Conditioning with treosulfan and fludarabine followed by allogeneic hematopoietic cell transplantation for high-risk hematologic malignancies.
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.
Nemecek
Eneida R
ER
Oregon Health and Science University, Portland, Oregon 97239, USA. nemeceke@ohsu.edu
Guthrie
Katherine A
KA
Sorror
Mohamed L
ML
Wood
Brent L
BL
Doney
Kristine C
KC
Hilger
Ralf A
RA
Scott
Bart L
BL
Kovacsovics
Tibor J
TJ
Maziarz
Richard T
RT
Woolfrey
Ann E
AE
Bedalov
Antonio
A
Sanders
Jean E
JE
Pagel
John M
JM
Sickle
Eileen J
EJ
Witherspoon
Robert
R
Flowers
Mary E
ME
Appelbaum
Frederick R
FR
Deeg
H Joachim
HJ
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
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine