In each of these large series, one patient died soon after rituximab administration as a result of overwhelming disease, and the main adverse event seen in these patients was reactivation of KS, which is intriguing and may have been attributable to the rapid B-cell depletion that is observed during rituximab therapy, or an immune reconstitution inflammatory syndrome to hitherto latent antigens [47]. Bower et al. [48] demonstrated after successful rituximab therapy, a significant reduction from baseline of the CD19 B-cell count, and reductions in the levels of the inflammatory cytokines
IL-5, IL-6 and IL-10. In the largest study to date [49], Bower et al. Belnacasan nmr identified 61 HIV-positive patients with histologically confirmed MCD (median follow-up, 4.2 years). Since 2003, 49 patients with newly diagnosed http://www.selleckchem.com/products/AZD2281(Olaparib).html MCD have been treated with rituximab with (n = 14) or without (n = 35)
etoposide. With rituximab-based treatment, the overall survival was 94% (95% CI: 87–100%) at 2 years and was 90% (95% CI: 81–100%) at 5 years compared with 42% (95% CI: 14–70%) and 33% (95% CI: 6–60%) in 12 patients treated before introduction of rituximab (log-rank p < 0.001). Four of 49 rituximab-treated patients have died; three died as a result of MCD within 10 days of diagnosis, and one died as a result of lymphoma in remission of MCD. Eight of 46 patients who achieved clinical remission suffered symptomatic, histologically confirmed MCD relapse. The median time to relapse was 2 years, and all have been successfully re-treated and are alive in remission. The 2- and 5-year progression-free survival rates for all 49 patients treated with rituximab-based therapy were 85% (95% CI: 74–95%) and 61% (95% CI: 40–82%), respectively. Gerard et al. [50] compared the incidence of NHL between patients who had received rituximab or not over 4.2 years of follow-up. In the group that did not receive rituximab (n = 65), 17 patients developed patient developed NHL (incidence, 4.2 of 1000 person-years). Based on the propensity
score-matching method, a significant decrease in the incidence of NHL was observed in patients who had been treated with rituximab (hazard ratio 0.09, 95% CI: 0.01–0.70). Ten Kaposi sarcoma (KS) exacerbations and one newly diagnosed KS IKBKE were observed in nine patients after rituximab therapy. Rituximab was associated with an 11-fold lower risk of developing lymphoma. KS exacerbation was the most challenging adverse event after rituximab therapy. Data from Stebbing et al. [30] showing that rising levels of HHV8 predicted relapses, suggested that combination therapy including rituximab should be considered. For immunocompetent patients the chemotherapy regimens for MCD are based on lymphoma schedules such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) [51].