Influence of creatinine levels on survival in patients with veno-occlusive disease treated with defibrotide = Influence of creatinine levels on survival in patients with veno-occlusive disease treated with defibrotide

다국어 초록 (Multilingual Abstract)

Background/Aims: Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is one of the most fatal complications of hematopoietic cell transplantation (HCT), and defibrotide is the only curative drug. We conducted this study to confirm the survival rate of VOD/SOS patients diagnosed in Korea and assess the efficacy of defibrotide.
Methods: Patients diagnosed with VOD/SOS after allogenic HCT between 2003 and 2020 were enrolled. We investigated day +100 survival rates and associated risk factors in patients who satisfied the modified Seattle criteria within 50 days of HCT.
Results: A total of 110 patients satisfied the modified Seattle criteria, of which 65.5% satisfied the Baltimore criteria. Thirty-seven patients were treated with defibrotide. The day +100 survival rate of the 110 patients was 65.3%. The survival rates in patients who did not meet the Baltimore criteria and in those who did were 86.8% and 53.7%, respectively (p = 0.001). The day +100 survival rate of patients treated with defibrotide was 50.5%. Among the patients receiving defibrotide, those whose creatinine levels were more than 1.2 times the baseline had a significantly lower survival rate at 26.7% (p = 0.014). On multivariate regression analysis, the hazard ratio of satisfaction of the Baltimore criteria was 4.54 (95% confidence interval [CI], 1.69 to 12.21; p = 0.003). In patients treated with defibrotide, the hazard ratio was 8.70 (95% CI, 2.26 to 33.45; p = 0.002), when creatinine was more than 1.2 times the baseline on administration.
Conclusions: The day +100 survival rate was significantly lower when the Baltimore criteria were satisfied, and when there was an increase in creatinine at the time of defibrotide administration.

참고문헌 (Reference)

1 Jones RJ, "Venoocclusive disease of the liver following bone marrow transplantation" 44 : 778-783, 1987

2 McDonald GB, "Venocclusive disease of the liver after bone marrow transplantation : diagnosis, incidence, and predisposing factors" 4 : 116-122, 1984

3 Richardson PG, "The use of defibrotide in blood and marrow transplantation" 2 : 1495-1509, 2018

4 Carreras E, "The incidence of veno-occlusive disease following allogeneic hematopoietic stem cell transplantation has diminished and the outcome improved over the last decade" 17 : 1713-1720, 2011

5 Richardson P, "Systematic review of defibrotide studies in the treatment of veno-occlusive disease/sinusoidal obstruction syndrome(VOD/SOS)" 54 : 1951-1962, 2019

6 Mohty M, "Sinusoidal obstruction syndrome/veno-occlusive disease : current situation and perspectives-a position statement from the European Society for Blood and Marrow Transplantation(EBMT)" 50 : 781-789, 2015

7 Park M, "Safety and effects of prophylactic defibrotide for sinusoidal obstruction syndrome in hematopoietic stem cell transplantation" 18 : 36-42, 2013

8 Mohty M, "Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients : a new classification from the European Society for Blood and Marrow Transplantation" 51 : 906-912, 2016

9 Chalandon Y, "Prevention of veno-occlusive disease with defibrotide after allogeneic stem cell transplantation" 10 : 347-354, 2004

10 Richardson PG, "Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure" 127 : 1656-1665, 2016

11 Fink JC, "Marked enzymuria after bone marrow transplantation : a correlate of veno-occlusive disease-induced"hepatorenal syndrome"" 6 : 1655-1660, 1995

12 Corbacioglu S, "Incidence of anicteric veno-occlusive disease/sinusoidal obstruction syndrome and outcomes with defibrotide following hematopoietic cell transplantation in adult and pediatric patients" 26 : 1342-1349, 2020

13 Ragoonanan D, "Improved detection of sinusoidal obstructive syndrome using pediatric-AYA diagnostic criteria and severity grading" 56 : 175-184, 2021

14 Carreras E, "How I manage sinusoidal obstruction syndrome after haematopoietic cell transplantation" 168 : 481-491, 2015

15 Coppell JA, "Hepatic veno-occlusive disease following stem cell transplantation : incidence, clinical course, and outcome" 16 : 157-168, 2010

16 Kernan NA, "Final results from a defibrotide treatment-IND study for patients with hepatic veno-occlusive disease/sinusoidal obstruction syndrome" 181 : 816-827, 2018

17 Richardson PG, "Earlier defibrotide initiation post-diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome improves day +100 survival following haematopoietic stem cell transplantation" 178 : 112-118, 2017

18 Tekgunduz E, "Does defibrotide prophylaxis decrease the risk of acute graft versus host disease following allogeneic hematopoietic cell transplantation?" 54 : 30-34, 2016

19 Corbacioglu S, "Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in pediatric patients : a new classification from the European society for blood and marrow transplantation" 53 : 138-145, 2018

20 Corbacioglu S, "Defibrotide in the treatment of children with veno-occlusive disease(VOD) : a retrospective multicentre study demonstrates therapeutic efficacy upon early intervention" 33 : 189-195, 2004

21 Strouse C, "Defibrotide for treatment of severe veno-occlusive disease in pediatrics and adults : an exploratory analysis using data from the center for international blood and marrow transplant research" 22 : 1306-1312, 2016

22 Corbacioglu S, "Defibrotide for the treatment of hepatic veno-occlusive disease : final results from the International Compassionate-Use Program" 22 : 1874-1882, 2016

23 Corbacioglu S, "Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation : an open-label, phase 3, randomised controlled trial" 379 : 1301-1309, 2012

24 Corbacioglu S, "Defibrotide for children and adults with hepatic veno-occlusive disease post hematopoietic cell transplantation" 11 : 885-898, 2017

25 Aziz MT, "Defibrotide : an oligonucleotide for sinusoidal obstruction syndrome" 52 : 166-174, 2018

26 Kammersgaard MB, "Assessment of the proposed EBMT pediatric criteria for diagnosis and severity grading of sinusoidal obstruction syndrome" 54 : 1406-1418, 2019

27 Blostein MD, "A comparison of clinical criteria for the diagnosis of veno-occlusive disease of the liver after bone marrow transplantation" 10 : 439-443, 1992