Risk assessment of relapse by lineage-specific monitoring of chimerism in children undergoing allogeneic stem cell transplantation for acute lymphoblastic leukemia

Autor: Sandra Preuner, Christina Peters, Ulrike Pötschger, Helga Daxberger, Gerhard Fritsch, Rene Geyeregger, André Schrauder, Arend von Stackelberg, Martin Schrappe, Peter Bader, Wolfram Ebell, Cornelia Eckert, Peter Lang, Karl-Walter Sykora, Johanna Schrum, Bernhard Kremens, Karoline Ehlert, Michael H. Albert, Roland Meisel, Anita Lawitschka, Georg Mann, Renate Panzer-Grümayer, Tayfun Güngör, Wolfgang Holter, Brigitte Strahm, Bernd Gruhn, Ansgar Schulz, Wilhelm Woessmann, Thomas Lion
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Haematologica, Vol 101, Iss 6 (2016)
Druh dokumentu: article
ISSN: 0390-6078
1592-8721
DOI: 10.3324/haematol.2015.135137
Popis: Allogeneic hematopoietic stem cell transplantation is required as rescue therapy in about 20% of pediatric patients with acute lymphoblastic leukemia. However, the relapse rates are considerable, and relapse confers a poor outcome. Early assessment of the risk of relapse is therefore of paramount importance for the development of appropriate measures. We used the EuroChimerism approach to investigate the potential impact of lineage-specific chimerism testing for relapse-risk analysis in 162 pediatric patients with acute lymphoblastic leukemia after allogeneic stem cell transplantation in a multicenter study based on standardized transplantation protocols. Within a median observation time of 4.5 years, relapses have occurred in 41/162 patients at a median of 0.6 years after transplantation (range, 0.13–5.7 years). Prospective screening at defined consecutive time points revealed that reappearance of recipient-derived cells within the CD34+ and CD8+ cell subsets display the most significant association with the occurrence of relapses with hazard ratios of 5.2 (P=0.003) and 2.8 (P=0.008), respectively. The appearance of recipient cells after a period of pure donor chimerism in the CD34+ and CD8+ leukocyte subsets revealed dynamics indicative of a significantly elevated risk of relapse or imminent disease recurrence. Assessment of chimerism within these lineages can therefore provide complementary information for further diagnostic and, potentially, therapeutic purposes aiming at the prevention of overt relapse. This study was registered at clinical.trials.gov with the number NC01423747.
Databáze: Directory of Open Access Journals
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