Details

Autor(en) / Beteiligte

• Dimitriou, Marios
• Mortera-Blanco, Teresa
• Tobiasson, Magnus
• Mazzi, Stefania
• Lehander, Madeleine
• Högstrand, Kari
• Karimi, Mohsen
• Walldin, Gunilla
• Jansson, Monika
• Vonlanthen, Sofie
• Ljungman, Per
• Langemeijer, Saskia
• Yoshizato, Tetsuichi
• Hellström-Lindberg, Eva
• Woll, Petter S.
• Jacobsen, Sten Eirik W.

Titel

Identification and surveillance of rare relapse-initiating stem cells during complete remission after transplantation

Ist Teil von

• Blood, 2024-03, Vol.143 (11), p.953-966

Erscheinungsjahr

2024

Beschreibungen/Notizen

• Abstract Relapse after complete remission (CR) remains the main cause of mortality after allogeneic stem cell transplantation for hematological malignancies and, therefore, improved biomarkers for early prediction of relapse remains a critical goal toward development and assessment of preemptive relapse treatment. Because the significance of cancer stem cells as a source of relapses remains unclear, we investigated whether mutational screening for persistence of rare cancer stem cells would enhance measurable residual disease (MRD) and early relapse prediction after transplantation. In a retrospective study of patients who relapsed and patients who achieved continuous-CR with myelodysplastic syndromes and related myeloid malignancies, combined flow cytometric cell sorting and mutational screening for persistence of rare relapse-initiating stem cells was performed in the bone marrow at multiple CR time points after transplantation. In 25 CR samples from 15 patients that later relapsed, only 9 samples were MRD-positive in mononuclear cells (MNCs) whereas flowcytometric-sorted hematopoietic stem and progenitor cells (HSPCs) were MRD-positive in all samples, and always with a higher variant allele frequency than in MNCs (mean, 97-fold). MRD-positivity in HSPCs preceded MNCs in multiple sequential samples, in some cases preceding relapse by >2 years. In contrast, in 13 patients in long-term continuous-CR, HSPCs remained MRD-negative. Enhanced MRD sensitivity was also observed in total CD34+ cells, but HSPCs were always more clonally involved (mean, 8-fold). In conclusion, identification of relapse-initiating cancer stem cells and mutational MRD screening for their persistence consistently enhances MRD sensitivity and earlier prediction of relapse after allogeneic stem cell transplantation.