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Pediatric Transplants

Feasibility study of preemptive withdrawal of immunosuppression based on chimerism testing in children undergoing myeloablative allogeneic transplantation for hematologic malignancies

Bone Marrow Transplantation volume 43, pages 469–476 (2009)Cite this article

Abstract

An increasing percentage of autologous cells (increasing chimerism) in the whole blood (WB) chimerism test following allogeneic transplant is related to a very high risk of relapse. Preemptive immunotherapy may decrease the risk of relapse in some patients. Our prospective multi-institutional study evaluated the feasibility of longitudinal chimerism testing in a central laboratory, compared WB, CD3+ and leukemia-specific lineage chimerism in patients with a variety of hematologic malignancies, and evaluated the feasibility of fast withdrawal of immunosuppression based on WB chimerism results. Centralized chimerism testing was feasible and showed low interassay variability. Increasing mixed chimerism (MC) in WB was not useful as a predictor of relapse in our study. The presence of full donor chimerism in WB, CD3+ and leukemia-specific lineages on all measurements was related to a significantly lower risk of relapse than the presence of MC in either subset (11 vs 71%, respectively; P=0.03). Increasing host chimerism in leukemia-specific lineage heralds relapse, but it was not detected early enough to allow immunotherapy. Further studies correlating lineage-specific chimerism and minimal residual disease are required. The goal of preemptive immunotherapy should be to achieve full donor chimerism in WB in CD3+ and leukemia-specific lineages.

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Acknowledgements

We would like to acknowledge the financial support provided by the Hellman Family Grant, which covered the expenses of chimerism testing for this study.

We thank Dr Stephen Grupp and Dr John Levine from the Stem Cell Sources Strategy Group of Pediatric Blood and Marrow Transplant Consortium for reviewing this study, offering their advice and their help in initiating multi-institutional cooperation, which made the study possible. We would also like to acknowledge the members of UCSF Immunogenetic Laboratory: Denice Kong, Victor Corpuz and David Sidebottom for their technical support and help in study coordination.

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Authors and Affiliations

  1. Department of Pediatrics, UCSF Medical Center, University of California, San Francisco, CA, USA

    B Horn, M Cowan, G Pelle-Day, E Cooperstein & L-A Baxter-Lowe

  2. Division of Pediatric Hematology, Oncology and Bone Marrow Transplantation, Kosair Children's Hospital, University of Louisville, Louisville, KY, USA

    S Soni & N Breslin

  3. Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA

    S Khan

  4. Department of Blood and Marrow Transplant, All Children's Hospital, St Petersburg, FL, USA

    A Petrovic

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  1. B Horn
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  6. M Cowan
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Correspondence to B Horn.

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Horn, B., Soni, S., Khan, S. et al. Feasibility study of preemptive withdrawal of immunosuppression based on chimerism testing in children undergoing myeloablative allogeneic transplantation for hematologic malignancies. Bone Marrow Transplant 43, 469–476 (2009). https://doi.org/10.1038/bmt.2008.339

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