Predicting Response to Therapy for Graft-vs-Host Disease (GvHD) with a Rapid Immune Function Assay.

Background: GvHD following allogeneic hematopoietic stem cell transplantation (allo-HSCT) increases morbidity and mortality and is difficult to predict for. We explored the use of a novel immune function assay to determine whether an immunologic response to changes in immunosuppressive therapy for GvHD could predict clinical response.

Methods: The FDA-approved Cylex ® Immune Cell Function assay (ICF) measures the response of whole blood CD4+ lymphocytes to stimulation with phytohemagglutinin (PHA) with as read-out ATP production. The assay is quick and results are available on the same day. Use of this test in solid-organ transplant recipients demonstrated its utility in monitoring changes in immunosuppressive therapy. A retrospective analysis of the ICF assay results from allo-HSCT patients treated at our center for acute or chronic GvHD was conducted.

Results: 13 GvHD events (11 chronic, 2 acute) occurring in 8 patients between 35 and 2118 days post-transplant (682 +/− 556 d) were analyzed. At diagnosis of GvHD, the average ICF value was 425 +/− 111 ng/mL ATP. Same day white blood cell (WBC) and absolute neutrophil count (ANC) values were 10.6 +/− 3.2 x 10³ cells/μL and 9.2 +/− 3.3 x 10³ cells/μL, respectively. Treatment for GvHD consisted of increasing calcineurin inhibitor dose and addition of prednisone and/or other immunosuppressants. Ten GvHD events responded to therapy within 10 +/−7 days with a corresponding significant decrease of ICF values from 430 +/− 109 ng/mL to 239 +/− 130 ng/mL (p=0.002) and a decrease of WBC from 11.2 to 8.0 x10³ cells/μL (p=0.027). ANC and C - reactive protein values were not statistically different (p=0.09 and p>0.5 respectively). In contrast, no significant decrease in the ICF values before and after therapy (406 to 465 ng/mL ATP) was observed for the 3 GvHD events that failed to respond to therapy.

Conclusion: These preliminary data suggest that the ICF assay is a good predictor of response of GvHD to immunosuppressive therapy and could be used to intensify immunosuppression early in non-responders.