PMID- 29945939
OWN - NLM
STAT- MEDLINE
DCOM- 20190416
LR  - 20190416
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 2
IP  - 12
DP  - 2018 Jun 26
TI  - The use of defibrotide in blood and marrow transplantation.
PG  - 1495-1509
LID - 10.1182/bloodadvances.2017008375 [doi]
AB  - Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a 
      potentially life-threatening complication of conditioning during hematopoietic 
      stem cell transplantation (HSCT) or chemotherapy without HSCT, with a 
      historically reported mean incidence of 13.7% post-HSCT. Typical symptoms of 
      VOD/SOS may include hyperbilirubinemia, painful hepatomegaly, weight gain, and 
      ascites. Defibrotide, a polydisperse mixture of predominantly single-stranded 
      polydeoxyribonucleotides, is currently the only therapy approved to treat hepatic 
      VOD/SOS with pulmonary/renal dysfunction (ie, multiorgan dysfunction/multiorgan 
      failure [MOD/MOF]) following HSCT in the United States and to treat severe 
      hepatic VOD/SOS post-HSCT in the European Union. In preclinical and human 
      studies, defibrotide has demonstrated profibrinolytic, antithrombotic, 
      anti-inflammatory, and angio-protective actions, thus promoting an anticoagulant 
      phenotype of the endothelium that protects and stabilizes the function of 
      endothelial cells. In a phase 3, historically controlled, multicenter trial in 
      adults and children with VOD/SOS and MOD/MOF (defibrotide: n = 102; controls 
      treated before defibrotide availability: n = 32), defibrotide resulted in 
      significantly greater day +100 survival following HSCT (38.2%) vs controls 
      (25.0%; propensity analysis-estimated between-group difference: 23%; P = .0109). 
      The most common adverse events (AEs) were hypotension and diarrhea; rates of 
      common hemorrhagic AEs were similar in the defibrotide and historical control 
      group (64% and 75%, respectively). In a phase 3 prophylaxis trial, defibrotide 
      was found to lower incidence of VOD/SOS in children (not an approved indication) 
      and reduce the incidence of graft-versus-host disease. This review describes the 
      development and clinical applications of defibrotide, focusing on its on-label 
      use in patients with VOD/SOS and MOD/MOF after HSCT.
CI  - (c) 2018 by The American Society of Hematology.
FAU - Richardson, Paul G
AU  - Richardson PG
AD  - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
FAU - Carreras, Enric
AU  - Carreras E
AD  - Spanish Bone Marrow Donor Program, Josep Carreras Leukemia Foundation and 
      Leukemia Research Institute, Barcelona, Spain.
FAU - Iacobelli, Massimo
AU  - Iacobelli M
AD  - Techitra s.r.l., Milan, Italy; and.
FAU - Nejadnik, Bijan
AU  - Nejadnik B
AD  - Galena Biopharma, San Ramon, CA.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Polydeoxyribonucleotides)
RN  - 438HCF2X0M (defibrotide)
SB  - IM
EIN - Blood Adv. 2018 Aug 14;2(15):1853. PMID: 30061309
MH  - Bone Marrow Transplantation/*adverse effects/methods
MH  - Fibrinolytic Agents/therapeutic use
MH  - Hematopoietic Stem Cell Transplantation/*adverse effects/methods
MH  - Hepatic Veno-Occlusive Disease/drug therapy/etiology
MH  - Humans
MH  - Multiple Organ Failure/diet therapy/etiology
MH  - Polydeoxyribonucleotides/*therapeutic use
PMC - PMC6020812
COIS- Conflict-of-interest disclosure: P.G.R. has served on advisory committees and 
      received research funding from Jazz Pharmaceuticals. E.C. has served on advisory 
      boards and the speakers bureau for, received research funding from, and provided 
      expert testimony for Gentium. M.I. was formerly an employee of Gentium. B.N. was 
      formerly an employee of Jazz Pharmaceuticals; in the course of employment, he 
      received stock options exercisable for, and other stock awards of, ordinary 
      shares of Jazz Pharmaceuticals plc.
EDAT- 2018/06/28 06:00
MHDA- 2019/04/17 06:00
PMCR- 2018/06/26
CRDT- 2018/06/28 06:00
PHST- 2017/11/03 00:00 [received]
PHST- 2018/04/30 00:00 [accepted]
PHST- 2018/06/28 06:00 [entrez]
PHST- 2018/06/28 06:00 [pubmed]
PHST- 2019/04/17 06:00 [medline]
PHST- 2018/06/26 00:00 [pmc-release]
AID - bloodadvances.2017008375 [pii]
AID - 2017/008375 [pii]
AID - 10.1182/bloodadvances.2017008375 [doi]
PST - ppublish
SO  - Blood Adv. 2018 Jun 26;2(12):1495-1509. doi: 10.1182/bloodadvances.2017008375.