Minimal Residual Disease in Peripheral Blood Stem Cell Harvests From High-risk Neuroblastoma Patients

Avigad, Smadar; Feinberg-Gorenshtein, Galina; Luria, Drorit; Jeison, Marta; Stein, Jerry; Grunshpan, A.; Sverdlov, Y; Ash, Susan; Yaniv, Isaac

doi:10.1097/mph.0b013e31818e532c

Cited by 8 publications

(14 citation statements)

References 23 publications

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“…On this new cohort, the persistence of MRD detected with RQ-PCR in PBSC predicts poorer overall survival (OS) in patients with HR-NB regardless of whether or not PBSC were re-injected or purged (P ¼ 0.04). Our findings are in line with Avigad et al [4], who demonstrated that patients harboring TH expression had reduced progression-free survival, and Corrias et al [5], who showed borderline negative effect of positive MRD on event-free survival (EFS) in patients rescued in CR (Table II). However, other studies showed no significant difference in OS between patients with positive or negative MRD in PBSC [1,5].…”

Section: Discussionsupporting

confidence: 92%

“…However, reports on the impact of MRD in PBSC are conflicting. Avigad et al [4] and Corrias et al [5] showed no correlation between MRD in PBSC and unfavorable outcome, while our previous studies suggested that positive MRD in PBSC was a poor prognostic factor [2,6]. Moreover, as MRD status in PBSC reflects pre-harvest bone marrow (BM) status, some authors have suggested that positive MRD in the BM shortly before PBSC collection might be a valuable predictive tool [7,8].…”

Section: Introductionmentioning

confidence: 88%

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Molecular assessment of minimal residual disease in PBSC harvests provides prognostic information in neuroblastoma

Chambon

Tchirkov

Pereira

et al. 2013

Pediatr Blood Cancer

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As almost all patients with high-risk neuroblastomas have autograft, we aimed to determine if minimal residual disease (MRD) quantified by RT-PCR for tyrosine hydroxylase in PBSC is prognostic in neuroblastomas. PBSC harvests from 38 children were analyzed. Seven had harvests positive for TH-mRNA. Patients with a positive MRD had a lower 2-year-overall-survival compared to those with negative MRD (P = 0.04) regardless of whether or not PBSC were re-infused. Patients in CR/VGPR group with positive MRD have hazard ratio of death at 7.3 [1.3-40.5]. In conclusion, molecular MRD status in PBSC of good response group may be of interest as a survival prognostic factor in high-risk neuroblastomas.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 88%

Molecular assessment of minimal residual disease in PBSC harvests provides prognostic information in neuroblastoma

Chambon

Tchirkov

Pereira

et al. 2013

Pediatr Blood Cancer

View full text Add to dashboard Cite

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“…Most previous studies of molecular MRD in patients with HR‐NB using qRT‐PCR for NB mRNA markers were performed at early time points during the disease and treatment course . Only a few patients were followed up with qRT‐PCR for longer periods.…”

Section: Discussionmentioning

confidence: 99%

“…Most previous studies of molecular MRD in patients with HR-NB using qRT-PCR for NB mRNA markers were performed at early time points during the disease and treatment course. [1][2][3][4][5][6][7][8][9] Only a few patients were followed up with qRT-PCR for longer periods. Two patients with HR-NB were monitored for 61 and 67 weeks, 10 and we previously reported one patient with HR-NB followed up for 157 weeks after diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…In high-risk neuroblastoma (HR-NB), a number of studies have shown that sensitive detection of circulating neuroblastoma mRNA markers using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was clinically significant. [1][2][3][4][5][6][7][8][9] In these studies, higher levels of minimal residual disease (MRD) in bone marrow (BM), peripheral blood (PB), and/or autologous PB stem cell (PBSC) harvests were associated with worse patient survival. MRD studies have generally been performed within 100 days following diagnosis, which corresponds to the end of consolidation therapy.…”

Section: Introductionmentioning

confidence: 99%

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Very long‐term molecular follow‐up of minimal residual disease in patients with neuroblastoma

Tchirkov

Grèze

Plantaz

et al. 2018

Pediatric Blood & Cancer

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In high-risk neuroblastoma (HR-NB), the clinical significance of long-term minimal residual disease (MRD) monitoring using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for neuroblastoma mRNAs has not been investigated. We report long-term MRD follow-ups of four patients with HR-NB throughout the disease (diagnosis, remission, and relapse) and treatment course (chemotherapy, autologous and allogeneic stem cell transplantation, and donor lymphocyte and natural killer cell infusions). The results showed the stability of mRNA marker expression after different treatments and demonstrated their validity to predict relapse and assess therapeutic response. This opens up the possibility of investigating the utility of long-term molecular monitoring of MRD in prospective multicenter studies.

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Circulating tumor cells in neuroblastoma: Current status and future perspectives

2022

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Neuroblastoma is the most common extracranial solid tumor in children, accounting for 10% to 20% of deaths of pediatric malignancies. Due to the poor prognosis and significant biological heterogeneity of neuroblastoma, it is essential to develop personalized therapeutics and monitor treatment response. Circulating tumor cells (CTCs), as one of the important analytes for liquid biopsy, could facilitate response assessment and outcome prediction for patients in a non‐invasive way. Several methods and platforms have been used for the enrichment and detection of CTCs. The enumeration of CTCs counts and evaluation of tumor‐specific mRNA transcript levels could provide prognostic information at diagnosis, during or after chemotherapy, and during the process of disease progression. So far, studies into neuroblastoma CTCs are only in the preliminary stages. The quality‐controlled large prospective cohort studies are needed to evaluate the clinical significance and statistical rigor of CTC detection methods. Moreover, there remains a lot to be explored and investigated in genotyping characterization of neuroblastoma (NB) CTCs and construction of in‐vitro or in‐vivo functional models. CTCs and circulating tumor DNA (ctDNA) analysis will be complementary in understanding tumor heterogeneity and evolution over the course of therapy for patients with NB in the future.

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Minimal Residual Disease in Peripheral Blood Stem Cell Harvests From High-risk Neuroblastoma Patients

Abstract: The correlation between an unfavorable outcome and high TH expression in patients' PBSC harvests was not significant. This indicates a need to increase sample size in a long-term clinical outcome study to clarify the importance of TH mRNA contamination in PBSC.

Cited by 8 publications

References 23 publications

Molecular assessment of minimal residual disease in PBSC harvests provides prognostic information in neuroblastoma

Molecular assessment of minimal residual disease in PBSC harvests provides prognostic information in neuroblastoma

Very long‐term molecular follow‐up of minimal residual disease in patients with neuroblastoma

Circulating tumor cells in neuroblastoma: Current status and future perspectives

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