The use of thiotepa in reduced toxicity conditioning regimens before hematopoietic stem cell transplantation in primary immunodeficiencies

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Abstract

The use of reduced toxicity conditioning regimens in patients with primary immunodeficiencies (PID) leads to the reduction of toxic effects of hematopoietic stem cell transplantation (HSCT). Currently, HSCT should result not only in disease control, but also in the improvement of the quality of life. We report the experience of HSCT in PID with TCRab+/CD19+ graft depletion after conditioning regimen containing treosulfan in combination with thiotepa as a second alkylating agent. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. A group of 79 PID patients aged 0.5–17.6 years (the median age was 3.1 years) received HSCT from HLA matched related (n = 5), unrelated (n = 34) and haploidentical (n = 40) donors. The incidence of acute graft-versus-host disease (GVHD) ≥ grade II was 21%, grade III GVHD was observed in 3.8%, and none of the patients had GVHD grade IV. There were no cases of severe toxicity, including venoocclusive disease and thrombotic microangiopathy. The incidence of primary and secondary graft failure was 15.4%. The overall survival was 82.3%. There was no statistical difference between overall survival rates of patients who underwent transplantation from different types of donors (p = 0.164). All deaths were transplant-related and were due to infections. The use of thiotepa in reduced toxicity conditioning regimen is effective and safe, and can be considered as an option for HSCT in PID.

About the authors

D. N. Balashov

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Author for correspondence.
Email: bala8@yandex.ru
ORCID iD: 0000-0003-2689-0569

Dmitry N. Balashov, Dr. Med. Sci., Head of the Department of Hematopoietic Stem Cell Transplantation No.2 

1 Samory Mashela St.,Moscow 117997, Russia 

 

Russian Federation

A. L. Laberko

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation;
R.M. Gorbacheva Research Institute for Pediatric Oncology, Hematology and Transplantation of the I.P. Pavlov First Saint Petersburg State Medical University of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-2354-2588

