Immunosuppressive therapy is used to treat and manage solid organ and bone marrow/stem
cell transplants; however, suboptimal dosing can lead to organ rejection and graft
failure. Immunosuppressant drugs require therapeutic drug monitoring (TDM) to ensure
dosing is adequate and therapeutic concentrations are achieved and maintained. The
optimal blood concentrations of these drugs are critical to minimize toxicity and
simultaneously prevent allograft rejection in an individual transplant patient. Often
life-long TDM is required necessitating hospital or laboratory visits for routine venous
blood sampling by phlebotomy. Immunosuppressive drugs, cyclosporine A (CYA), tacrolimus
(TAC), and sirolimus (SIR) require routine TDM. This entails immunocompromised people
leaving their homes for laboratory visits, potentially increasing their risk of acquiring
infections.
TDM for CYA, TAC, and SIR are required due to their narrow therapeutic targets: CYA
150-400 ng/mL, TAC 5-12 ng/mL, and SIR 4-12 ng/mL. CYA, TAC, and SIR are primarily
distributed in erythrocytes and should be quantified in whole blood. Immunoassays and the
liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays are the two commonly
used methods of TDM for CYA, TAC, and SIR. While immunoassays provide an accurate
measurement of concentrations, they often have some limitations on specificity. LC-MS/MS
assays are very specific and efficient since they can quantify multiple analytes with a
single method. At the Children's Hospital of Philadelphia (CHOP), the clinical TDM
immunoassays for CYA, TAC, and SIR require 0.5-1.0 mL of blood. TDM immunoassays require
blood collection by a trained practitioner.
Volumetric absorptive microsampling (VAMS) with an FDA-approved Tasso-M20 device allows
for the accurate and precise collection of a fixed volume of blood from a capillary
needle without the need for phlebotomy. The Tasso-M20 (FDA Class 1 exempt device)
consists of a sample head with a lancet that is activated with the push of a button to
accurately and painlessly collect blood samples from the deltoid (or similar) muscle
(capillary sampling) of the subjects on all four tips (17.5 µL each). An LC-MS/MS assay
with 20 µL blood, as obtained by the Tasso device, was shown to provide the required test
range for TDM of trough values. This microsampling technique could be utilized clinically
to promote the provision of TDM in children but has not been studied for
immunosuppressive drugs (CYA, TAC, and SIR) in children.
Children and their parents/guardians who consent to the optional sub-study will be
administered a brief survey after one study visit, to ask about their perceptions of the
two methods of blood collection that they experienced at the visit.