Conditioning with treosulfan and fludarabine followed by allogeneic hematopoietic cell transplantation for high-risk hematologic malignancies

Biol Blood Marrow Transplant. 2011 Mar;17(3):341-50. doi: 10.1016/j.bbmt.2010.05.007. Epub 2010 May 26.

Abstract

In this prospective study 60 patients of median age 46 (range: 5-60 years), with acute myelogenous leukemia (AML; n = 44), acute lymphoblastic leukemia (ALL; n = 3), or myelodysplastic syndrome (MDS; n = 13) were conditioned for allogeneic hematopoietic cell transplantation with a treosulfan/fludarabine (Flu) combination. Most patients were considered at high risk for relapse or nonrelapse mortality (NRM). Patients received intravenous treosulfan, 12 g/m(2)/day (n = 5) or 14 g/m(2)/day (n = 55) on days -6 to -4, and Flu (30 mg/m(2)/day) on days -6 to -2, followed by infusion of marrow (n = 7) or peripheral blood stem cells (n = 53) from HLA-identical siblings (n = 30) or unrelated donors (n = 30). All patients engrafted. NRM was 5% at day 100, and 8% at 2 years. With a median follow-up of 22 months, the 2-year relapse-free survival (RFS) for all patients was 58% and 88% for patients without high-risk cytogenetics. The 2-year cumulative incidence of relapse was 33% (15% for patients with MDS, 34% for AML in first remission, 50% for AML or ALL beyond first remission and 63% for AML in refractory relapse). Thus, a treosulfan/Flu regimen was well tolerated and yielded encouraging survival and disease control with minimal NRM. Further trials are warranted to compare treosulfan/Flu to other widely used regimens, and to study the impact of using this regimen in more narrowly defined groups of patients.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / adverse effects
  • Antineoplastic Agents, Alkylating / pharmacokinetics
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Busulfan / administration & dosage
  • Busulfan / adverse effects
  • Busulfan / analogs & derivatives*
  • Busulfan / pharmacokinetics
  • Busulfan / therapeutic use
  • Child
  • Child, Preschool
  • Female
  • Hematologic Neoplasms / drug therapy
  • Hematologic Neoplasms / metabolism
  • Hematologic Neoplasms / therapy*
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy
  • Myelodysplastic Syndromes / metabolism
  • Myelodysplastic Syndromes / therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Recurrence
  • Risk Factors
  • Survival Analysis
  • Transplantation Conditioning / methods*
  • Vidarabine / administration & dosage
  • Vidarabine / adverse effects
  • Vidarabine / analogs & derivatives*
  • Vidarabine / pharmacokinetics
  • Vidarabine / therapeutic use
  • Young Adult

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • treosulfan
  • Vidarabine
  • Busulfan
  • fludarabine