title: A phase I study in adults of clofarabine combined with high-dose melphalan as reduced-intensity conditioning for allogeneic transplantation.
abstract: Clofarabine is a novel purine nucleoside analog with immunosuppressive and antileukemia activity. We performed a phase I study of the combination of clofarabine plus melphalan as a reduced-intensity conditioning regimen for allogeneic stem cell transplantation in patients with acute myelogenous leukemia. Patients over age 18 in complete remission or with active disease (up to 50% marrow blasts) who had a matched related or unrelated donor were eligible. The conditioning regimen consisted of escalating doses of clofarabine plus melphalan, followed by allogeneic stem cell transplantation. Sixteen patients (median age, 63 years) were treated at 3 dose levels; 4 of these patients had primary induction failure, and 3 were in first relapse. One patient at dose level 2 and 1 patient at dose level 3 died of multiorgan toxicity; no other dose-limiting toxicities were seen. All other patients at both doses of clofarabine studied demonstrated complete engraftment by day 30, with a median time to absolute neutrophil count recovery of 14 days, and 16 days for platelet recovery. With a median follow-up of 17 months, only 2 patients relapsed, and 4 patients died. Clofarabine plus melphalan at dose level 2 is a well-tolerated conditioning regimen with activity in patients with advanced acute myelogenous leukemia.
authors.affiliation: Department of Hematology/Hematopoietic Cell Transplantation, City of Hope, Duarte, California 91010, USA. mkirschb@yahoo.com
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kirschbaum
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Stein
authors.forename: Leslie
authors.initials: L
authors.lastname: Popplewell
authors.forename: Maria
authors.initials: M
authors.lastname: Delioukina
authors.forename: Robert
authors.initials: R
authors.lastname: Chen
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Nakamura
authors.forename: David
authors.initials: D
authors.lastname: Snyder
authors.forename: Joel
authors.initials: J
authors.lastname: Conrad
authors.forename: Simon F
authors.initials: SF
authors.lastname: Lacey
authors.forename: Paul
authors.initials: P
authors.lastname: Frankel
authors.forename: Andrew
authors.initials: A
authors.lastname: Dagis
authors.forename: Auayporn
authors.initials: A
authors.lastname: Nademanee
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001087:Arabinonucleosides / Q000008:administration & dosage / Q000009:adverse effects; D000077866:Clofarabine; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D000077866:Clofarabine; D008558:Melphalan