Impact of Minimal Residual Disease Detection Prior to Autologous Stem Cell Transplantation for Post-transplant Outcome in High Risk Neuroblastoma

Abstract

Purpose:

Autologous stem cell transplantation (SCT) has become standard therapy in high risk stage IV neuroblastoma (NB) patients. Residual NB cells in the bone marrow (BM) shortly before SCT may shape the overall survival.

Methods:

Thus, we sought to thoroughly investigate minimal residual disease (MRD) in BM prior to SCT using conventional and real time RT-PCR for tyrosine hydroxylase (TH) as well as morphology. To avoid influence of residual NB cells in the stem cell harvest, 17 patients transplanted with MRD negative grafts (n=11 CD34-selected and n=6 unmanipulated) are included in the final analysis, only.

Results:

35% of these patients are alive with a median follow up of 8.6 years. In the BM of 9/17 patients residual NB cells could be detected < 40 d before SCT. These patients had a significant lower overall survival compared to patients without BM involvement based on combined RT-PCR and morphology results (11% vs. 62%, p=0.026) or using RT-PCR, only (p=0.01). In contrast morphology on its own did not lead to a significant discrimination between both groups.

Conclusion:

Our results obtained in a small cohort of stage IV NB patients suggest that MRD diagnostic in the BM shortly before SCT might be a valuable predictive tool for these patients but requires conformation in a multicenter study.

Zusammenfassung

Hintergrund:

Die autologe Stammzelltransplantation (SZT) ist Standardtherapie bei Patien­ten mit Hochrisiko-Neuroblastom (NB) Stadium IV. Residuale NB-Zellen im Knochenmark (KM) vor SZT können das Überleben beeinflussen.

Methoden:

Die minimale Resterkrankung (MRD) im KM vor SZT wurde mithilfe konventioneller und Real-time RT-PCR für Tyrosinhydroxylase (TH) sowie Morphologie untersucht. In dieser retrospektiven Evaluation wurden 17 Patienten aufgenommen, die ein MRD negatives Transplantat (n=17) erhielten.

Ergebnisse:

35% der Patienten leben mit einem medianen Follow-up von 8,6 Jahren. Im KM von 9/17 Patienten konnten wir residuale NB-Zellen <40 Tage vor SZT nachweisen. Diese Patien­ten hatten ein signifikant geringeres Überleben gegenüber Patienten ohne KM-Infiltration, basierend auf den kombinierten RT-PCR-Morphologieergebnissen (11% vs. 62%, p=0.026) oder nur mittels RT-PCR (p=0.01). Alleinige morphologische Untersuchungen führten nicht zur Diskriminierung zwischen beiden Gruppen.

Schlussfolgerung:

Unsere Ergebnisse in einer kleinen Gruppe von Stadium-IV-NB-Patienten ­wiesen darauf hin, dass MRD-Diagnostik im KM kurz vor SZT ein prädiktiver Faktor für das Überleben sein könnte, was aber in einer multizentrischen Studie bestätigt werden muss.

Key words

high risk neuroblastoma - minimal residual disease - autologous stem cell ­transplantation - bone marrow

Schlüsselwörter

Hochrisiko-Neuroblastom - minimale Resterkrankung - Stammzelltransplantation - Knochenmark

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