title: Phase-2 trial of an intensified conditioning regimen for allogeneic hematopoietic cell transplant for poor-risk leukemia.
abstract: Patients with poor-risk leukemia have a high relapse rate despite allogeneic transplant. We report on the phase-2 trial of an intensified allogeneic transplant regimen whose aim was tolerable toxicity and durable remission. Study patients (n=30) had unfavorable first remission cytogenetics, progression from myelodysplasia or active disease due to induction failure or relapse. Conditioning was i.v. BU, targeted to a first-dose plasma area under the curve (AUC) of 700-900 μM min, VP-16 at 30 mg/kg of adjusted ideal body weight and fractionated TBI (FTBI) at 1200 cGy in 10 fractions. GVHD prophylaxis was CsA and mycophenolate mofetil. Regimen-related toxicities (Bearman) included grade II mucositis in 29 patients (97%) and grade III in one patient, grade II-III sinusoidal obstructive syndrome in 2 patients (7%), and grade 2-3 (CTC) skin toxicity in 8 patients (27%). The 30- and 100-day TRMs were 0 and 7% respectively. The median follow-up was 83.7 months (60.7-96.4) for surviving patients. The 5-year overall and disease-free survival was 40% for all patients. Cumulative 5-year relapse incidence (RI) was 23% and TRM was 37%. We have shown promising OS and RI in these poor-risk patients, who typically have few curative options.
authors.affiliation: Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010-3000, USA. astein@coh.org
authors.forename: A S
authors.initials: AS
authors.lastname: Stein
authors.forename: M R
authors.initials: MR
authors.lastname: O'Donnell
authors.forename: T W
authors.initials: TW
authors.lastname: Synold
authors.forename: A C
authors.initials: AC
authors.lastname: Dagis
authors.forename: A
authors.initials: A
authors.lastname: Tsirunyan
authors.forename: A P
authors.initials: AP
authors.lastname: Nademanee
authors.forename: P M
authors.initials: PM
authors.lastname: Parker
authors.forename: V A
authors.initials: VA
authors.lastname: Pullarkat
authors.forename: D S
authors.initials: DS
authors.lastname: Snyder
authors.forename: R T
authors.initials: RT
authors.lastname: Spielberger
authors.forename: J Y C
authors.initials: JY
authors.lastname: Wong
authors.forename: J C
authors.initials: JC
authors.lastname: Alvarnas
authors.forename: S H
authors.initials: SH
authors.lastname: Thomas
authors.forename: S J
authors.initials: SJ
authors.lastname: Forman
mesh_terms: D000328:Adult; D002066:Busulfan / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation; D055815:Young Adult
chemical_list: D005047:Etoposide; D002066:Busulfan