Therapeutic Monitoring: Monitoring Intracellular Cystine in White Blood Cells (WBC, Leukocytes)

We recommend that WBC cystine be measured just before a dose of cysteeamine, near the "trough" of cysteamine (the time of lowest drug level). As opposed to CystagonTM, the absolute trough comes a little later with ProcysbiTM, about a half hour after the dose, but the small difference in WBC cystine is less of a consideration than the practical concerns about precise timing after a dose, as larger differences could arise if sampling is delayed.
There are two types of testing available: (1) The older mixed leukocyte test, which requires immediate preparation but can permit freezing of samples prior to shipping, and (2) the newer granulocyte test, which does not require extra steps before shipping, but does have critical packaging and shipping requirements. Horizon Pharma has kindly set up a program to assist with drawing, packaging and shipping (the TranscendRare program).

The simplest method is the granulocyte testing arranged through the TranscendRare program).
  1. Traditional method-- Mixed Leukocytes:

    This method depends upon isolation of leukocytes immediately after blood drawing. Isolation of leukocytes involves a series of simple steps, but requires some time. The stabilized, pelleted leukocytes can be kept frozen for a few days until it is express-mailed to our laboratory. This method is recommended for samples which are drawn outside the range of next morning express shipping. In other cases, the granulocyte method is generally preferable, because so much less preparation time is required at the point-of-care.

    Details of the method are available here, including full step-by-step process illustration. Each step is simple, but the intermediate samples cannot be left unattended, so the entire process requires a >2h time commitment.

    We can arrange to send kits with materials needed for this preparation; see WBC test kit request form.
    In remote regions, where express shipping of frozen samples is not feasible, the pellets may be placed onto standard bloodspot filter paper, dried thoroughly and shipped at room temperature.
  2. Newer method-- Granulocytes:

    :For this method, whole blood can be sent in a yellow-top (ACD- solution A) tube, refrigerated (not frozen) and sent by express shipping to our lab on the same day it is drawn (Monday through Thursday).
    1. Coordinated by the Horizon TranscendRare program:

      Sample drawing, materials and expenses for shipping, and financial assistance for the test itself may be covered through their program, making testing much easier. For information, contact the TranscendRare Program.
    2. Independent preparation and shipping of samples:

      If the lab is able to draw, prepare and ship the sample independently, it is very important that these instructions are followed to ensure the integrity of the sample is maintained:
      1. SPECIMEN MUST BE SHIPPED THE SAME DAY AS COLLECTION TO ARRIVE AT OUR LABORATORY THE FOLLOWING MORNING FOR PROCESSING. PLEASE COLLECT AND SHIP SPECIMENS MONDAY-THURSDAY; WE ARE CLOSED WEEKENDS AND HOLIDAYS.
      2. See instructions for packaging shipments here.
      3. Label the package "KEEP REFRIGERATED. DO NOT FREEZEor place appropriate safe handling label.  failure to do so may result in the carrier freezing the package in the plane, and as a result freezing the blood.
      4. The specimen must be shipped by Fed-Ex Priority Overnight the same day as sample was collected.

      Sample Requirement: Blood, ≥2.0 ml in ACD-Solution A (yellow-top). Refrigerate within 1 hour of collection. (DO NOT FREEZE)

      Shipping Address: See contact information.
      Packaging materials are illustrated here.
      Samples should be accompanied by the UCSD Biochemical Genetics and Metabolomics standard requisition form.

Diagnosis of Cystinosis