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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: MSC
• Intervention / Treatment: Biological: mesenchymal stromal cells

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lei Gao, M.D., Ph.D.; Phone Number: 023-68774330; Email: gaolei7765@163.com

Study Locations

• China
  • Chongqing, China
    • Second Affiliated Hospital, Army Medical University, PLA
  • Shapingba District
    • Chongqing, Shapingba District, China, 410000
      • Xinqiao Hospital
      • Contact: Jidong Huang; Phone Number: 13228683818; Email: hjdyh@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Screening patients for allogeneic hematopoietic stem cell transplantation;
2. No gender limit, age ≥18 years old and ≤60 years old;
3. KPS score >60 points, expected survival period >3 months;
4. Those without serious functional damage to important organs throughout the body;
5. The patient has no other contraindications to hematopoietic stem cell transplantation
6. Voluntary test and informed consent.

Exclusion Criteria:

1. Have severe heart, kidney or liver dysfunction;
2. Those combined with other malignant tumors need treatment;
3. There are clinical symptoms of brain dysfunction or severe mental illness and the inability to understand or follow the research protocol;
4. Patients who cannot be guaranteed to complete the necessary treatment plan and follow-up observation;
5. Patients with severe acute allergic reactions;
6. Clinically uncontrolled active infection;
7. Patients who are participating in other clinical trials;
8. Researchers believe that the subject is not suitable for clinical trials for other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSCs treatment group	Biological: mesenchymal stromal cells; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: ShiCang Yu
• Collaborators: Xinqiao Hospital of Chongqing
• Investigators: Study Chair: Lei Gao, Xinqiao Hospital

Publications and helpful links

General Publications

• Kong Y, Song Y, Tang FF, Zhao HY, Chen YH, Han W, Yan CH, Wang Y, Zhang XH, Xu LP, Huang XJ. N-acetyl-L-cysteine improves mesenchymal stem cell function in prolonged isolated thrombocytopenia post-allotransplant. Br J Haematol. 2018 Mar;180(6):863-878. doi: 10.1111/bjh.15119. Epub 2018 Feb 2.
• Michalicka M, Boisjoli G, Jahan S, Hovey O, Doxtator E, Abu-Khader A, Pasha R, Pineault N. Human Bone Marrow Mesenchymal Stromal Cell-Derived Osteoblasts Promote the Expansion of Hematopoietic Progenitors Through Beta-Catenin and Notch Signaling Pathways. Stem Cells Dev. 2017 Dec 15;26(24):1735-1748. doi: 10.1089/scd.2017.0133. Epub 2017 Nov 27.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: November 6, 2023
• First Submitted That Met QC Criteria: December 12, 2023
• First Posted (Estimated): December 15, 2023

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: allo-HSCT; PGF
• Other Study ID Numbers: MSC4PGF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data often contains sensitive information, such as personal details, medical history, or financial records. Protecting the privacy and confidentiality of participants is of utmost importance. Sharing such data without proper safeguards could violate privacy regulations or ethical considerations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No