급성 이식편대숙주병 예방을 위한 Tacrolimus 적정 혈중농도 설정
Optimal Level of Tacrolimus to Prevent Acute Graft-Versus-Host Disease
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Background : Graft versus host disease (GVHD) is a major adverse effect of allogeneic stem cell transplantation and acute graft versus host disease (aGVHD) occurs in 40~50% of recipients. The incidence of aGVHD is higher with unrelated transplantation of incompatible human leukocyte antigen (HLA) and tacrolimus has been shown to be an effective immunosuppressant to prevent from aGVHD. Although there are studies to compare the incidence of GVHD with target blood concentration of tacrolimus, it is hard to conclude the optimal concentration of tacrolimus because of the difference in the study population and practice settings. The aim of this study is to evaluate the optimal concentration of tacrolimus to prevent aGVHD by analyzing the related factors of aGVHD incidence and side effects of tacrolimus. Methods : This study was retrospectively conducted on Korean adult patients who received tacrolimus after hematopoietic stem cell transplantation from July 2014 to June 2015. This study analyzed the concentration of tacrolimus according to the incidence of aGVHD and its related factors, and side effects of tacrolimus in each range of concentrations. Results : Among the 115 patients aGVHD occurred in 90 (78.3%) patients and the mean concentration of tacrolimus within 100 days post transplantation was 8.14 ng/ml in aGVHD group and 9.66 ng/ml in non aGVHD group (p=0.015). Mean concentration at 3 week post transplantation was 8.87 ng/ml in grade II-IV aGVHD and 10.09 ng/ml in grade 0-I aGVHD (p=0.048). The incidence of aGVHD was significantly lower with the mean concentration of tacrolimus within 100 days of post transplantation of ≥12 ng/ml group than others. In the analysis of side effect of tacrolimus, hyperkalemia was higher in ≥12 ng/ml group than <8 ng/ml group (p=0.02). Conclusion : In our study, the mean concentration of tacrolimus of 12 ng/ml within 100 days after transplantation tends to lower the incidence of aGVHD.
Abstract
Background : Graft versus host disease (GVHD) is a major adverse effect of allogeneic stem cell transplantation and acute graft versus host disease (aGVHD) occurs in 40~50% of recipients. The incidence of aGVHD is higher with unrelated transplantation of incompatible human leukocyte antigen (HLA) and tacrolimus has been shown to be an effective immunosuppressant to prevent from aGVHD. Although there are studies to compare the incidence of GVHD with target blood concentration of tacrolimus, it is hard to conclude the optimal concentration of tacrolimus because of the difference in the study population and practice settings. The aim of this study is to evaluate the optimal concentration of tacrolimus to prevent aGVHD by analyzing the related factors of aGVHD incidence and side effects of tacrolimus. Methods : This study was retrospectively conducted on Korean adult patients who received tacrolimus after hematopoietic stem cell transplantation from July 2014 to June 2015. This study analyzed the concentration of tacrolimus according to the incidence of aGVHD and its related factors, and side effects of tacrolimus in each range of concentrations. Results : Among the 115 patients aGVHD occurred in 90 (78.3%) patients and the mean concentration of tacrolimus within 100 days post transplantation was 8.14 ng/ml in aGVHD group and 9.66 ng/ml in non aGVHD group (p=0.015). Mean concentration at 3 week post transplantation was 8.87 ng/ml in grade II-IV aGVHD and 10.09 ng/ml in grade 0-I aGVHD (p=0.048). The incidence of aGVHD was significantly lower with the mean concentration of tacrolimus within 100 days of post transplantation of ≥12 ng/ml group than others. In the analysis of side effect of tacrolimus, hyperkalemia was higher in ≥12 ng/ml group than <8 ng/ml group (p=0.02). Conclusion : In our study, the mean concentration of tacrolimus of 12 ng/ml within 100 days after transplantation tends to lower the incidence of aGVHD.
