Treosulfan-Based Conditioning Regimen in Haematopoietic Stem Cell Transplantation with TCRαβ/CD19 Depletion in Nijmegen Breakage Syndrome

Treosulfan-Based Conditioning Regimen in Haematopoietic Stem Cell Transplantation with TCRαβ/CD19 Depletion in Nijmegen Breakage Syndrome

Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to malignancies. HSCT appears to cure immunodeficiency, but remains challenging due to limited experience in long-term risks of transplant-associated toxicity and malignanci...

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Bibliographic Details
Published in:Journal of clinical immunology Vol. 40; no. 6; pp. 861 - 871
Main Authors: Laberko, Alexandra, Sultanova, Elvira, Gutovskaya, Elena, Radygina, Svetlana, Deripapa, Elena, Kantulaeva, Aishat, Trakhtman, Pavel, Brilliantova, Varvara, Starichkova, Julia, Shcherbina, Anna, Maschan, Michael, Maschan, Alexei, Balashov, Dmitry
Format: Journal Article
Language:English
Published: New York Springer US 01-08-2020
Springer Nature B.V
Subjects:
Biomedical and Life Sciences
Biomedicine
Busulfan
CD19 antigen
Chimerism
Cyclophosphamide
DNA repair
Fludarabine
Graft rejection
Graft-versus-host reaction
Grafts
Hematopoietic stem cells
Hepatitis
Immunodeficiency
Immunology
Infectious Diseases
Internal Medicine
Lymphocytes B
Lymphocytes T
Lymphoma
Medical Microbiology
Myeloid cells
Nijmegen breakage syndrome
Original Article
Rhabdomyosarcoma
Stem cell transplantation
Thymoglobulin
Toxicity
Transplants & implants
Treosulfan
TCRαβ/CD19 depletion
Haematopoietic stem cell transplantation
Treosulfan
DNA repair disorder
Nijmegen breakage syndrome
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Summary:Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to malignancies. HSCT appears to cure immunodeficiency, but remains challenging due to limited experience in long-term risks of transplant-associated toxicity and malignancies. Twenty NBS patients received 22 allogeneic HSCTs with TCRαβ/CD19+ graft depletion with fludarabine 150 mg/m 2 , cyclophosphamide 20–40 mg/kg and thymoglobulin 5 mg/kg based conditioning regimens (CRs). Twelve patients additionally received low-dose busulfan 4 mg/kg (Bu group) and 10 patients (including 2 recipients of a second HSCT) treosulfan (Treo group) 30 g/m 2 . Overall and event-free survival were 0.75 vs 1 ( p =  0.16) and 0.47 vs 0.89 ( p =  0.1) in the Bu and Treo groups, respectively. In the Bu group, four patients developed graft rejection, and three died: two died of de novo and relapsed lymphomas and one died of adenoviral hepatitis. The four living patients exhibited split chimerism with predominantly recipient myeloid cells and predominantly donor T and B lymphocytes. In Treo group, one patient developed rhabdomyosarcoma. There was no difference in the incidence of GVHD, viral reactivation, or early toxicity between either group. Low-dose Bu-containing CR in NBS leads to increased graft failure and low donor myeloid chimerism. Treo-CR followed by TCRαβ/CD19-depleted HSCT demonstrates a low level of early transplant-associated toxicity and enhanced graft function with stable donor chimerism.
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ISSN:0271-9142
1573-2592
DOI:10.1007/s10875-020-00811-9