MSCs With or Without Peripheral Blood Stem Cell for Treatment of Poor Graft Function and Delayed Platelet Engraftment

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy of mesenchymal stem cells (MSCs) with or without granulocyte colony-stimulating factor (G-CSF) mobilized peripheral stem cells (PBSC) in treating patients experiencing poor graft function or delayed platelet engraftment after allogeneic hematopoietic stem cell transplantation.

Detailed Description
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Allogeneic hematopoietic stem cell transplantation(allo-HSCT) is the only cure for many hematologic diseases. However, about 5-27% of patients would suffer from poor graft function (PGF) and more recipients might develop delayed platelet engraftment (DPE) after allo-HSCT. These complications are associated with considerable mortality related to infections or hemorrhagic complications. Treatment of PGF and DPE usually involves hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) and thrombopoietin (TPO), or second transplantation, but these methods have dismal effect or even a significant risk of graft-versus-host disease (GVHD). Mesenchymal stem cells (MSCs) are a form of multipotent adult stem cells that can be isolated from bone marrow (BM), adipose tissue, and cord blood. Clinical applications of human MSCs include improving hematopoietic engraftment, preventing and treating graft-versus-host disease after allo-HSCT and so on. Some studies have shown that MSCs combined with PBSC or cord blood could be useful to improve engraftment after HSCT. Several reports suggested MSCs might be effective in the treatment of PGF. However, the efficacy of MSCs as single-drug treatment for PGF or DPE is unsatisfactory in our previous study. Therefore, in the present study, G-CSF mobilized PBSC will be used combined with MSCs in the patients with PGF or DPE after allo-HSCT.

Official Title
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Mesenchymal Stem Cells With or Without G-CSF Mobilized Peripheral Blood Stem Cell for Treatment of Poor Graft Function and Delayed Platelet Engraftment After Allogeneic Hematopoietic Stem Cell Transplant

Conditions
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Stem Cell Transplantation, Hematopoietic, Poor Graft Function, Delayed Platelet Engraftment, Hematological Diseases

Intervention / Treatment
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* Biological: PBSC
* Biological: MSCs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age：14-65 years PGF or DPE after allo-HSCT Subjects (or their legally acceptable representatives) must have signed an informed consent document Exclusion Criteria: Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure) Patients with any conditions not suitable for the trial (investigators' decision)

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSCs&PBSC<br>PBSC will be intravenously infused at a dose of 2×10^8/kg. MSCs will be intravenously infused at a dose of 1×10^6 cells/kg once per week or until complete response(CR) . If the patients do not achieve CR or partial remission (PR) within 4 weeks, they will swithed to other therapy. If the patients achieve PR within 4 weeks, a second course of the same treatment will be given. | Biological: PBSC<br> <br> Biological: MSCs<br> <br> |
| Experimental: MSCs<br>MSCs will be intravenously infused at a dose of 1×10^6 cells/kg once per week or until CR. If the patients have no response (NR) within 4 weeks, they will switch to other therapy. If the patients achieve PR within 4 weeks, a second course of the same treatment will be given. | Biological: MSCs<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Hematopoietic Recovery | Hematopoietic reconstitution post-transplantation is defined as reconstitution of both neutrophil and platelet numbers. Neutrophil reconstitution is defined as occurring on the first 3 consecutive days with an neutrophil(NEU)>0.5×10^9/L, and platelet (PLT) reconstitution is defined as the first >20×10^9/L for 3 consecutive days. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of graft-versus-host disease | Graft-versus-host disease (GVHD) includes acute GVHD and chronic GVHD. | 1 year | 
| Incidence of infections | Infections include bacterial, invasive fungal and viral infections | 1 year | 
| Incidence of primary underlying disease relapse |  | 1 year | 
| Incidence of acute toxicity | Acute toxicity mainly involves the heart,live and kidney. | up to 100 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Poor Graft Function, Delayed platelet engraftment, Peripheral Blood Stem Cell, Mesenchymal Stem Cells, Allogeneic hematopoietic stem cell transplantation