Rc. Seeger et al., Quantitative tumor cell content of bone marrow and blood as a predictor ofoutcome in stage IV neuroblastoma: A Children's Cancer Group Study, J CL ONCOL, 18(24), 2000, pp. 4067-4076
Purpose: 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 and Methods: Patients with stage IV neuroblastoma (N = 466) regist
ered on Children's Cancer Group study 3891 received five cycles of inductio
n chemotherapy and were randomized either to myeloablative chemoradiotherap
y with autologous purged bone marrow rescue or to nonmyeloablative chemothe
rapy. Subsequently, they were randomized to 13-cis-retinoic acid or no furt
her treatment. Immunocytologic analyses of bone marrow and blood were perfo
rmed at diagnosis, week 4, week 12, bone marrow collection, and end inducti
on and were correlated with tumor biology, clinical variables, treatment re
gimen, and event-free survival (EFS).
Results: Immunocytology identified neuroblastoma cells in bone marrow of 81
% at diagnosis, 55% at 4 weeks, 27% at 12 weeks, 19% at bone marrow collect
ion, 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 incr
easing 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 d
ecreased EFS (P =.003). The prognostic impact of immunocytology was indepen
dent of morphologically detected bone marrow disease, MYCN status, and seru
m ferritin level in bivariate Cox analyses.
Conclusion: Immunocytologic quantification of neuroblastoma cells in bone m
arrow and blood at diagnosis and in bone marrow during induction chemothera
py provides prognostic information that can identify patients with very hig
h-risk disease who should be considered for experimental therapy that might
improve outcome. J Clin Oncol 18:4061-4076. (C) 2000 by American Society o
f Clinical Oncology.