Blood concentration of tacrolimus and age predict tacrolimus-induced left ventricular dysfunction after bone marrow transplantation in adults
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Tacrolimus (TAC) is used for the prophylaxis and treatment of acute graft-versus-host disease after bone marrow transplantation (BMT). However, few have reported on TAC-induced left ventricular hypertrophy. This study aimed to assess the relationship between blood concentration of TAC and development of TAC-induced left ventricular (TI-LV) dysfunction in adult BMT patients with hematologic malignant diseases, and to evaluate whether TAC concentration can predict TI-LV dysfunction occurrence in these patients.
We enrolled 16 consecutive patients (mean age 44.6 ± 13.0 years) who received TAC after BMT. Echocardiography was performed before and after BMT, and blood concentrations of TAC were evaluated in terms of AUC15 (area sum of TAC > 15 ng/ml during follow-up). We assessed the relationship between AUC15 and development of TI-LV dysfunction after TAC.
During the follow-up period (mean duration 47.6 ± 13.7 days), interventricular septum thickness (IVST, P = 0.001) and posterior wall thickness (PWT, P < 0.001) increased, and E′ decreased (P = 0.006). AUC15 was associated with post-IVST (R = 0.627, P = 0.009), post-PWT (R = 0.669, P = 0.005), and post-E′ (R = − 0.767, P = 0.001). In multivariate analysis, AUC15 and age independently predicted the increase in IVST and PWT and decrease in E′ after BMT. The combination of AUC15 and older age predicted post-PWT with a sensitivity of 77.8% and specificity of 71.4%.
TAC concentrations should be maintained at < 15 ng/ml and age should be considered in patients undergoing BMT to avoid TI-LV dysfunction.
KeywordsTacrolimus-induced left ventricular dysfunction Bone marrow transplantation Echocardiography Hematologic malignant disease Adult
I would like to express my deep gratitude to Dr. Yurie Saito, Dr. Hiroyuki Kambayashi, and Dr. Masahiko Fukatsu for their help in collecting clinical data.
Compliance with ethical standards
Conflicts of interest
Kohko Kanazawa, Masumi Iwai-Takano, Satoru Kimura, and Tetsuya Ohira declare that they have no conflicts of interest.
This study was approved by the institutional review board of Ohta Nishinouchi Hospital, and it employed an opt-out consent approach. The study complied with the principles of the Declaration of Helsinki.
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