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Correlation between low CSA plasma concentration and severity of acute GvHD in bone marrow transplantation
H Schmidt1, G Ehninger, R Dopfer
1Department of Internal Medicine II, Children Hospital, Tübingen, Federal Rep[ublic of Germany.
Insights
This study found that lower ciclosporin A (CSA) levels before graft-versus-host disease (GvHD) onset correlated with GvHD severity after bone marrow transplantation (BMT). Achieving higher CSA plasma concentrations may reduce GvHD.
Area of Science:
- Hematology
- Immunology
- Pharmacology
Background:
- Bone marrow transplantation (BMT) is a crucial treatment for hematologic malignancies.
- Graft-versus-host disease (GvHD) remains a significant complication following allogeneic BMT.
- Ciclosporin A (CSA) is commonly used to prevent GvHD, but its efficacy and optimal dosing require further investigation.
Purpose of the Study:
- To evaluate the relationship between ciclosporin A (CSA) serum levels and the incidence and severity of graft-versus-host disease (GvHD) post-bone marrow transplantation (BMT).
- To determine a target plasma CSA concentration for effective GvHD prophylaxis.
Main Methods:
- Retrospective analysis of 51 patients undergoing BMT between 1982 and 1986.
- Monitoring of CSA serum levels and assessment of GvHD incidence and severity (Grades 0-IV).
- Comparison of CSA levels in patients who developed different grades of GvHD.
Main Results:
- Despite CSA treatment, 80% of patients experienced acute GvHD (Grades 0-II), and 20% developed severe GvHD (Grades III-IV).
- Significantly lower average CSA serum levels were observed 2-4 days before the onset of severe GvHD (Grades III-IV).
- Major CSA side effects included tremor, hypertension, hepatotoxicity, and nephrotoxicity.
Conclusions:
- Lower plasma CSA concentrations are associated with an increased risk of severe GvHD following BMT.
- Achieving plasma CSA concentrations above 250 ng/ml may be necessary to effectively reduce GvHD severity.
- Therapeutic drug monitoring of CSA is crucial for optimizing GvHD prophylaxis in BMT patients.
Abstract:
Between 1982 and 1986 51 patients were treated with ciclosporin a (CSA) to prevent graft versus host disease (GvHD) after bone marrow transplantation (BMT). Major side effects of the drug were tremor, hypertension, hepatotoxicity and nephrotoxicity. Acute GvHD 0 degree to II degree occurred in 80% of our patients, and GvHD III degree and IV degree in 20% despite the use of CSA. Two to four days before the onset of GvHD, CSA serum levels were significantly lower on the average in patients who developed GvHD III degree and IV degree compared to the others. Our data indicate that plasma CSA concentrations higher than 250 ng/ml should be achieved to reduce the severity of GvHD after BMT.