Umbilical Cord Mesenchymal Stem Cells in the Treatment of Moderate/Severe Chronic Graft-versus-host Disease

Inclusion Criteria:

1. Age 14-70 (≥14, ≤70) one year old, no gender limit;
2. The subject voluntarily participates in the study, and he or his legal guardian signsthe "Informed Consent";
3. CGVHD occurred after transplantation of allogeneic hematopoietic stem cells (umbilicalcord blood, bone marrow or mobilized peripheral blood) with the primary disease ofhematological malignancy, and was diagnosed as moderate/severe cGVHD according to the "Chinese Expert Consensus on the Diagnosis and Treatment of cGVHD (2021 Edition)";
4. Those who are tolerant to the first-line standard treatment regimen (glucocorticoidwith or without calcineurin inhibitor):

1. The organ damage that has been involved in the past is aggravated; 2) People with neworgan involvement; 3) No improvement in symptoms and signs after 1 month of regularmedication (such as glucocorticoid therapy alone, progress in the initial 2 weeks, noimprovement in 6-8 weeks, consider glucocorticoid resistance); 4) At 2 months, prednisonecannot be reduced to less than 1.0mg/kg/d; 5. EOCG score ≤ 3 points.

Exclusion Criteria:

• Patients with any of the following cannot be included in this study:

1. Serum virological examination showed that hepatitis C virus (HCV) antibody, Treponemapallidum (TP) antibody or human immunodeficiency virus (HIV) antibody test resultswere positive;
2. People with severe hepatic vein occlusive disease or sinus vein occlusive syndrome;
3. According to the evaluation of the investigator, patients with cytomegalovirus (CMV)enteritis, transplantation-related thrombotic microangiopathy (TA-TMA), andgastrointestinal infections caused by diarrhea cannot be ruled out clinically; thepathological diagnosis criteria of CMV enteritis are: intestinal mucosa. Large cellsof basic inclusion bodies, immunohistochemical CMV early/late antigen positive,intestinal mucosal homogenate CMV nucleic acid PCR positive;
4. Patient renal function: creatinine clearance rate <30mL/min; creatinine clearance rateis calculated by Cockcroft-Gault formula: Ccr(ml/min)=[(140-age)×weight (kg)]/(72×serum creatinine( mg/dL), for women, according to the calculation result × 0.85), the unit of creatinine should be paid attention to during the calculation ofcreatinine clearance;
5. Within 6 months before enrollment, there is evidence that the patient has otherdiseases or their physiological conditions may interfere with the evaluation resultsof this test, or the complications are severely life-threatening, including but notlimited to uncontrolled infections, pulmonary hypertension, severe Cardiacinsufficiency (NYHA class III and IV), unstable angina or acute myocardial infarction,refractory hypertension (defined as the simultaneous use of 3 different types ofantihypertensive drugs [one of which is a diuretic] Higher than 180/110mmHg) (subjectto the diagnosis of hospitalized medical records), etc.;
6. Patients with active malignant solid tumors within the first 5 years of the study,except for radically cured cervical cancer, in situ localized prostate cancer andnon-melanoma skin cancer;
7. Patients with myelofibrosis;
8. People who suffer from mental or neurological diseases and cannot express their wishescorrectly;
9. Those who have a history of severe allergies to blood components or blood products, orthose who have a history of allergies to heterologous proteins;
10. Breastfeeding women, or female patients who have pregnancy plans or egg donation plansfrom the start of the study to the follow-up period, and male patients (or theirpartners) have birth plans or sperm donation plans from the start of the study to thefollow-up period, and are unwilling to take contraceptive measures ；
11. Those determined by the investigator to be unsuitable to participate in this clinicaltrial;
12. Those who have participated in other clinical trials within the previous month.