Devizzi Liliana, Guidetti Anna, Tarella Corrado, Magni Michele, Matteucci Paola, Seregni Ettore, Chiesa Carlo, Bombardieri Emilio, Di Nicola Massimo, Carlo-Stella Carmelo, Gianni Alessandro M
Cristina Gandini Medical Oncology and Department of Nuclear Medicine, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, Milan, Italy.
J Clin Oncol. 2008 Nov 10;26(32):5175-82. doi: 10.1200/JCO.2008.16.8294. Epub 2008 Oct 14.
To develop high-dose myeloablative therapy for CD20(+) non-Hodgkin's lymphoma (NHL) as a safe and widely applicable regimen.
Patients with relapsed/refractory (n = 25) or de novo high-risk (n = 5) NHL received one myeloablative dose of yttrium-90 ((90)Y)-ibritumomab tiuxetan after five chemotherapy courses, including three cycles of anthracycline- or platinum-containing regimens, one cycle of cyclophosphamide (4 to 7 g/m(2)), and one cycle of cytarabine (12 to 24 g/m(2)). The only exclusion criteria were CNS lymphoma and Eastern Cooperative Oncology Group performance status of more than 3. Primary end points were overall survival (OS) and event-free survival (EFS). Secondary end points included safety and applicability of high-dose (90)Y-ibritumomab tiuxetan. To minimize hematologic toxicity, stem cells were reinfused at days 7 and 14 after (90)Y-ibritumomab tiuxetan.
Thirteen patients received (90)Y-ibritumomab tiuxetan 0.8 mCi/kg, and 17 patients received 1.2 mCi/kg. At 1.2 mCi/kg, the radiation absorbed by critical nonhematologic organs approached the protocol-defined upper safety limit, defining this as the recommended dose for subsequent studies. Hematologic toxicity was mild to moderate and of short duration. Infections occurred in 27% of patients (none had a severity grade greater than 3). After a median observation time of 30 months (range, 22 to 48 months), no myeloid secondary malignancy or chromosomal abnormality was observed, the OS rate was 87%, and the EFS rate was 69%.
High-dose (90)Y-ibritumomab tiuxetan seems to be an innovative myeloablative regimen with unprecedented short-term toxicity and wide applicability. Further studies are required to assess its long-term safety and role in the management of CD20(+) NHL.
开发用于CD20(+)非霍奇金淋巴瘤（NHL）的大剂量清髓疗法，作为一种安全且广泛适用的方案。
复发/难治性（n = 25）或初治高危（n = 5）NHL患者在接受五个化疗疗程后接受一剂清髓剂量的钇-90（90Y）-替伊莫单抗，这五个化疗疗程包括三个周期的含蒽环类药物或铂类药物的方案、一个周期的环磷酰胺（4至7 g/m²）以及一个周期的阿糖胞苷（12至24 g/m²）。唯一的排除标准是中枢神经系统淋巴瘤和东部肿瘤协作组体能状态大于3。主要终点是总生存期（OS）和无事件生存期（EFS）。次要终点包括大剂量90Y-替伊莫单抗的安全性和适用性。为使血液学毒性降至最低，在90Y-替伊莫单抗给药后的第7天和第14天回输干细胞。
13例患者接受0.8 mCi/kg的90Y-替伊莫单抗，17例患者接受1.2 mCi/kg。在1.2 mCi/kg剂量时，关键非血液学器官吸收的辐射接近方案规定的安全上限，因此将此剂量定义为后续研究的推荐剂量。血液学毒性为轻度至中度，持续时间短。27%的患者发生感染（无一例严重程度超过3级）。经过30个月（范围为22至48个月）的中位观察期后，未观察到髓系继发性恶性肿瘤或染色体异常，OS率为87%，EFS率为69%。
大剂量90Y-替伊莫单抗似乎是一种创新的清髓方案，具有前所未有的短期毒性和广泛适用性。需要进一步研究来评估其长期安全性以及在CD20(+) NHL治疗中的作用。