Moscow; Saint Petersburg

Russian Federation

Yu. V. Skvortsova

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-0566-053X

Moscow

Russian Federation

A. P. Vasilieva

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0003-3949-248X

Moscow

Russian Federation

A. K. Idarmacheva

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0001-5962-1264

Moscow

Russian Federation

E. R. Sultanova

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0003-0319-3699

Moscow

Russian Federation

E. I. Gutovskaya

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-3800-8927

Moscow

Russian Federation

L. N. Shelikhova

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0003-0520-5630

Moscow

Russian Federation

M. A. Maschan

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-0016-6698

Moscow

Russian Federation

References

  1. Lum S.H., Hoenig M., Gennery A.R., Slatter M.A. Conditioning Regimens for Hematopoietic Cell Transplantation in Primary Immunodeficiency. Curr Allergy Asthma Rep 2019; 19: 52. doi: 10.1007/s11882-019-0883-1
  2. Wehr C., Gennery A.R., Lindemans C., Schulz A., Hoenig M., Marks R., et al. Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency. J Allergy Clin Immunol 2015; 135: 988–97.e6. doi: 10.1016/j.jaci.2014.11.029
  3. Güngör T., Teira P., Slatter M., Stussi G., Stepensky P., Moshous D., et al. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study. Lancet 2014; 383 (9915): 436–48. doi: 10.1016/S01406736(13)62069-3
  4. Shah N.N., Freeman A.F., Su H., Cole K., Parta M., Moutsopoulos N.M., et al. Haploidentical related donor hematopoietic stem cell transplantation for dedicator-of-cytokinesis 8 defi y using post-transplantation cyclophosphamide. Biol Blood Marrow Transplant 2017; 23: 980–90. doi: 10.1016/j.bbmt.2017.03.016
  5. Leiding J.W., Okada S., Hagin D., Abinun M., Shcherbina A., Balashov D.N., et al. Hematopoietic stem cell transplantation in patients with gain-ofunction signal transducer and activator of transcription 1 mutations. J Allergy Clin Immunol 2018; 141: 704–17. doi: 10.1016/j.jaci.2017.03.049
  6. Slatter M.A., Boztug H., Potschger U., Sykora K.W., Lankester A., Yaniv I., et al. Treosulfan-based conditioning regimens for allogeneic haematopoietic stem cell transplantation in children with non-malignant diseases. Bone Marrow Transplant 2015; 50 (12): 1536–41. doi: 10.1038/bmt.2015.171
  7. Bertaina A., Merli P., Rutella S., Pagliara D., Bernardo M.E., Masetti R., et al. HLA-haploidentical stem cell transplantation after removal of ab+ T and B cells in children with nonmalignant disorders. Blood 2014; 124: 822–6. doi: 10.1182/blood-2014-03-563817
  8. Balashov D., Shcherbina A., Maschan M., Trakhtman P., Skvortsova Y., Shelikhova L., et al. Single-Center Experience of Unrelated and Haploidentical Stem Cell Transplantation with TCRab and CD19 Depletion in Children with Primary Immunodeficiency Syndromes. Biol Blood Marrow Transplant 2015, 21: 1955–62. doi: 10.1016/j.bbmt.2015.07.008
  9. [Electronic resource] URL: http://esid. org/Working-Parties/Registry/Diagnosis-criteria (accessed 06.06.2024).
  10. Балашов Д.Н., Гутовская Е.И., Козловская С.Н., Радыгина С.А., Лаберко А.Л., Масчан А.А. Применение плериксафора и гранулоцитарного колониестимулирующего фактора в кондиционировании перед трансплантацией гемопоэтических стволовых клеток у пациентов с синдромом Вискотта–Олдрича. Вопросы гематологии/онкологии и иммунологии в педиатрии 2017; 16 (3): 55–8. doi: 10.24287/1726-1708-2017-16-3-55-58 [Balashov D.N., Gutovskaya E.I., Kozlovskaya S.N., Radygina S.A., Laberko A.L., Maschan A.A. The use of plerixafor and G-CSF during conditioning for hematopoietic stem cell transplantation in a patient with Wiscott–Aldrich syndrome. Pediatric Hematology/Oncology and Immunopathology 2017; 16 (3): 55–8. (In Russ.)].
  11. Balashov D., Laberko A., Shcherbina A., Trakhtman P., Abramov D., Gutovskaya E., et al. Conditioning Regimen with Plerixafor Is Safe and Improves the Outcome of TCRab+ and CD19+ Cell-Depleted Stem Cell Transplantation in Patients with Wiskott–Aldrich Syndrome. Biol Blood Marrow Transplant 2018; 24 (7): 1432– 40. doi: 10.1016/j.bbmt.2018.03.006
  12. Jagasia M.H., Greinix H.T., Arora M., Williams K.M., Wolff D., Cowen E.W., et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant 2015; 21 (3): 389–401.e1. doi: 10.1016/j.bbmt.2014.12.001
  13. Arora M., Cutler C.S., Jagasia M.H., Pidala J., Chai X., Martin P.J., et al. Late Acute and Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 2016; 22 (3): 449–55. doi: 10.1016/j.bbmt.2015.10.018
  14. Shah R.M., Elfeky R., Nademi Z., Quasim W., Amorolia P., Chiesa R., et al. T-cell receptor ab+ and CD19+ cell-depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency. J Allergy Clin Immunol 2017; 141 (4): 1417–26. doi: 10.1016/j.jaci.2017.07.008
  15. Laberko A., Bogoyavlenskaya A., Shelikhova L., Shekhovtsova Z., Balashov D., Voronin K., et al. Risk factors for and the clinical impact of cytomegalovirus and Epstein-Barr virus infections in pediatric recipients of TCR-a/band CD19-depleted grafts. Biol Blood Marrow Transplant 2017; 23 (2): 483–90. doi: 10.1016/j.bbmt.2016.12.635
  16. Богоявленская А.А., Лаберко А.Л., Шелихова Л.Н., Шеховцова Ж.Б., Балашов Д.Н., Воронин К.А. и др. Герпесвирусные инфекции у реципиентов аллогенной трансплантации гемопоэтических стволовых клеток с TCRabи CD19-деплецией: факторы риска и прогноз. Вопросы гематологии/ онкологии и иммунологии в педиатрии 2017; 16 (1): 10–21. doi: 10.24287/17261708-2017-16-1-10-21 [Bogoyavlenskaya A.A., Laberko A.L., Shelikhova L.N., Shekhovtsova Z.B., Balashov D.N., Voronin K.A., et al. Herpesvirus infection following allogenic hematopoietic stem cell transplantation with TCRab and CD19 depletion: risk factors and outcome. Pediatric Hematology/Oncology and Immunopathology 2017; 16 (1): 10–21. (In Russ.)].
  17. Laberko A., Sultanova E., Gutovskaya E., Shipitsina I., Shelikhova L., Kurnikova E., et al. Mismatched related vs matched unrelated donors in TCRab/CD19-depleted HSCT for primary immunodeficiencies Blood 2019; 134 (20): 1755–63. doi: 10.1182/blood.2019001757
  18. Hiwarkar P., Gajdosova E., Qasim W., Worth A., Breuer J., Chies R., et al. Frequent Occurrence of Cytomegalovirus Retinitis During Immune Reconstitution Warrants Regular Ophthalmic Screening in High-Risk Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients. Clin Infect Dis 2014; 58 (12): 1700–6. doi: 10.1093/cid/ciu201
  19. Gennery A.R., Slatter M.A., Grandin L., Taupin P., Cant A.J., Veys P., et al; European Society for Immunodefi y. Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better? J Allergy Clin Immunol 2010; 126 (3): 602–10. doi: 10.1016/j.jaci.2010.06.015

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Copyright (c) 2025 Balashov D.N., Laberko A.L., Skvortsova Y.V., Vasilieva A.P., Idarmacheva A.K., Sultanova E.R., Gutovskaya E.I., Shelikhova L.N., Maschan M.A.

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