Kushner B H, Gulati S C, Kwon J H, O'Reilly R J, Exelby P R, Cheung N K
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cancer. 1991 Jul 15;68(2):242-7. doi: 10.1002/1097-0142(19910715)68:2<242::aid-cncr2820680204>3.0.co;2-p.
Long-term results are presented of 28 patients who were diagnosed with neuroblastoma at more than 12 months of age and who received melphalan 180 mg/m2 (n = 6) or 240 mg/m2 (n = 22) to consolidate remissions of Stage IV disease or to control refractory disease. Twenty-four patients also received dianhydrogalactitol 180 to 240 mg/m2, and 11 received total body irradiation 450 to 600 cGy. Autologous bone marrow transplantation (ABMT) was performed with marrow that was unpurged (n = 2) or purged ex vivo (n = 26) with 6-hydroxydopamine (6-OHDA) 20 micrograms/ml plus ascorbate 200 micrograms/ml. The median time to an absolute neutrophil count of 500/microliters was 21 days and to self-sustaining platelet counts more than 20,000/microliters, 28 days. One patient required infusion of unpurged reserve marrow. Two groups of patients underwent ABMT: (1) 17 patients (Group I) who were in first remission a median of 7 months after diagnosis; and (2) 11 patients (Group II) who had refractory disease or were in second remission. For Group I, event-free survival was 29% at 12 months and 6% at 24 months post-ABMT. All Group II patients died of disease or ABMT-related toxicity. Overall, of the 28 patients, one is a long-term relapse-free survivor; five died of ABMT-related toxicity; ten patients with tumors present at ABMT had progressive disease within 6 months of ABMT; and 12 patients with no measurable disease at ABMT relapsed 4 to 32 months (median, 12) post-ABMT. Among the latter, six relapses involved the primary site, and six were restricted to distant sites. These results--in accord with the long-term outcome in other series--suggest that for neuroblastoma high-dose melphalan cannot be relied on to ablate residual disease or to salvage patients with refractory tumors. In addition, the pattern of relapse in several patients could be explained by infusion of incompletely purged autografts; this would support recent laboratory evidence that 6-OHDA/ascorbate is a suboptimal purging method.
本文报告了28例12个月以上诊断为神经母细胞瘤的患者的长期结果。这些患者接受了美法仑180mg/m²（n = 6）或240mg/m²（n = 22）治疗，以巩固IV期疾病的缓解或控制难治性疾病。24例患者还接受了二脱水半乳糖醇180至240mg/m²治疗，11例接受了全身照射450至600cGy。自体骨髓移植（ABMT）使用未净化的骨髓（n = 2）或用20μg/ml 6-羟基多巴胺（6-OHDA）加200μg/ml抗坏血酸进行体外净化的骨髓（n = 26）。绝对中性粒细胞计数达到500/μl的中位时间为21天，血小板计数达到自我维持水平超过20,000/μl的中位时间为28天。1例患者需要输注未净化的备用骨髓。两组患者接受了ABMT：（1）17例患者（I组）在诊断后中位7个月处于首次缓解期；（2）11例患者（II组）患有难治性疾病或处于第二次缓解期。对于I组，ABMT后12个月无事件生存率为29%，24个月为6%。II组所有患者均死于疾病或与ABMT相关的毒性。总体而言，28例患者中，1例为长期无复发生存者；5例死于与ABMT相关的毒性；10例ABMT时存在肿瘤的患者在ABMT后6个月内疾病进展；12例ABMT时无可测量疾病的患者在ABMT后4至32个月（中位，12个月）复发。在后者中，6例复发涉及原发部位，6例局限于远处部位。这些结果——与其他系列的长期结果一致——表明，对于神经母细胞瘤，高剂量美法仑不能依赖于消除残留疾病或挽救难治性肿瘤患者。此外，几名患者的复发模式可以通过输注未完全净化的自体移植物来解释；这将支持最近的实验室证据，即6-OHDA/抗坏血酸是一种次优的净化方法。
