| aim:At present,allogeneic hematopoietic stem cell transplantation(Allo-HSCT)is considered to be an effective way to cure a variety of benign and malignant hematological diseases.The occurrence and extent of GVHD is a major factor that influences the prognosis of Allo-HSCT which limits the application of allo-HSCT considerably as well.What’s worse,cGVHD severely affects the life quality of patients after transplantation.Nowadays,the first-line treatment of GVHD is usually corticosteroid or corticosteroid combined with calcineurin inhibitor(such as cyclosporine and tacrolimus),which is effective to merely half of patients suffering from GVHD.Those patients who don’t react to first-line treatment are named corticosteroid-refractory GVHD(SR-GVHD).Considering that there is no standard treatment for SR-GVHD,different treatment centers vary greatly with regard to its therapeutic regimen.The principle for the treatment of SR-GVHD is long-term use of large doses of immunosuppressive agents,resulting in severe toxic side effects accompanied with its poor efficacy.Therefore,for patients received Allo-HSCT,a new therapeutic drug is needed urgently than ever,and the new drug must have the following feature: while effectively controlling GVHD,the drug can preserve the function of the immune system as much as possible,so that the immune system of certain patients can maintain high sensitivity to pathogens and tumor cells,reducing the incidence of infection,recurrence and secondary tumors in patients who have received allo-HSCT already.In recent years,more and more studies have shown that ruxolitinib plays an important role in controlling inflammation,regulating the subsets and functions of immune cell,and inhibiting leukemia cell growth,and preliminary clinical research results also show that ruxolitinib treatment mitigates the symptom of acute and chronic GVHD after HSCT significantly,and that its inhibition to the immune system is also mild.Based on the current status of GVHD treatment and theinitial efficacy of ruxolitinib treatment for acute and chronic SR-GVHD after allo-HSCT,this study aims to further investigate the efficacy and safety of low-does ruxolitinib(5-10 mg,qd)combined with immunosuppressive agents for the treatment of acute and chronic SR-GVHD after allo-HSCT.Method: we retrospectively analyzed 38 patients administered ruxolitinib(5-10 mg,qd)for SR-aGVHD or SR-cGVHD following allo-HSCT at the Union Hospital of Tongji Medical College,Huazhong University of Science and Technology(May 2017 to March 2018).Overall response rate(ORR),time to best response,malignancy relapse rate,infection rate and treatment-related adverse events(AEs)were assessed.Results:The analysis included 10 patients with SR-aGVHD(grade III/IV,n=9)and 28 patients with SR-cGVHD(moderate/severe,n=24).For the SR-aGVHD and SR-cGVHD groups,respectively:median number of previous GVHD therapies was 2(range: 1-3)and 2(1-4);median follow-up time was 2.5 months(1.5-4 months)and 5months(1.5-10 months);median time to best response was 1 month(0.5-2.5 months)and 3 months(1-9.5months);and ORR was 100%(complete response rate,80%)and82.1%(complete response rate,10.7%)with a response observed in all GVHD-affected organs.The malignancy relapse rates for the SR-aGVHD and SR-cGVHD groups were 10.0% and 10.7%,respectively.Reactivation rates for cytomegalovirus,Epstein-Barr virus and varicella-zoster virus,respectively,were30.0%,10.0% and 0% for the SR-aGVHD group and 0%,14.3% and 7.1% for the SR-cGVHD group.There were no treatment-related AEs of grade ≥2.Conclusions: Ruxolitinib was effective and safe as salvage therapy for SR-GVHD. |
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