Immune Ablation and Stem Cell Rescue in Two Pediatric Patients with Progressive Severe Chronic Graft-Versus-Host Disease

Autor: Jaspar Kloehn, Anne Kruchen, Kerstin Schütze, Katharina Wustrau, Johanna Schrum, Ingo Müller
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 23, Iss 23, p 15403 (2022)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms232315403
Popis: Transplantation of allogeneic hematopoietic stem cells represents an established treatment for children with high-risk leukemia. However, steroid-refractory chronic graft-versus-host disease (SR-cGvHD) represents a severe life-threatening complication, for which there is no standard therapy. After failing several lines of immunosuppressive and biological treatment, we applied an immunoablative therapy with re-transplantation of purified CD34+ donor stem cells to reset the aberrant immune system. Two pediatric patients, who had been transplanted for high-risk acute lymphoblastic leukemia, underwent the procedure. Interestingly, enough stem cells could be mobilized, harvested, and purified to be used as grafts more than one year after allogeneic transplantation under intensive immunosuppressive therapy and ongoing SR-cGvHD. With a follow-up of 8 and 22 months, respectively, both patients are without immunosuppressive therapy and do not show signs of active disease. Regeneration of skin manifestations started promptly, other damaged organs did not progress and continue to show recovery from severe fibrotic transformation. Bone marrow function is robust and T cell receptor repertoires showed polyclonal immune reconstitution. In conclusion, stem cell harvest and re-transplantation of human CD34+-selected allogeneic stem cells is possible and represents a new therapeutic option in SR-cGvHD by resetting a profoundly disturbed immune network.
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