Defibrotide Shows Efficacy in the Prevention of Sinusoidal Obstruction Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation : A Retrospective Study

Article Article scientifique Article Defibrotide Shows Efficacy in the Prevention of Sinusoidal Obstruction Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation : A Retrospective Study eng 2022-08-08 2022-11 author Chalandon Yves Division of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address: yves.chalandon@hcuge.ch. 644957 Département de médecine (DEMED) author Mamez Anne-Claire Division of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland. 918000 author Giannotti Federica Division of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland. 918560 author Beauverd Yan Division of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland. 515148 author Dantin Carole Alice Division of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland. 90319 author Mahne Elif Division of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland. 402559 author Mappoura Maria Division of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland. 863815 author Bernard Fanette Cansearch Research platform for pediatric oncology and hematology, Faculty of Medicine, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Geneva, Switzerland; Division of Pediatric Oncology and Hematology, Department of Women, Child and Adolescent, University Geneva Hospitals, Geneva, Switzerland. 810499 author De Ramon Ortiz Carmen Julia Division of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland. 898352 author Stephan Caroline Division of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland. 515584 author Morin Sarah Division of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland. 935831 author Ansari Djaberi Marc Georges Faculty of Medicine, University of Geneva, Geneva, Switzerland; Cansearch Research platform for pediatric oncology and hematology, Faculty of Medicine, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Geneva, Switzerland; Division of Pediatric Oncology and Hematology, Department of Women, Child and Adolescent, University Geneva Hospitals, Geneva, Switzerland. 61572 Département de Pédiatrie, Gynécologie et Obstétrique (PETRI) author Simonetta Federico Division of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland. 936876 Département de médecine (DEMED) author Masouridi Levrat Stavroula Division of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland. 844685 Département de médecine (DEMED) 765.e1-765.e9 10.1016/j.jtct.2022.08.003 35953029 2666-6367 Sinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a well-known complication of allogeneic hematopoietic stem cell transplantation (HSCT) associated with a mortality rate of up to 85%. Defibrotide has shown efficacy in treatment of SOS/VOD. Moreover, evidence exists supporting the efficacy of defibrotide as SOS/VOD prophylaxis. We have previously reported our single center experience on 52 HSCT recipients receiving defibrotide as SOS/VOD prophylaxis, which has shown that the patients did not develop any SOS/VOD under this prophylaxis. The aim of the present study was to see if we can confirm the previous results, mainly on the decrease incidence of SOS/VOD, as well as improve event-free survival (EFS) on a larger study population. We extended our previous study in a single-center retrospective analysis to include 237 consecutive patients (248 transplantations) who underwent transplantation between 1999 and 2009 for hematological diseases and receiving intravenous defibrotide as prophylaxis. This cohort was compared to 241 patients (248 transplantations) treated before 1999 or after 2009 when defibrotide prophylaxis was not routinely used in our center. Median follow-up for the study group was 10 (range 2-16) years and for the control group 2.7 (range 1-18) years. None of the 237 patients in the defibrotide group developed SOS/VOD. The cumulative incidence (CI) of SOS/VOD was 0% in the defibrotide group as compared to 4.8% (95% confidence interval [CI], 2.6-8%; P= .00046) in the control group. There was also a better 1-year EFS with 38% (95% CI, 32%-44%) in the defibrotide group versus 28% (95% CI, 22%-34%) (P= .00969) and decreased cumulative incidence of acute graft-versus-host disease (GvHD) in the defibrotide group 31% (95% CI, 25%-37%) versus 42% (95% CI, 36%-48%) (P= .026). The 1-year overall survival, relapse incidence, and non-relapse mortality were not statistically different. Multivariable analysis, performed taking into account clinical factors known to influence the risk of SOS/VOD, confirmed the favorable impact of defibrotide on SOS/VOD (HR 1.38e-08 [95% CI, 3.28e-09-5.80e-08]; P< .00001). Conversely, multivariable analysis failed to confirm the impact of defibrotide on 1-year EFS or acute GvHD. This large retrospective study on SOS/VOD-prophylaxis with defibrotide suggests that this approach may be of benefit. These results need to be confirmed in a prospective randomized trial. Allogeneic stem cell transplantation Defibrotide Prophylaxis Veno-occlusive disease Humans Hepatic Veno-Occlusive Disease / drug therapy Retrospective Studies Prospective Studies Graft vs Host Disease / prevention & control Hematopoietic Stem Cell Transplantation / adverse effects Dewey 616 Dewey 618 58 Département de pédiatrie, gynécologie et obstétrique 223 56 Département de médecine 221 false 564 Oncologie et hématologie pédiatriques 907 1216 Leucémie et transplantation allogénique de cellules souches hématopoïétiques 982 1426 Thérapie cellulaire et transplantation 1054 Transplantation and cellular therapy 28 11 4f80a851-a657-45c3-b6e8-f485732f08c0 Article (Published version) Public 1-s2.0-S2666636722015202-main.pdf 751497 application/pdf CC BY-4.0 d93c87761078c43e32e629a418aff897e50d2011132fc9ddefea7d42b9d89bf6 openAccess Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique Faculté de médecine / Section de médecine clinique / Département de médecine

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Defibrotide Shows Efficacy in the Prevention of Sinusoidal Obstruction Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation : A Retrospective Study	Transplantation and cellular therapy			2022	139	216

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