Assessment of chimerism and immunomodulation to prevent post-transplantation relapse in childhood acute myeloblastic leukemia: is it the right approach?

Abstract

Relapse of acute myeloblastic leukemia (AML) after first allogenic hematopoietic stem-cell transplantation (allo-HSCT) is a fatal complication. Sixty-five children transplanted for AML were included in a prospective national study from June 2005 to July 2008 to explore the feasibility of preemptive immune modulation based on the monitoring of blood chimerism. Relapse occurred in 23 patients (35%). The median time between the last complete chimerism and relapse was 13.5 days (2-138). Prompt discontinuation of cyclosporin and the administration of donor lymphocyte infusions (DLIs) based on chimerism monitoring failed as a preemptive tool, either for detecting relapse or certifying long-term remission.

Keywords:

• Acute myeloid leukemia
• chimerism
• immunotherapy
• donor lymphocyte infusions
• relapse of acute myeloblastic leukemia
• stem cell transplantation

Acknowledgments

The authors would like to thank all members of the pediatric group of SFGM-TC. They also especially thank all biologists who contributed to the determination of chimerism in each center: D. Reviron, JP. Dessaint, L. Prin, F. Dufosse, V. Dubois, D. Masson, A. Moine, H. Avet Loiseau, L. Lode, C. Bastard, A. Bernard, M. Pourtein, A. Tchirkov, P. Tieberghien, C. Ferrand, P. Oudet, and MP. Gaub.

We would like to thank Mrs. Sandrine Pall-Kondolff who worked on this study as a clinical research assistant. Finally, we also thank all the children and their parents for their contributions.

Authorship and disclosure

The authors declare no conflicts of interest.

Authors' contributions

Elie COUSIN wrote the paper. Elie COUSIN performed the research. Virginie GANDEMER and Pierre BORDIGONI designed the research study. Jean-Francois ELIAOU, Gilbert SEMANA, Philippe JONVEAUX, Severine DRUNAT contributed essential reagents or tools. Elie COUSIN, Virginie GANDEMER, Emmanuel OGER analysed the data.

Yves BERTRAND, Sophie PERTUISEL, Cecile POCHON, Claire GALAMBRUN, Pauline SIMON, Benedicte BRUNO, Catherine PAILLARD, Pascale SCHNEIDER, Pierre ROHRLICH, Régis PEFFAULT DE LA TOUR, Claire FREYCON and Jean-Hugues DALLE, provided substantial data for the research study.

All the authors contributed substantially to the revising of the manuscript. All authors read and approved the final manuscript.

We would like to thank Marie CHARDIN MD, Nathalie GARNIER MD, Dominique PLANTAZ for their constructive reviews.

ORCID

Elie Cousin https://orcid.org/0000-0001-9967-8599

Additional information

Funding

Supported by the Programme Hospitalier de Recherche Clinique 2003, a public non‐profit organization.