Defibrotide in hematopoietic stem cell transplantation: A multicenter survey study of the Spanish Hematopoietic Stem Cell Transplantation Group (GETH)
Por:
Vicent, MG, de Heredia, CD, de Pablo, JG, Molina, B, Regueiro, A, Martinez, AP, Palomo, P, Corral, LL, Garcia, E, Fernandez, JM, Perez, A, Jimenez, MJ, Guerreiro, M, Vallejo, C, Gallardo, AI, Lopez, O, Benito, A, Marsal, J, Duarte, M, Bento, L, Badell, I, Pedraza, A, Ubieto, AJ, Gonzalez, P, Centurion, IG, Costilla, L, Belendez, C, Esquirol, A, Espigado, I, Lavilla, E, Diaz, MA
Publicada:
1 jun 2021
Ahead of Print:
1 mar 2021
Resumen:
Background Defibrotide is approved in European Union for the treatment of severe sinusoidal obstruction syndrome (SOS) after HSCT. However, it has also been used for SOS prophylaxis, moderate SOS and in other complications such as transplant-associated thrombotic microangiopathy (TAM). The objective of this study was to evaluate current uses, effectiveness and safety of defibrotide in patients with HSCT.
Methods This multicenter, retrospective study included patients treated with defibrotide for any indication at 28 HSCT centers of the Grupo Espanol de Trasplante Hematopoyetico (GETH) including the pediatric subgroup Grupo Espanol de Trasplante de Medula en Ninos (GETMON).
Results Three hundred and eighty eight patients treated with defibrotide between January 2011 and December 2018 were included. 253 patients were children, and 135 patients were adults. In total, 332 transplants were allogeneic, and the remainder were autologous. Main indications for defibrotide use were severe/very severe SOS in 173 patients, SOS prophylaxis in 135 patients, moderate SOS in 41 patients, TAM in six patients and suspected SOS in 33 patients. Overall survival (OS) at day +100 in the SOS prophylaxis group was 89% (95% CI, 87%-91%). In the group of patients with moderate and severe/very severe SOS, the OS at day +100 was 80% (95% CI, 74%-86%) and 62% (95% CI, 59%-65%), respectively (P = .0015). With a longer follow-up, median of 2 years (4 months-7 years), OS was 63% (95% CI, 59%-67%) in the SOS prophylaxis patients. OS for patients with moderate and severe/very severe SOS groups was 53% (95% CI, 47%-61%) and 26% (95% CI, 22%-30%), respectively (P = .006). 191 patients died, and SOS was the main cause of death in 23 patients (12%).
Conclusions Defibrotide has an acceptable safety profile with an improved response in severe/very severe SOS compared with historical controls, mainly in pediatric patients. Use of defibrotide for prophylaxis may improve prognosis of patients at high risk of complications due to endothelial damage such as those who receive a second transplant. SOS has an important impact on the HSCT long-term survival, as can be concluded from our study.
Filiaciones:
Vicent, MG:
Hosp Nino Jesus, BMT Unit, Madrid, Spain
de Heredia, CD:
Hosp Vall de Hebron, BMT Unit, Barcelona, Spain
de Pablo, JG:
Hosp Nino Jesus, BMT Unit, Madrid, Spain
Molina, B:
Hosp Nino Jesus, BMT Unit, Madrid, Spain
Regueiro, A:
Hosp Clin Santiago, BMT Unit, Santiago De Compostela, Spain
Martinez, AP:
Hosp La Paz, BMT Unit, Madrid, Spain
Palomo, P:
Hosp Cent Asturias, BMT Unit, Oviedo, Spain
Corral, LL:
Hosp Univ Salamanca, BMT Unit, Salamanca, Spain
Garcia, E:
Hosp Reina Sofia, BMT Unit, Cordoba, Spain
Fernandez, JM:
Hosp La Fe, BMT Unit, Valencia, Spain
Perez, A:
Hosp Clin, BMT Unit, Valencia, Spain
Jimenez, MJ:
Hosp Germans Trias, BMT Unit, Barcelona, Spain
Guerreiro, M:
Hosp La Fe, BMT Unit, Valencia, Spain
Vallejo, C:
Hosp Univ Donosti, BMT Unit, San Sebastian, Spain
Gallardo, AI:
Hosp Reg Malaga, BMT Unit, Malaga, Spain
Lopez, O:
Hosp Morales Meseguer, BMT Unit, Murcia, Spain
Benito, A:
Hosp Reg Malaga, BMT Unit, Malaga, Spain
Marsal, J:
Hosp St Joan Deu, BMT Unit, Barcelona, Spain
Duarte, M:
Hosp Marques Valdecilla, BMT Unit, Santander, Spain
Bento, L:
Hosp Son Espases, BMT Unit, Mallorca, Spain
Badell, I:
Hosp Santa Creu & Sant Pau, BMT Unit, Barcelona, Spain
Pedraza, A:
Hosp Clin Barcelona, BMT Unit, Barcelona, Spain
Ubieto, AJ:
Hosp Doce Octubre, BMT Unit, Madrid, Spain
Gonzalez, P:
Hosp Virgen de las Nieves, BMT Unit, Granada, Spain
Centurion, IG:
Hosp Gregorio Maranon, BMT Unit, Madrid, Spain
Costilla, L:
Hosp Miguel Servet, BMT Unit, Zaragoza, Spain
Belendez, C:
Hosp Gregorio Maranon, BMT Unit, Madrid, Spain
Esquirol, A:
Hosp Santa Creu & Sant Pau, BMT Unit, Barcelona, Spain
Espigado, I:
Hosp Virgen del Rocio, BMT Unit, Seville, Spain
Lavilla, E:
Hosp Univ Lugo, BMT Unit, Lugo, Spain
Diaz, MA:
Hosp Nino Jesus, BMT Unit, Madrid, Spain
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