Quantitative chimerism in CD3-negative mononuclear cells predicts prognosis in acute myeloid leukemia patients after hematopoietic stem cell transplantation.

Abstract

Relapse is a major complication of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (SCT). The objective of our study was to evaluate chimerism monitoring on the CD3-negative mononuclear cells by RQ-PCR to predict relapse of patients allografted for AML and to compare its performance with WT1 quantification. A cohort of 100 patients undergoing allogenic SCT for AML was retrospectively analyzed in a single institution. Patients without complete chimerism, defined as less than 0.01% of recipient's DNA in CD3-negative cells, had a significantly higher risk of relapse and a lower overall survival (p < 0.001). An increase in the percentage of recipient DNA in CD3-negative cells was associated with an increased risk of relapse (p < 0.001) but not with overall survival. Comparable performances between monitoring of CD3-negative cell chimerism and WT1 expression to predict relapse was observed up to more than 90 days before hematological relapse, with sensitivity of 82% and 78%, respectively, and specificity of 100% for both approaches. Quantitative specific chimerism of the CD3-negative mononuclear fraction, enriched in blastic cells, is a new and powerful tool for monitoring measurable residual disease and could be used for AML patients without available molecular markers.

• Authors: Anne Bouvier, Jérémie Riou, Sylvain Thépot, Aurélien Sutra Del Galy, Sylvie François, Aline Schmidt, Corentin Orvain, Marie-Hélène Estienne, Alban Villate, Damien Luque Paz, Laurane Cottin, Bénédicte Ribourtout, Annaëlle Beucher, Yves Delneste, Norbert Ifrah, Valérie Ugo, Mathilde Hunault-Berger, Odile Blanchet
• Journal: Leukemia (Leukemia) Vol. 34 Issue 5 Pg. 1342-1353 (05 2020) ISSN: 1476-5551 [Electronic] England
• PMID: 31768015 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• CD3 Complex
• WT1 Proteins
• WT1 protein, human

Topics

• Adolescent
• Adult
• Aged
• Biomarkers, Tumor (metabolism)
• CD3 Complex (metabolism)
• Chimerism
• Female
• Follow-Up Studies
• Hematopoietic Stem Cell Transplantation (mortality)
• Humans
• Leukemia, Myeloid, Acute (metabolism, pathology, therapy)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (metabolism, pathology, therapy)
• Neoplasm, Residual (metabolism, pathology, therapy)
• Prognosis
• Retrospective Studies
• Survival Rate
• Transplantation, Homologous
• WT1 Proteins (metabolism)
• Young Adult