title: Conditioning with treosulfan and fludarabine followed by allogeneic hematopoietic cell transplantation for high-risk hematologic malignancies.
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.
authors.affiliation: Oregon Health and Science University, Portland, Oregon 97239, USA. nemeceke@ohsu.edu
authors.forename: Eneida R
authors.initials: ER
authors.lastname: Nemecek
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Guthrie
authors.forename: Mohamed L
authors.initials: ML
authors.lastname: Sorror
authors.forename: Brent L
authors.initials: BL
authors.lastname: Wood
authors.forename: Kristine C
authors.initials: KC
authors.lastname: Doney
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Hilger
authors.forename: Bart L
authors.initials: BL
authors.lastname: Scott
authors.forename: Tibor J
authors.initials: TJ
authors.lastname: Kovacsovics
authors.forename: Richard T
authors.initials: RT
authors.lastname: Maziarz
authors.forename: Ann E
authors.initials: AE
authors.lastname: Woolfrey
authors.forename: Antonio
authors.initials: A
authors.lastname: Bedalov
authors.forename: Jean E
authors.initials: JE
authors.lastname: Sanders
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.forename: Eileen J
authors.initials: EJ
authors.lastname: Sickle
authors.forename: Robert
authors.initials: R
authors.lastname: Witherspoon
authors.forename: Mary E
authors.initials: ME
authors.lastname: Flowers
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: H Joachim
authors.initials: HJ
authors.lastname: Deeg
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D012008:Recurrence; D012307:Risk Factors; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine