54-P: FRACTIONATED DONOR CHIMERISM (FDC) ANALYSIS IN THE DETECTION AND TREATMENT OF GVHD IN SOLID ORGAN TRANSPLANTATION – DIAGNOSTIC AND THERAPEUTIC IMPLICATIONS

• Published in: Human immunology Vol. 73; p. 84
• Main Authors: Amador, Alexandra C., McCue, Jennifer, Gonzalez, Rogelio, Tekin, Akin, Selvaggi, Gennaro, Garcia, Jennifer, Tzakis, Andreas G., Ruiz, Phillip
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.10.2012
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2012.07.180

Graft-versus-host disease (GVHD) a rare but serious complication following liver and multivisceral tx carries a poor prognosis with mortality approaching 90-95%. Diagnosis is often delayed due to early symptom similarity to more common diagnoses. Rapid detection of GVHD and early initiation of therapy, may lead to improved survival for patients. Purpose: Evaluate the efficacy of FDC analysis for rapid diagnosis and treatment initiation for GVHD. Donor Chimerism(DC) was evaluated using ABI STR reagents. Pre-txp donor and recipient genotypes were determined from pre-txp blood or FFPE tissues. Post txp peripheral blood fractionation for B, T and myeloid cells was performed (RoboSep, StemCell Tech.). Analysis was run on DNA from fractionated and unfractionated cells. Multiviceral and liver txp patients with GVHD were tested using routine chimerism analysis. Those with ⩾10% unfractionated DC had poor outcome despite treatment and eventually expired. Unfractionated analysis gave a skewed impression (DC=22%) of patient’s chimerism while fractionation showed 100% donor T cells and recipient myeloid cells. Following extensive therapy, 100% donor T cells remained and the patient died. Another patient presented with <2% unfractionated DC. On fractionation, T cells were 7% donor. Patient was successfully treated and 0% DC was found within 2 weeks of therapy initiation. GVHD in solid organ transplantation can have dire consequences and once DC in T cells reaches certain levels, the outcome may be fatal. Early diagnosis in suspected GVHD should include fractionated chimerism analysis to differentiate from other common complications. Once documented, GVHD therapy may be followed with chimeric subpopulation values to ensure donor T cells are eliminated from the peripheral circulation.