Dose-escalated treosulphan in combination with cyclophosphamide as a new preparative regimen for allogeneic haematopoietic stem cell transplantation in patients with an increased risk for regimen-related complications
| Autor: | D. W. Beelen, Axel A. Fauser, Nadezda Basara, R A Hilger, Mathias Freund, Joachim Hahn, M E Scheulen, Rudolf Trenschel, Jochen Casper, Joachim Baumgart, Bernd Hertenstein, Ernst Holler, Heidrun A. Mylius, Uwe Pichlmeier |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male medicine.medical_specialty Transplantation Conditioning Cyclophosphamide Treosulfan Risk Assessment Gastroenterology chemistry.chemical_compound Recurrence Cause of Death White blood cell Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Transplantation Homologous Pharmacokinetics Antineoplastic Agents Alkylating Busulfan Aged Preparative Regimen Transplantation Dose-Response Relationship Drug business.industry Graft Survival Hematopoietic Stem Cell Transplantation Hematology Middle Aged Survival Analysis Nitrogen mustard Surgery Regimen Haematopoiesis medicine.anatomical_structure chemistry Hematologic Neoplasms Female business medicine.drug |
| Zdroj: | Bone Marrow Transplantation. 35:233-241 |
| ISSN: | 1476-5365 0268-3369 |
| DOI: | 10.1038/sj.bmt.1704784 |
| Popis: | Treosulphan has recently demonstrated antileukaemic activity and potent haematopoietic stem cell toxicity. Dose-escalated treosulphan (3 x 12 or 3 x 14 g/m2) combined with cyclophosphamide (Cy) was chosen for a new preparative regimen before allogeneic haematopoietic stem cell transplantation in 18 patients (median age 44, range 19-64 years) with haematological malignancies, considered ineligible for other myeloablative preparative regimens. Pharmacokinetic studies demonstrated rapid treosulphan plasma clearance and a dose-dependent increase of its maximum plasma concentrations and area under the concentration-time curves. Rapid and sustained white blood cell and platelet recovery and full donor chimerism was attained in all evaluable patients. Nonhaematological regimen-related CTC grades 3-4 adverse events were transient and predominantly consisted of cardiac (28%), gastrointestinal (39%), and hepatic (39%) toxicities. The 1-year nonrelapse mortality was 22%. Principal causes of transplant-related lethal events were infections in three of four affected patients. Only one patient died from regimen-related cardiac toxicity. The 1-year relapse estimate is 22%, overall and progression-free survival estimates are 67 and 56%, respectively. In conclusion, this new treosulphan and Cy combination is an effective, comparatively well-tolerated myeloablative preparative regimen even in patients with an increased risk for regimen-related toxic complications. |
| Databáze: | OpenAIRE |
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