High-sensitivity immunocytologic analysis of neuroblastoma cells in paired blood and marrow samples

J Hematother. 1998 Aug;7(4):361-6. doi: 10.1089/scd.1.1998.7.361.


High-sensitivity immunocytochemistry was used to evaluate the relative frequency of neuroblastoma cells in bone marrow and peripheral blood in patients with neuroblastoma (NB). A total of 51 concomitant paired blood and marrow samples (102 total) from 35 patients with NB (age 4 months-31 years; stage 29 stage IV, 4 stage III, 2 stage IVS; 14 at diagnosis, 18 in relapse, 12 during treatment, and 7 off-therapy) were analyzed. Cytospins containing up to 10(6) cells each were prepared using the mononuclear cell (MNC) fraction. For immunocytologic staining, a primary mouse monoclonal anti-GD2 antibody (3F8), a secondary antimouse biotinylated antibody, and a streptavidin-alkaline phosphatase complex were used. A minimum of two cytospins containing a mean of 1.4 x 10(6) total MNCs was analyzed in addition to a negative and a positive control. No circulating tumor cells were detected when the concomitant marrow samples were negative or had <10 positive cells per 106 MNC (23 of 51 samples). Of the 18 marrow samples positive at 10-10,000 cells per 106 MNC, 6 had detectable NB cells in the corresponding blood sample, whereas for marrow samples with >10,000 NB cells per 10(6) MNC (1%), the concomitant blood sample was positive for 9 of the 10. When both marrow and blood samples were positive (15 BM-PB pairs), NB cell frequency was significantly lower in blood, with a mean difference of 2.14 logs (median 2.22, range -0.16-4.8, standard error 0.38). In patients with NB, circulating tumor cell frequencies seem to be substantially lower than in concomitant marrow samples, with a mean difference of >2 logs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Bone Marrow / pathology*
  • Brain Neoplasms / blood
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / pathology*
  • Child
  • Child, Preschool
  • Humans
  • Immunohistochemistry / methods*
  • Infant
  • Mice
  • Neoplasm, Residual
  • Neuroblastoma / blood
  • Neuroblastoma / diagnosis
  • Neuroblastoma / pathology*
  • Recurrence
  • Sensitivity and Specificity