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Graft Manipulation

TCR-alpha/beta and CD19 depletion and treosulfan-based conditioning regimen in unrelated and haploidentical transplantation in children with acute myeloid leukemia

Bone Marrow Transplantation volume 51, pages 668–674 (2016)Cite this article

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Abstract

We evaluated the depletion of TCR-alpha/beta cells from the graft of children with high-risk AML, who received transplantation from unrelated (n=20) and haploidentical donors (n=13). The preparative regimen included treosulfan, melphalan, fludarabine and anti-thymocyte globulin. Grafts were PBSC engineered by TCR-alpha/beta and CD19 depletion. The graft contained a median of 9 × 106/kg of CD34+ and 20 × 103/kg of αβ-T cells. Post-transplant immune suppression included tacrolimus till day +30 and Mtx in 21 patients, tacrolimus in 5, Mtx in 2 and no prophylaxis in 5 patients. Sixteen patients received native or TCR-alpha/beta-depleted donor lymphocytes at a median of 47 (40–204) days. Median follow-up is 1.76 years. Primary engraftment was achieved in 33 patients (100%). Cumulative incidence of acute GvHD (aGvHD) grade 2–3 was 39 (26–60)%, half of them had skin-only aGvHD. Cumulative incidence of chronic GvHD was 30(18–50)%. Transplant-related mortality is 10(4–26)%. Event-free survival (EFS) is 60(43–76)% and overall survival (OS) is 67(50–84)% at 2 years. In a subgroup of patients, who received transplantation in CR, EFS is 66(48–84)% and OS−72(53–90)% at 2 years. Our data suggest that TCR-alpha/beta and CD19 depletion is a robust method of graft manipulation, which can be used to engineer grafts for children with AML

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Acknowledgements

We would wish to thank the BMT Unit staff, especially doctors Olga Tatarinova, Elena Gutovskaya, Daria Shasheleva, Zhanna Shekhovtsova, Irina Shipitsina, Rimma Khismatullina, Vera Tzetlina. ‘Podari Zhizn’ charitable fund for continued support of the transplantation program. Stefan Morsch stiftung for years of collaboration in unrelated transplantation.

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Authors and Affiliations

  1. Department of hematopoietic stem cell transplantation, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia,

    M Maschan, L Shelikhova, M Ilushina, D Balashov, M Persiantseva, Y Skvortsova, A Laberko & A Maschan

  2. Blood bank and hematopoietic stem cell processing laboratory, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia,

    E Kurnikova, Y Muzalevskii & A Kazachenok

  3. Laboratory of hematopoietic stem cell transplantation biology, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia,

    E Boyakova & S Glushkova

  4. Laboratory of molecular biology, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia,

    V Bobrynina & V Kalinina

  5. Laboratory of cytogenetics and molecular genetics, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia,

    Y Olshanskaya

  6. Department of pediatric hematology and oncology, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia,

    D Baidildina, G Novichkova & A Maschan

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  1. M Maschan
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  2. L Shelikhova
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  6. D Balashov
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  8. Y Skvortsova
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  9. A Laberko
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  10. Y Muzalevskii
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  11. A Kazachenok
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  12. S Glushkova
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  13. V Bobrynina
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  14. V Kalinina
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  15. Y Olshanskaya
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  16. D Baidildina
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  18. A Maschan
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Correspondence to M Maschan.

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Maschan, M., Shelikhova, L., Ilushina, M. et al. TCR-alpha/beta and CD19 depletion and treosulfan-based conditioning regimen in unrelated and haploidentical transplantation in children with acute myeloid leukemia. Bone Marrow Transplant 51, 668–674 (2016). https://doi.org/10.1038/bmt.2015.343

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