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

• Published in: Bone marrow transplantation (Basingstoke) Vol. 48; no. 4; pp. 491 - 501
• Main Authors: Beier, R, Schulz, A, Hönig, M, Eyrich, M, Schlegel, P-G, Holter, W, Stachel, K D, Ehlert, K, Greil, J, Nürnberger, W, Wößmann, W, Bader, P, Urban, C, Müller, I, Suttorp, M, Sauer, M, Gruhn, B, Meisel, R, Zimmermann, M, Sykora, K-W
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2013; Nature Publishing Group
• Subjects: 631/250/1904; 692/699/67/1990/283; 692/699/67/2332; 692/700/565/1436; Acute toxicity; Adolescent; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antineoplastic Agents, Alkylating - administration & dosage; Austria - epidemiology; Biological and medical sciences; Bone marrow; Bone Marrow Transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Busulfan - administration & dosage; Busulfan - analogs & derivatives; Cell Biology; Child; Child, Preschool; Children; Common Variable Immunodeficiency - mortality; Common Variable Immunodeficiency - therapy; Conditioning; Disease-Free Survival; Diseases; Female; Fludarabine; Follow-Up Studies; Germany - epidemiology; Health aspects; Health risks; Hematologic and hematopoietic diseases; Hematology; Hematopoietic stem cells; Humans; Infant; Internal Medicine; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Malignancy; Medical sciences; Medicine; Medicine & Public Health; Melphalan; Metabolic disorders; Metabolism, Inborn Errors - mortality; Metabolism, Inborn Errors - therapy; Myeloablative Agonists - administration & dosage; Neoplasms - mortality; Neoplasms - therapy; original-article; Pediatrics; Public Health; Registries; Remission; Risk; Risk Factors; Risk groups; Stem cell transplantation; Stem Cells; Survival; Survival Rate; Toxicity; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation Conditioning - methods; Treosulfan; Europe; Germany; Austria; inborn errors of metabolism; leukaemia; treosulfan; haematopoietic SCT; children; long-term follow-up; Human; Antineoplastic agent; Hematology; Leukemia; Alkanediol; Metabolic diseases; Malignant hemopathy; Treosulfan; Enzymopathy; Long term; Congenital disease; Alkanesulfonic acid; Alkylating agent; Follow up study; Child; Hematopoietic stem cell transplantation; Cancer
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2012.188

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.