Long-term follow-up of children conditioned with Treosulfan: German and Austrian experience

Abstract

We report the long-term follow-up of children transplanted with Treosulfan (TREO)-based conditioning in Germany and Austria. Nine centres reported a total of 109 transplantations. Patients were stratified according to the paediatric TRM risk score derived from the paediatric BMT registry (PRST) and compared with the historical transplant population of this registry. Underlying diseases were malignancies, immunodeficiencies, and haematologic and metabolic disorders. TREO total dose ranged from 21-42 g/m 2 . Additional conditioning drugs included fludarabine, thiotepa, melphalan, CY and/or TBI. EFS at 3 years for non-malignant and malignant diseases was 88% and 49%, respectively. Leukaemia patients in remission had a survival of 51% at 3 years; nonremission patients relapsed and died within 18 months. TRM and OS in the low-risk groups 0 and 1 were similar to PRST controls. TRM in the high-risk groups 2 and 3 was markedly lower (9% vs 28% and 13% vs 53%, respectively) than in the PRST group, but OS was similar.In conclusion, TREO-based conditioning regimens in children resulted in excellent engraftment and long-term survival in nonmalignant disease. In high-risk malignancy, low acute toxicity was followed by low TRM but it did not translate into increased survival.

Treosulfan-Based Conditioning and Hematopoietic Cell Transplantation for Nonmalignant Diseases: A Prospective Multicenter Trial

“…al. reported the outcomes of 109 pediatric patients with hematologic malignancies or nonmalignant disorders [41]. Patients were conditioned with treosulfan (21–42 g/m 2 ) combined with various agents including fludarabine, cyclophosphamide, thiotepa, melphalan, total body irradiation, or anti-T cell serotherapy followed by HLA-matched or mismatched marrow or cord blood grafts.…”

Treosulfan-based conditioning regimens for allogeneic haematopoietic stem cell transplantation in children with non-malignant diseases

“…The 3-year OS in this cohort was 0.83 (±0.02), which is consistent with other published series. 4,5,7,8,[15][16][17] Treosulfan is shown to be a safe and effective Abbreviations: AST = aspartate transaminase; CNS = central nervous system; PN = peripheral neurological; VOD = veno-occlusive disease.…”

“…Since then, treosulfan has increasingly been used for paediatric patients undergoing HSCT for both malignant and nonmalignant diseases. [5][6][7][8][9][10][11][12] An increasing number of patients with non-malignant disorders are eligible for HSCT and these patients present different challenges compared with those with malignant diseases: children with inherited disorders such as SCID often come to transplant as infants under 1 year of age with organ damage and co-morbidities. GvHD, which may be associated with a beneficial GvL effect in patients with high-risk haematological diseases, is of no added value in controlling the underlying genetic illness and may adversely affect subsequent immune reconstitution and have an unnecessarily negative impact on HSCT-related morbidity and quality of life in the short and long term.…”

Treosulfan-based conditioning regimen for children and adolescents with hemophagocytic lymphohistiocytosis

“…In a series of immunodeficiencies, 3 of 4 HLH patients died, 15 whereas 2 patients in another cohort are long-term survivors. 16 The rate of additional cellular therapy after first HSCT (including second HSCT, administration of DLI, and stem cell boost) was high in the cohort with HLA-mismatched (9/10) donors (86%) while it was only 9% if the donor was HLA-matched (10/10) (P=0.018). This finding particularly points to the need to optimize the conditioning regimen for HLA-mismatched HSCT.…”