Tumour cell contamination of autologous stem cells grafts in high-risk neuroblastoma: the good news?

Handgretinger, Rupert; Leung, Wing; Ihm, K; Lang, Peter; Klingebiel, Thomas; Niethammer, D.

doi:10.1038/sj.bjc.6601014

Cited by 31 publications

(25 citation statements)

References 31 publications

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“…The results presented here do not confirm those by Handgretinger et al (15) who showed a favorable effect of the infusion of tumor cell -contaminated CD34 + cells on stage IV patients survival. In that study (15), contaminant neuroblasts were detected by anti-GD2 immunofluorescence, and it was suggested that systemic administration of low number of tumor cells during hematopoietic reconstitution induced an effective anti-neuroblastoma immune response.…”

Section: Discussioncontrasting

confidence: 56%

“…In that study (15), contaminant neuroblasts were detected by anti-GD2 immunofluorescence, and it was suggested that systemic administration of low number of tumor cells during hematopoietic reconstitution induced an effective anti-neuroblastoma immune response. Discrepancy between our and Handgretinger's results (15) may be due to cross antigen presentation of certain CD34 epitopes found in primary neuroblastoma cells and cell lines (22,23).…”

Section: Discussionmentioning

confidence: 99%

“…Quite surprisingly, Handgretinger et al reported that survival of neuroblastoma patients, rescued with purified CD34 + cells, inversely correlated with the amount of neuroblastoma cells contamination detected by immunofluorescence technique. The authors (15) suggested that a small amount of graft contamination might induce a protective antitumor immune response. In conclusion, the contribution of tumor cells to subsequent relapse and to overall and event-free survival remains controversial.…”

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confidence: 99%

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Peripheral Blood Stem Cell Tumor Cell Contamination and Survival of Neuroblastoma Patients

Corrias¹,

Haupt²,

Carlini³

et al. 2006

Clinical Cancer Research

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Purpose: Contribution of peripheral blood stem cell (PBSC) contaminating tumor cells to subsequent relapse and overall survival of neuroblastoma patients remains controversial. Experimental Design: Neuroblastoma cell contamination of 27 PBSC harvests from stage IV neuroblastoma patients was assessed by quantitative RT-PCR for both tyrosine hydroxylase (TH) and GD2 synthase (GD2-s). The effect of PBSC contamination on survival was then analyzed. Results: Seven PBSC tested negative for both markers; 19 were positive for GD2-s, 6 for TH, with 5 positive for both. Survival of the 20 patients with positive PBSC did not differ from that of the patients with negative PBSC (log-rank test, P = 0.134 and 0.218 for event-free survival and overall survival, respectively). By considering the TH and GD2-s results independently, a borderline (P = 0.053) negative effect on event-free survival was observed in patients reinfused with GD2-s-positive PBSC. When the status at transplant was taken into account, only the event-free survival of the patients rescued when in complete remission with GD2-s-negative PBSC was better, although not significantly, than that of patients infused with GD2-s-positive PBSC. Conclusions: Our results obtained in a small cohort of homogeneously treated stage IV patients suggest that patient survival is not affected by PBSC contamination with the exception of a borderline negative effect on event-free survival in patients rescued when in complete remission.

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Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Peripheral Blood Stem Cell Tumor Cell Contamination and Survival of Neuroblastoma Patients

Corrias¹,

Haupt²,

Carlini³

et al. 2006

Clinical Cancer Research

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“…This lack of correlation has never been reported before for neuroblastoma patients and challenges the tenet that reinfusion of contaminated PBSC increases the likelihood of relapse. In addition, the present results raise doubts about the superiority of selected CD34 cells over unselected PBSC in reducing relapse risk (9,28) and about the postulated antitumor effect of contaminated PBSC in neuroblastoma patients (29).…”

Section: Discussionmentioning

confidence: 43%

Detection of Neuroblastoma Cells in Bone Marrow and Peripheral Blood by Different Techniques

Corrias¹,

Faulkner

Pistorio

et al. 2004

Clinical Cancer Research

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“…Surprisingly, we detected some expression of all markers except PHOX2B in CD34 ϩ samples. There is some discussion in the literature regarding whether reinfusion of a contaminated harvest is correlated with worse survival prospects (5,6,39,40 ). To avoid falsepositive detection of tumor mRNA in these harvests, we recommend that a cutoff level for the CD34 ϩ fraction be used for markers expressed in this subset.…”

Section: Discussionmentioning

confidence: 99%

Detecting Minimal Residual Disease in Neuroblastoma: The Superiority of a Panel of Real-Time Quantitative PCR Markers

et al. 2009

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Background: PCR-based detection of minimal residual disease (MRD) in neuroblastoma (NB) patients can be used for initial staging and monitoring therapy response in bone marrow (BM) and peripheral blood (PB). PHOX2B has been identified as a sensitive and specific MRD marker; however, its expression varies between tumors. Therefore, a panel of markers could increase sensitivity. Methods: To identify additional MRD markers for NB, we selected genes by comparing SAGE (serial analysis of gene expression) libraries of healthy and NB tissues followed by extensive real-time quantitative PCR (RQ-PCR) testing in samples of tumors (n = 56), control BM (n = 51), PB (n = 37), and cell subsets. The additional value of a panel was determined in 222 NB samples from 82 Dutch stage 4 NB patients (54 diagnosis BM samples, 143 BM samples during/after treatment, and 25 PB samples). Results: We identified 2 panels of specific RQ-PCR markers for MRD detection in NB patients: 1 for analysis of BM samples (PHOX2B, TH, DDC, CHRNA3, and GAP43) and 1 for analysis of PB samples (PHOX2B, TH, DDC, DBH, and CHRNA3). These markers all showed high expression in NB tumors and no or low expression in control BM or PB samples. In patients’ samples, the PHOX2B marker detected most positive samples. In PB samples, however, 3 of 7 PHOX2B-negative samples were positive for 1 or more markers, and in BM examinations during treatment, 7% (6 of 86) of the PHOX2B-negative samples were positive for another marker. Conclusions: Because of differences in the sensitivities of the markers in BM and PB, we advise the use of 2 different panels to detect MRD in these compartments.

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Tumour cell contamination of autologous stem cells grafts in high-risk neuroblastoma: the good news?

Cited by 31 publications

References 31 publications

Peripheral Blood Stem Cell Tumor Cell Contamination and Survival of Neuroblastoma Patients

Peripheral Blood Stem Cell Tumor Cell Contamination and Survival of Neuroblastoma Patients

Detection of Neuroblastoma Cells in Bone Marrow and Peripheral Blood by Different Techniques

Detecting Minimal Residual Disease in Neuroblastoma: The Superiority of a Panel of Real-Time Quantitative PCR Markers

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