Send to

Choose Destination
Blood Adv. 2019 Sep 10;3(17):2550-2561. doi: 10.1182/bloodadvances.2019000631.

Dose-escalated interleukin-2 therapy for refractory chronic graft-versus-host disease in adults and children.

Author information

Division of Hematology-Oncology, Boston Children's Hospital, Boston, MA.
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston MA.
Harvard Medical School, Boston, MA.
Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA.
Harvard School of Public Health, Boston, MA.
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston MA.
Dermatology Program, Division of Immunology, Boston Children's Hospital, Boston, MA; and.
Masonic Cancer Center and Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN.


Low-dose interleukin-2 (IL-2) therapy for chronic graft-versus-host disease (cGVHD) generates a rapid rise in plasma IL-2 levels and CD4+CD25+CD127-Foxp3+ regulatory T-cell (CD4Treg) proliferation, but both decrease over time despite continued daily administration. To test whether IL-2 dose escalation at the time of anticipated falls in plasma levels could circumvent tachyphylaxis and enhance CD4Treg expansion, we conducted a phase 1 trial in 10 adult and 11 pediatric patients with steroid-refractory cGVHD ( NCT02318082). Daily IL-2 was initiated in children and adults (0.33 × 106 and 0.67 × 106 IU/m2 per day, respectively). Dose escalations were scheduled at weeks 2 and 4 to a maximum dose of 1 × 106 IU/m2 per day in children and 2 × 106 IU/m2 per day in adults. Patients continued at their maximum tolerated dose (MTD) until week 8. Children tolerated IL-2 dose escalation with partial responses (PRs) in 9 of 11 patients (82%) at multiple cGVHD sites, including lung. Patient-reported outcome scores for skin and lung improved significantly in pediatric patients. In contrast, 5 of 10 adults required dose reduction, and only 2 of 7 evaluable patients (29%) had PRs at week 8. CD4Tregs and natural killer cells expanded in both cohorts without significant changes in conventional CD4+ T cells (Tcons) or CD8+ T cells. Children achieved a higher median CD4Treg/Tcon ratio at week 8 (0.4 vs 0.18, P = .02) despite lower IL-2 doses. We show for the first time that low-dose IL-2 is safe and effective in children with advanced cGVHD. In adults, escalation above the previously defined MTD did not improve CD4Treg expansion or clinical response.

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center