Allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies after dose-escalated treosulfan/fludarabine conditioning.

Abstract

PURPOSE:

Treosulfan was introduced recently as a conditioning agent for allogeneic blood stem-cell transplantation. The favorable nonhematologic toxicity profile at 3 x 10 g/m(2) was the basis for dose escalation in this prospective, multicenter trial.

PATIENTS AND METHODS:

Fifty-six patients with various hematologic malignancies who were not eligible for standard conditioning were treated with one of three doses: 10 g/m(2), 12 g/m(2), or 14 g/m(2) of intravenous treosulfan, which was administered on days -6 to -4 combined with fludarabine 30 mg/m(2) on days -6 to -2. Patients in complete remission (CR; 42%) or non-CR (58%) received grafts from matched related (47%) or matched unrelated (51%) donors; one patient had a mismatched related donor (2%).

RESULTS:

No engraftment failure occurred. Overall, extramedullary toxicity and the nonrelapse mortality rate at 2 years (20%) were low and did not increase with dose. Cumulative incidence of relapse/progression reached 31%. The overall survival and progression-free survival rates were 64% and 49%, respectively, in the total study population. An inverse dose dependency of relapse incidence was indicated in the subgroup receiving transplantations from matched related donors (P = .0568).

CONCLUSION:

Treosulfan-based conditioning was feasible at all three doses. The 3 x 14 g/m(2) dose was selected for additional studies, because it combines desired characteristics of low toxicity and a low relapse rate.

• Authors: Jochen Casper, Daniel Wolff, Wolfgang Knauf, Igor W Blau, Tapani Ruutu, Liisa Volin, Hannes Wandt, Kerstin Schäfer-Eckart, Jerzy Holowiecki, Sebastian Giebel, Johan Aschan, Axel R Zander, Nicolaus Kröger, Inken Hilgendorf, Joachim Baumgart, Heidrun A Mylius, Uwe Pichlmeier, Mathias Freund
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 20 Pg. 3344-51 (Jul 10 2010) ISSN: 1527-7755 [Electronic] United States
• PMID: 20498405 (Publication Type: Evaluation Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• treosulfan
• Vidarabine
• Busulfan
• fludarabine

Topics

• Adolescent
• Adult
• Busulfan (administration & dosage, analogs & derivatives)
• Drug Therapy, Combination
• Feasibility Studies
• Female
• Hematologic Neoplasms (drug therapy, mortality, therapy)
• Hematopoietic Stem Cell Transplantation
• Humans
• Male
• Middle Aged
• Transplantation Conditioning
• Transplantation, Homologous
• Vidarabine (administration & dosage, analogs & derivatives)