Late-onset hepatic veno-occlusive disease after allografting: report of two cases with atypical clinical features successfully treated with defibrotide.
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Keywords
Leukemia
Abstract
Hepatic Veno-occlusive disease (VOD) is a potentially severe complication of hematopoietic stem cell transplantation (HSCT). Here we report two patients receiving an allogeneic HSCT who developed late onset VOD with atypical clinical features. The two patients presented with only few risk factors, namely, advanced acute leukemia, a myeloablative busulphan-containing regimen and received grafts from an unrelated donor. The first patient did not experience painful hepatomegaly and weight gain and both patients showed only a mild elevation in total serum bilirubin level. Most importantly, the two patients developed clinical signs beyond day 21 post-HSCT. Hepatic transjugular biopsy confirmed the diagnosis of VOD. Intravenous defibrotide was promptly started leading to a marked clinical improvement. Based on our experience, liver biopsy may represent a useful diagnostic tool when the clinical features of VOD are ambiguous. Early therapeutic intervention with defibrotide represents a crucial issue for the successful outcome of patients with VOD.
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References
REFERENCES
1. Carreras E, et al. Veno-occlusive disese of the liver after hemopoietic cell transplantation. Eur J Haematol 2000;64: 281-291.
2. McDonald, G.B., Hinds, M.S., Fisher, L.D., et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Annals of Internal Medicine 1993; 118, 255–267.
3. Jones, R.J., Lee, K.S., Beschorner, W.E., et al. Venoocclusive disease of the liver following bone marrow transplantation. Transplantation, 1987;44, 778–783.
4. Lee, J.L., Gooley, T., Bensinger, W., et al. Veno-occlusive disease of the liver after busulfan, melphalan, and thiotepa conditioning therapy: incidence, risk factors, and outcome.
Biology of Blood and Marrow Transplantation, 1999;5, 306–315.
5. Coppell JA, Richardson PG, Soiffer R, Martin PL, Kernan NA, Chen A et al. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant 2010;16: 157-168.
6. Mohty M, Malard F, Abecassis M, et al. 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. BMT 2016, 1-7.
7. Bearman SI, et al. The syndrome of hepatic veno-occlusive disease after marrow transplantation. Blood 1995; 85:3005-20.
8. Carreras E, Bertz H, Arcese W, et al. Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: A prospective cohort study of the European Group for Blood and Marrow Transplantation: European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party. Blood 1998;92:3599-604.
9. Cesaro, S., Pillon, M., Talenti, E., et al. A prospective survey on incidence, risk factors and therapy of hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation. Haematologica, 2005;90, 1396–1404.
10. Dignan FL, Wynn RF, Hadzic N, et al. BCSH/BSBMT guideline: diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation. BJH 2013, 163, 444-457.
11. DeLeve, L.D., Shulman, H.M. & McDonald, G.B. (2002) Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). Seminars in Liver Disease, 22, 27.
12. Shulman, H.M., Gown, A.M. & Nugent, D.J. (1987) Hepatic veno-occlusive disease after bone marrow transplantation. Immunohistochemical identi?cation of the material within occluded central venules. The American Journal of Pathology, 127, 549–558
13. Shulman, H.M., Fisher, L.B., Schoch, H.G., Henne, K.W. & McDonald, G.B. (1994) Veno-occlusive disease of the liver after marrow transplantation: histological correlates of clinical signs and symptoms. Hepatology, 19, 1171–1181.
14. Kis b, Pamarthi V, Fan C-M et al. Safety and Utility of Transjugular Liver Biopsy in Hematopoietic Stem Cell Transplant Recipients. J Vasc Interv Radiol 2013; 24:85–89
15. Richardson, P.G., Elias, A.D., Krishnan, A., et al. Treatment of severe veno-occlusive disease with de?brotide: compassionate use results in response without signi?cant toxicity in a high-risk population. Blood, 1998;92, 737–744.
16. Richardson PG, Smith AR, Triplett BM, et al. Early Initiation of Defibrotide in Patients with Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome Following Hematopoietic Stem Cell Transplantation Improves Day +100 Survival. ASH 2015. Poster Abs.
17. Corbacioglu S, Greil J, Peters C., et al. Defibrotide in the treatment of children with veno-occlusive disease (VOD): a retrospective multicentre study demonstrates therapeutic efficacy upon early intervention. BMT 2004; Jan;33(2):189-95.
18. Bearman, S.I., Anderson, G.L., Mori, M., Hinds, M.S., Shulman, H.M. & McDonald, G.B. (1993) Venoocclusive disease of the liver: development of a model for predicting fatal outcome after marrow transplantation. Journal of Clinical Oncology, 11, 1729–1736.
19. Chopra R, Eaton JD, Grassi A, Potter M, Shaw B, Salat C, et al. Defibrotide for the treatment of hepatic veno-occlusive disease: Results of the European compassionate-use study. Br J Haematol 2000;111:1122-9.
