TY - JOUR
T1 - Outcome of haematopoietic stem cell transplantation in dyskeratosis congenita
AU - Fioredda, Francesca
AU - Iacobelli, Simona
AU - Korthof, Elisabeth T.
AU - Knol, Cora
AU - van Biezen, Anja
AU - Bresters, Dorine
AU - Veys, Paul
AU - Yoshimi, Ayami
AU - Fagioli, Franca
AU - Mats, Brune
AU - Zecca, Marco
AU - Faraci, Maura
AU - Miano, Maurizio
AU - Arcuri, Luca
AU - Maschan, Michael
AU - O'Brien, Tracey
AU - Diaz, Miguel A.
AU - Sevilla, Julian
AU - Smith, Owen
AU - Peffault de Latour, Regis
AU - de la Fuente, Josue
AU - Or, Reuven
AU - Van Lint, Maria T.
AU - Tolar, Jakub
AU - Aljurf, Mahmoud
AU - Fisher, Alain
AU - Skorobogatova, Elena V.
AU - Diaz de Heredia, Cristina
AU - Risitano, Antonio
AU - Dalle, Jean Hugues
AU - Sedláček, Petr
AU - Ghavamzadeh, Ardeshir
AU - Dufour, Carlo
N1 - Publisher Copyright:
© 2018 British Society for Haematology and John Wiley & Sons Ltd
PY - 2018/10
Y1 - 2018/10
N2 - Dyskeratosis congenita (DC) is a genetic multisystem disorder with frequent involvement of the bone marrow. Haematopoietic stem cell transplantation (HSCT) is the only definitive cure to restore haematopoiesis, even though it cannot correct other organ dysfunctions. We collected data on the outcome of HSCT in the largest cohort of DC (n = 94) patients ever studied. Overall survival (OS) and event-free survival (EFS) at 3 years after HSCT were 66% and 62%, respectively. Multivariate analysis showed better outcomes in patients aged less than 20 years and in patients transplanted from a matched, rather than a mismatched, donor. OS and EFS curves tended to decline over time. Early lethal events were infections, whereas organ damage and secondary malignancies appeared afterwards, even a decade after HSCT. A non-myeloablative conditioning regimen appeared to be most advisable. Organ impairment present before HSCT seemed to favour the development of chronic graft-versus-host disease and T-B immune deficiency appeared to enhance pulmonary fibrosis. According to the present data, HSCT in DC is indicated in cases of progressive marrow failure, whereas in patients with pre-existing organ damage, this should be carefully evaluated. Further efforts to investigate treatment alternatives to HSCT should be encouraged.
AB - Dyskeratosis congenita (DC) is a genetic multisystem disorder with frequent involvement of the bone marrow. Haematopoietic stem cell transplantation (HSCT) is the only definitive cure to restore haematopoiesis, even though it cannot correct other organ dysfunctions. We collected data on the outcome of HSCT in the largest cohort of DC (n = 94) patients ever studied. Overall survival (OS) and event-free survival (EFS) at 3 years after HSCT were 66% and 62%, respectively. Multivariate analysis showed better outcomes in patients aged less than 20 years and in patients transplanted from a matched, rather than a mismatched, donor. OS and EFS curves tended to decline over time. Early lethal events were infections, whereas organ damage and secondary malignancies appeared afterwards, even a decade after HSCT. A non-myeloablative conditioning regimen appeared to be most advisable. Organ impairment present before HSCT seemed to favour the development of chronic graft-versus-host disease and T-B immune deficiency appeared to enhance pulmonary fibrosis. According to the present data, HSCT in DC is indicated in cases of progressive marrow failure, whereas in patients with pre-existing organ damage, this should be carefully evaluated. Further efforts to investigate treatment alternatives to HSCT should be encouraged.
KW - bone marrow failure
KW - dyskeratosis congenita
KW - haematopoietic stem cell transplantation
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U2 - 10.1111/bjh.15495
DO - 10.1111/bjh.15495
M3 - Article
C2 - 29984823
AN - SCOPUS:85050608456
SN - 0007-1048
VL - 183
SP - 110
EP - 118
JO - British journal of haematology
JF - British journal of haematology
IS - 1
ER -