DeNardo G L, Lewis J P, DeNardo S J, O'Grady L F
Division of Hematology and Oncology, School of Medicine, University of California, Davis.
Cancer. 1994 Mar 1;73(5):1425-32. doi: 10.1002/1097-0142(19940301)73:5<1425::aid-cncr2820730517>3.0.co;2-d.
Although chronic lymphocytic leukemia is usually indolent and responsive to treatment early in its course, later stages are characterized by inexorable progression despite standard treatment so that new therapies are needed. Because malignant lymphocytes have characteristic surface antigens, the role of monoclonal antibodies is worthy of intensive investigation.
Five patients with refractory chronic lymphocytic leukemia were treated with a novel radioimmunoconjugate, 131I-Lym-1, reactive with antigenic sites on malignant B lymphocytes. 131I-Lym-1 was given to the patients in doses of 20-65 mCi at 2-6-week intervals.
Radioimmunoconjugate treatment using 131I-Lym-1 induced objective responses with dramatic reduction in lymphadenopathy and, in two patients, normalization of leukocyte counts. However, lymphocytes continued to be the dominate cells in the peripheral blood and bone marrow. Because these patients had advanced disease associated with preexisting peripheral cytopenias, requiring repeated transfusions, and recurrent infections, hematopoietic toxicity from 131I-Lym-1 was difficult to evaluate. The patients seemed to tolerate at least 200 mCi of 131I given at these dose levels, and intervals before toxicity added to their existing peripheral cytopenias. Radionuclide doses in excess of 300 mCi aggravated preexisting thrombocytopenia.
Although the data raise the possibility of a role for 131I-Lym-1 monoclonal antibody in the treatment of chronic lymphocytic leukemia, strategies to address the radionuclide-induced thrombocytopenia are essential before this intervention can become a clinically useful therapeutic modality for chronic lymphocytic leukemia.
尽管慢性淋巴细胞白血病通常进展缓慢，病程早期对治疗有反应，但晚期的特点是即便采用标准治疗仍会不可阻挡地进展，因此需要新的治疗方法。由于恶性淋巴细胞具有特征性的表面抗原，单克隆抗体的作用值得深入研究。
5例难治性慢性淋巴细胞白血病患者接受了一种新型放射免疫偶联物131I-Lym-1治疗，该偶联物可与恶性B淋巴细胞上的抗原位点发生反应。以20 - 65毫居里的剂量，每隔2 - 6周给患者注射一次131I-Lym-1。
使用131I-Lym-1进行放射免疫偶联物治疗可诱导客观反应，淋巴结病显著减轻，2例患者白细胞计数恢复正常。然而，淋巴细胞仍然是外周血和骨髓中的主要细胞。由于这些患者患有晚期疾病，伴有先前存在的外周血细胞减少，需要反复输血以及反复感染，因此难以评估131I-Lym-1的造血毒性。在这些剂量水平下，患者似乎能够耐受至少200毫居里的131I，且在毒性增加到其现有的外周血细胞减少之前有一定的间隔时间。超过300毫居里的放射性核素剂量会加重先前存在的血小板减少。
尽管这些数据提示131I-Lym-1单克隆抗体在慢性淋巴细胞白血病治疗中可能发挥作用，但在这种干预措施成为慢性淋巴细胞白血病临床上有用的治疗方式之前，解决放射性核素诱导的血小板减少的策略至关重要。
