title: Incidence and risk factors for early hepatotoxicity and its impact on survival in patients with myelofibrosis undergoing allogeneic hematopoietic cell transplantation.
abstract: Allogeneic hematopoietic cell transplantation (HCT) is commonly associated with hepatic complications. Patients with myelofibrosis (MF) often develop liver dysfunction in the early posttransplantation period; however, this has not yet been studied in a systematic fashion. We retrospectively evaluated 53 patients with MF who underwent HCT to assess the prevalence of acute liver toxicity and risk factors and the impact on survival. We compared the prevalence of acute hepatic complications in that group and a matched control group of 53 patients with myelodysplastic syndrome (MDS). In the MF group, during the first 6 weeks after HCT, the incidence of mild (34.2-102.6 μM), moderate (102.6-342 μM), and severe (>342 μM) hyperbilirubinemia was 34%, 40%, and 4%, respectively (normal, <22 μM). The incidence of mild/moderate transaminitis (2-10 times the upper limit of normal) was 23%, and that of severe transaminitis (>10 times the upper limit of normal) was 6%. Veno-occlusive disease as defined by the Baltimore criteria was observed in 19 patients (36%) in the MF group. Compared with MDS, MF was associated with a significantly higher incidence of moderate/severe hyperbilirubinemia (44% versus 21%; P = .02) and veno-occlusive disease (36% versus 19%; P = .05). A history of portal hypertension, biopsy-proven hepatic iron overload, or splanchnic vein thrombosis was a strong predictor of moderate/severe hyperbilirubinemia (P = .02). Acute hepatocellular injury with moderate/severe hyperbilirubinemia or transaminitis was associated with inferior survival at 12 months (P = .02) in the MF group. We conclude that patients with MF are at significant risk of early hepatotoxicity after HCT, which is associated with an adverse impact on survival.
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kit Man
authors.initials: KM
authors.lastname: Wong
authors.forename: Eshetu G
authors.initials: EG
authors.lastname: Atenafu
authors.forename: Dennis
authors.initials: D
authors.lastname: Kim
authors.forename: John
authors.initials: J
authors.lastname: Kuruvilla
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lipton
authors.forename: Hans
authors.initials: H
authors.lastname: Messner
authors.forename: Vikas
authors.initials: V
authors.lastname: Gupta
mesh_terms: D000328:Adult; D000368:Aged; D002170:Canada / Q000453:epidemiology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D006932:Hyperbilirubinemia / Q000453:epidemiology / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D015994:Incidence; D008099:Liver / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000453:epidemiology / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D055728:Primary Myelofibrosis / Q000453:epidemiology / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D016019:Survival Analysis; D013997:Time Factors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous