Cyclosporine area under the curve after allogeneic hematopoietic stem cell transplantation is an indicator of Epstein-Barr virus DNAemia
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Cyclosporine area under the curve after allogeneic hematopoietic stem cell transplantation is an indicator of Epstein-Barr virus DNAemia. / Christopeit, Maximilian; Janssen, Nils; Weber, Thomas; Bacher, Ulrike; Lautenschläger, Christine; Oehme, Albrecht; Kekulé, Alexander S; Schmoll, Hans-Joachim.
In: LEUKEMIA LYMPHOMA, Vol. 54, No. 1, 01.2013, p. 133-7.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Cyclosporine area under the curve after allogeneic hematopoietic stem cell transplantation is an indicator of Epstein-Barr virus DNAemia
AU - Christopeit, Maximilian
AU - Janssen, Nils
AU - Weber, Thomas
AU - Bacher, Ulrike
AU - Lautenschläger, Christine
AU - Oehme, Albrecht
AU - Kekulé, Alexander S
AU - Schmoll, Hans-Joachim
PY - 2013/1
Y1 - 2013/1
N2 - Epstein-Barr virus (EBV) DNAemia and reactivation is a typical complication after allogeneic hematopoietic stem cell transplantation (HSCT). The degree of immunosuppression is closely linked to the risk of developing EBV DNAemia. An association of cyclosporine levels with EBV DNAemia has not been interrogated. Here, we analyzed cyclosporine levels in 58 patients after allogeneic HSCT. We discovered a wide range of cyclosporine trough level variation in the individual patient (median coefficient of variation [CV] 0.29, range 0.19-0.78). To overcome this high intra-individual variation in serum trough levels of cyclosporine, we calculated respective areas under the curve (AUC) and performed correlations with EBV DNAemia in 28 stem cell recipients at increased risk for EBV DNAemia. This resulted in a significant association of high cyclosporine AUC (> 6000 ng/mL × days) with EBV DNAemia after day 30 (relative risk [RR] 6.067, 95% confidence interval [CI] 1.107-33.238, p = 0.038). Conversely, mean cyclosporine values (threshold 200 ng/mL) between days 0 and 30 were not found to correlate with EBV DNAemia after day 30. Furthermore, CD3 + CD8 + graft content was inversely correlated with EBV DNAemia after day 30. These findings might establish a clinical role for the AUC of cyclosporine.
AB - Epstein-Barr virus (EBV) DNAemia and reactivation is a typical complication after allogeneic hematopoietic stem cell transplantation (HSCT). The degree of immunosuppression is closely linked to the risk of developing EBV DNAemia. An association of cyclosporine levels with EBV DNAemia has not been interrogated. Here, we analyzed cyclosporine levels in 58 patients after allogeneic HSCT. We discovered a wide range of cyclosporine trough level variation in the individual patient (median coefficient of variation [CV] 0.29, range 0.19-0.78). To overcome this high intra-individual variation in serum trough levels of cyclosporine, we calculated respective areas under the curve (AUC) and performed correlations with EBV DNAemia in 28 stem cell recipients at increased risk for EBV DNAemia. This resulted in a significant association of high cyclosporine AUC (> 6000 ng/mL × days) with EBV DNAemia after day 30 (relative risk [RR] 6.067, 95% confidence interval [CI] 1.107-33.238, p = 0.038). Conversely, mean cyclosporine values (threshold 200 ng/mL) between days 0 and 30 were not found to correlate with EBV DNAemia after day 30. Furthermore, CD3 + CD8 + graft content was inversely correlated with EBV DNAemia after day 30. These findings might establish a clinical role for the AUC of cyclosporine.
KW - Adult
KW - Aged
KW - Confounding Factors (Epidemiology)
KW - Cyclosporine
KW - Epstein-Barr Virus Infections
KW - Female
KW - Hematopoietic Stem Cell Transplantation
KW - Herpesvirus 4, Human
KW - Humans
KW - Immunosuppressive Agents
KW - Male
KW - Middle Aged
KW - ROC Curve
KW - Risk Factors
KW - Transplantation, Homologous
KW - Viremia
KW - Young Adult
KW - Journal Article
U2 - 10.3109/10428194.2012.705001
DO - 10.3109/10428194.2012.705001
M3 - SCORING: Journal article
C2 - 22721496
VL - 54
SP - 133
EP - 137
JO - LEUKEMIA LYMPHOMA
JF - LEUKEMIA LYMPHOMA
SN - 1042-8194
IS - 1
ER -