| Objective:Clinical benefit with ruxolitinib as a salvage therapeutic agent in steroid-refractory acute graft-versus-host disease(a GVHD)has been reported.The purpose of this study is to explore the efficacy and safety profile of preemptive administration of ruxolitinib for patients with GVHD after hematopoietic stem cell transplantation(HSCT),and to determine the optimal timing of start of ruxolitinib treatment.Methods:We conducted a multi-center retrospective study to analyze the overall response rate at day 28 and the amelioration of GVHD after preemptive treatment of ruxolitinib in patients with GVHD post-HSCT(ethics review number:2020KY020).A total of 69patients(50 males/19 females)with GVHD(43 a GVHD/26 c GVHD)treated at Fujian Medical University Union Hospital(Fuzhou,China),Xiamen University Affiliated Zhongshan Hospital(Xiamen,China)and The First Affiliated Hospital of Xiamen University(Xiamen,China)from July 2015 to October 2019 were enrolled.The patients were divided into 3 groups according to the starting time of GVHD treatment with the preemptive ruxolitinib:shorter than 3 days(≤3 day,24,34.8%),between days 3～7(3～7days,16,23.2%)and more than 7 days(>7 days,29,42.0%).Treatment responses,safety and outcome of patients were compared among groups.Data were analyzed using Statistical Product and Service Solutions(SPSS)statistical software version 24.0.The one-way ANOVA was applied to analysis quantitative data among 3 groups.Comparison of enumeration data was usingχ~2 test.Survival analysis was performed using Kaplan-Meier survival analysis.A p<0.05 was considered statistically significant.Results:These three groups were well matched demographically.There were no significant differences in conditioning regimens,donor types,CD34~+cells infusion,GVHD prophylaxis regimens and primary treatment among 3 groups.The median time to response of≤3 days group,3～7 days group and>7 days group was 18(6～234),21(7～69)and 28(9～123)days,respectively.The≤3 d group showed a best overall response rate(ORR)at day 28 after treatment than 3～7 d group and>7 d group(a GVHD:100.0%vs90.9%vs 84.6%,P=0.164;c GVHD:100.0%vs 100.0%vs 87.5%,P=1.000;).The≤3 d group and 3～7 d group had a similar complete response rate(CRR)at day 28 after treatment,which was markedly better than>7 d group(a GVHD:73.7%vs 72.7%vs46.2%,P=0.361;c GVHD:40.0%vs 60.0%vs 0.0%,P=0.012;).The cumulative incidence of complete response among 3 groups were 90.3%(≤3 d group),84.4%(3～7d group)and 40.5%(>7 d group),respectively(P<0.001).The clinical GVHD scores dropped significantly in≤3 d group than 3～7 d group and>7 d group(-1.83 grade vs-1.25 grade vs-1.07 grade,P=0.016)at day 28 after treatment.The≤3 d group showed a better 1-year-overall survival(OS)than 3～7 d group(91.7%vs 75.4%,HR:0.40;95%CI:0.07～2.45)and>7 d group(91.7%vs 81.5%,HR:0.48;95%CI:0.11～2.24).Cytopenia(26/69,37.7%)and virus reactivation(26/69,37.7%)were the most common adverse events during ruxolitinib treatment.Incidence and severity of adverse reactions did not differ significantly among groups(P>0.05).Conclusion:When preemptive administration ruxolitinib is initiated rapidly,remarkable efficacy on amelioration of GVHD can be achieved without significant adverse effects.Larger randomized trials are needed to confirm efficacy. |
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