Cheung N K, Kushner B H, Cheung I Y, Kramer K, Canete A, Gerald W, Bonilla M A, Finn R, Yeh S J, Larson S M
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
J Clin Oncol. 1998 Sep;16(9):3053-60. doi: 10.1200/JCO.1998.16.9.3053.
To eradicate minimal residual disease with anti-G(D2) monoclonal antibody 3F8 in stage 4 neuroblastoma (NB) diagnosed at more than 1 year of age.
Thirty-four patients were treated with 3F8 at the end of chemotherapy. Most had either bone marrow (n=31) or distant bony metastases (n=29). Thirteen patients were treated at second or subsequent remission (group I) and 12 patients in this group had a history of progressive/persistent disease after bone marrow transplantation (BMT); 21 patients were treated in first remission following N6 chemotherapy (group II).
Before 3F8 treatment, 23 patients were in complete remission CR, eight in very good partial remission (VGPR), one in partial remission (PR), and two had microscopic foci in marrow. Twenty-five had evidence of NB by at least one measurement of occult/minimal tumor (iodine 131[(131)I]-3F8 imaging, marrow immunocytology, or marrow reverse-transcriptase polymerase chain reaction [RT-PCR]). Acute self-limited toxicities of 3F8 treatment were severe pain, fever, urticaria, and reversible decreases in blood counts and serum complement levels. There was evidence of response by immunocytology (six of nine), by GAGE RT-PCR (seven of 12), and by (131)I-3F8 scans (six of six). Fourteen patients are alive and 13 (age 1.8 to 7.4 years at diagnosis) are progression-free (40 to 130 months from the initiation of 3F8 treatment) without further systemic therapy, none with late neurologic complications. A transient anti-mouse response or the completion of four 3F8 cycles was associated with significantly better survival.
Despite high-risk nature of stage 4 NB, long-term remission without autologous (A)BMT can be achieved with 3F8 treatment. Its side effects were short-lived and manageable. The potential benefits of 3F8 in consolidating remission warrant further investigations.
使用抗G(D2)单克隆抗体3F8清除1岁以上诊断为4期神经母细胞瘤（NB）的微小残留病。
34例患者在化疗结束时接受3F8治疗。大多数患者有骨髓转移（n = 31）或远处骨转移（n = 29）。13例患者在第二次或后续缓解期接受治疗（I组），该组中有12例患者在骨髓移植（BMT）后有疾病进展/持续的病史；21例患者在N6化疗后的首次缓解期接受治疗（II组）。
在3F8治疗前，23例患者处于完全缓解（CR），8例处于非常好的部分缓解（VGPR），1例处于部分缓解（PR），2例在骨髓中有微小病灶。25例患者通过至少一项隐匿/微小肿瘤测量（碘131[(131)I]-3F8显像、骨髓免疫细胞学或骨髓逆转录酶聚合酶链反应[RT-PCR]）有NB证据。3F8治疗的急性自限性毒性包括严重疼痛、发热、荨麻疹以及血细胞计数和血清补体水平的可逆性下降。有免疫细胞学反应证据（9例中的6例）、GAGE RT-PCR反应证据（12例中的7例）和(131)I-3F8扫描反应证据（6例中的6例）。14例患者存活，13例（诊断时年龄1.8至7.4岁）无疾病进展（自3F8治疗开始起40至130个月），无需进一步全身治疗，均无晚期神经并发症。短暂的抗小鼠反应或完成四个3F8周期与显著更好的生存率相关。
尽管4期NB具有高风险性质，但3F8治疗可实现无需自体（A）BMT的长期缓解。其副作用短暂且可控。3F8在巩固缓解方面的潜在益处值得进一步研究。
