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.
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.
Uderzo
C
C
Centro Trapianti di Midollo Osseo, Clinica Pediatrica e, Ospedale San Gerardo di Monza Università di Milano Bicocca, Milano, Italy. cornelio.uderzo@pediatriamonza.it
Pillon
M
M
Corti
P
P
Tridello
G
G
Tana
F
F
Zintl
F
F
Nysom
K
K
Galambrun
C
C
Fagioli
F
F
Varotto
S
S
Messina
C
C
Verdeguer
A
A
Urban
C
C
Faraci
M
M
Dini
G
G
Fedeli
S
S
Tichelli
A
A
Rovelli
A
A
Socié
G
G
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
D018943:Anthracyclines