Mesenchymal Stem Cells for Treatment of Poor Graft Function After Allogeneic Hematopoietic Stem Cell Transplantation

Study Overview
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Brief Summary
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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective approach for treating both benign and malignant blood disorders. It primarily involves high-dose chemotherapy to eliminate tumor cells within the patient's body, as well as to suppress the recipient's hematopoiesis and immune function. The transplantation replaces the recipient's original hematopoietic stem cells (HSCs) with donor-derived HSCs, thereby reconstructing the donor's hematopoietic and immune functions to achieve disease cure. Poor graft function (PGF) following transplantation, which refers to inadequate engraftment of the transplanted hematopoietic stem cells, is one of the major factors limiting the effectiveness of allo-HSCT. Mesenchymal stromal cells (MSCs), identified within the bone marrow stroma, are a type of non-hematopoietic multipotent stem cells. Several studies, including previous research by our research team, suggest that MSCs can improve the bone marrow hematopoietic microenvironment by secreting various cytokines. This leads to the promotion of hematopoietic stem cell proliferation and differentiation, enhancement of hematopoietic function, and support for hematopoiesis as well as direct or indirect promotion of vascular regeneration in damaged tissues and organs. Therefore, exploring the efficacy of umbilical cord-derived MSCs in treating poor graft function after allo-HSCT, observing the recovery of blood parameters in patients with poor engraftment, monitoring transplantation-related complications and immune reconstitution, and conducting preliminary investigations into the underlying mechanisms can contribute to the exploration of new clinical techniques for the treatment of PGF following allo-HSCT.

Official Title
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Clinical Study of MSCs for Treatment of Poor Graft Function After Allogeneic Hematopoietic Stem Cell Transplantation

Conditions
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MSC

Intervention / Treatment
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* Biological: mesenchymal stromal cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Screening patients for allogeneic hematopoietic stem cell transplantation; No gender limit, age ≥18 years old and ≤60 years old; KPS score >60 points, expected survival period >3 months; Those without serious functional damage to important organs throughout the body; The patient has no other contraindications to hematopoietic stem cell transplantation Voluntary test and informed consent. Exclusion Criteria: Have severe heart, kidney or liver dysfunction; Those combined with other malignant tumors need treatment; There are clinical symptoms of brain dysfunction or severe mental illness and the inability to understand or follow the research protocol; Patients who cannot be guaranteed to complete the necessary treatment plan and follow-up observation; Patients with severe acute allergic reactions; Clinically uncontrolled active infection; Patients who are participating in other clinical trials; Researchers believe that the subject is not suitable for clinical trials for other reasons.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSCs treatment group<br> | Biological: mesenchymal stromal cells<br>* On the basis of conventional PGF treatment for poor implantation, the enrolled patients were injected with 1×10^6/kg mesenchymal stem cells of cord blood weekly for 4 consecutive weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Hemogram recovery of patients with poor graft function after treatment | White blood cells: neutrophil engraftment is defined as neutrophils exceeding 0.5×10^9/L for 3 consecutive days; red blood cells: hemoglobin is not less than 70g/L, and is free of blood transfusion; Platelets: Complete response is defined as platelet count ≥50×10^9/L, continuous for 7 days without platelet transfusion; Partial response (PR) is defined as platelet count (20 50)×10^9/L, continuous Weaning from platelet transfusion at 7 days; no response (NR) is defined as 8 weeks of use at the maximum tolerated dose, platelet count <20×10^9/L or not weaning from platelet transfusion | 20 40 days after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infection rate | Unexpected problems that may occur to the patient or others | 20 40 days after transplantation | 
| graft-versus-host disease | Graft-versus-host disease (GVHD) is a potentially serious complication of allogeneic stem cell transplantation and reduced-intensity allogeneic stem cell transplantation. | within the initial 30 to 60 days or further | 
| survival rate | 1-year overall survival and disease-free survival | 1 year after transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allo-HSCT, PGF