Safety and Efficacy of Umbilical Cord Blood-Derived Mesenchymal Stem Cells in the Treatment of Long-Term Cytopenia After CAR-T Therapy

Exclusion Criteria17

• Patients with any of the following conditions are prohibited from enrolling in this study:
• Having received other anti-tumor treatments (including but not limited to chemotherapy, radiotherapy, targeted therapy, immunotherapy, or hematopoietic stem cell transplantation) that may affect the hematopoietic system or blood cell count within 1 month before the screening period after CAR-T cell infusion;
• Significant bone marrow infiltration by tumor cells during the screening period (for ALL: bone marrow morphological examination showing leukemia cell proportion > 5%; for multiple myeloma (MM) and lymphoma: bone marrow flow cytometry showing positive minimal residual disease (MRD), or bone marrow pathological immunohistochemistry showing lymphoma/clonal plasma cell infiltration);
• Presence of any of the following conditions within 1 week before the first dose administration: infection with hemodynamic instability (requiring vasoactive drug support); deep fungal infection confirmed by imaging or microbiology (e.g., invasive aspergillosis, bloodstream infection, etc.); Pneumocystis jirovecii pneumonia, active tuberculosis, viremia (cytomegalovirus, parvovirus B19, etc.), and viral pneumonia (cytomegalovirus, COVID-19 virus, influenza virus, adenovirus, parainfluenza virus, etc.); as well as other severe infections that may affect hematopoiesis as judged by the investigator;
• Serum creatinine or blood urea nitrogen ≥ 1.5 times the upper limit of normal (ULN);
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times ULN; total bilirubin ≥ 1.5 times ULN;
• Other severe and/or uncontrolled diseases, or conditions that may affect study participation as judged by the investigator, including but not limited to: severe cardiac rhythm or conduction abnormalities (e.g., ventricular arrhythmias requiring clinical intervention, second-degree to third-degree atrioventricular block, etc.), corrected QT interval using Fridericia's formula (QTcF) > 480 ms on electrocardiogram; New York Heart Association (NYHA) heart function classification of Grade Ⅲ-Ⅳ; uncontrolled diabetes mellitus (glycated hemoglobin \[HbA1c\] > 9%); refractory hypertension; chronic obstructive pulmonary disease (forced expiratory volume in 1 second \[FEV1\] < 50% of predicted value), etc.;
• History of arteriovenous thrombosis or atherosclerosis;
• Positive for anti-human immunodeficiency virus (HIV) antibody or anti-Treponema pallidum specific antibody; positive for hepatitis B surface antigen (HBsAg); or positive for hepatitis B core antibody with hepatitis B virus deoxyribonucleic acid (HBV-DNA) > ULN; or hepatitis C virus ribonucleic acid (HCV-RNA) > ULN;
• A history of or current malignant solid tumor (except cured non-invasive basal cell or squamous cell carcinoma of the skin and/or other cured carcinoma in situ; except other malignant tumors that have achieved clinical cure for > 5 years with no recurrence within 5 years);
• Within 6 months after allogeneic hematopoietic stem cell transplantation, or donor cell chimerism rate ≤ 95%, or presence of active acute graft-versus-host disease (aGVHD) of Grade Ⅱ or higher, or moderate to severe chronic graft-versus-host disease (cGVHD);
• Having received a live vaccine within 4 weeks before the first dose administration, or planning to receive any live vaccine during the study period;
• Pregnant or lactating female patients;
• Patients with mental disorders;
• Participation in any other study drug trial (including vaccine trials) or exposure to other study drugs within 4 weeks or 5 half-lives (whichever is longer) before the first dose administration;
• Patients who refuse to sign the informed consent form;
• Other conditions deemed unsuitable for study inclusion by the investigator.