SIGNS OF RENAL OR PULMONARY DYSFUNCTION

Be alert for the possible signs of renal or pulmonary dysfunction

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Renal dysfunction may include1-3

  • Decreased urinary output
  • Elevated creatinine levels (≥1.5 x baseline)
  • Decreased creatinine clearance
  • Decreased glomerular filtration rate
  • Need for dialysis
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Pulmonary dysfunction may include2-5

  • Pulmonary infiltrates
  • Pleural effusion
  • Reduced oxygen saturation
  • Need for supplemental oxygen (nasal cannula)
  • Ventilator dependence

VOD/SOS is a potentially life-threatening complication of HSCT that can progress rapidly5-7

  • VOD/SOS with multi-organ dysfunction has one of the highest mortality rates among post-HSCT complications6,8-13
  • VOS/SOS is primarily associated with conditioning regimens that affect the endothelial cells within the sinusoids of the liver6,14

RAPIDLY PROGRESSIVE

In a study that assessed VOD/SOS after HSCT

~30% TO ~50%

of cases developed multi-organ dysfunction7,a

 

DEADLY

Overall mortality in VOD/SOS with multi-organ dysfunction was

84%

according to 19 studies that determined mortality from VOD/SOS6,b

UNDERDIAGNOSED

In a retrospective study15,c

UNDERDIAGNOSED UNDERDIAGNOSED - mobile

VOD/SOS-RELATED MULTI-ORGAN FAILURE IS AN UNDER-REPORTED CAUSE OF DEATH15,c

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aBased on a study conducted by Carreras et al that used 2 sets of diagnostic criteria to estimate the incidence of VOD/SOS after HSCT.7

bBased on 19 studies (235 patients) that specifically determined mortality from severe VOD/SOS, as reported within a meta-analysis of 135 studies performed between 1979 and 2007.6

cBased on retrospectively applying modified Seattle, classic EBMT/Baltimore, or late EBMT criteria using data collected from the last month before multi-organ failure–induced death.15

IMPORTANT SAFETY INFORMATION AND INDICATION

Contraindications

Defitelio is contraindicated in the following conditions:

Indication

Defitelio® (defibrotide sodium) is indicated for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT).

IMPORTANT SAFETY INFORMATION

Contraindications

Defitelio is contraindicated in the following conditions:

  • Concomitant administration with systemic anticoagulant or fibrinolytic therapy
  • Known hypersensitivity to Defitelio or to any of its excipients

Indication

Defitelio® (defibrotide sodium) is indicated for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT).

IMPORTANT SAFETY INFORMATION

Contraindications

Defitelio is contraindicated in the following conditions:

  • Concomitant administration with systemic anticoagulant or fibrinolytic therapy
  • Known hypersensitivity to Defitelio or to any of its excipients

Warnings and Precautions

Hemorrhage

Defitelio may increase the risk of bleeding in patients with VOD after HSCT. Do not initiate Defitelio in patients with active bleeding. Monitor patients on Defitelio for signs of bleeding. If bleeding occurs, withhold or discontinue Defitelio.

Concomitant systemic anticoagulant or fibrinolytic therapy may increase the risk of bleeding and should be discontinued prior to Defitelio treatment. Consider delaying Defitelio administration until the effects of the anticoagulant have abated.

Hypersensitivity Reactions

Hypersensitivity reactions including rash, urticaria, and angioedema have occurred in less than 2% of patients treated with Defitelio. One case of an anaphylactic reaction was reported in a patient who had previously received Defitelio. Monitor patients for hypersensitivity reactions, especially if there is a history of previous exposure. If a severe hypersensitivity reaction occurs, discontinue Defitelio, treat according to the standard of care, and monitor until symptoms resolve.

Most Common Adverse Reactions

The most common adverse reactions (incidence ≥10% and independent of causality) with Defitelio treatment were hypotension, diarrhea, vomiting, nausea, and epistaxis.

Please see full Prescribing Information.

Indication

Defitelio® (defibrotide sodium) is indicated for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT).

