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

Chambon, F.; Tchirkov, Andréï; Pereira, Bruno; Rochette, Emmanuelle; Deméocq, F.; Kanold, Justyna

doi:10.1002/pbc.24538

Cited by 11 publications

(15 citation statements)

References 19 publications

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“…We did an additional analysis of our TLDA data using only TH and PHOX2B expression to compare with other studies. 6–8 Our patients with a detectable signal with either TH or PHOX2B also had significantly worse outcome compared with those patients with an undetectable signal. A higher number of patients had a detectable signal with the five-gene than with the two-gene analysis, providing more sensitive or less specific, or both, tumour mRNA detection.…”

Section: Discussionmentioning

confidence: 80%

“…Smaller series have shown conflicting results regarding the prognostic value of minimum tumour detection in PBSC. 6–8 Data from other groups support the prognostic significance of QrtPCR detection of neuroblastoma mRNA in bone marrow. 28,29 An international task force is currently assessing QrtPCR methodologies to reach a consensus for implementing this technology.…”

Section: Discussionmentioning

confidence: 86%

“…Blood has no or fewer neuroblastoma cells detectable by immunocytology even when bone marrow is positive. 5 Quantitative real-time PCR (QrtPCR) can detect neuroblastoma mRNA in PBSC, 6–8 although the effect of infusing these PBSC has not been defined. We postulated that immunomagnetic bead purging would decrease tumour burden in PBSC and improve outcome.…”

Section: Introductionmentioning

confidence: 99%

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Purged versus non-purged peripheral blood stem-cell transplantation for high-risk neuroblastoma (COG A3973): a randomised phase 3 trial

Kreissman

Seeger

Matthay

et al. 2013

The Lancet Oncology

268

287

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Summary Background Myeloablative chemoradiotherapy and immunomagnetically purged autologous bone marrow transplantation has been shown to improve outcome for patients with high-risk neuroblastoma. Currently, peripheral blood stem cells (PBSC) are infused after myeloablative therapy, but the effect of purging is unknown. We did a randomised study of tumour-selective PBSC purging in stem-cell transplantation for patients with high-risk neuroblastoma. Methods Between March 16, 2001, and Feb 24, 2006, children and young adults (<30 years) with high-risk neuroblastoma were randomly assigned at diagnosis by a web-based system (in a 1:1 ratio) to receive either nonpurged or immunomagnetically purged PBSC. Randomisation was done in blocks stratified by International Neuroblastoma Staging System stage, age, MYCN status, and International Neuroblastoma Pathology classification. Patients and treating physicians were not masked to treatment assignment. All patients were treated with six cycles of induction chemotherapy, myeloablative consolidation, and radiation therapy to the primary tumour site plus metaiodobenzylguanidine avid metastases present before myeloablative therapy, followed by oral isotretinoin. PBSC collection was done after two induction cycles. For purging, PBSC were mixed with carbonyl iron and phagocytic cells removed with samarium cobalt magnets. Remaining cells were mixed with immunomagnetic beads prepared with five monoclonal antibodies targeting neuroblastoma cell surface antigens and attached cells were removed using samarium cobalt magnets. Patients underwent autologous stem-cell transplantation with PBSC as randomly assigned after six cycles of induction therapy. The primary endpoint was event-free survival and was analysed by intention-to-treat. The trial is registered with ClinicalTrials.gov, number NCT00004188. Findings 495 patients were enrolled, of whom 486 were randomly assigned to treatment: 243 patients to receive non-purged PBSC and 243 to received purged PBSC. PBSC were collected from 229 patients from the purged group and 236 patients from the non-purged group, and 180 patients from the purged group and 192 from the non-purged group received transplant. 5-year event-free survival was 40% (95% CI 33–46) in the purged group versus 36% (30–42) in the non-purged group (p=0·77); 5-year overall survival was 50% (95% CI 43–56) in the purged group compared with 51% (44–57) in the non-purged group (p=0·81). Toxic deaths occurred in 15 patients during induction (eight in the purged group and seven in the non-purged group) and 12 during consolidation (eight in the purged group and four in the non-purged group). The most common adverse event reported was grade 3 or worse stomatitis during both induction (87 of 242 patients in the purged group and 93 of 243 patients in the non-purged group) and consolidation (131 of 177 in the purged group vs 145 of 191 in the non-purged group). Serious adverse events during induction were grade 3 or higher decreased cardiac function (four of 242 in the purged gr...

