title: Allo-SCT conditioning for myelodysplastic syndrome and acute myeloid leukemia with clofarabine, cytarabine and ATG.
abstract: The application of myeloablative Allo-SCT is limited by its associated morbidity and mortality. Reduced-intensity conditioning regimens attempt to diminish these, but are associated with a higher risk of disease relapse. Given the evidence of activity of clofarabine and cytarabine in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), we explored a novel reduced-intensity conditioning regimen based on this backbone. Patients received clofarabine 40 mg/m(2) i.v. on days -6 to -2, cytarabine 1 g/m(2) i.v. on days -6 to -2 and anti-thymocyte globulin (ATG) 1 mg/kg on day -4 and 2.5 mg/kg x 2 days on days -3 and -2. Seven patients were enrolled. Their median age was 54 years; three were with MDS and four with AML. The median duration of neutropenia was 14 days and that of thrombocytopenia was 22 days. Toxicities included hand-foot syndrome (57% grade 2), elevated alanine aminotransferase (ALT) (57% grade 3), elevated aspartate aminotransferase (AST) (86% grade 3) and hyperbilirubinemia (29% grade 3-5). No acute GVHD was observed. Enrollment to the trial was halted after three of the first seven patients expired on days +15, +26 and +32. Three of the four surviving patients have relapsed with a median TTP of 152 days. This regimen was not sufficiently immunosuppressive to ensure engraftment, and was associated with substantial morbidity and mortality.
authors.affiliation: Section of Leukemia and Bone Marrow Transplantation, Division of Oncology, Washington University School of Medicine, Saint Louis, MO 63110, USA. mmartin@dom.wustl.edu
authors.forename: M G
authors.initials: MG
authors.lastname: Martin
authors.forename: G L
authors.initials: GL
authors.lastname: Uy
authors.forename: E
authors.initials: E
authors.lastname: Procknow
authors.forename: K
authors.initials: K
authors.lastname: Stockerl-Goldstein
authors.forename: A
authors.initials: A
authors.lastname: Cashen
authors.forename: P
authors.initials: P
authors.lastname: Westervelt
authors.forename: C N
authors.initials: CN
authors.lastname: Abboud
authors.forename: K
authors.initials: K
authors.lastname: Augustin
authors.forename: J
authors.initials: J
authors.lastname: Luo
authors.forename: J F
authors.initials: JF
authors.lastname: DiPersio
authors.forename: R
authors.initials: R
authors.lastname: Vij
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000008:administration & dosage* / Q000009:adverse effects; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001087:Arabinonucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D000077866:Clofarabine; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy*; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D000227:Adenine Nucleotides; D000961:Antilymphocyte Serum; D000964:Antimetabolites, Antineoplastic; D001087:Arabinonucleosides; D007166:Immunosuppressive Agents; D003561:Cytarabine; D000077866:Clofarabine