Mones Jodi V, Coleman Morton, Kostakoglu Lale, Furman Richard R, Chadburn Amy, Shore Tsiporah B, Muss Daniel, Stewart Patricia, Kroll Stewart, Vallabhajosula Shankar, Goldsmith Stanley J, Leonard John P
Center for Lymphoma and Myeloma, Division of Hematology/Oncology, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY 10021, USA.
Leuk Lymphoma. 2007 Feb;48(2):342-8. doi: 10.1080/10428190601059720.
Radioimmunotherapy (RIT) with tositumomab and iodine 131 tositumomab can produce durable and complete responses in relapsed/refractory low-grade Non-Hodgkin's lymphoma. Patients with bone marrow involvement (BMI) with tumor >25% of the intertrabecular space are generally excluded from RIT because of risk of excessive hematologic toxicity. The authors conducted a dose-escalation study of tositumomab and iodine 131 tositumomab to determine whether RIT is feasible in this population. Patients had baseline BMI of >25% and platelet count of >or=150,000/mm3. In contrast to the usual 75 cGy total body dose of radiation, dose escalation of Iodine I 131 tositumomab began at a total body dose of 45 cGy, and increased to 55 cGy in a second cohort. Dose-limiting toxicity (DLT) was defined as absolute neutrophil count <500 cells/mm3 or platelets <25,000/mm3 for >17 days, or absolute neutrophil count <750/mm3 or platelets <50,000/mm3 for >24 days. Eleven subjects were enrolled (8 at 45 cGy and 3 at 55 cGy). Estimated BMI ranged from 30 to 65% (median approximately 40%). Patients had received a median of three prior chemotherapies (range 1 - 6). One of the six evaluable patients treated at 45 cGy experienced DLT. Three patients received 55 cGy, one had hematologic DLT concurrent with lymphoma progression and extensive BMI at relapse. Three of 11 (27%) patients received hematologic supportive care. Two patients had objective responses of 1 and 42.4+ months, respectively. RIT with attenuated dose iodine 131 tositumomab for patients with >25% BMI has acceptable toxicity and can result in lymphoma responses.
使用托西莫单抗和碘131托西莫单抗进行放射免疫治疗（RIT）可在复发/难治性低度非霍奇金淋巴瘤中产生持久且完全的缓解。骨髓受累（BMI）且肿瘤占小梁间隙>25%的患者通常因存在血液学毒性过高的风险而被排除在RIT治疗之外。作者开展了一项托西莫单抗和碘131托西莫单抗的剂量递增研究，以确定RIT在该人群中是否可行。患者的基线BMI>25%且血小板计数≥150,000/mm³。与通常75 cGy的全身照射剂量不同，碘131托西莫单抗的剂量递增从45 cGy的全身剂量开始，并在第二个队列中增加到55 cGy。剂量限制性毒性（DLT）定义为绝对中性粒细胞计数<500个细胞/mm³或血小板<25,000/mm³持续超过17天，或绝对中性粒细胞计数<750/mm³或血小板<50,000/mm³持续超过24天。共纳入11名受试者（45 cGy组8名，55 cGy组3名）。估计的BMI范围为30%至65%（中位数约为40%）。患者既往接受化疗的中位数为3次（范围1 - 6次）。在45 cGy剂量下接受治疗的6名可评估患者中有1名出现DLT。3名患者接受了55 cGy治疗，其中1名在淋巴瘤进展和复发时出现广泛BMI的同时发生了血液学DLT。11名患者中有3名（27%）接受了血液学支持治疗。2名患者分别获得了1个月和42.4 +个月的客观缓解。对于BMI>25%的患者，使用剂量降低的碘131托西莫单抗进行RIT具有可接受的毒性，并可导致淋巴瘤缓解。
