Heparanase Polymorphisms: Influence on Incidence of Hepatic Sinusoidal Obstruction Syndrome in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2014 Oct 23

PMID 25335953

Citations 16

Authors

Claudia Seifert

Susan Wittig

Clemens Arndt

Bernd Gruhn

Affiliations

Soon will be listed here.

Abstract

Purpose: Sinusoidal obstruction syndrome (SOS) is a life-threatening early complication after hematopoietic stem cell transplantation (HSCT), and until now, examinations about the influence of genetic risk factors are extremely rare. The purpose of this study was to identify an association between heparanase (HPSE) single nucleotide polymorphisms (SNPs) and SOS in children undergoing allogeneic HSCT.

Methods: We retrospectively analyzed the distribution of the both HPSE SNPs rs4693608 and rs4364254 and the occurrence of SOS after allogeneic HSCT in 160 children with malignant and non-malignant diseases.

Results: Patients with HPSE genotypes GG or AG of rs4693608 (G>A) had a significantly reduced incidence of SOS on day 100 after HSCT compared to patients with genotype AA (4.7 vs. 14.3 %, P = 0.038). In addition, incidence of SOS in patients with genotype CC or CT of rs4364254 (C>T) was significantly decreased in comparison with patients with genotype TT (2.3 vs. 14.7 %, P = 0.004). Interestingly, no patient with genotype CC developed SOS. Because both SNPs co-occur in vivo, we generated subsets: AA-TT, GG-CC, and a group with remaining SNP combinations. We found significant differences between all three patient groups (P = 0.035). Patients with AA-TT showed the highest incidence of SOS (16.7 %), while SOS did not appear in patients with GG-CC (0 %) and residual combinations were numerically in-between (4.9 %). An impact caused by main patient and donor characteristics, established risk factors for SOS, and conditioning regimen could be excluded in multivariate analyses.

Conclusions: HPSE polymorphisms turned out to be significant independent risk factors (P = 0.030) for development of SOS and should be evaluated in further trials.

Citing Articles

Hepatic Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease (SOS/VOD) Primary Prophylaxis in Patients Undergoing Hematopoietic Stem Cell Transplantation: A Network Meta-Analysis of Randomized Controlled Trials.

Sousa-Pimenta M, Martins A, Estevinho L, Vaz C, Leite L, Mariz J J Clin Med. 2024; 13(22).

PMID: 39598060 PMC: 11594704. DOI: 10.3390/jcm13226917.

Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill.

Evangelidis P, Evangelidis N, Kalmoukos P, Kourti M, Tragiannidis A, Gavriilaki E Curr Issues Mol Biol. 2024; 46(5):4787-4802.

PMID: 38785556 PMC: 11119915. DOI: 10.3390/cimb46050288.

Biomarkers for early complications post hematopoietic cell transplantation: Insights and challenges.

Balakrishnan B, Kulkarni U, Pai A, Stallon Illangeswaran R, Mohanan E, Mathews V Front Immunol. 2023; 14:1100306.

PMID: 36817455 PMC: 9932777. DOI: 10.3389/fimmu.2023.1100306.

The HPSE Gene Insulator-A Novel Regulatory Element That Affects Heparanase Expression, Stem Cell Mobilization, and the Risk of Acute Graft versus Host Disease.

Ostrovsky O, Baryakh P, Morgulis Y, Mayorov M, Bloom N, Beider K Cells. 2021; 10(10).

PMID: 34685503 PMC: 8534152. DOI: 10.3390/cells10102523.

Analysis of risk factors for hepatic sinusoidal obstruction syndrome following allogeneic hematopoietic stem cell transplantation in pediatric patients.

Kloehn J, Brodt G, Ernst J, Gruhn B J Cancer Res Clin Oncol. 2021; 148(6):1447-1455.

PMID: 34255148 PMC: 9114040. DOI: 10.1007/s00432-021-03732-1.

References

Chopra R, Eaton J, Grassi A, Potter M, Shaw B, Salat C . Defibrotide for the treatment of hepatic veno-occlusive disease: results of the European compassionate-use study. Br J Haematol. 2001; 111(4):1122-9. DOI: 10.1046/j.1365-2141.2000.02475.x. View

Corbacioglu S, Honig M, Lahr G, Stohr S, Berry G, Friedrich W . Stem cell transplantation in children with infantile osteopetrosis is associated with a high incidence of VOD, which could be prevented with defibrotide. Bone Marrow Transplant. 2006; 38(8):547-53. DOI: 10.1038/sj.bmt.1705485. View

Richardson P, Murakami C, Jin Z, Warren D, Momtaz P, Hoppensteadt D . Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure: response without significant toxicity in a high-risk population and factors predictive of outcome. Blood. 2002; 100(13):4337-43. DOI: 10.1182/blood-2002-04-1216. View

Mitsiades C, Rouleau C, Echart C, Menon K, Teicher B, Distaso M . Preclinical studies in support of defibrotide for the treatment of multiple myeloma and other neoplasias. Clin Cancer Res. 2009; 15(4):1210-21. PMC: 4401498. DOI: 10.1158/1078-0432.CCR-08-1270. View

