title: Serum bilirubin levels and mortality after myeloablative allogeneic hematopoietic cell transplantation.
abstract: Many patients who undergo hematopoietic cell transplantation experience liver injury. We examined the association of serum bilirubin levels with nonrelapse mortality by day +200, testing the hypothesis that the duration of jaundice up to a given point in time provides more prognostic information than either the maximum bilirubin value or the value at that point in time. We studied 1,419 consecutive patients transplanted from allogeneic donors. Total serum bilirubin values up to day +100, death, or relapse were retrieved-along with nonrelapse mortality by day +200 as an outcome measure--using Cox regression models with each bilirubin measure modeled as a time-dependent covariate. The bilirubin value at a particular point in time provided the best fit to the model for mortality. With bilirubin at a point in time modeled as an 8th-degree polynomial, an increase in bilirubin from 1 to 3 mg/dL is associated with a mortality hazard ratio of 6.42. An increase from 4 to 6 mg/dL yields a hazard ratio of 2.05, and an increase from 10 to 12 mg/dL yields a hazard ratio of 1.17. Among patients who were deeply jaundiced, survival was related to the absence of multiorgan failure and to higher platelet counts. In conclusion, the value of total serum bilirubin at a particular point in time after transplant carries more informative prognostic information than does the maximum or average value up to that point in time. The increase in mortality for a given increase in bilirubin value is larger when the starting value is lower.
authors.affiliation: Section of Clinical Statistics, Clinical Research Division, Fred Hutchinson Cancer Research Center, and the University of Washington School of Medicine, Seattle, WA 98109-1024, USA.
authors.forename: Ted A
authors.initials: TA
authors.lastname: Gooley
authors.forename: Pankaj
authors.initials: P
authors.lastname: Rajvanshi
authors.forename: H Gary
authors.initials: HG
authors.lastname: Schoch
authors.forename: George B
authors.initials: GB
authors.lastname: McDonald
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001663:Bilirubin / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006801:Humans; D006932:Hyperbilirubinemia / Q000503:physiopathology; D007223:Infant; D007565:Jaundice / Q000097:blood / Q000150:complications / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D010976:Platelet Count; D016016:Proportional Hazards Models; D012720:Severity of Illness Index; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D019653:Myeloablative Agonists; D001663:Bilirubin