An increased risk of life-threatening infection was also observed when the results of three Phase II studies were pooled, combining rituximab with the infusional CDE chemotherapy regimen in 74 patients with ARL [50]. However, subsequent Phase II studies of R-CHOP (without maintenance rituximab) from Europe did not show an increased risk of infectious deaths, instead showing that rituximab was beneficial [14,17]. The AMC went on to perform a randomized

study of DA-EPOCH with either concurrent or sequential rituximab [19]. Concurrent administration was superior, with no increase in infectious deaths, but outcome in both groups was excellent, supporting the efficacy and tolerability of concurrent rituximab. A recent click here meta-analysis of prospective studies has confirmed the benefit in response rate and overall survival (OS) of the addition of rituximab to chemotherapy [20]. A pooled analysis of both AMC studies mentioned above suggested that R-EPOCH resulted in superior response rates and survival compared to R-CHOP [18], although these regimens have not been compared

in any randomized study. Importantly, the R-EPOCH study was performed during a later time period (2002–2006) than the R-CHOP study (1998–2002), suggesting other variables, including supportive EX 527 chemical structure care and antiretroviral drug options, may have differed. Consistent with this, the patients treated with R-EPOCH routinely received concurrent antifungal and antibacterial prophylaxis, which was omitted from those treated earlier with R-CHOP. The AMC have recently reported the results of a prospective, multicentre Phase II trial of R-CHOP, but with pegylated, liposomal doxorubicin in order to limit toxicity. Of note, HAART was continued during chemotherapy. The treatment was well tolerated without any deaths from infection, even in those with a low CD4 cell count, thus supporting the inclusion of rituximab in treatment regimens. However, the response rate was inferior to that reported in prior studies (overall response 76.5%, CR 47.5%) [51]. Thus, the addition of rituximab to chemotherapy is now recommended PD184352 (CI-1040) for DLBCL in HIV-positive patients. Although the use of rituximab is contentious in patients with a CD4 count <50 cells/μL

[27], with appropriate antimicrobial prophylaxis (cotrimoxazole, fluconazole, aciclovir, azithromycin), pre-emptive G-CSF and prompt treatment of opportunistic infection, rituximab is recommended for all patients with DLBCL. The rate of overall response (CR and partial remission; PR) and CR to R-CHOP chemotherapy is reported to be around 66–87% and 58–77%, respectively [14,17,27,29]. In one study with long follow-up, the 8-year OS was 46% [52]. (See Table 4.5 for summary of R+ chemotherapy studies in HIV-positive patients.) R-EPOCH (Concurrent rituximab only) As mentioned, the IPI score at diagnosis is prognostic of outcome, such that those patients with high-risk disease (IPI score 3–5) have a lower response rate and overall survival to standard chemotherapy [17,27].