TY - JOUR
T1 - Minimal residual disease detection in autologous stem cell grafts from patients with high risk neuroblastoma
AU - GPOH MRD Study Group
AU - van Wezel, Esther M
AU - Stutterheim, Janine
AU - Vree, Florentien
AU - Zappeij-Kannegieter, Lily
AU - Decarolis, Boris
AU - Hero, Barbara
AU - Berthold, Frank
AU - Schumacher-Kuckelkorn, Roswitha
AU - Simon, Thorsten
AU - Fiocco, Marta
AU - Voermans, Carlijn
AU - van Noesel, Max M
AU - Caron, Huib N
AU - van der Schoot, C Ellen
AU - Tytgat, Godelieve A M
N1 - © 2015 Wiley Periodicals, Inc.
PY - 2015/8
Y1 - 2015/8
N2 - BACKGROUND: The clinical significance of minimal residual disease (MRD) detected by real-time quantitative PCR (qPCR) in autologous stem cell grafts in high risk neuroblastoma is still controversial. In this retrospective multicenter study, autologous stem cell grafts of a large cohort were studied using a panel of RNA markers.PROCEDURE: From 104 patients with high risk neuroblastoma, who received autologous stem cell transplantation as first line treatment, 66 peripheral blood stem cells (PBSC) and 38 CD34+ selected grafts were retrospectively collected at 2 Dutch and 12 German centers between 1997 and 2010. To investigate graft contamination qPCR was performed by using 5 neuroblastoma specific markers (PHOX2B, TH, DDC, CHRNA3, and DBH).RESULTS: In PBSC 6/66 (9%) and in CD34+ selected grafts 3/38 (8%) samples were contaminated. Graft contamination was not associated with an unfavorable outcome (5-years OS, 66% vs. 50.5%; P=0.6 and 5-years EFS, 22% vs. 35%, P=0.7). In multivariate Cox analysis BM MRD at time of harvest was significantly associated with survival (P=0.008 OS and P=0.002 EFS), but graft contamination was still not associated with an unfavorable outcome (P=0.9 OS and P=1 EFS).CONCLUSIONS: Graft contamination is very infrequent in this retrospective cohort of patients with no or minimal BM disease prior to stem cell collection and does not influence outcome in univariate and multivariate analysis. The presence of MRD at time of harvest is a strong outcome predictor. However, these results will have to be verified in a large prospective study.
AB - BACKGROUND: The clinical significance of minimal residual disease (MRD) detected by real-time quantitative PCR (qPCR) in autologous stem cell grafts in high risk neuroblastoma is still controversial. In this retrospective multicenter study, autologous stem cell grafts of a large cohort were studied using a panel of RNA markers.PROCEDURE: From 104 patients with high risk neuroblastoma, who received autologous stem cell transplantation as first line treatment, 66 peripheral blood stem cells (PBSC) and 38 CD34+ selected grafts were retrospectively collected at 2 Dutch and 12 German centers between 1997 and 2010. To investigate graft contamination qPCR was performed by using 5 neuroblastoma specific markers (PHOX2B, TH, DDC, CHRNA3, and DBH).RESULTS: In PBSC 6/66 (9%) and in CD34+ selected grafts 3/38 (8%) samples were contaminated. Graft contamination was not associated with an unfavorable outcome (5-years OS, 66% vs. 50.5%; P=0.6 and 5-years EFS, 22% vs. 35%, P=0.7). In multivariate Cox analysis BM MRD at time of harvest was significantly associated with survival (P=0.008 OS and P=0.002 EFS), but graft contamination was still not associated with an unfavorable outcome (P=0.9 OS and P=1 EFS).CONCLUSIONS: Graft contamination is very infrequent in this retrospective cohort of patients with no or minimal BM disease prior to stem cell collection and does not influence outcome in univariate and multivariate analysis. The presence of MRD at time of harvest is a strong outcome predictor. However, these results will have to be verified in a large prospective study.
KW - Adolescent
KW - Aromatic-L-Amino-Acid Decarboxylases/genetics
KW - Child
KW - Child, Preschool
KW - Homeodomain Proteins/genetics
KW - Humans
KW - Infant
KW - Neoplasm, Residual/pathology
KW - Neoplastic Cells, Circulating/pathology
KW - Neuroblastoma/pathology
KW - Real-Time Polymerase Chain Reaction
KW - Receptors, Nicotinic/genetics
KW - Retrospective Studies
KW - Stem Cell Transplantation
KW - Transcription Factors/genetics
KW - Transplantation, Autologous
UR - http://www.scopus.com/inward/record.url?scp=84932195586&partnerID=8YFLogxK
U2 - 10.1002/pbc.25507
DO - 10.1002/pbc.25507
M3 - Article
C2 - 25939774
SN - 1545-5009
VL - 62
SP - 1368
EP - 1373
JO - Pediatric blood & cancer
JF - Pediatric blood & cancer
IS - 8
ER -