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Purged versus non-purged peripheral blood stem-cell transplantation for high-risk neuroblastoma (COG A3973): a randomised phase 3 trial

Kreissman

Seeger

Matthay

et al. 2013

The Lancet Oncology

268

287

View full text Add to dashboard Cite

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“…В нашем Центре для всех 116 пациентов с нейро-бластомой высокого риска удалось собрать более 2,5×10 6 /кг CD34+ клеток за один аферез, для 109 (94%) -более 5×10 6 /кг. Выявление определяемых количеств минимальной остаточной болезни (МОБ), несомненно, оказывает влияние на выживаемость пациентов с нейробласто-мой высокого риска [31][32][33][34][35]. Помимо применения биологических агентов с целью воздействия на МОБ, долгое время во многих центрах применялись раз-личные технологии иммуномагнитной очистки про-дуктов афереза от опухолевых клеток, призванные улучшить результаты после проведения АутоТГСК [32,36].…”

Section: в рисунокunclassified

Results of mobilization, apheresis and autoreinfusion of hematopoietic stem cells in children with neuroblastoma: role of monitoring the count of CD34+ cells in peripheral blood

Kurnikova¹,

Kumukova²,

Guz³

et al. 2017

VGOIP

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“…The detection of NB minimal residual disease (MRD) in blood and bone marrow of patients with metastatic NB was developed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for tyrosine hydroxylase ( TH ), paired-like homeobox 2b ( PHOX2B ) and doublecortin ( DCX ) transcripts (20–22). These transcripts represent useful and clinically significant biomarkers of MRD in the blood and bone marrow of metastatic NB cells.…”

Section: Introductionmentioning

confidence: 99%

RT-qPCR for PHOX2B mRNA is a highly specific and sensitive method to assess neuroblastoma minimal residual disease in testicular tissue

et al. 2017

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Neuroblastoma (NB) is the most common type of extracranial solid tumor in children with a high prevalence in toddlers. For childhood cancer survivors, preservation of reproductive potential is an important factor for quality of life. The optimization of NB minimal residual disease (MRD) detection in testicular tissue is crucial to evaluate the risk of malignant cell reintroduction. The first step in the present study was to assess the accuracy of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to detect tyrosine hydroxylase (TH), paired-like homeobox 2b (PHOX2B) and doublecortin (DCX) mRNA expression in frozen/thawed testicular tissues of patients with non-obstructive azoospermia (NOA) contaminated (in vitro model) with an increasing number of IMR-32 and SK-N-SH NB cells. Testicular tissues were frozen by slow or snap freezing. The second step was to determine the expression levels of these markers in testicular samples from 4 pre-pubertal males (2 with stage IV NB and 2 with non-NB malignancy). The yield of extracted RNA was similar in testicular samples frozen by slow or snap freezing. In the in vitro model, TH and DCX transcripts were detected in uncontaminated testicular tissues, whereas PHOX2B mRNA was not detected. There was a strong positive association between the number of NB cells used for contamination and PHOX2B transcript levels. For IMR-32 and SK-N-SH NB cell lines, specificity and sensitivity rates of detection were 100% for PHOX2B following in vitro contamination with 10 tumor cells. In testicular samples from pre-pubertal males with and without NB, PHOX2B mRNA expression was not observed, but high expression levels of TH and DCX mRNA were detected, which were similar to expression detected in the in vitro model. Among the markers used in blood and bone marrow for NB MRD studies, the detection of PHOX2B transcripts by RT-qPCR may provide an accurate assessment of NB cells in testicular tissues from males who require fertility preservation.

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

Cited by 11 publications

References 19 publications

Purged versus non-purged peripheral blood stem-cell transplantation for high-risk neuroblastoma (COG A3973): a randomised phase 3 trial

Purged versus non-purged peripheral blood stem-cell transplantation for high-risk neuroblastoma (COG A3973): a randomised phase 3 trial

Results of mobilization, apheresis and autoreinfusion of hematopoietic stem cells in children with neuroblastoma: role of monitoring the count of CD34+ cells in peripheral blood

RT-qPCR for PHOX2B mRNA is a highly specific and sensitive method to assess neuroblastoma minimal residual disease in testicular tissue

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