Risk factors analysis and defibrotide efficacy in the treatment of children and adults with sinusoidal obstructive syndrome/veno-occlusive liver disease after allogeneic hematopoietic stem cell transplantation
M. M. Kanunnikov,
J. Z. Rakhmanova, 
M. V. Barabanshikova,
N. V. Levkovsky,
A. I. Wafina,
O. V. Paina,
T. A. Bykova,
Е. V. Semenova,
О. V. Goloshapov,
E. V. Morozova,
I. S. Mоiseev,
L. S. Zubarovskaya
M. V. Barabanshikova,
N. V. Levkovsky,
A. I. Wafina,
O. V. Paina,
T. A. Bykova,
Е. V. Semenova,
О. V. Goloshapov,
E. V. Morozova,
I. S. Mоiseev,
L. S. Zubarovskaya https://doi.org/10.24884/1607-4181-2020-27-4-62-70
Abstract
Introduction. Sinusoidal obstructive syndrome (SOS)/veno-occlusive liver disease (VOD) is one of the most dangerous complication of allogeneic hematopoietic stem cell transplantation (alloHSCT).
The objective of our study was to analyze risk factors associated with SOS/VOD in children and adults after alloHSCT.
Methods and materials. The study included 76 patients who were diagnosed with the development of SOS/VOD after alloHSCT performed in Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation between 2001 and 2019. 25 patients (32.9 %) were younger than 18 years, 51 patients (68.1 %) — 18 years and older. Among them, 17 patients were treated with defibrotide at a dose of 25 mg/kg per day, median therapy duration — 21 day.
Results. One-year overall survival (OS) was significantly higher when partial and complete response to the therapy was achieved — 45 %, than when there was no response — 0 % in the general group (p = 0.001). According to the results of multivariate analysis of unrelated alloHSCT HR 2.040 (95 %CI 1.112-3.744, р = 0.021), acute GVHD HR 0.496 (95 % CI 0.272-0.903, р = 0.022), moderate/severe SOS/VOD HR 2.423 (95 % CI 1.298-4.524, p = 0.005) statistically significantly influenced the 1-year OS. Defibrotide and accompanying therapy did not significantly influence the 1-year OS in children and adults (n=76) - 53 % and 54 % (p=0.86), respectively. In a multivariate analysis. unrelated alloHSCT HR 8.172 (95 %CI 2.176-30.696, р=0.002) and moderate and severe SOS/VOD HR 9.077 (95 % CI 2.425-33.978, р=0.001) significantly influenced the 1-year OS in the pediatric group.
Conclusion. The understanding of risk factors of adverse prognosis in patients SOS/VOD facilitates selection of patients who will benefit the most from therapy with defibrotide. Early administration of defibrotide in the course of VOD/SOS is crucial to achieve response.
About the Authors
M. M. Kanunnikov
Pavlov University
Russian Federation
Competing Interests:
Russian Federation
Kanunnikov Mikhail М. - Hematologist, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov University.
Saint Petersburg.
Competing Interests:
Authors declare no conflict of interest.
J. Z. Rakhmanova
Pavlov University
Russian Federation
Competing Interests:
Russian Federation
Rakhmanova Jemal Z. - Pediatrician, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov University.
Saint Petersburg.
Competing Interests:
Authors declare no conflict of interest.
M. V. Barabanshikova
Pavlov University
Russian Federation
Competing Interests:
Russian Federation
Barabanshikova Maria V. - Cand. of Sci. (Med.), Senior Research Fellow of the Department of Pediatric Oncology, Hematology and Transplantology, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov University.
Saint Petersburg.
Competing Interests:
Authors declare no conflict of interest.
N. V. Levkovsky
Pavlov University
Russian Federation
Competing Interests:
Russian Federation
Levkovsky Nikita V. - Student, Pavlov University.
Saint Petersburg.
Competing Interests:
Authors declare no conflict of interest.
A. I. Wafina
Pavlov University
Russian Federation
Competing Interests:
Russian Federation
Wafina Alia I. - Student, Pavlov University.
Saint Petersburg.
Competing Interests:
Authors declare no conflict of interest.
O. V. Paina
Pavlov University
Russian Federation
Competing Interests:
Russian Federation
Paina Olesya V. - Cand. of Sci. (Med.), Head of the Department of Bone Marrow Transplantation for Children № 1 of the Clinic of the Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov University.
Saint Petersburg.
Competing Interests:
Authors declare no conflict of interest.
T. A. Bykova
Pavlov University
Russian Federation
Competing Interests:
Russian Federation
Bykova Тatjana А. - Cand. of Sci. (Med.), Head of the Department of Bone Marrow Transplantation for Children with Orphan Diseases, of the Clinic of the Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov University.
Saint Petersburg.
Competing Interests:
Authors declare no conflict of interest.
Е. V. Semenova
Pavlov University
Russian Federation
Competing Interests:
Russian Federation
Semenova Еlena V. - Dr. of Sci. (Med.), Professor of the Department of Hematology, Transfusiology and Transplantology, Dean of the Faculty of Pediatrics, Pavlov University.
Saint Petersburg.
Competing Interests:
Authors declare no conflict of interest.
О. V. Goloshapov
Pavlov University
Russian Federation
Competing Interests:
Russian Federation
Goloshapov Oleg V. - Head of the Department of Resuscitation and Intensive Care of the Clinic of the Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov University.
Saint Petersburg.
Competing Interests:
Authors declare no conflict of interest.
E. V. Morozova
Pavlov University
Russian Federation
Competing Interests:
Russian Federation
Morozova Еlena V. - Cand. of Sci. (Med.), Associate Professor of the Department of Hematology, Transfusiology and Transplantology, Pavlov University.
Saint Petersburg.
Competing Interests:
Authors declare no conflict of interest.
I. S. Mоiseev
Pavlov University
Russian Federation
Competing Interests:
Russian Federation
Mоiseev Ivan S. - Dr. of Sci. (Med.), Associate Professor, Deputy Director for Scientific Work, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov University.
Saint Petersburg.
Competing Interests:
Authors declare no conflict of interest.
L. S. Zubarovskaya
Pavlov University
Russian Federation
Competing Interests:
Russian Federation
Zubarovskaya Ludmila S. - Dr. of Sci. (Med.), Professor, Head of the Department of Pediatric Oncology, Hematology and Transplantology, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov University.
Saint Petersburg.
Competing Interests:
Authors declare no conflict of interest.
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Kanunnikov M.M., Rakhmanova J.Z., Barabanshikova M.V., Levkovsky N.V., Wafina A.I., Paina O.V., Bykova T.A., Semenova Е.V., Goloshapov О.V., Morozova E.V., Mоiseev I.S., Zubarovskaya L.S. Risk factors analysis and defibrotide efficacy in the treatment of children and adults with sinusoidal obstructive syndrome/veno-occlusive liver disease after allogeneic hematopoietic stem cell transplantation. The Scientific Notes of the Pavlov University. 2020;27(4):62-70. (In Russ.) https://doi.org/10.24884/1607-4181-2020-27-4-62-70
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