title: Prolonged administration of interferon-alpha in patients with chronic-phase Philadelphia chromosome-positive chronic myelogenous leukemia before allogeneic bone marrow transplantation may adversely affect transplant outcome.
abstract: To assess the influence of pretransplant cytoreductive therapy with special reference to interferon-alpha (IFN-alpha) treatment on major endpoints of allogeneic bone marrow transplantation (BMT), we studied 133 consecutive patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) in first chronic phase who received marrow grafts from HLA-identical family (n = 103) or alternative donors (n = 30) at a referral-based transplant center. Fifty of these patients (38%) were previously exposed to IFN-alpha for a median duration of 14 months (range, 1 to 61 months), whereas 83 patients (62%) exclusively received hydroxyurea and/or busulfan therapy between 1 and 129 months (median, 15 months) pretransplant. Using the categorized treatment duration with each pretransplant cytoreductive agent as a measure for individual patient exposure to each agent, prolonged ( > 12 months) IFN-alpha administration was identified as the sole significant pretransplant therapy-related predictor of transplant outcome by proportional hazards regression analysis. The adjusted risk ratio (RR) of transplant-related mortality (TRM) was 2.5-fold higher (95% confidence limits [95% CL], 1.4 to 4.5; P < .004) compared with other pretransplant therapy and this was mainly attributable to a 3.1-fold higher RR (95% CL, 1.4 to 6.4; P < .005) of fatal posttransplant infections after prolonged IFN-alpha treatment pretransplant. Marrow graft failure developed exclusively among 7 of 30 patients (23%) with donors other than HLA-identical family members and was further restricted to patients who had been previously exposed to IFN-alpha. The probability of graft failure was 49% +/- 28% in 17 patients pretreated with IFN-alpha compared with 0% for the other 13 patients with mismatched family or unrelated donors (P < .008). In addition, a significant delay in neutrophil and platelet count reconstitution was observed among patients with donors other than HLA-identical family members after pretransplant IFN-alpha exposure. No influence of pretransplant cytoreductive therapy on either acute and chronic graft-versus-host disease or leukemic relapse was detected in this study. As a consequence of its adverse effect on TRM, prolonged pretransplant IFN-alpha treatment was independently associated with a 2.5-fold lower likelihood (95% CL, 1.4 to 4.5; P < .003) of 5-year overall survival and with a 2.3-fold lower likelihood (95% CL, 1.3 to 4.2; P < .004) of 5-year disease-free survival postransplant after adjustment for other significant prognostic factors in multivariate analysis.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Bone Marrow Transplantation, University Hospital of Essen, Germany.
authors.forename: D W
authors.initials: DW
authors.lastname: Beelen
authors.forename: U
authors.initials: U
authors.lastname: Graeven
authors.forename: A H
authors.initials: AH
authors.lastname: Elmaagacli
authors.forename: N
authors.initials: N
authors.lastname: Niederle
authors.forename: O
authors.initials: O
authors.lastname: Kloke
authors.forename: B
authors.initials: B
authors.lastname: Opalka
authors.forename: U W
authors.initials: UW
authors.lastname: Schaefer
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000401:mortality; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000150:complications; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D016898:Interferon-alpha