Prognostic influence of minimal residual disease detected by flow cytometry and peripheral blood stem cell transplantation by CD34+ selection in childhood advanced neuroblastoma.
OBJECTIVE
To determine whether neuroblastoma (NB) minimal residual disease (MRD) in bone marrow (BM) detected by flow cytometry could predict prognosis and whether tumor cell purging by CD34(+) cell selection prior to transplantation will impact on disease-free survival.


METHODS
NB MRD in BM was evaluated by flow cytometry with CD45-FITC-/CD81-PE+/CD56-PECy5+ monoclonal antibodies cocktail. Peripheral blood stem cell (PBSC) was enriched via positive CD34(+) cell selection by magnetic-activated cell separation system (MACS).


RESULTS
Eleven of 31 patients with CD45(-)/CD81+/CD56+ cells by flow cytometry at diagnosis became negative after an average of four courses of chemotherapy. All 11 patients remained alive without evidence of disease. Thirteen of the 20 patients with positive MRD relapsed and 1 patient died from disease (mean 25.8 months). There was a significant difference between these two groups. MRD in BM was tested before PBSC transplantation (PBSCT) for 19 NB patients. Fourteen was negative, 4 of them relapsed and 10 patients remained alive without evidence of disease. Another 5 patients with positive MRD, all of them relapsed (mean 17 months after PBSCT) with a significant difference between these two groups. Fourteen of 19 PBSC were purged with CD34(+) selection procedure. Six of 14 relapsed (mean 18.43 months after PBSCT). Five patients did not purge for CD34(+) selection, and 3 of them relapsed with no significant difference between these two groups.


CONCLUSIONS
Positive MRD in BM after an average of four courses of chemotherapy and before PBSCT is an unfavorable factor for stage IV NB. CD34(+) selection purging for PBSCT may not improve the prognosis for children with neuroblastoma in advanced stage.
Cai
Jiao-Yang
JY
Department of Hematology/Oncology, XinHua Hospital/Shanghai Children's Medical Center, Shanghai Jiao Tong University, School of Medicine, 1678 DongFang Road, Shanghai 200127, China.
Tang
Yan-Jing
YJ
Jiang
Li-Min
LM
Pan
Ci
C
Chen
Jing
J
Tang
Jing-Yan
JY
D018952:Antigens, CD34 / Q000032:analysis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000188:drug therapy; D009447:Neuroblastoma / Q000175:diagnosis* / Q000188:drug therapy; D036102:Peripheral Blood Stem Cell Transplantation; D011379:Prognosis; D012008:Recurrence; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D018952:Antigens, CD34