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Haematologica. 2016 Jun;101(6):741-6. doi: 10.3324/haematol.2015.135137. Epub 2016 Feb 11.

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

Author information

1
Children's Cancer Research Institute, Vienna, Austria.
2
St. Anna Children's Hospital, Vienna, Austria.
3
University Medical Center Schleswig-Holstein and Christian-Albrechts-University Kiel, Department of Pediatrics, Kiel, Germany.
4
Charité, University Medicine Berlin, Germany.
5
Johann Wolfgang Goethe University, Frankfurt, Germany.
6
University Hospital Tübingen, Germany.
7
Hannover Medical School, Hannover, Germany.
8
University Hospital UKE, Hamburg, Germany.
9
University Hospital Essen, Germany.
10
University Children's Hospital Münster, Germany (current address: Medical University Greifswald, Germany).
11
Dr. von Hauner University Children's Hospital, München, Germany.
12
University Hospital Düsseldorf, Germany.
13
University Children's Hospital Zürich, Division of Stem Cell Transplantation, Switzerland.
14
Children's University Hospital Erlangen, Germany St. Anna Children's Hospital, Vienna, Austria Department of Pediatrics, Medical University Vienna, Austria.
15
Pediatric Hematology and Oncology, University Medical Center Freiburg, Germany.
16
University Hospital Jena, Germany.
17
University Hospital Ulm, Germany.
18
University Children's Hospital Giessen, Germany.
19
Children's Cancer Research Institute, Vienna, Austria Department of Pediatrics, Medical University Vienna, Austria thomas.lion@ccri.at.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01423747.

PMID:
26869631
PMCID:
PMC5013947
DOI:
10.3324/haematol.2015.135137
[Indexed for MEDLINE]
Free PMC Article

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