Horwitz Steven M, Negrin Robert S, Blume Karl G, Breslin Sheila, Stuart Monic J, Stockerl-Goldstein Keith E, Johnston Laura J, Wong Ruby M, Shizuru Judith A, Horning Sandra J
Division of Oncology, Stanford University Medical Center, Ste 202, 1000 Welch Rd, Palo Alto, CA 94304, USA.
Blood. 2004 Feb 1;103(3):777-83. doi: 10.1182/blood-2003-04-1257. Epub 2003 Aug 7.
Based on the favorable safety profile and the independent activity of rituximab in B-cell lymphoma, we evaluated its efficacy and toxicity after high-dose therapy (HDT) and autologous hematopoietic cell transplantation (HCT). Thirty-five patients with diffuse large cell (25 patients), mantle cell (3 patients), transformed (3 patients), or other (4 patients) subtypes of B-cell lymphoma received HDT followed by a purged autologous graft. The rituximab schedule was 4 weekly infusions (375 mg/m(2)) starting at day 42 after HCT and, for patients 5 to 35, a second 4-week course 6 months after HCT. All planned therapy was completed in 29 patients. With 30 months' median follow-up, the 2-year event-free survival (EFS) rate was 83% and the overall survival (OS) rate was 88%. For 21 patients with relapsed or refractory large cell lymphoma, the EFS rate was 81% and the OS rate was 85%. Grades 3 to 4 neutropenia occurred in 19 (54%) patients. A prospective study of immune reconstitution included measurements of lymphocyte subsets, immunoglobulins, and response to vaccination. Serious infections were not observed despite delayed B-cell recovery in all patients and suppressed immunoglobulin G (IgG) levels and low pneumococcus antibody titers in a subset. Rituximab after HDT and HCT is feasible, and these phase 2 data support the current US Intergroup phase 3 trial in recurrent/refractory diffuse large cell lymphoma.
基于利妥昔单抗在B细胞淋巴瘤中良好的安全性和独立活性，我们评估了其在大剂量治疗（HDT）及自体造血细胞移植（HCT）后的疗效和毒性。35例弥漫大细胞（25例）、套细胞（3例）、转化型（3例）或其他（4例）亚型的B细胞淋巴瘤患者接受了HDT，随后进行净化的自体移植物移植。利妥昔单抗的给药方案为在HCT后第42天开始每周静脉输注4次（375 mg/m²），对于5至35号患者，在HCT后6个月进行第二个4周疗程。29例患者完成了所有计划的治疗。中位随访30个月，2年无事件生存率（EFS）为83%，总生存率（OS）为88%。对于21例复发或难治性大细胞淋巴瘤患者，EFS为81%，OS为85%。19例（54%）患者发生3至4级中性粒细胞减少。一项关于免疫重建的前瞻性研究包括淋巴细胞亚群、免疫球蛋白的测量以及对疫苗接种的反应。尽管所有患者的B细胞恢复延迟，部分患者免疫球蛋白G（IgG）水平受到抑制且肺炎球菌抗体滴度较低，但未观察到严重感染。HDT和HCT后使用利妥昔单抗是可行的，这些2期数据支持美国目前针对复发/难治性弥漫大细胞淋巴瘤的3期组间试验。
