title: Long-term outcomes in patients with high-risk myeloid malignancies following matched related donor hematopoietic cell transplantation with myeloablative conditioning of BU, etoposide and CY.
abstract: Patients with high-risk or advanced myeloid malignancies have limited effective treatment options. These include high-dose therapy followed by allogeneic hematopoietic cell transplantation (HCT). We report a single-institution, long-term follow-up of 96 patients, median age 50 (range, 20-60) years, who received HLA-matched related HCT between 1992 and 2007. All patients were treated with a uniform preparatory regimen intended to enhance the widely used regimen of BU and CY that included: BU 16.0 mg/kg (days -8 to -5), etoposide 60 mg/kg (day -4), CY 60 mg/kg (day -2) with GVHD prophylaxis of CsA or FK506 and prednisone. Disease status at transplantation was high-risk AML (n=41), CML in second chronic phase or blast crisis (n=8), myelofibrosis and myeloproliferative disorders (n=8), and myelodysplasia (n=39). Thirty-six percent (n=35) of patients received BM whereas 64% (n=61) received G-CSF-mobilized PBPC. With a median follow-up of 5.6 years (range, 1.6-14.6 years) actuarial 5-year OS was 32% (95% CI 22-42) and 5-year EFS was 31% (95% CI 21-41). Relapse rate was 24% (95% CI 15-33) at 2 and 5 years. Nonrelapse mortality was 29% (95% CI 20-38) at day 100 and 38% (95% CI 29-47) at 1 year. Cumulative incidence of acute (grade II-IV) and extensive chronic GVHD was 27% (95% CI 18-36) and 29% (95% CI 18-40), respectively. There was no statistically significant difference in OS (31 vs 32%, P=0.89) or relapse rates (17 vs 28%, P=0.22) for recipients of BM vs PBPC, respectively. These results confirm that patients with high-risk or advanced myeloid malignancies can achieve long-term survival following myeloablative allogeneic HCT with aggressive conditioning.
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Naik
authors.forename: R
authors.initials: R
authors.lastname: Wong
authors.forename: S
authors.initials: S
authors.lastname: Arai
authors.forename: J
authors.initials: J
authors.lastname: Brown
authors.forename: G
authors.initials: G
authors.lastname: Laport
authors.forename: R
authors.initials: R
authors.lastname: Lowsky
authors.forename: D
authors.initials: D
authors.lastname: Miklos
authors.forename: J
authors.initials: J
authors.lastname: Shizuru
authors.forename: K
authors.initials: K
authors.lastname: Blume
authors.forename: R
authors.initials: R
authors.lastname: Negrin
authors.forename: L
authors.initials: L
authors.lastname: Johnston
mesh_terms: D000328:Adult; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003587:Cytomegalovirus / Q000502:physiology; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000601:surgery*; D015470:Leukemia, Myeloid, Acute / Q000601:surgery*; D008875:Middle Aged; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D014775:Virus Activation
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide; D002066:Busulfan