Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, People's Republic of China.
Med Oncol. 2012 Jun;29(2):1237-41. doi: 10.1007/s12032-011-9974-0. Epub 2011 May 10.
The association of prolonged rituximab therapy and hepatitis B virus (HBV) reactivation in diffuse large B-cell lymphoma (DLBCL) and the role of lamivudine prophylaxis remain undefined. The prevalence and mortality of HBV reactivation in HBsAg-positive patients with DLBCL undergoing rituximab-based treatment, who received prophylactic treatment with or without lamivudine, were retrospectively analyzed. From January 2003 to December 2009, there were 50 patients enrolled in the study, among of which 30 received the prophylactic treatment of lamivudine and 20 without prophylactic treatment of lamivudine. Among of the 50 patients, seven patients received further rituximab maintenance, once every 3 months for 2 years. Compared with lamivudine treatment group, it showed that there was significantly higher prevalence of HBV reactivation (60.0% vs 13.3%, P = .001), severe hepatitis (45.0% vs 6.7%, P = .004), and mortality (25.0% vs 3.3%, P = .032) in non-lamivudine prophylactic group; however, there was no statistically significant difference in the HBV DNA levels at reactivation (3.94 × 10(6) vs 8.30 × 10(5) copies/ml, P = .47) and the time from first dose of rituximab to HBV reactivation(207 vs 386 days, P = .28). For patients undergoing further rituximab maintanence treatment, the prevalence and mortality of HBV reactivation were 71.4 and 28.6%, respectively. The prevalence and mortality of HBV reactivation are 66.7% vs 75.0% (P = 1.00) and 0 vs 50.0% (P = .43) in lamivudine prophylactic and non-lamivudine prophylactic groups, respectively. The effect of lamivudine prophylaxis on preventing HBV reactivation was found to be less in patients undergoing longer duration of rituximab treatment. A longer duration of rituximab treatment contributed to higher morbidity and mortality of HBV reactivation in HbsAg-positive patients with DLBCL. Further study is warranted for the optimal management of hepatitis caused by HBV reactivation.
利妥昔单抗治疗时间延长与乙型肝炎病毒（HBV）再激活在弥漫性大 B 细胞淋巴瘤（DLBCL）中的相关性，以及拉米夫定预防治疗的作用仍不明确。本研究回顾性分析了 HBsAg 阳性的接受利妥昔单抗为基础治疗的 DLBCL 患者中，接受或未接受拉米夫定预防治疗的患者中 HBV 再激活的发生率和死亡率。从 2003 年 1 月至 2009 年 12 月，共有 50 例患者入组本研究，其中 30 例接受了拉米夫定预防治疗，20 例未接受拉米夫定预防治疗。在 50 例患者中，有 7 例接受了进一步的利妥昔单抗维持治疗，每 3 个月一次，共 2 年。与拉米夫定治疗组相比，非拉米夫定预防组 HBV 再激活的发生率更高（60.0% vs 13.3%，P =.001）、重型肝炎的发生率更高（45.0% vs 6.7%，P =.004）和死亡率更高（25.0% vs 3.3%，P =.032）；但两组 HBV DNA 再激活时的水平（3.94×10(6) vs 8.30×10(5)拷贝/ml，P =.47）和从利妥昔单抗首剂量到 HBV 再激活的时间（207 天 vs 386 天，P =.28）无统计学差异。对于接受进一步利妥昔单抗维持治疗的患者，HBV 再激活的发生率和死亡率分别为 71.4%和 28.6%。在接受拉米夫定预防治疗和未接受拉米夫定预防治疗的患者中，HBV 再激活的发生率和死亡率分别为 66.7% vs 75.0%（P = 1.00）和 0 vs 50.0%（P =.43）。在接受利妥昔单抗治疗时间较长的患者中，拉米夫定预防治疗对预防 HBV 再激活的效果较差。利妥昔单抗治疗时间延长与 HBsAg 阳性的 DLBCL 患者 HBV 再激活的发病率和死亡率升高有关。需要进一步研究以优化 HBV 再激活引起的肝炎的管理。