20. Richardson PG, Murakami C, Jin Z, Warren D, Momtaz P, Hoppensteadt D, et al. 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;100:4337-43.
21. Richardson PG, Soiffer R, Antin J, Jin Z, Kurtzberg J, Martin P, et al. Defibrotide (DF) for the treatment of severe veno-occlusive disease (sVOD) and multi-organ failure (MOF) post SCT: Final results of a multi-center, randomized, dose-finding trial. Blood 2006;108:178.
22. Richardson PG, Riches ML, Kernan NA, et al. Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure. Blood. 2016;127(13):1656-65.
1. Carreras E, et al. Veno-occlusive disese of the liver after hemopoietic cell transplantation. Eur J Haematol 2000;64: 281-291.
2. McDonald, G.B., Hinds, M.S., Fisher, L.D., et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Annals of Internal Medicine 1993; 118, 255–267.
3. Jones, R.J., Lee, K.S., Beschorner, W.E., et al. Venoocclusive disease of the liver following bone marrow transplantation. Transplantation, 1987;44, 778–783.
4. Lee, J.L., Gooley, T., Bensinger, W., et al. Veno-occlusive disease of the liver after busulfan, melphalan, and thiotepa conditioning therapy: incidence, risk factors, and outcome.
Biology of Blood and Marrow Transplantation, 1999;5, 306–315.
5. Coppell JA, Richardson PG, Soiffer R, Martin PL, Kernan NA, Chen A et al. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant 2010;16: 157-168.
6. Mohty M, Malard F, Abecassis M, et al. 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. BMT 2016, 1-7.
7. Bearman SI, et al. The syndrome of hepatic veno-occlusive disease after marrow transplantation. Blood 1995; 85:3005-20.
8. Carreras E, Bertz H, Arcese W, et al. Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: A prospective cohort study of the European Group for Blood and Marrow Transplantation: European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party. Blood 1998;92:3599-604.
9. Cesaro, S., Pillon, M., Talenti, E., et al. A prospective survey on incidence, risk factors and therapy of hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation. Haematologica, 2005;90, 1396–1404.
10. Dignan FL, Wynn RF, Hadzic N, et al. BCSH/BSBMT guideline: diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation. BJH 2013, 163, 444-457.
11. DeLeve, L.D., Shulman, H.M. & McDonald, G.B. (2002) Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). Seminars in Liver Disease, 22, 27.
12. Shulman, H.M., Gown, A.M. & Nugent, D.J. (1987) Hepatic veno-occlusive disease after bone marrow transplantation. Immunohistochemical identi?cation of the material within occluded central venules. The American Journal of Pathology, 127, 549–558
13. Shulman, H.M., Fisher, L.B., Schoch, H.G., Henne, K.W. & McDonald, G.B. (1994) Veno-occlusive disease of the liver after marrow transplantation: histological correlates of clinical signs and symptoms. Hepatology, 19, 1171–1181.
14. Kis b, Pamarthi V, Fan C-M et al. Safety and Utility of Transjugular Liver Biopsy in Hematopoietic Stem Cell Transplant Recipients. J Vasc Interv Radiol 2013; 24:85–89
15. Richardson, P.G., Elias, A.D., Krishnan, A., et al. Treatment of severe veno-occlusive disease with de?brotide: compassionate use results in response without signi?cant toxicity in a high-risk population. Blood, 1998;92, 737–744.
16. Richardson PG, Smith AR, Triplett BM, et al. Early Initiation of Defibrotide in Patients with Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome Following Hematopoietic Stem Cell Transplantation Improves Day +100 Survival. ASH 2015. Poster Abs.
17. Corbacioglu S, Greil J, Peters C., et al. Defibrotide in the treatment of children with veno-occlusive disease (VOD): a retrospective multicentre study demonstrates therapeutic efficacy upon early intervention. BMT 2004; Jan;33(2):189-95.
18. Bearman, S.I., Anderson, G.L., Mori, M., Hinds, M.S., Shulman, H.M. & McDonald, G.B. (1993) Venoocclusive disease of the liver: development of a model for predicting fatal outcome after marrow transplantation. Journal of Clinical Oncology, 11, 1729–1736.
19. Chopra R, Eaton JD, Grassi A, Potter M, Shaw B, Salat C, et al. Defibrotide for the treatment of hepatic veno-occlusive disease: Results of the European compassionate-use study. Br J Haematol 2000;111:1122-9.
20. Richardson PG, Murakami C, Jin Z, Warren D, Momtaz P, Hoppensteadt D, et al. 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;100:4337-43.
21. Richardson PG, Soiffer R, Antin J, Jin Z, Kurtzberg J, Martin P, et al. Defibrotide (DF) for the treatment of severe veno-occlusive disease (sVOD) and multi-organ failure (MOF) post SCT: Final results of a multi-center, randomized, dose-finding trial. Blood 2006;108:178.
22. Richardson PG, Riches ML, Kernan NA, et al. Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure. Blood. 2016;127(13):1656-65.