ASSOCIATION BETWEEN PRETRANSPLANT INTERFERON-ALPHA AND OUTCOME AFTER UNRELATED DONOR MARROW TRANSPLANTATION FOR CHRONIC MYELOGENOUS LEUKEMIA IN CHRONIC PHASE

Treatment options for patients diagnosed with chronic myelogenous leuk emia (CML) in chronic phase (CP) who lack a suitable related donor for marrow transplantation include hydroxyurea, interferon-alpha (IFN-alp ha), or transplantation from an unrelated donor (URD). Most studies su pport the view that treatment with IFN-alpha results in prolonged surv ival compared with hydroxyurea therapy. Some patients are offered URD transplantation as a second-line treatment; however, the impact of pre transplant IFN-alpha on the outcome of URD transplantation is uncertai n. To address this question, we evaluated the effect of pretransplant IFN-alpha therapy in 184 patients undergoing URD transplantation for C ML 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, res pectively, 1 to 5, 6 to 12, and more than 12 months before transplant. Pretransplant IFN-alpha therapy administered for greater than or equa l to 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% Cl, 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 immunosuppressiv e therapy. Other variables associated with mortality included HLA-DRB1 or DOB1 (but not HLA-A or B) mismatched donors, age greater than 50 y ears, weight greater than or equal to 110% of ideal body weight, and t he absence of cytomegalovirus (CMV) or fungal prophylaxis, For patient s treated with IFN-alpha for less than 6 months before transplant, who were less than or equal to 50 years of age, received a HLA-A, B, DRB1 , and DQB1 matched URD transplant, and received CMV and fungal prophyl axis after transplant (0 = 48), survival was 87% +/- 5% at 5 years. Th ese data provide a rationale for immediate transplantation in preferen ce to extended treatment with IFM-alpha when the patient is less than or equal to 50 years of age and has an HLA-compatible unrelated volunt eer donor. (C) 1998 by The American Society of Hematology.