title: Association between pretransplant interferon-alpha and outcome after unrelated donor marrow transplantation for chronic myelogenous leukemia in chronic phase.
abstract: Treatment options for patients diagnosed with chronic myelogenous leukemia (CML) in chronic phase (CP) who lack a suitable related donor for marrow transplantation include hydroxyurea, interferon-alpha (IFN-alpha), or transplantation from an unrelated donor (URD). Most studies support the view that treatment with IFN-alpha results in prolonged survival compared with hydroxyurea therapy. Some patients are offered URD transplantation as a second-line treatment; however, the impact of pretransplant IFN-alpha on the outcome of URD transplantation is uncertain. To address this question, we evaluated the effect of pretransplant IFN-alpha therapy in 184 patients undergoing URD transplantation for CML in CP at a single center. Of the 184 patients, 114 did not receive IFN-alpha, whereas 22, 23, and 25 patients received IFN-alpha for, respectively, 1 to 5, 6 to 12, and more than 12 months before transplant. Pretransplant IFN-alpha therapy administered for > or = 6 months was associated with an increased risk of severe (grades III-IV) acute graft-versus-host disease (GVHD; relative risk [RR], 3.0; 95% confidence interval [CI], 1.4 to 6.2; P = .004) and mortality (RR, 2. 1; 95% CI, 1.3 to 3.5; P = .003) relative to less than 6 months or no IFN-alpha therapy. Increased mortality occurred between 100 and 365 days after transplant (P = .005), was limited to patients with severe acute GVHD, and was due to chronic GVHD refractory to immunosuppressive therapy. Other variables associated with mortality included HLA-DRB1 or DQB1 (but not HLA-A or B) mismatched donors, age greater than 50 years, weight > or = 110% of ideal body weight, and the absence of cytomegalovirus (CMV) or fungal prophylaxis. For patients treated with IFN-alpha for less than 6 months before transplant, who were < or = 50 years of age, received a HLA-A, B, DRB1, and DQB1 matched URD transplant, and received CMV and fungal prophylaxis after transplant (n = 48), survival was 87% +/- 5% at 5 years. These data provide a rationale for immediate transplantation in preference to extended treatment with IFN-alpha when the patient is < or = 50 years of age and has an HLA-compatible unrelated volunteer donor.
authors.affiliation: Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA 98109, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Morton
authors.forename: T
authors.initials: T
authors.lastname: Gooley
authors.forename: J A
authors.initials: JA
authors.lastname: Hansen
authors.forename: F R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: B
authors.initials: B
authors.lastname: Bruemmer
authors.forename: J W
authors.initials: JW
authors.lastname: Bjerke
authors.forename: R
authors.initials: R
authors.lastname: Clift
authors.forename: P J
authors.initials: PJ
authors.lastname: Martin
authors.forename: E W
authors.initials: EW
authors.lastname: Petersdorf
authors.forename: J E
authors.initials: JE
authors.lastname: Sanders
authors.forename: R
authors.initials: R
authors.lastname: Storb
authors.forename: K M
authors.initials: KM
authors.lastname: Sullivan
authors.forename: A
authors.initials: A
authors.lastname: Woolfrey
authors.forename: C
authors.initials: C
authors.lastname: Anasetti
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D014184:Transplantation, Homologous
chemical_list: D016898:Interferon-alpha