value of maintaining a high RDI. For instance, an alternative strategy to intensify RDI by shortening the intervals between cycles of chemotherapy, such as bi-weekly CHOP, may be promising [22]. Indeed, Groupe d’Etudes de Lymphomes de L’Adulte (GELA) is now conducting a phase III prospective randomized trial to assess the difference between eight cycles of bi-weekly R-CHOP and three-weekly R-CHOP.