IngentaConnect Treosulfan and fludarabine low-toxicity conditioning for allogene...

Authors: Holowiecki, Jerzy¹; Giebel, Sebastian¹; Wojnar, Jerzy¹; Krawczyk-Kulis, Malgorzata¹; Markiewicz, Miroslaw¹; Holowiecka-Goral, Aleksandra¹; Freund, Mathias²; Casper, Jochen²

Source: British Journal of Haematology, Volume 142, Number 2, July 2008 , pp. 284-292(9)

Publisher: Blackwell Publishing

Abstract:

Summary

Allogeneic haematopoietic stem cell transplantation (alloHSCT) is the only treatment of proven long-term efficacy in chronic myeloid leukaemia (CML), although high non-relapse mortality (NRM) observed after conventional myeloablative conditioning limits its applicability. This phase II trial evaluated the efficacy and toxicity of a new preparative regimen consisting of treosulfan 3 × 14 g/m² and fludarabine 5 × 30 mg/m², in patients with CML in chronic phase. Among the 40 patients included, 18 received alloHSCT from a sibling and 22 from an unrelated donor. All patients engrafted with 92·5% of cases achieving complete donor chimaerism by day +100. All but one patient had achieved complete cytogenetic remission on day +100. Grade III or IV non-haematological toxicities included: neutropenic fever (10%), nausea/vomiting (10%), elevated liver enzymes (5%) and infection (2·5%). The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 22·5% and extensive chronic GVHD, 14%. The 2-year probability of overall survival, leukaemia-free survival and NRM was 85%, 82·5% and 15% respectively. At 1 year post-transplant, 85% of survivors had a Karnofsky index of 100%. We concluded that treosulfan and fludarabine conditioning is a low-toxicity regimen with high anti-leukaemic potential that seems feasible in CML patients referred for alloHSCT.

Keywords: treosulfan; HSC transplantation; CML

Document Type: Research article

DOI: 10.1111/j.1365-2141.2008.07179.x

Affiliations: 1: Department of Haematology and BMT, Silesian Medical University, Katowice, Poland 2: Department of Haematology and Oncology, University of Rostock, Rostock, Germany

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Treosulfan and fludarabine low-toxicity conditioning for allogeneic haematopoietic stem cell transplantation in chronic myeloid leukaemia