IMPORTANT SAFETY INFORMATION

Contraindications

Defitelio is contraindicated in the following conditions:

  • Concomitant administration with systemic anticoagulant or fibrinolytic therapy
  • Known hypersensitivity to Defitelio or to any of its excipients

Warnings and Precautions

Hemorrhage

Defitelio may increase the risk of bleeding in patients with VOD after HSCT. Do not initiate Defitelio in patients with active bleeding. Monitor patients on Defitelio for signs of bleeding. If bleeding occurs, withhold or discontinue Defitelio.

Concomitant systemic anticoagulant or fibrinolytic therapy may increase the risk of bleeding and should be discontinued prior to Defitelio treatment. Consider delaying Defitelio administration until the effects of the anticoagulant have abated.

Hypersensitivity Reactions

Hypersensitivity reactions including rash, urticaria, and angioedema have occurred in less than 2% of patients treated with Defitelio. One case of an anaphylactic reaction was reported in a patient who had previously received Defitelio. Monitor patients for hypersensitivity reactions, especially if there is a history of previous exposure. If a severe hypersensitivity reaction occurs, discontinue Defitelio, treat according to the standard of care, and monitor until symptoms resolve.

Most Common Adverse Reactions

The most common adverse reactions (incidence ≥10% and independent of causality) with Defitelio treatment were hypotension, diarrhea, vomiting, nausea, and epistaxis.

Please see full Prescribing Information.

HSCT=hematopoietic stem-cell transplantation; MOA=mechanism of action; MOD=multi-organ dysfunction; SOS=sinusoidal obstruction syndrome; VOD=veno-occlusive disease.

References: 1. Ng CK, Chan MH, Tai MH, et al. Hepatorenal syndrome. Clin Biochem Rev. 2007;28(1):11-17. 2. 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):1656-1665. 3. 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. Bone Marrow Transplant. 2016;51(7):906-912. 4. Richardson PG, Murakami C, Jin Z, 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(13):4337-4343. 5. McDonald GB, Hinds MS, Fisher LD, et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med. 1993;118(4):255-267. 6. Coppell JA, Richardson PG, Soiffer R, et al. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant. 2010;16(2):157-168. 7. Carreras E, Díaz-Beyá M, Rosiñol L, et al. 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):1713-1720. 8. Gratwohl A, Hermans J, Apperley J, et al; Working Party Chronic Leukemia of the European Group for Blood and Marrow Transplantation. Acute graft-versus-host disease: grade and outcome in patients with chronic myelogenous leukemia. Blood. 1995;86(2):813-818. 9. Schuster MG, Cleveland AA, Dubberke ER, et al. Infections in hematopoietic cell transplant recipients: results from the organ transplant infection project, a multicenter, prospective, cohort study. Open Forum Infect Dis. 2017;4(2):1-7. 10. Panoskaltsis-Mortari A, Griese M, Madtes DK, et al; American Thoracic Society Committee on Idiopathic Pneumonia Syndrome. An official American Thoracic Society research statement: noninfectious lung injury after hematopoietic stem cell transplantation: idiopathic pneumonia syndrome. Am J Respir Crit Care Med. 2011;183(9):1262-1279. 11. Chang L, Frame D, Braun T, et al. Engraftment syndrome after allogeneic hematopoietic cell transplantation predicts poor outcomes. Biol Blood Marrow Transplant. 2014;20(9):1407-1417. 12. Afessa B, Tefferi A, Litzow MR, et al. Diffuse alveolar hemorrhage in hematopoietic stem cell transplant recipients. Am J Respir Crit Care Med. 2002;166(5):641-645. 13. Fan K, McArthur J, Morrison RR, et al. Diffuse alveolar hemorrhage after pediatric hematopoietic stem cell transplantation. Front Oncol. 2020;10:1757. 14. Carreras E. How I manage sinusoidal obstruction syndrome after haematopoietic cell transplantation. Br J Haematol. 2015;168(4):481-491. 15. Bazarbachi AH, Al Hamed R, Labopin M, et al. Underdiagnosed veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) as a major cause of multi-organ failure in acute leukemia transplant patients: an analysis from the EBMT Acute Leukemia Working Party. Bone Marrow Transplant. 2021;56(4):917-927.