title: Impact of cumulative anthracycline dose, preparative regimen and chronic graft-versus-host disease on pulmonary and cardiac function in children 5 years after allogeneic hematopoietic stem cell transplantation: a prospective evaluation on behalf of the EBMT Pediatric Diseases and Late Effects Working Parties.
abstract: This prospective study focused on risk factors and clinical outcome of pulmonary and cardiac late effects after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We prospectively evaluated 162 children by pulmonary function tests (PFTs) and cardiac shortening fraction (SF) before allo-HSCT and yearly up to the 5th year of follow-up. The 5-year cumulative incidence of lung and cardiac impairment was 35 (hazard rate=0.03) and 26% (hazard rate=0.06), respectively. Patients presenting abnormal PFTs and SF at last follow-up were 19 and 13%, respectively, with a median Lansky performance status of 90% (70-100). Chronic graft-versus-host disease (c-GVHD) was the major risk factor for reduced lung function in univariate (P=0.02) and multivariate analysis (P=0.02). Total body irradiation (TBI) alone and TBI together with pre-transplant anthracycline administration were significant risk factors for reduced cardiac function in univariate analysis, only (P=0.04 and 0.004, respectively). In conclusion, our prospective study demonstrates an asymptomatic post-allo-HSCT deterioration of pulmonary and cardiac function in some long-term survivors, who had been transplanted in childhood, and thus emphasizes the need for lifelong cardiopulmonary monitoring and the development of new strategies both to reduce pre-transplant cardiotoxic regimens and to treat more efficiently c-GVHD.
authors.affiliation: Centro Trapianti di Midollo Osseo, Clinica Pediatrica e, Ospedale San Gerardo di Monza Università di Milano Bicocca, Milano, Italy. cornelio.uderzo@pediatriamonza.it
authors.forename: C
authors.initials: C
authors.lastname: Uderzo
authors.forename: M
authors.initials: M
authors.lastname: Pillon
authors.forename: P
authors.initials: P
authors.lastname: Corti
authors.forename: G
authors.initials: G
authors.lastname: Tridello
authors.forename: F
authors.initials: F
authors.lastname: Tana
authors.forename: F
authors.initials: F
authors.lastname: Zintl
authors.forename: K
authors.initials: K
authors.lastname: Nysom
authors.forename: C
authors.initials: C
authors.lastname: Galambrun
authors.forename: F
authors.initials: F
authors.lastname: Fagioli
authors.forename: S
authors.initials: S
authors.lastname: Varotto
authors.forename: C
authors.initials: C
authors.lastname: Messina
authors.forename: A
authors.initials: A
authors.lastname: Verdeguer
authors.forename: C
authors.initials: C
authors.lastname: Urban
authors.forename: M
authors.initials: M
authors.lastname: Faraci
authors.forename: G
authors.initials: G
authors.lastname: Dini
authors.forename: S
authors.initials: S
authors.lastname: Fedeli
authors.forename: A
authors.initials: A
authors.lastname: Tichelli
authors.forename: A
authors.initials: A
authors.lastname: Rovelli
authors.forename: G
authors.initials: G
authors.lastname: Socié
mesh_terms: D000293:Adolescent; D018943:Anthracyclines / Q000008:administration & dosage* / Q000009:adverse effects; D002302:Cardiac Output; D002648:Child; D002675:Child, Preschool; D004452:Echocardiography; D005260:Female; D006086:Graft vs Host Disease / Q000503:physiopathology / Q000517:prevention & control*; D006331:Heart Diseases / Q000209:etiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D008171:Lung Diseases / Q000209:etiology*; D008297:Male; D011446:Prospective Studies; D012129:Respiratory Function Tests; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014184:Transplantation, Homologous / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines