Minimal residual disease detection in autologous stem cell grafts from patients with high risk neuroblastoma.
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.


METHODS
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.
Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands and Landsteiner Laboratory of the AMC, University of Amsterdam, Amsterdam, The Netherlands.|Department of Pediatric Oncology, Emma Children's Hospital, Academical Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Esther M
EM
van Wezel
Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands and Landsteiner Laboratory of the AMC, University of Amsterdam, Amsterdam, The Netherlands.|Department of Pediatric Oncology, Emma Children's Hospital, Academical Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Janine
J
Stutterheim
Department of Pediatric Oncology, Emma Children's Hospital, Academical Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Florentien
F
Vree
Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands and Landsteiner Laboratory of the AMC, University of Amsterdam, Amsterdam, The Netherlands.
Lily
L
Zappeij-Kannegieter
Children's Hospital, University of Cologne, Pediatric Hematology and Oncology, Cologne, Germany.
Boris
B
Decarolis
Children's Hospital, University of Cologne, Pediatric Hematology and Oncology, Cologne, Germany.
Barbara
B
Hero
Children's Hospital, University of Cologne, Pediatric Hematology and Oncology, Cologne, Germany.
Frank
F
Berthold
Children's Hospital, University of Cologne, Pediatric Hematology and Oncology, Cologne, Germany.
Roswitha
R
Schumacher-Kuckelkorn
Children's Hospital, University of Cologne, Pediatric Hematology and Oncology, Cologne, Germany.
Thorsten
T
Simon
Department of Biostatistics, Leiden University Medical Center and Dutch Childhood Oncology Group, The Hague, Netherlands.
Marta
M
Fiocco
Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands and Landsteiner Laboratory of the AMC, University of Amsterdam, Amsterdam, The Netherlands.
Carlijn
C
Voermans
Department of Pediatric Oncology, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, The Netherlands.
Max M
MM
van Noesel
Department of Pediatric Oncology, Emma Children's Hospital, Academical Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Huib N
HN
Caron
Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands and Landsteiner Laboratory of the AMC, University of Amsterdam, Amsterdam, The Netherlands.
C Ellen
CE
van der Schoot
Department of Pediatric Oncology, Emma Children's Hospital, Academical Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Godelieve A M
GA
Tytgat
D000293:Adolescent; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D018365:Neoplasm, Residual / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D009447:Neuroblastoma / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D011978:Receptors, Nicotinic / Q000235:genetics; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D014157:Transcription Factors / Q000235:genetics; D014182:Transplantation, Autologous
D001142:Aromatic-L-Amino-Acid Decarboxylases; D018398:Homeodomain Proteins; D011978:Receptors, Nicotinic; D014157:Transcription Factors; C109220:NBPhox protein; C000595218:DDC protein, human
MRD; PBSC; autologous stem cell transplantation; high risk; neuroblastoma