Association Between Pretransplant Interferon-α 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-α (IFN-α), or transplantation from an unrelated donor (URD). Most studies support the view that treatment with IFN-α 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-α on the outcome of URD transplantation is uncertain. To address this question, we evaluated the effect of pretransplant IFN-α therapy in 184 patients undergoing URD transplantation for CML in CP at a single center. Of the 184 patients, 114 did not receive IFN-α, whereas 22, 23, and 25 patients received IFN-α for, respectively, 1 to 5, 6 to 12, and more than 12 months before transplant. Pretransplant IFN-α therapy administered for ≥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-α 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 ≥110% of ideal body weight, and the absence of cytomegalovirus (CMV) or fungal prophylaxis. For patients treated with IFN-α for less than 6 months before transplant, who were ≤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-α when the patient is ≤50 years of age and has an HLA-compatible unrelated volunteer donor.