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ADCC can improve graft vs leukemia effect after T- and B-cell depleted haploidentical stem cell transplantation in pediatric B-lineage ALL

Bone Marrow Transplantation volume 54, pages 689–693 (2019)Cite this article

Abstract

Posttransplant relapsed B-cell precursor ALL can be cured by 2nd hematopoietic stem cell transplantation (HSCT) in 20% of patients. The major cause of death after second HSCT is leukemic relapse. One reliable predictor for survival after 2nd-HSCT are posttransplant MRD levels. Patients with detectable or increase of MRD are likely to relapse. Patients in complete molecular remission show the best leukemia-free survival and lowest cumulative incidence (CI) of relapse. As patients who undergo second or subsequent HSCT are high-risk patients, we evaluated the prophylactic use of the chimeric Fc-optimized CD19-4G7SDIE-mAb. Posttransplant relapsed CD19+ BCP-ALL patients, who underwent a second or subsequent haplo-HSCT from a T- and B-cell depleted graft received posttransplant prophylactic CD19-4G7SDIE-mAb treatment on compassionate use in complete molecular remission, to increase the antileukemic activity of the new reconstituting immune system by recruiting Fc-expressing effector cells. NK cells recovered early and robust. The 3 year overall survival in 15 evaluable patients was 56%, the 3 year event-free survival was 55% and the CI of relapse 38%. Compared to a historical control group, the CI of relapse was markedly lower and consecutively the EFS higher. Posttransplant-targeted therapy may overcome the need for unspecific GvL effect of undesired GvHD, that can cause severe morbidity and mortality. Due to a low adverse event profile the CD19-4G7SDIE-mAb may be suitable for broad administration to consolidate posttransplant MRD negativity.

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Acknowledgements

We acknowledge financial support by the Deutsche Forschungsgemeinschaft (DFG), CRC685 Immunotherapy, the Bundesministerium für Bildung und Forschung (BMBF iVac ALL, BMBF GO-Bio 0315096/0316070), the Reinhold Beitlich Stiftung, the Deutsche José Carreras Leukämie-Stiftung, the Stefan Morsch Stiftung, the Förderverein für krebskranke Kinder Tübingen, the Stiftung des Fördervereins für krebskranke Kinder e.V. Tübingen, the Elterninitiative Kinderkrebsklinik e.V.Düsseldorf, Hilfe für krebskranke Kinder Frankfurt e.V., the German Cancer Consortium (DKTK) and the German Cancer Research Center (DKFZ) Heidelberg, Germany. Publication of this supplement was sponsored by Gilead Sciences Europe Ltd, Cell Source, Inc., The Chorafas Institute for Scientific Exchange of the Weizmann Institute of Science, Kiadis Pharma, Miltenyi Biotec, Celgene, Centro Servizi Congressuali, Almog Diagnostic.

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  1. These authors contributed equally: Peter Lang, Rupert Handgretinger

Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, University Children’s Hospital, University of Tuebingen, Tuebingen, Germany

    Patrick Schlegel, Anne-Marie Lang, Michaela Döring, Martin Ebinger, Ursula Holzer, Florian Heubach, Christian Seitz, Barbara Lang, Thomas Eichholz, Peter Lang & Rupert Handgretinger

  2. Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tuebingen, Germany

    Gundram Jung

  3. Department of Pediatric Hematology and Oncology, University Children’s Hospital, Charité Berlin, Germany

    Johannes H. Schulte, Patrick Hundsdörfer & Angelika Eggert

  4. Department for Stem Cell Transplantation and Immunology, Clinic for Children and Adolescents, University Hospital Frankfurt, Frankfurt, Germany

    Hermann Kreyenberg

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  1. Patrick Schlegel
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Correspondence to Peter Lang.

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Schlegel, P., Jung, G., Lang, AM. et al. ADCC can improve graft vs leukemia effect after T- and B-cell depleted haploidentical stem cell transplantation in pediatric B-lineage ALL. Bone Marrow Transplant 54 (Suppl 2), 689–693 (2019). https://doi.org/10.1038/s41409-019-0606-1

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