DeNardo G L, DeNardo S J, Macey D J, Shen S, Kroger L A
University of California Davis Medical Center, Sacramento 95816.
Cancer. 1994 Feb 1;73(3 Suppl):1038-48. doi: 10.1002/1097-0142(19940201)73:3+<1038::aid-cncr2820731343>3.0.co;2-8.
The radiation dose-limiting toxicity from radioimmunotherapy has been myelotoxicity in the absence of bone marrow reconstitution (transplantation). Myelotoxicity can be assessed directly by biopsy examination of the bone marrow and indirectly by peripheral blood counts. In patients with B-cell malignancies, thrombocytopenia has been the initial and most severe manifestation of 131I-Lym-1 radiation toxicity from treatment. Manifestations of myelotoxicity varied greatly among the patients and from one treatment dose to another in the same patient, suggesting that additional factors were present. There was an increased likelihood of Grade 3-4 hematopoietic toxicity after 131I-Lym-1 treatment if the patient had peripheral blood cell abnormalities before undergoing 131I-Lym-1 treatment. Fractionation of the total 131I-Lym-1 dose was associated with less toxicity. In many patients, myelotoxicity could not be explained by marrow radiation dose (0.36 +/- 0.13 rads per administered mCi) from 131I-Lym-1 in the blood and body alone. Bone marrow examination and 131I-Lym-1 imaging usually provided evidence for additional marrow radiation from 131I-Lym-1-targeting of marrow malignancy and also for residual toxic effects from prior treatment in these patients. Immunohistologic and imaging examination of the bone marrow performed with the intended treatment antibody allowed assessment of extent of marrow malignancy and prediction of degree of myelotoxicity from subsequent treatment. Treatment programs (and protocols) for radioimmunotherapy should incorporate these methods into the decision process. Larger amounts of 131I-Lym-1 can be used in patients selected to have relatively normal peripheral blood cell counts and normocellular bone marrows uninvolved by the malignancy. These observations appear to be relevant to the maximum tolerated dose in radioimmunotherapy for other malignancies as well.
在未进行骨髓重建（移植）的情况下，放射免疫疗法的辐射剂量限制毒性一直是骨髓毒性。骨髓毒性可通过骨髓活检检查直接评估，也可通过外周血细胞计数间接评估。在B细胞恶性肿瘤患者中，血小板减少一直是131I-Lym-1治疗所致辐射毒性的初始且最严重表现。骨髓毒性的表现因患者个体差异很大，且同一患者在不同治疗剂量下也有所不同，这表明存在其他影响因素。如果患者在接受131I-Lym-1治疗前外周血细胞异常，那么接受131I-Lym-1治疗后出现3-4级造血毒性的可能性会增加。131I-Lym-1总剂量的分次给药与较低的毒性相关。在许多患者中，仅血液和体内131I-Lym-1的骨髓辐射剂量（每给药毫居里0.36±0.13拉德）无法解释骨髓毒性。骨髓检查和131I-Lym-1成像通常能提供证据，证明131I-Lym-1靶向骨髓恶性肿瘤会带来额外的骨髓辐射，也能证明这些患者先前治疗产生的残留毒性作用。使用预期治疗抗体对骨髓进行免疫组织学和成像检查，有助于评估骨髓恶性肿瘤的程度，并预测后续治疗的骨髓毒性程度。放射免疫疗法的治疗方案应将这些方法纳入决策过程。对于外周血细胞计数相对正常且骨髓未受恶性肿瘤累及的正常细胞骨髓的患者，可使用更大剂量的131I-Lym-1。这些观察结果似乎也与其他恶性肿瘤放射免疫疗法的最大耐受剂量相关。
