title: Incidence, characteristics and risk factors of marked hyperbilirubinemia after allogeneic hematopoietic cell transplantation with reduced-intensity conditioning.
abstract: To analyze the incidence, characteristics and risk factors of hyperbilirubinemia after allogeneic hematopoietic cell transplantation with reduced-intensity conditioning (allo-RIC), we conducted a retrospective study in three Spanish centers. We analyzed 452 consecutive patients receiving allo-RIC. Of these, 92 patients (20%) developed marked hyperbilirubinemia (>4 mg/day or >68.4 μM) after allo-RIC. The main causes of marked hyperbilirubinemia after transplant were cholestasis due to GVHD or sepsis (n=57, 62%) and drug-induced cholestasis (n=13, 14%). A total of 22 patients with marked hyperbilirubinemia (24%) underwent liver biopsy. The most frequent histological finding was iron overload alone (n=6) or in combination with other features (n=6). In multivariate analysis, the risk factors for marked hyperbilirubinemia after allo-RIC were non-HLA-identical sibling donors (hazard ratio (HR) 2.2 (95% confidence interval (CI) 1.4-3.6) P=0.001), female donors to male recipients (HR 2.1 (95% CI 1.3-3.3) P=0.003) and high levels of bilirubin and γ-glutamyl transpeptidase before transplant (HR 4.5 (95% CI 2.5-8.4) P<0.001 and HR 4.6 (95% CI 2.6-8.1) P<0.001, respectively). Patients with marked hyperbilirubinemia showed higher 4-year nonrelapse mortality (HR 1.3 (95% CI 1-1.7), P=0.02) and lower 4-year OS (HR 1.4 (95%CI 1.3-1.7), P<0.001) than patients without. In conclusion, we confirm that marked hyperbilirubinemia is frequent and diverse after allo-RIC. Development of marked hyperbilirubinemia after allo-RIC is associated with worse outcome of the procedure.
authors.affiliation: Department of Hematology, Hospital de la Santa Creu i Sant Pau de Barcelona, Barcelona, Spain. pebarba@vhebron.net
authors.forename: P
authors.initials: P
authors.lastname: Barba
authors.forename: R
authors.initials: R
authors.lastname: Martino
authors.forename: J A
authors.initials: JA
authors.lastname: Perez-Simón
authors.forename: F
authors.initials: F
authors.lastname: Fernández-Avilés
authors.forename: J L
authors.initials: JL
authors.lastname: Piñana
authors.forename: D
authors.initials: D
authors.lastname: Valcárcel
authors.forename: I
authors.initials: I
authors.lastname: Campos-Varela
authors.forename: L
authors.initials: L
authors.lastname: Lopez-Anglada
authors.forename: M
authors.initials: M
authors.lastname: Rovira
authors.forename: S
authors.initials: S
authors.lastname: Novelli
authors.forename: L
authors.initials: L
authors.lastname: Lopez-Corral
authors.forename: E
authors.initials: E
authors.lastname: Carreras
authors.forename: J
authors.initials: J
authors.lastname: Sierra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D006932:Hyperbilirubinemia / Q000097:blood / Q000209:etiology / Q000401:mortality* / Q000473:pathology; D015994:Incidence; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D035781:Siblings; D015996:Survival Rate; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous