Abstract

<div>Abstract<p><b>Purpose:</b> GVHD after allogeneic hematopoietic stem cell transplantation (alloSCT) has been associated with low numbers of circulating CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup> regulatory T cells (Tregs). Because Tregs express high levels of the interleukin (IL)-2 receptor, they may selectively expand <i>in vivo</i> in response to doses of IL-2 insufficient to stimulate T effector T-cell populations, thereby preventing GVHD.</p><p><b>Experimental Design:</b> We prospectively evaluated the effects of ultra low-dose (ULD) IL-2 injections on Treg recovery in pediatric patients after alloSCT and compared this recovery with Treg reconstitution post alloSCT in patients without IL-2. Sixteen recipients of related (<i>n</i> = 12) or unrelated (<i>n</i> = 4) donor grafts received ULD IL-2 post hematopoietic stem cell transplantation (HSCT; 100,000–200,000 IU/m<sup>2</sup> ×3 per week), starting </p><p><b>Results:</b> No grade 3/4 toxicities were associated with ULD IL-2. CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup> Tregs increased from a mean of 4.8% (range, 0%–11.0%) pre IL-2 to 11.1% (range, 1.2%–31.1%) following therapy, with the greatest change occurring in the recipients of matched related donor (MRD) transplants. No IL-2 patients developed grade 2–4 acute GVHD (aGVHD), compared with 4 of 33 (12%) of the comparator group who did not receive IL-2. IL-2 recipients retained T cells reactive to viral and leukemia antigens, and in the MRD recipients, only 2 of 13 (15%) of the IL-2 patients developed viral infections versus 63% of the comparator group (<i>P</i> = 0.022).</p><p><b>Conclusions:</b> Hence, ULD IL-2 is well tolerated, expands a Treg population <i>in vivo</i>, and may be associated with a lower incidence of viral infections and GVHD. <i>Clin Cancer Res; 20(8); 2215–25. ©2014 AACR</i>.</p></div>

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