Abstract
Graft-versus-host disease (GVHD), especially steroid-refractory GVHD, remains a life-threatening complication after hematopoietic stem cell transplantation (HSCT). The effect of the JAK1/2 kinase inhibitor ruxolitinib on treating steroid-refractory acute GVHD has been verified by the REACH1/2 study; however, its safety and efficacy in patients with steroid-refractory chronic GVHD (SR-cGVHD) remain unclear. In this retrospective study, 70 patients received ruxolitinib as a salvage therapy for SR-cGVHD. Twenty-four weeks after ruxolitinib treatment, the overall response rate (ORR) was 74.3% (52/70), including 34 patients who achieved complete remission (CR) and 18 who achieved partial remission (PR). The main adverse event was cytopenia, which occurred in 51.4% (36/70) of patients. After ruxolitinib treatment, the percentage of CD4 cells increased from 18.20% to 23.22% (P<0.001), while the percentages of NK (CD16+CD56+) cells and regulatory T cells (CD4+CD127 ± CD25+) decreased (P<0.001, P<0.001). Among the B cell subsets, the proportion of total B cells approximately tripled from 3.69% to 11.16% (P<0.001). Moreover, we observed a significant increase in IL-10 levels after ruxolitinib treatment (P=0.025) and a remarkable decrease in levels of suppression of tumorigenicity 2 (ST2) from 229.90 ng/ml to 72.65 ng/ml. The median follow-up after the initiation of ruxolitinib treatment was 401 (6-1076) days. The estimated one-year overall survival rate of the whole group was 66.0% (54.4–77.6%, 95% CI), and the one-year overall survival rate of patients with mild and moderate cGVHD was 69.6% (57.4–81.8%, 95% CI), which was better than that of patients with severe cGVHD (31.3%, 0.0–66.2%, 95% CI) (P=0.002). Patients who achieved a CR and PR achieved better survival outcomes (84.5%, 73.9–95.1%, 95% CI) than those who showed NR to ruxolitinib treatments (16.7%, 0–34.3%, 95% CI) (P<0.001). At the final follow-up, cGVHD relapse occurred in six patients after they reduced or continued their ruxolitinib doses. Collectively, our results suggest that ruxolitinib is potentially a safe and effective treatment for SR-cGVHD.
Highlights
Hematopoietic stem cell transplantation (HSCT) has been one of the most important therapies for hematological malignancies
On May 24, 2019, ruxolitinib was approved by the Food and Drug Administration (FDA) as a treatment for steroid-refractory aGVHD (SR-aGVHD) in adult and pediatric patients aged 12 years and older [15]
Forty-two patients had previously experienced acute graft-versus-host disease (GVHD), and 4 of them had been treated with ruxolitinib
Summary
Hematopoietic stem cell transplantation (HSCT) has been one of the most important therapies for hematological malignancies. On May 24, 2019, ruxolitinib was approved by the Food and Drug Administration (FDA) as a treatment for steroid-refractory aGVHD (SR-aGVHD) in adult and pediatric patients aged 12 years and older [15]. In 2015, Zeiser et al first reported that ruxolitinib produced encouraging results in cGVHD therapy [16]. In 2020, Zeiser et al reported that ruxolitinib showed superior efficacy to the best available therapy (BAT) in a phase 3 trial of patients with SRcGVHD. We report a singlecenter retrospective study of 70 patients who received ruxolitinib as a salvage therapy for steroid-refractory cGVHD (SR-cGVHD) in our center between March 2017 and December 2019 to evaluate the safety and efficacy of ruxolitinib after HSCT
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