Minimal disease detection in peripheral blood and bone marrow from patients with non-metastatic neuroblastoma

Yáñez, Yania; Grau, Elena; Oltra, Silvestre; Cañete, Adela; Martı́nez, Francisco; Orellana, Carmen; Noguera, Rosa; Palanca, Sarai; Castel, Victoria

doi:10.1007/s00432-011-0997-x

Cited by 21 publications

(31 citation statements)

References 34 publications

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“…As suggested for anti-GD2 antibody and metaiodobenzylguanidine (MIBG) therapies (11), the various treatment protocols might affect these inconsistencies. Although the quantity of MRD in PB and/or BM samples predicts tumor relapse and patient outcome, conflicting results have been reported with regard to the prognostic value of MRD monitoring using various MRD markers (14)(15)(16). Given that CTCs in the PB and DTCs in the BM define the main faces of MRD in the clinics, these inconsistencies may imply genetic and phenotypic heterogeneity of CTCs and DTCs (20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

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Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients

et al. 2015

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Abstract. Neuroblastoma is an aggressive solid tumor that leads to tumor relapse in more than half of high-risk patients. Minimal residual disease (MRD) is primarily responsible for tumor relapses and may be detected in peripheral blood (PB) and bone marrow (BM) samples. To evaluate the disease status and treatment response, a number of MRD detection protocols based on either common or distinct markers for PB and BM samples have been reported. However, the correlation between the expression of MRD markers in PB and BM samples remains elusive in the clinical samples. In the present study, the expression of 11 previously validated MRD markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) was determined in 23 pairs of PB and BM samples collected from seven high-risk neuroblastoma patients at the same time point, and the sample was scored as MRD-positive if one of the MRD markers exceeded the normal range. Although the number of MRD-positive samples was not significantly different between PB and BM samples, the two most sensitive markers for PB samples (CRMP1 and KIF1A) were different from those for BM samples (PHOX2B and DBH). There was no statistically significant correlation between the expression of MRD markers in the PB and BM samples. These results suggest that MRD markers were differentially expressed in PB and BM samples from high-risk neuroblastoma patients.

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Section: Discussionmentioning

confidence: 99%

“…However, the rationale for introducing the current protocols into the clinics remains unclear (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients

et al. 2015

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“…These protocols used various sets and quantities of MRD markers, including 3 markers (DCX, PHOX2B and TH) (4), 5 markers (CHGA, DCX, DDC, PHOX2B and TH) (5), 6 markers (CHRNA3, DBH, DDC, GAP43, PHOX2B and TH) (6), 7 markers (B4GALNT1, DCX, DDC, ELAV4, PHOX2B, STX and TH) (7), 8 markers (CCND1, CRMP1, DDC, GABRB3, ISL1, KIF1A, PHOX2B and TACC2) (8), and 11 markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) (9). The clinical significance of MRD monitoring in neuroblastoma patients remains to be established (5,7,10,11). The present study reports two high-risk neuroblastoma patients whose MRD was consecutively monitored using 11 markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) during their course of treatment (9).…”

Section: Introductionmentioning

confidence: 99%

Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients

et al. 2016

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Abstract. Neuroblastoma is an aggressive pediatric tumor accounting for ~15% of cancer-associated mortalities in children. Despite the current intensive therapy, >50% of high-risk patients experience tumor relapse or regrowth caused by the activation of minimal residual disease (MRD). Although several MRD detection protocols using various reverse transcription-quantitative polymerase chain reaction (RT-qPCR) markers have been reported to evaluate the therapeutic response and disease status of neuroblastoma patients, their clinical significance remains elusive. The present study reports two high-risk neuroblastoma patients, whose MRD was consecutively monitored using 11 RT-qPCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) during their course of treatment. The two patients initially responded to the induction therapy and reached MRD-negative status. The patients' MRD subsequently became positive with no elevation of their urinary homovanillic acid, urinary vanillylmandelic acid and serum neuron-specific enolase levels at 13 or 19 weeks prior to the clinical diagnosis of tumor relapse or regrowth. The present cases highlight the possibility of consecutive MRD monitoring using 11 markers to enable an early detection of tumor relapse or regrowth in high-risk neuroblastoma patients.

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“…These findings suggest that TH expression at diagnosis might be a significant factor in future methods of risk stratification for NB. Some studies examined the clinical implication of positive TH expression in non-metastatic NB [19,23]. Yanez et al [23] reported an association of positive TH expression in PB at diagnosis with a higher probability of relapse in patients with non-metastatic NB.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies examined the clinical implication of positive TH expression in non-metastatic NB [19,23]. Yanez et al [23] reported an association of positive TH expression in PB at diagnosis with a higher probability of relapse in patients with non-metastatic NB. These findings suggest that some patients with localized tumors (by conventional diagnostic modalities) might have disseminated micrometastatic disease and therefore might benefit from upstaging and more aggressive treatment [24].…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Tyrosine Hydroxylase mRNA Transcripts in Peripheral Blood at Diagnosis in Patients with Neuroblastoma

et al. 2016

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PurposeThe purpose of this study is to investigate the clinical significance of tyrosine hydroxylase (TH) expression in peripheral blood (PB) at diagnosis in patients with neuroblastoma.Materials and MethodsTH mRNA expression in PB was measured by reverse transcription quantitative real-time polymerase chain reaction in 210 patients who were newly diagnosed with neuroblastoma from July 2005 to June 2015 and the clinical significance of TH expression in PB at diagnosis was evaluated.ResultsTH expression was positive in 60 patients (28.6%). Fifty of 60 TH-positive patients had metastatic tumors and the remaining 10 had localized tumors. TH expression was associated with high-risk features (i.e., advanced stage, older age, unfavorable pathology, and MYCN amplification) at diagnosis. Among TH-positive patients, higher TH expression level was observed in high-risk patients than in low- or intermediate-risk patients (p=0.035). The probability of 5-year progression-free survival (PFS) was lower in TH-positive patients than in TH-negative patients (63.8±6.9% vs. 94.7±2.1%, p < 0.001). In analysis confined to high-risk patients, the 5-year probability of PFS remained lower in TH-positive patients (55.7±8.2% vs. 89.6±5.8%, p < 0.001). Among TH-positive patients, a higher expression level of TH was associated with a worse outcome. In multivariate analyses, positive TH expression in PB at diagnosis was an independent poor prognostic factor for PFS.ConclusionThe treatment intensity should be tailored according to TH expression in PB at diagnosis.

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Minimal disease detection in peripheral blood and bone marrow from patients with non-metastatic neuroblastoma

Cited by 21 publications

References 34 publications

Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients

Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients

Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients

Clinical Significance of Tyrosine Hydroxylase mRNA Transcripts in Peripheral Blood at Diagnosis in Patients with Neuroblastoma

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