Unknown

Dataset Information

0

Organ-specific response after low-dose interleukin-2 therapy for steroid-refractory chronic graft-versus-host disease.


ABSTRACT: Despite new therapeutic options, treatment of steroid-refractory chronic graft-versus-host disease (SR-cGVHD) remains challenging as organ involvement and clinical manifestations are highly variable. In previous trials of low-dose interleukin-2 (LD IL-2), we established the safety and efficacy of LD IL-2 for the treatment of SR-cGVHD. In the present report, we combined five phase 1 or 2 clinical trials conducted at our center to investigate organ-specific response rate, coinvolvement of organs, predictors of organ-specific response, and its possible association with immune response. For the 105 adult patients included in this report, the overall response rate after 8 or 12 weeks of LD IL-2 was 48.6% and 53.3%, including late responses in patients who continued treatment for extended periods. Skin was the most frequent organ involved (84%). The organ-specific response rate was highest in liver (66.7%) followed by the gastrointestinal tract (62.5%), skin (36.4%), joint/muscle/fascia (34.2%), and lung (19.2%). In multivariable analysis, shorter time from diagnosis of cGVHD to IL-2 initiation, shorter time from transplant to IL-2 initiation, and fewer prior therapies were associated with overall response as well as skin response. For immunologic correlates, the ratio of regulatory T cells:conventional T cells (ie, CD4Treg:CD4Tcon) ratio at 1 week was significantly higher in patients with overall and skin response; skin response was significantly associated with lower number of total CD3 T cells, CD4Tcon cells, and CD8 T cells and a higher number of B cells. For lung responders, terminal effector memory cell counts were lower within all T-cell populations compared with nonresponders. Organ-specific mechanisms of injury should be investigated, and organ-specific targeted therapies need to be developed.

SUBMITTER: Kim HT 

PROVIDER: S-EPMC9636330 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Organ-specific response after low-dose interleukin-2 therapy for steroid-refractory chronic graft-versus-host disease.

Kim Haesook T HT   Koreth John J   Whangbo Jennifer J   Nikiforow Sarah S   Reynolds Carol G CG   Stowe Peter P   Ho Vincent T VT   Cutler Corey C   Antin Joseph H JH   Soiffer Robert J RJ   Ritz Jerome J  

Blood advances 20220801 15


Despite new therapeutic options, treatment of steroid-refractory chronic graft-versus-host disease (SR-cGVHD) remains challenging as organ involvement and clinical manifestations are highly variable. In previous trials of low-dose interleukin-2 (LD IL-2), we established the safety and efficacy of LD IL-2 for the treatment of SR-cGVHD. In the present report, we combined five phase 1 or 2 clinical trials conducted at our center to investigate organ-specific response rate, coinvolvement of organs,  ...[more]

Similar Datasets

| S-EPMC1895490 | biostudies-literature
| S-EPMC8058632 | biostudies-literature
| S-EPMC8511171 | biostudies-literature
| S-EPMC6737411 | biostudies-literature
| S-EPMC9647832 | biostudies-literature
2023-12-19 | PXD012036 | Pride
| S-EPMC6102256 | biostudies-other
| S-EPMC9515381 | biostudies-literature
| S-EPMC7705269 | biostudies-literature
| S-EPMC11588829 | biostudies-literature