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

Abstract

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/m2, 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/m2. 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.

• Authors: Alexandra Laberko, Elvira Sultanova, Elena Gutovskaya, Svetlana Radygina, Elena Deripapa, Aishat Kantulaeva, Pavel Trakhtman, Varvara Brilliantova, Julia Starichkova, Anna Shcherbina, Michael Maschan, Alexei Maschan, Dmitry Balashov
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 40 Issue 6 Pg. 861-871 (08 2020) ISSN: 1573-2592 [Electronic] Netherlands
• PMID: 32602054 (Publication Type: Journal Article)

Chemical References

• Antigens, CD19
• Immunosuppressive Agents
• Myeloablative Agonists
• Receptors, Antigen, T-Cell, alpha-beta
• treosulfan
• Busulfan

Topics

• Antigens, CD19 (metabolism)
• Busulfan (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Female
• Graft Rejection
• Graft Survival (immunology)
• Graft vs Host Disease (etiology, prevention & control)
• Hematopoietic Stem Cell Transplantation (adverse effects, methods)
• Humans
• Immunosuppressive Agents (administration & dosage, adverse effects, therapeutic use)
• Lymphocyte Depletion (methods)
• Male
• Myeloablative Agonists (administration & dosage, therapeutic use)
• Nijmegen Breakage Syndrome (diagnosis, mortality, therapy)
• Postoperative Care
• Prognosis
• Receptors, Antigen, T-Cell, alpha-beta (metabolism)
• Retrospective Studies
• T-Lymphocytes (immunology, metabolism)
• Transplantation Chimera
• Transplantation Conditioning (adverse effects, methods)
• Treatment Outcome