Treatment of refractory chronic graft-versus-host disease with interleukin-2
Ivan S. Moiseev, E.A. Burmina, Olga V. Pirogova, Olga A. Slesarchuk, Sergej N. Bondarenko, Boris V. Afanasyev
R. M. Gorbacheva Memorial Institute of Children Hematology and Transplantation, First St. Petersburg I. Pavlov State Medical University, St. Petersburg, Russia
Refractory or relapsed chronic graft-versus-host disease (cGVHD) is the complication of allogeneic hematopoietic stem cell transplantation (HCT) that significantly affects life quality, may be associated with morbidity and mortality and has limited treatment options. After promising results from Dana-Farber Cancer Institute about treatment of steroid-refractory cGVHD with interleukin-2 (IL-2)  and a number of in vitro studies, we commenced a pilot trial of IL-2 in this group of patients (pts). Patients and methods: 16 adult pts (median age 22, range 16-51 y.o.) with refractory cGVHD were enrolled. Six pts were on steroids upon inclusion. 11 patients had severe (NIH) cGVHD, 6, moderate. Eight pts developed bronchiolitis obliterans (BO). Pts received IL-2 as subcutaneous injections (1 MIU 3 times a week) and continued other cGVHD treatments (a median of 2 medications, range 1 to 3). Median duration of treatment was 2,5 moths (range 1 to 8 months). Response was assessed by physician assessment (clinical response), improvement in NIH scores and Karnofsky score. Any objective positive response was defined as improvement, in either NIH or Karnofsky scores. Results: Partial clinical response was observed in 5 pts, complete response in 2 pts with overall response of 44%. 4/6 patients discontinued steroids and 2 patients with complete response discontinued all cGVHD medications. In general, there was an improvement of Karnofsky Index in 25% of cases (median change 0%, range -20 to +20%), reduction in NIH severity scores in 37.5% of pts (median change 0, range -8 to +5), stable %FEV1 level (mean change -2, range -22 to +17%), and any objective response in 44% of pts. There were no statistically significant clinical predictive parameters for the response. During the treatment, there was a median of 1 bacterial infection (range 0-3), 0 opportunistic viral (range 0-2), 0 invasive fungal (range 0-1) infectious episodes. Non-relapse mortality was 12% (2 pts) over a median 21-month follow-up. Conclusion: Our preliminary data indicate that a proportion of patients respond well to IL-2 therapy, but absence of clinical predictive parameters for response requires further studies to elucidate biomarkers to redict response.
- Koreth J, Matsuoka K, Kim HT et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011; 365 (22): 2055-66.
Host-versus-gra disease, chronic, interleukin 2, treatment