Treosulfan/fludarabine as an allogeneic hematopoietic stem cell transplant conditioning regimen for high-risk patients

Am J Hematol. 2008 Sep;83(9):717-20. doi: 10.1002/ajh.21240.

Abstract

In recent years, new conditioning regimens have been explored in patients not eligible for conventional transplant with the aim to reduce transplant-related mortality. In a phase II multicentric prospective trial, we investigated the safety and feasibility of the treosulfan-fludarabine combination prior to allogeneic hematopoietic stem cell transplant in patients with various hematological malignancies not eligible for conventional regimens because of previous intensive treatment, older age, and comorbidities. Forty-six consecutive patients, median age 48 years (range 17-69), were enrolled. Sixteen of them were in complete remission, and 20 had a HSCT comorbidity index > or = 1. Forty-four patients had regular and sustained engraftment, and 39 out of 40 evaluable patients developed complete chimerism. Nonhematological toxicity was limited. Risk of transplant-related mortality was 9% (95% CI, 2-17%) at day +100 and plotted at 15% (95% CI, 7-22%) after 7 months. The estimated overall survival and progression-free survival with a median follow-up of 20 months were 51% and 38%, respectively. The estimated 30 months progression-free survival for patients transplanted in remission was 56%. The treosulfan-fludarabine combination is a reduced-toxicity but myeloablative regimen that can be proposed to patients not fitting criteria for conventional transplant regimens. Longer follow-up and further prospective studies are necessary to evaluate this regimen.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Busulfan / administration & dosage
  • Busulfan / adverse effects
  • Busulfan / analogs & derivatives*
  • Busulfan / therapeutic use
  • Chemical and Drug Induced Liver Injury / etiology
  • Combined Modality Therapy
  • Comorbidity
  • Digestive System Diseases / chemically induced
  • Feasibility Studies
  • Female
  • Graft vs Host Disease / chemically induced
  • Hematologic Neoplasms / drug therapy
  • Hematologic Neoplasms / surgery
  • Hematopoietic Stem Cell Transplantation* / mortality
  • Humans
  • Kidney Diseases / chemically induced
  • Male
  • Middle Aged
  • Myeloablative Agonists / administration & dosage
  • Myeloablative Agonists / adverse effects
  • Myeloablative Agonists / therapeutic use*
  • Prospective Studies
  • Reoperation
  • Risk
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods*
  • Transplantation Conditioning / mortality
  • Transplantation, Homologous
  • Vidarabine / administration & dosage
  • Vidarabine / adverse effects
  • Vidarabine / analogs & derivatives*
  • Vidarabine / therapeutic use

Substances

  • Myeloablative Agonists
  • treosulfan
  • Vidarabine
  • Busulfan
  • fludarabine