@article{Rami S. Komrokji_Adam W. Mailloux_Dung-Tsa Chen_Mikkael A. Sekeres_Ronald Paquette_William J. Fulp_Chiharu Sugimori_Jennifer Paleveda-Pena_Jaroslaw P. Maciejewski_Alan F. List_Pearlie K. Epling-Burnette_2014, place={Pavia, Italy}, title={A phase II multicenter rabbit anti-thymocyte globulin trial in patients with myelodysplastic syndromes identifying a novel model for response prediction}, volume={99}, url={https://haematologica.org/article/view/7081}, DOI={10.3324/haematol.2012.083345}, abstractNote={Immune dysregulation is a mechanism contributing to ineffective hematopoiesis in a subset of myelodysplastic syndrome patients. We report the first US multicenter non-randomized, phase II trial examining the efficacy of rabbit(r)-anti-thymocyte globulin using 2.5 mg/kg/day administered daily for 4 doses. The primary end point was hematologic response; secondary end points included duration of response, time to response, time to progression, and tolerance. Nine (33%;95% confidence interval=17%–54%) of the 27 patients treated experienced durable hematologic improvement in an intent-to-treat analysis with a median time to response and median response duration of 75 and 245 days, respectively. While younger age is the most significant factor favoring equine(e)-anti-thymocyte globulin response, treatment outcome on this study was independent of age (<em>P</em>=0.499). A shorter duration between diagnosis and treatment showed a positive trend (<em>P</em>=0.18), but International Prognostic Scoring System score (<em>P</em>=0.150), karyotype (<em>P</em>=0.319), and age-adjusted bone marrow cellularity (<em>P</em>=0.369) were not associated with response classification. Since activated T-lymphocytes are the primary cellular target of anti-thymocyte globulin, a T-cell expression profiling was conducted in a cohort of 38 patients consisting of rabbit and equine-antithymocyte globulin-treated patients. A model containing disease duration, CD8 terminal memory T cells and T-cell proliferation-associated-antigen expression predicted response with the greatest accuracy using a leave-one-out cross validation approach. This profile categorized patients independent of other covariates, including treatment type and age using a leave-one-out-cross-validation approach (75.7%). Therefore, rabbit-anti-thymocyte globulin has hematologic remitting activity in myelodysplastic syndrome and a T-cell activation profile has potential utility classifying those who are more likely to respond (<em>NCT00466843 <a href="http://clinicaltrials.gov">clinicaltrials.gov</a></em&gt;).}, number={7}, journal={Haematologica}, author={Rami S. Komrokji and Adam W. Mailloux and Dung-Tsa Chen and Mikkael A. Sekeres and Ronald Paquette and William J. Fulp and Chiharu Sugimori and Jennifer Paleveda-Pena and Jaroslaw P. Maciejewski and Alan F. List and Pearlie K. Epling-Burnette}, year={2014}, month={Jul.}, pages={1176-1183} }