Microsampling Assays for Immunosuppressive Drugs in Children

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.

Inclusion criteria

• Males and females <18 years of age
• Weight greater than 5 kg
• Receiving CYA, TAC, and/or SIR as standard of care
• Has scheduled/anticipated blood draw to quantify the concentration of CYA, TAC, and SIR* for clinical indications
• Parental/guardian permission (informed consent), and subject's assent if applicable.

Exclusion criteria

• Unable to provide blood samples.

• Potential subjects and their parents/guardians may be approached prior to having a blood draw scheduled if they meet all other eligibility criteria.

Sub-Study Criteria:

Sub-study criteria for child participants will not differ from the main study. Adult participants are required to be a parent/legal guardian of a study subject.