Analysis Of Risk Factors Of Chronic Graft Versus Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation In 369 Patients

BackgroundChronic graft versus host disease is one of the most common long-term complications following allogeneic hematopoietic stem cell transplantation,which seriously affects the quality of patient's life and increases transplant-related mortality^[1].With medical treatment advances,we have succeeded in reducing the incidence of aGVHD,but almost no progress has been made in the prevention of cGVHD.According to statistics,after allogeneic hematopoietic stem cell transplantation the incidence rate of cGVHD is estimated at 30%⁷0%^[2,3].cGVHD causes systemic changes in multiple organ functions,mainly involving the skin,lungs,gastrointestinal tract,liver,reproductive system,etc,and affects the long-term survival of patients,and improves the medical treatment charges^[4].The main causes of cGVHD-related mortality are immunosuppression induced by long-term applications of immunosuppressant agents,as well as organ dysfunction caused by cGVHD.In the past,cGVHD was defined as GVHD that existed after 100 days of allo-HSCT,regardless of clinical characteristics.The National Institutes of Health?NIH?consensus meeting working group first proposed the 2005 cGVHD diagnosis and grading standards.The main diagnostic criteria were based on clinical manifestations,and put forward the cGVHD?mild,moderate and severe?global severity scores^[5].The clinical characteristics for cGVHD are complicated.In recent years,some studies have analyzeed various risk factors of cGVHD.The most common risk factors are aGVHD,the use of peripheral blood stem cell grafts,female donors of male recipients,and HLA mismatches,use of unrelated donors and older patients.However,more comprehensive disease factors and pathogenesis still remain to be further discussed.The prognosis of patients with extensive cGVHD is generally considered to be poor,while the prognosis of patients with mild cGVHD is similar to that of patients without cGVHD.The analysis of the risk factors and prognosis of patients with cGVHD is to provide help for us that whether we intervene in cGVHD patients and what kind of treatment we take.ObjectiveTo investigate the clinical features,risk factors and prognosis of chronic graft versus host disease patients after allogeneic hematopoietic stem cell transplantation.MethodsWe study 369 patients with allogeneic hematopoietic stem cells in the First Affiliated Hospital of Zhengzhou University from January 1,2010 to October 1,2017.Among them,142 cases developed cGVHD.The clinical features,related risk factors and prognosis of patients with cGVHD were analyzed.result1.In 396 patients,the median age was 24?1⁶0?years;The follow-up deadline was February 1,2018,and the median follow-up time was 456?101²953?days.In142 patients with cGVHD,the morbidity was 38.48%,the median time was 194?77²500?days,and 79 cases with mild cGVHD,63 cases with moderate to severe cGVHD.2.The median time for neutrophil engraftment was 13?7²4?days,and the median time for platelet engraftment was 15?7³1?days;The median number of CD34+cells transfused was 4.9?1.53²7.55?×10⁶/Kg,and the median number of mononuclear cells?MNC?was 5.8?2.1²9.10?×10⁸/Kg.3.Among 142 cases of cGVHD patients,there were 88 cases of skin cGVHD,accounting 61.97%,17 cases with systemic scleroderma,accounting 11.97%;there were 62 cases of oral cGVHD,the ratio was 43.66%;there were 59 cases of liver cGVHD,the proportion of 41.55%;there were 36 cases of eye cGVHD,with a ratio of 25.35%;there were 15 cases of lung cGVHD,involving 10.56%;there were 19cases with digestive tract,the ratio was 13.38%.4.The difference between the two groups in the cGVHD group and the non-cGVHD group was not statistically significant in gender,diagnosis,and conditioning regimen including ATG or not,donor source,donor-recipient gender,doner-recipient blood type,disease status before transplantation,the number of CD34+and MNC cells.There was a statistically significant difference in the patient's age,HLA matching,and aGVHD?P<0.05?.Multivariate analysis showed that the patient's age?P=0.035?and previous aGVHD?P=0.000?were important risk factors for the development of cGVHD.5.By the end of follow-up,there was no significant difference in the overall survival rate between the cGVHD group and the non-cGVHD group?P=0.538?.There was a statistically significant difference in the overall survival rate between the mild cGVHD group and moderate-severe cGVHD group?P=0.001?.There was no significant difference in the overall survival rate between the the mild cGVHD group and the non-cGVHD group?P=0.127?.There was a statistically significant difference in the overall survival rate between the moderate-severe cGVHD group and the non-cGVHD group?P=0.006?.Conclusion1.This study showes that patient's older age and previous occurrence of aGVHD are risk factors of cGVHD,the prevention and treatment of aGVHD can reduce the incidence of cGVHD.2.The overall survival rate in the moderate-severe cGVHD group is lower,and effective measures need to be taken to prevent and treat moderate-severe cGVHD.