Ostrovsky O, Korostishevsky M, Levite I, Leiba M, Galski H, Vlodavsky I . Association of heparanase gene (HPSE) single nucleotide polymorphisms with hematological malignancies. Leukemia. 2007; 21(11):2296-303. DOI: 10.1038/sj.leu.2404821. View

Elbahlawan L, McArthur J, Quasney M, Pei D, Srivastava K, Dahmer M . Association of IL-1β -511 polymorphism with severe veno-occlusive disease in pediatric-matched allogeneic hematopoietic stem cell transplantation. J Pediatr Hematol Oncol. 2012; 34(3):175-9. DOI: 10.1097/MPH.0b013e3182427575. View

Rocha V, Porcher R, Fernandes J, Filion A, Bittencourt H, Silva Jr W . Association of drug metabolism gene polymorphisms with toxicities, graft-versus-host disease and survival after HLA-identical sibling hematopoietic stem cell transplantation for patients with leukemia. Leukemia. 2008; 23(3):545-56. DOI: 10.1038/leu.2008.323. View

Platzbecker U, Bornhauser M . SOS for veno-occlusive disease: defibrotide prophylaxis. Lancet. 2012; 379(9823):1277-8. DOI: 10.1016/S0140-6736(12)60067-1. View

Maradei S, Maiolino A, de Azevedo A, Colares M, Bouzas L, Nucci M . Serum ferritin as risk factor for sinusoidal obstruction syndrome of the liver in patients undergoing hematopoietic stem cell transplantation. Blood. 2009; 114(6):1270-5. DOI: 10.1182/blood-2009-03-212282. View

10.

Ouachee-Chardin M, Elie C, de Saint Basile G, Le Deist F, Mahlaoui N, Picard C . Hematopoietic stem cell transplantation in hemophagocytic lymphohistiocytosis: a single-center report of 48 patients. Pediatrics. 2006; 117(4):e743-50. DOI: 10.1542/peds.2005-1789. View

11.

McKoy J, Angelotta C, Bennett C, Tallman M, Wadleigh M, Evens A . Gemtuzumab ozogamicin-associated sinusoidal obstructive syndrome (SOS): an overview from the research on adverse drug events and reports (RADAR) project. Leuk Res. 2006; 31(5):599-604. DOI: 10.1016/j.leukres.2006.07.005. View

12.

Corbacioglu S, Cesaro S, Faraci M, Valteau-Couanet D, Gruhn B, Rovelli A . Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial. Lancet. 2012; 379(9823):1301-9. DOI: 10.1016/S0140-6736(11)61938-7. View

13.

Ho V, Revta C, Richardson P . Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: update on defibrotide and other current investigational therapies. Bone Marrow Transplant. 2007; 41(3):229-37. DOI: 10.1038/sj.bmt.1705899. View

14.

Barker C, Butzner J, Anderson R, Brant R, Sauve R . Incidence, survival and risk factors for the development of veno-occlusive disease in pediatric hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2003; 32(1):79-87. DOI: 10.1038/sj.bmt.1704069. View

15.

Richardson P, Soiffer R, Antin J, Uno H, Jin Z, Kurtzberg J . Defibrotide for the treatment of severe hepatic veno-occlusive disease and multiorgan failure after stem cell transplantation: a multicenter, randomized, dose-finding trial. Biol Blood Marrow Transplant. 2010; 16(7):1005-17. PMC: 2956581. DOI: 10.1016/j.bbmt.2010.02.009. View

16.

Coppell J, Richardson P, Soiffer R, Martin P, Kernan N, Chen A . Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant. 2009; 16(2):157-68. PMC: 3018714. DOI: 10.1016/j.bbmt.2009.08.024. View

17.

Qureshi A, Marshall L, Lancaster D . Defibrotide in the prevention and treatment of veno-occlusive disease in autologous and allogeneic stem cell transplantation in children. Pediatr Blood Cancer. 2008; 50(4):831-2. DOI: 10.1002/pbc.21425. View

18.

Carreras E, Diaz-Beya M, Rosinol L, Martinez C, Fernandez-Aviles F, Rovira M . The incidence of veno-occlusive disease following allogeneic hematopoietic stem cell transplantation has diminished and the outcome improved over the last decade. Biol Blood Marrow Transplant. 2011; 17(11):1713-20. DOI: 10.1016/j.bbmt.2011.06.006. View

19.

Ostrovsky O, Korostishevsky M, Shafat I, Mayorov M, Ilan N, Vlodavsky I . Inverse correlation between HPSE gene single nucleotide polymorphisms and heparanase expression: possibility of multiple levels of heparanase regulation. J Leukoc Biol. 2009; 86(2):445-55. PMC: 2796676. DOI: 10.1189/jlb.1208735. View

20.

Toh H, McAfee S, Sackstein R, Cox B, Colby C, Spitzer T . Late onset veno-occlusive disease following high-dose chemotherapy and stem cell transplantation. Bone Marrow Transplant. 1999; 24(8):891-5. DOI: 10.1038/sj.bmt.1701994. View