Seeger R C, Reynolds C P, Gallego R, Stram D O, Gerbing R B, Matthay K K
Department of Pediatrics, University of Southern California School of Medicine and Childrens Hospital, Los Angeles, USA.
J Clin Oncol. 2000 Dec 15;18(24):4067-76. doi: 10.1200/JCO.2000.18.24.4067.
This study investigated the prognostic value of quantifying tumor cells in bone marrow and blood by immunocytology in children with high-risk, metastatic neuroblastoma.
Patients with stage IV neuroblastoma (N = 466) registered on Children's Cancer Group study 3891 received five cycles of induction chemotherapy and were randomized either to myeloablative chemoradiotherapy with autologous purged bone marrow rescue or to nonmyeloablative chemotherapy. Subsequently, they were randomized to 13-cis-retinoic acid or no further treatment. Immunocytologic analyses of bone marrow and blood were performed at diagnosis, week 4, week 12, bone marrow collection, and end induction and were correlated with tumor biology, clinical variables, treatment regimen, and event-free survival (EFS).
Immunocytology identified neuroblastoma cells in bone marrow of 81% at diagnosis, 55% at 4 weeks, 27% at 12 weeks, 19% at bone marrow collection, and 14% at end induction. Tumor cells were detected in blood of 58% at diagnosis and 5% at collection. There was an adverse effect on EFS of increasing tumor cell concentration in bone marrow at diagnosis (P =.04), at 12 weeks (P =.006), at bone marrow collection (P <.001), and at end induction (P =.07). Positive blood immunocytology at diagnosis was associated with decreased EFS (P: =.003). The prognostic impact of immunocytology was independent of morphologically detected bone marrow disease, MYCN status, and serum ferritin level in bivariate Cox analyses.
Immunocytologic quantification of neuroblastoma cells in bone marrow and blood at diagnosis and in bone marrow during induction chemotherapy provides prognostic information that can identify patients with very high-risk disease who should be considered for experimental therapy that might improve outcome.
本研究调查了通过免疫细胞学法对高危转移性神经母细胞瘤患儿骨髓和血液中的肿瘤细胞进行定量分析的预后价值。
登记参加儿童癌症组3891研究的IV期神经母细胞瘤患者（N = 466）接受了5个周期的诱导化疗，然后被随机分为接受清髓性放化疗及自体净化骨髓解救或非清髓性化疗。随后，他们又被随机分为接受13 - 顺式维甲酸治疗或不再接受进一步治疗。在诊断时、第4周、第12周、骨髓采集时以及诱导结束时对骨髓和血液进行免疫细胞学分析，并将其与肿瘤生物学、临床变量、治疗方案和无事件生存期（EFS）相关联。
免疫细胞学检测发现，诊断时81%的患者骨髓中有神经母细胞瘤细胞，第4周时为55%，第12周时为27%，骨髓采集时为19%，诱导结束时为14%。诊断时58%的患者血液中检测到肿瘤细胞，采集时为5%。诊断时（P = 0.04）、第12周时（P = 0.006）、骨髓采集时（P < 0.001）以及诱导结束时（P = 0.07），骨髓中肿瘤细胞浓度增加对EFS有不良影响。诊断时血液免疫细胞学阳性与EFS降低相关（P = 0.003）。在双变量Cox分析中，免疫细胞学的预后影响独立于形态学检测到的骨髓疾病、MYCN状态和血清铁蛋白水平。
在诊断时以及诱导化疗期间对骨髓和血液中的神经母细胞瘤细胞进行免疫细胞学定量分析可提供预后信息，能够识别出高危疾病患者，这些患者应考虑接受可能改善预后的实验性治疗。
