Single-Center Retrospective Study Of Case Series On Efficacy Of First-Line And Second-Line Treatment For Chronic Graft-Versus-Host Disease

BackgroundAllogeneic hematopoietic stem cell transplantation（allo-HSCT）has been widely used in the treatment of hematological malignant and non-malignant diseases with an excellent performance.Chronic graft-versus-host disease（c GVHD）is one of the most common late complications after transplantation,as well as a major cause of non-relapse mortality.Without impairing graft-versus-tumor effect,it becomes the focus of attention how to better alleviate symptom so as to reduce the risk of non-relapse mortality（NRM）.Although corticosteroid-related side effects will never be ignored,corticosteroid with or without calcineurin inhibitor is still the first-line therapy for moderate/severe c GVHD,with an approximate response rate of 50%yet.Nevertheless,this data only roots in foreign research reports and there are very few reports on curative effect analysis among Chinese patients.So there is a need for more cases of data on our Chinese patients.In addition,patients diagnosed as steroid-refractory or steroid-dependent c GVHD need to turn to second-line anti-rejection drugs for salvage treatment.There is a large amount of alternative medicines,of which Imatinib and Sirolimus are both commonly used second-line drugs with many related clinical studies,however the reports on efficacy of two drugs differs.In the lack of peer to peer contrastive study,there is a debate upon which one is superior,and it’s necessary to conduct clinical researches to answer these clinical questions.Objective1.To evaluate efficacy and prognosis of steroid as first-line treatment for Chinese patients with c GVHD.2.To compare the efficacy and prognosis of Imatinib versus Sirolimus as second-line treatment for c GVHD patients.Materials and Methods1.In this study,90 patients diagnosed with moderate/severe c GVHD in our center from March 2017 to October 2020 and treated with corticosteroid(prednisone with an initial dose of 1mg.kg^-1.d^-1)as first-line treatment were analyzed retrospectively,statistical analysis on these patients was operated in terms of clinical characteristics,response rate,overall survival,drug safety and so on,drawing corresponding conclusion subsequently.2.In this study,33 patients diagnosed with steroid-refractory c GVHD（SR-c GVHD）in our center from September 2017 to December 2020 were analyzed retrospectively.The patients were divided into Imatinib group（Imatinib at a dose range of 100～400mg/d）or Sirolimus group（Sirolimus at a dose range of 2～4mg/d）according to the type of second-line treatment.A retrospective cohort study was conducted to analyze and compare the two groups in terms of response rate,short-term survival,drug-related adverse events and so on.Results1.The 6-month overall response rate（ORR）of 90 patients was 53.3%（48/90）,with a complete response rate（CRR）of 6.7%（6/90）and a partial response rate（PRR）of 46.7%（42/90）.In the order of 6-month ORR of involved organs,6-month ORR of lower gastrointestinal tract,upper gastrointestinal tract,liver,esophagus,skin,joints and fascia,eyes,month and lungs was 56.3%（9/16）,55.0%（11/20）,51.0%（25/49）,50.0%（4/8）,46.2%（30/65）,44.4%（8/18）,43.9%（18/41）,40.8%（20/49）and 25.0%（4/16）,respectively.The3-year overall survival（OS）and 3-year non-relapse mortality（NRM）of 90 patients was 79.6%（95%CI 66.4%～88.1%）and 12.2%（95%CI 0.7%～40.6%）,respectively.Responders to initial therapy performed significantly better than non-responders in terms of OS and NRM（P=0.003,P=0.009）.The 2-year cumulative incidence of relapse of 90 patients was 12.6%（95%CI 2.1%～33.2%）,with no significant difference between responders and non-responders（P=0.349）.During the course of steroid therapy,1 patient had another therapeutic option due to a poor control of blood glucose level,4 patients died due to infection,and 3 patients died due to treatment failure after relapse.2.For patients with c GVHD accepting Imatinib or Sirolimus as second-line treatment,6-month ORR was 62.5%and 41.2%（P=0.303）,while 1-year ORR was 73.3%and 43.8%（P=0.149）,6-month CRR was 12.5%and 23.5%（P=0.656）,while 1-year CRR was 20.0%and 31.3%（P=0.685）,respectively,and no statistical significance was observed between the2 groups.The patients with Imatinib treatment achieved better outcomes than those treated with Sirolimus in terms of 2-year OS and 2-year DFS（P=0.041,P=0.043）.There was no significant difference in the occurrence of drug-related toxicity between the 2 groups.Conclusions1.After 6-month treatment of steroid,alleviation of symptom can be seen among half of patients with c GVHD.Responders after 6-month steroid treatment perform better in OS and NRM.2.Imatinib and Sirolimus shows similar response rate to SR-c GVHD after allo-HSCT,but the former is superior to the latter in terms of short-term OS and DFS.