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Low-dose donor memory T-cell infusion after TCR alpha/beta depleted unrelated and haploidentical transplantation: results of a pilot trial

Bone Marrow Transplantation volume 53, pages 264–273 (2018)Cite this article

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Abstract

Recovery of immunity is delayed in recipients of T-depleted grafts. Adoptive transfer of memory T-cells may improve immune response to common pathogens. A cohort of 53 patients with malignant (n = 36) and non-malignant conditions (n = 17) received TCR alpha/beta depleted grafts from haploidentical (n = 25) or MUD (n = 28) donors. Donor lymphocytes were depleted of CD45RA-positive cells. At a median of 48 days after transplantation, patients received DLI at 25 × 103/kg CD3 cells from haploidentical or 100 × 103/kg CD3 from MUD donors. Up to 3 doses of donor lymphocytes were administered at monthly intervals, escalating to 100 × 103/kg in haploidentical transplants and 300 × 103/kg in MUD transplants. At a median follow-up of 23 months, the cumulative incidence of de novo acute GVHD after DLI is 2% (1 of 43), while the rate of reactivation of preexisting aGVHD was 50% (5 of 10). The transplant-related mortality is 6%. The overall survival rates are 80% and 88% in malignant and non-malignant conditions, respectively. Among patients with absent CMV-specific immune reactivity at baseline (n = 31) expansion of CMV-specific T-cells was demonstrated in 20 (64.5%) within 100 days. Infusions of low dose donor memory T-lymphocytes are safe and constitute a simple measure to prevent infections in the setting of alpha/beta T cell-depleted transplantation.

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Acknowledgements

The authors thank the physicians and nursing staff of the Hematopoietic stem cell transplantation Units 1 and 2 for outstanding patient care, the staff of Molecular biology, Microbiology and Transplant biology laboratories for excellent service, Marina Persiantseva and Susanne Morsch for unrelated donor search, Dmitriy Pershin and Victoria Kiseleva for technical assistance. We are grateful to the “Podari Zhizn” foundation for continued support of the care of the patients and research in the field of hematopoietic stem cell transplantation.

Author contributions

MM planned the study, performed the analysis and wrote the manuscript. SB collected the data and wrote the manuscript. LS, AM, DB, and GN planned the study, analyzed the data and reviewed the manuscript. JS established the database. EK, YM, AK and PT performed graft and cell therapy product processing and formulation. EB, EO, NK and VZ performed immunomonitoring and cell therapy product quality control and contributed to the Methods section.

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Authors and Affiliations

  1. Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev National Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia

    Michael Maschan, Sergey Blagov, Larisa Shelikhova, Zhanna Shekhovtsova, Dmitriy Balashov & Alexei Maschan

  2. Statistics, Dmitriy Rogachev National Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia

    Julia Starichkova

  3. Transfusion Medicine Service, Dmitriy Rogachev National Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia

    Elena Kurnikova, Yakov Muzalevskii, Alexei Kazachenok & Pavel Trakhtman

  4. Transplantation Immunology and Immunotherapy Laboratory, Dmitriy Rogachev National Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia

    Elena Boyakova

  5. Stem Cell Physiology Laboratory, Dmitriy Rogachev National Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia

    Elena Osipova, Natalia Khripkova & Vladimir Zhogov

  6. Medical Department, Dmitriy Rogachev National Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia

    Galina Novichkova

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  1. Michael Maschan
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Correspondence to Michael Maschan.

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Conflict of interest

MM delivered lectures at Miltenyi Biotec satellite symposia at EBMT 2013 and EBMT 2016 annual meetings. Rest of the authors declare to have no conflict of interest.

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The study was approved by Ethics committee of the Dmitriy Rogachev Federal Center of pediatric hematology, oncology and immunology.

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Maschan, M., Blagov, S., Shelikhova, L. et al. Low-dose donor memory T-cell infusion after TCR alpha/beta depleted unrelated and haploidentical transplantation: results of a pilot trial. Bone Marrow Transplant 53, 264–273 (2018). https://doi.org/10.1038/s41409-017-0035-y

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