Clinical Efficacy And Safety Of Ruxolitinib In The Treatment Of Chronic Graft-versus-host Disease

Objective:To study the clinical effect and safety of ruxolitinib in the treatment of chronic graft-versus host disease(cGVHD).Methods:We collected Clinical data of Forty-two patients with cGVHD who received allogeneic hematopoietic stem cell transplantation from January 1,2016 to February 1,2019 in the 920th hospital of the joint logistic support force of the Chinese people's liberation army,And every patient was administered with ruxolitinib to treat cGVHD,the study was completed on May 1,2019.According to the 2014 National Institutes of Health(NIH)consensus on cGVHD diagnostic criteria and severity classification,there are two specific treatment regimens:1.Patients diagnosed as chronic graft-versus host disease with the skin,mouth,eyes,joints or genital tract involvement were advised to use ruxolitinib 5mg/d(When patient weighs more than 25kg,or ruxolitinib was administered in combination with a potent CYP3A4 inhibitor or fluconazole,the total dose was halved)on the basis of the original immunosuppressant therapy,The efficacy was evaluated after 1 month.If no improvement was found,the amount was increased to 5mg bid,and the total amount per day was no more than 20mg.The final efficacy was evaluated to CR or the optimal efficacy was continued for another 1 month,,and the reduction began,and the reduction ended within 6-12 months;2.Patients diagnosed as chronic graft-versus host disease with lung,liver or gastrointestinal tract involvement were advised to use ruxolitinib 5mg/d(When patient weighs more than 25kg,or ruxolitinib was administered in combination with a potent CYP3A4 inhibitor or fluconazole,the total dose was halved)and methylprednisolone 1mg/kg on the basis of the original imnunosuppressant therapy,When the efficacy was evaluated to CR or the best efficacy was achieved,the reduction of methylprednisolone(1/8 of the total weekly reduction)was slowly started.After the methylprednisolone reduction,the reduction of ruxolitinib was started,and the reduction of of ruxolitinib was completed within 6-12 months.The efficacy was evaluated at 1 month and 3 months after treatment with ruxolitinib.Results:1.Forty-two patients with cGVHD after allogeneic hematopoietic stem cell transplantation were included in the study,including 19 males and 22 females.The median age was 23(3-55)years,and the median follow-up time was 11(4-40 months.2.Among the 42 patients included in this study,a total of 19 patients developed aGVHD after transplantation,including 15 patients with grade ?-?(35%)and 4 patients with grade ?-?(9.5%).3.Among the 42 patients with cGVHD,12 had mild cGVHD,23 had moderate cGVHD,and 7 had severe cGVHD.Among them,skin involvement was 37(88.1%),liver involvement 4(9.5%),oral involvement 12(28.6%),eye involvement 4(9.5%),gastrointestinal involvemet 5(11.9%),lung involvement 10(23.8%),joint and fascia involvement 3(7.1%),and genital tract involvement 1(2.3%).4.Among the 42 patients with cGVHD,The ORR of skin,mouth,eyes,gastrointestinal tract,liver,lungs and joints after 1 month of treatment with ruxolitinib were 73.8%,83.3%,91.7%,80%,100%,90%and 0%,respectively.after 3 months,The ORR of skin,mouth,eyes,gastrointestinal tract,liver,lung and joint were 100%,100%,100%,80%,100%,100%and 90%,respectively.ORR was 85.7%(36/42)and 95.2%(40/42)at 1 month and 3 months after treatment with ruxolitinib,respectively.5.In the process of this study,6 patients developed pulmonary infection,among which 1 patients had poor treatment effect on pulmonary infection and eventually died.Bleeding events occurred in 4 patients.In 12 patients,human cytomegalovirus and epstein-barr virus infection or the virus copy number continued to rise;Bone marrow suppression was evident in 8 patients.6.During the follow-up period of this study,4 patients(9.5%)died,includingl patient who died of disease recurrence after transplantation.One patient died from a severe lung infection.One patient developed pulmonary cGVHD(obstructive bronchitis syndrome)after transplantation,and died from progressive lung symptoms eventually.One patient died due to poor gastrointestinal cGVHD control.During the follow-up period,the OS at 6 months and 12 months were 95.2%(40/42)and 90.5%(38/42),respectively.Conclusion:ruxolitinib has significant efficacy in the treatment of chronic graft-versus-host disease,while retaining graft-versus lekemia effect,with low toxic side effects,and adverse reactions is preventable and tolerable.