Blood Res.  2013 Mar;48(1):55-57. 10.5045/br.2013.48.1.55.

Hepatic veno-occlusive disease resulting in tacrolimus toxicity after allogeneic hematopoietic stem cell transplantation

• Shin SH
• Yahng SA
• Yoon JH
• Lee SE
• Cho BS
• Kim YJ

• KMID: 2270728
• DOI: http://doi.org/10.5045/br.2013.48.1.55

Abstract

Tacrolimus is a widely used immunosuppressive agent for the prophylaxis of graft-versus-host disease in allogeneic hematopoietic stem cell transplantation (HSCT). Since tacrolimus is primarily metabolized by the liver, hepatic dysfunction may affect its metabolism. Hepatic veno-occlusive disease (VOD) is an early complication of HSCT that results in hepatic dysfunction, suggesting that VOD may affect tacrolimus metabolism. We report a case of hepatic VOD accompanied by a sustained high blood trough level of tacrolimus despite its discontinuation. The findings of this case suggest that the elimination of tacrolimus can be markedly delayed in patients with hepatic VOD, and that the clinician should carefully modulate the drug dosage for these patients.

Keyword

Tacrolimus; Veno-occlusive disease; Hematopoietic stem cell transplantation

MeSH Terms

Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
Hepatic Veno-Occlusive Disease
Humans
Liver
Tacrolimus
Tacrolimus

Figure

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  Fig. 1 The clinical course of the patient with hepatic veno-occlusive disease resulting in tacrolimus toxicity after hematopoietic stem cell transplantation. Abbreviation: VOD, veno-occlusive disease.

Reference

1. Przepiorka D, Devine S, Fay J, Uberti J, Wingard J. Practical considerations in the use of tacrolimus for allogeneic marrow transplantation. Bone Marrow Transplant. 1999; 24:1053–1056. PMID: 10578154.

2. Iwasaki K. Metabolism of tacrolimus (FK506) and recent topics in clinical pharmacokinetics. Drug Metab Pharmacokinet. 2007; 22:328–335. PMID: 17965516.

3. Ratanatharathorn V, Nash RA, Przepiorka D, et al. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood. 1998; 92:2303–2314. PMID: 9746768.

4. Kumar S, DeLeve LD, Kamath PS, Tefferi A. Hepatic venoocclusive disease (sinusoidal obstruction syndrome) after hematopoietic stem cell transplantation. Mayo Clin Proc. 2003; 78:589–598. PMID: 12744547.

5. Mori T, Shimizu T, Yamazaki R, Nakazato T, Ikeda Y, Okamoto S. Altered metabolism of tacrolimus in hepatic veno-occlusive disease. Transpl Int. 2005; 18:1215–1217. PMID: 16162110.

6. Jain AB, Venkataramanan R, Cadoff E, et al. Effect of hepatic dysfunction and T tube clamping on FK 506 pharmacokinetics and trough concentrations. Transplant Proc. 1990; 22:57–59. PMID: 1689900.

7. Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation. Clin Pharmacokinet. 2004; 43:623–653. PMID: 15244495.

8. Shulman HM, Gown AM, Nugent DJ. Hepatic veno-occlusive disease after bone marrow transplantation. Immunohistochemical identification of the material within occluded central venules. Am J Pathol. 1987; 127:549–558. PMID: 2438942.

9. McLean AJ, Morgan DJ. Clinical pharmacokinetics in patients with liver disease. Clin Pharmacokinet. 1991; 21:42–69. PMID: 1914341.

10. Boswell GW, Bekersky I, Fay J, et al. Tacrolimus pharmacokinetics in BMT patients. Bone Marrow Transplant. 1998; 21:23–28. PMID: 9486490.

11. Jusko WJ, Piekoszewski W, Klintmalm GB, et al. Pharmacokinetics of tacrolimus in liver transplant patients. Clin Pharmacol Ther. 1995; 57:281–290. PMID: 7535213.

12. Nieto Y, Russ P, Everson G, et al. Acute pancreatitis during immunosuppression with tacrolimus following an allogeneic umbilical cord blood transplantation. Bone Marrow Transplant. 2000; 26:109–111. PMID: 10918414.

13. Eidelman BH, Abu-Elmagd K, Wilson J, et al. Neurologic complications of FK 506. Transplant Proc. 1991; 23:3175–3178. PMID: 1721398.