Determination of cyclosporine levels in central venous blood samples versus peripheral blood samples: a clinical validation study

An allogeneic stem cell transplantion (alloSCT) is used for various
haematological diseases. It involves the intravenous infusion of blood-forming
stem cells from a donor. After an alloSCT, alloreactivity can occur in two
directions. Host-versus-graft alloreactivity resulting in rejection of the
graft and graft-versus-host alloreactivity which may result in
graft-versus-host-disease (GVHD). The transplantation is successful if the
graft is not rejected by the patient and the blood cell formation has been
taken over completely by the donor stem cells. In addition, it is important
that GVHD, caused by donor T-cells attacking the healthy cells and tissues of
the patient, does not occur or only to a limited extent. For this reason,
during and after the transplantation immunosuppressive medication is needed to
suppress the alloreactive T cells. One of the most important immunosuppressants
is cyclosporine A (CsA).

The large pharmacokinetic variability of immunosuppressants between patients
can lead to under- and overexposure with serious consequences. To ensure
adequate exposure to immunosuppressants, drug doses are adjusted based on
measurements of whole blood concentration, also called therapeutic drug
monitoring. During the first days to weeks after transplantation, patients are
treated with CsA intravenously (iv), because patients may have symptoms of
nausea, vomiting, and mucositis prohibiting the swallowing of tablets. During
this period, CsA levels are measured three times a week in peripheral blood
taken by means of a venipuncture even though all patients have a central venous
catheter (CVC).

Patients experience the venipunctures as burdensome as punctures are often
difficult due to the previous chemotherapy patients have received. In addition,
as laborants are needed to perform the venipunctures, the procedure may lead to
errors due to miscommunication between the nurses and the laboratory staff.
Therefore, the aim of the current study is to investigate whether CsA levels
measured in central venous blood samples collected by the nurses give reliable
values. To determine if levels are indeed reliable, levels will be compared to
the level of CsA measured in peripheral blood collected by means of a
venipuncture at the same time.

Similar studies have already been performed. However, the opinions of
researchers about the reliability of a central venous CsA level during
simultaneous central administration are different. The interpretation of the
available studies is complicated by the use of different types of CVCs and
different methods to prevent so-called contamination of the collected blood
sample. Conclusions cannot be translated directly into daily practice in the
clinical haematology department of the EMC. Therefore, a practice-oriented
study will be set up to test whether the results of the centrally collected CsA
blood level are reliable when CsA is administered simultaneously using a
silicone CVC.

The aim of the study is to compare the CsA level in blood collected with a
venipuncture with the CsA level in blood collected from the CVC during
administration of CsA through the CVC. This to test the reliability of CsA
levels in central venous blood samples. Furthermore, the effect of prolonged
intravenous administration of CsA on the CsA levels in central venous blood
samples will be examined

The study will have a quantitative research. This in order to gain numerical
insight into the research problem of the CsA blood level and also to gain
insight into the experiences of the nurses.

The patient's blood will be drawn from the CVC three times a week as long as
the patient receives the cyclosporine intravenously. On average this will be 2
to 3 weeks adding up to 6 to 9 blood samples. Risk and strain is not expected
as blood is already taken from the CVC, this will be an additional blood
collection with 10ml blood.