Liu S Y, Eary J F, Petersdorf S H, Martin P J, Maloney D G, Appelbaum F R, Matthews D C, Bush S A, Durack L D, Fisher D R, Gooley T A, Bernstein I D, Press O W
Department of Medicine, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, USA.
J Clin Oncol. 1998 Oct;16(10):3270-8. doi: 10.1200/JCO.1998.16.10.3270.
Radioimmunotherapy (RIT) is a promising treatment approach for B-cell lymphomas. This is our first opportunity to report long-term follow-up data and late toxicities in 29 patients treated with myeloablative doses of iodine-131-anti-CD20 antibody (anti-B1) and autologous stem-cell rescue.
Trace-labeled biodistribution studies first determined the ability to deliver higher absorbed radiation doses to tumor sites than to lung, liver, or kidney at varying amounts of anti-B1 protein (0.35, 1.7, or 7 mg/kg). Twenty-nine patients received therapeutic infusions of single-agent (131)I-anti-B1, given at the protein dose found optimal in the biodistribution study, labeled with amounts of (131)I (280 to 785 mCi [10.4 to 29.0 GBq]) calculated to deliver specific absorbed radiation doses to the normal organs, followed by autologous stem-cell support.
Major responses occurred in 25 patients (86%), with 23 complete responses (CRs; 79%). The nonhematopoietic dose-limiting toxicity was reversible cardiopulmonary insufficiency, which occurred in two patients at RIT doses that delivered > or = 27 Gy to the lungs. With a median follow-up time of 42 months, the estimated overall and progression-free survival rates are 68% and 42%, respectively. Currently, 14 of 29 patients remain in unmaintained remissions that range from 27+ to 87+ months after RIT. Late toxicities have been uncommon except for elevated thyroid-stimulating hormone (TSH) levels found in approximately 60% of the subjects. Two patients developed second malignancies, but none have developed myelodysplasia (MDS).
Myeloablative (131)I-anti-B1 RIT is relatively well tolerated when given with autologous stem-cell support and often results in prolonged remission durations with few late toxicities.
放射免疫疗法（RIT）是一种有前景的B细胞淋巴瘤治疗方法。这是我们首次报告29例接受大剂量碘-131-抗CD20抗体（抗B1）及自体干细胞救援治疗患者的长期随访数据和晚期毒性反应。
微量标记生物分布研究首先确定了在不同剂量抗B1蛋白（0.35、1.7或7mg/kg）下，向肿瘤部位输送比肺、肝或肾更高吸收辐射剂量的能力。29例患者接受了单药（131）I-抗B1的治疗性输注，剂量为生物分布研究中发现的最佳蛋白剂量，标记的（131）I量（280至785mCi[10.4至29.0GBq]）经计算可向正常器官输送特定吸收辐射剂量，随后给予自体干细胞支持。
25例患者（86%）出现主要反应，其中23例完全缓解（CR；79%）。非造血剂量限制性毒性为可逆性心肺功能不全，2例患者在RIT剂量下出现，该剂量向肺部输送≥27Gy。中位随访时间为42个月，估计总生存率和无进展生存率分别为68%和42%。目前，29例患者中有14例在RIT后处于未维持缓解状态，缓解期从27 +至87 +个月不等。除约60%的受试者促甲状腺激素（TSH）水平升高外，晚期毒性反应并不常见。2例患者发生了第二原发恶性肿瘤，但均未发生骨髓增生异常综合征（MDS）。
大剂量（131）I-抗B1 RIT联合自体干细胞支持时耐受性相对良好，且常导致缓解期延长，晚期毒性反应较少。