참고문헌 (32)
- Lennard AL, "Stem cell transplantation", BMJ, 321(7258), pp.433~437 (2000)
- Passweg JR, "Hematopoietic SCT in Europe : data and trends in 2011", Bone Marrow Transplant, 48(9), pp.1161~1167 (2013)
- Fortune K, "Tacrolimus in hematopoietic stem cell transplantation", Expert Opin Drug Metab Toxicol, 5(7), pp.835~841 (2009)
- Ferrara JL, "Advances in the clinical management of GVHD", Best Pract Res Clin Haematol, 21(4), pp.677~682 (2008)
- Ratanatharathorn V, "Chronic graft-versus-host disease : clinical manifestation and therapy", Bone Marrow Transplant, 28(2), pp.121~129 (2001)
- Nash RA, "FK506 in combination with methotrexate for the prevention of graft-versus-host disease after marrow transplantation from matched unrelated donors", Blood, 88(9), pp.3634~3641 (1996)
- Pidala J, "Graft-vs-host disease following allogeneic hematopoietic cell transplantation", Cancer Control, 18(4), pp.268~276 (2011)
- Arai S, "Management of graft-versus-host disease", Blood Rev, 14(4), pp.190~204 (2000)
- Nash RA, "Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors", Blood, 96(6), pp.2062~2068 (2000)
- Ratanatharathorn V, "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, 92(7), pp.2303~2314 (1998)
- Przepiorka D, "Tacrolimus and minidose methotrexate for prevention of acute graft-versushost disease after matched unrelated donor marrow transplantation", Blood, 88(11), pp.4383~4389 (1996)
- Uberti JP, "Tacrolimus as monotherapy or combined with minidose methotrexate for graftversus-host disease prophylaxis after allogeneic peripheral blood stem cell transplantation : long-term outcomes", Bone Marrow Transplant, 34(5), pp.425~431 (2004)
- Felipe CR, "The impact of ethnic miscegenation on tacrolimus clinical pharmacokinetics and therapeutic drug monitoring", Clin Transplant, 16(4), pp.262~272 (2002)
- Park K, "A randomized, open-label, two-period, crossover bioavailability study of two oral formulations of tacrolimus in healthy Korean adults", Clin Ther, 29(1), pp.154~162 (2007)
- Scott LJ, "Tacrolimus-A further update of its use in the management of organ transplantation", Drugs, 63(12), pp.1247~1297 (2003)
- Jusko WJ, "Consensus document : therapeutic monitoring of tacrolimus(FK-506)", Ther Drug Monit, 17(6), pp.606~614 (1995)
- 여미진, "조혈모세포 이식환자에서의 현행 tacrolimus 치료방법 평가", 한국임상약학회지, 20(3), pp.193~199 (2010), 한국임상약학회
- Przepiorka D, "Relationship of tacrolimus whole blood levels to efficacy and safety outcomes after unrelated donor marrow transplantation", Biol Blood Marrow Transplant, 5(2), pp.94~97 (1999)
- Couriel DR, "Phase II", III randomized study comparing two different tacrolimus blood levels for the prevention of graft-versushost disease(GVHD), 2005, pp.106(11), 45a-a~
- Mori T, "Effect of early posttransplantation tacrolimus concentration on the development of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation from unrelated donors", Biol Blood Marrow Transplant, 18(2), pp.229~234 (2012)
- Ringden O, "The highest leukaemia-free survival after allogeneic bone marrow transplantation is seen in patients with grade I acute graft-versus-host disease. Acute and Chronic Leukaemia Working Parties of the European Group for Blood and Marrow Transplantation (EBMT)", Leuk Lymphoma, 24(1-2), pp.71~79 (1996)
- Paul A, "2014Evidence-Based Guideline for the Management of High Blood Pressure in Adults : Report From the Panel Members Appointed to the Eighth Joint National Committee(JNC 8)", JAMA, 311(5), pp.507~520 (2014)
- "Psychiatry &the Law: Forensic Psychiatric Resource Page" (1999)[URL]
- Wingard JR, "Relationship of tacrolimus (FK506)whole blood concentrations and efficacy and safety after HLA-identical sibling bone marrow transplantation", Biol Blood Marrow Transplant, 4(3), pp.157~163 (1998)
- Przepiorka D, "Tacrolimus does not abrogate the increased risk of acute graft-versus-host disease after unrelated-donor marrow transplantation with allelic mismatching at HLA-DRB1 and HLA-DQB1", Biol Blood Marrow Transplant, 6, pp.190~197 (2000)
- Cuter C AJ, "Thomas’ Hematopoietic Cell Transplantation", pp.1287~1303 (2009), Wiley-Blackwell
- Devine SM, "The outcome of unrelated donor bone marrow transplantation in patients with hematologic malignancies using tacrolimus(FK506)and low dose methotrexate for graft-versus-host disease prophylaxis", Biol Blood Marrow Transplant, 3(1), pp.25~33 (1997)
- Przepiorka D, "Tacrolimus for prevention of graft-versus-host disease after mismatched unrelated donor cord blood transplantation", Bone Marrow Transplant, 23(12), pp.1291~1295 (1999)
- Marks DI, "The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first and second complete remission", Blood, 116(3), pp.366~374 (2010)
- Medd PG, "Evidence for a GVL effect following reduced-intensity allo-SCT in ALL : a British Society of Blood and Marrow Transplantation study", Bone Marrow Transplant, 48(7), pp.982~987 (2013)
- Flowers ME, "Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria", Blood, 117(11), pp.3214~3219 (2011)
- Chao, NJ, "Thomas’ Hematopoietic Cell Transplantation", pp.1257~1274 (2009), Wiley-Blackwell