Cellular Immune Function Assay (ImmuKnow) Values during Treatment of Chronic Gvhd Status with Combined Immunosuppressive Drug and Extracorporeal Photopheresis Therapy

Abstract

Introduction Chronic graft-versus-host disease (cGVHD) is the leading cause of allogeneic hematopoietic stem cell transplantation (alloHSCT) related mortality and morbidity with limited understanding of its pathophysiology. The Cyclex ImmuKnow (IK) test, quantitatively measures the intracellular adenosine triphosphate levels in stimulated T cells. The IK test was FDA approved in 2002 as a functional measure of cell-mediated immunity (CMI) in the immunosuppressed population demonstrating predictive value in acute GVHD but its role in cGVHD is unclear. Methods We conducted a retrospective analysis of the role of IK in 8 alloHSCT. Four patients had a diagnosis of AML, two each had ALL and AA/MDS. All patients had IK drawn at initial diagnosis of cGVHD; five developed refractory cGVHD requiring photopheresis and had IK drawn during the period of ECP. The IK assay results were stratified as: low (0-225 ng/ml), normal (225-525 ng/ml) and high (>525 ng/ml). Results Of the 8 patients with cGVHD, at the time of diagnosis 6 had low IK, 1 was normal, and 1 was high. All of them were on two or more immune suppressive agents (IST) during the time of assay measurement. Post ECP levels did not vary significantly compared to pre-ECP levels except for one patient (Patient 3, Fig. 1) with high IK level (737 ng/ml) at diagnosis of cGVHD and subsequently had significant drop in her IK level after ECP (256 ng/ml at 60 days and 158 ng/ml at 140 days from the start of photopheresis). Discussion The IK values did not correlate with degree of chronic GVHD or its response to treatment with IST and ECP although it should be noted that cGVHD remained stable in all but one patient during the period of IK measurement. Nonetheless, in one patient with increased IK levels at the diagnosis of cGVHD IK decreased over time with slow improvement in her cGVHD, suggesting that levels might show some correlation with the treatment in responding patients. Longitudinal measurements over time may help to adjust IST, and further studies with standardized timing seem warranted.